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      • abstract_of_study<p>\n  </p>\n<table align=\"right\" border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"98%\">\n <tbody>\n <tr>\n <td style=\"width: 18.1%;\">\n <p>\n <strong>Protocol Title</strong></p>\n </td>\n <td style=\"width: 81.9%;\">\n <p>\n A Phase 3, Double-blind, Randomized, Placebo-controlled, Multicenter Study of GBT440 Administered Orally to Patients with Sickle Cell Disease</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 18.1%;\">\n <p>\n <strong>Protocol Number</strong></p>\n </td>\n <td style=\"width: 81.9%;\">\n <p>\n GBT440-031</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 18.1%;\">\n <p>\n <strong>Sponsor </strong></p>\n </td>\n <td style=\"width: 81.9%;\">\n <p>\n Global Blood Therapeutics, Inc.<br />\n 400 East Jamie Court Suite #101<br />\n South San Francisco, CA  94080</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 18.1%;\">\n <p>\n <strong>Study Drug</strong></p>\n </td>\n <td style=\"width: 81.9%;\">\n <p style=\"margin-left: 12.95pt;\">\n ·    GBT440 capsules or tablets, 300 mg each, administered orally</p>\n <p style=\"margin-left: 12.95pt;\">\n ·    Matching placebo, administered orally</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 18.1%;\">\n <p>\n <strong>Number of Clinical Sites</strong></p>\n </td>\n <td style=\"width: 81.9%;\">\n <p>\n The study will be conducted at approximately 75 international clinical sites.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 18.1%; height: 48px;\">\n <p>\n <strong>Number of Study Participants</strong></p>\n </td>\n <td style=\"width: 81.9%; height: 48px;\">\n <p>\n Approximately 340 total participants with Sickle Cell Disease (SCD), adults and adolescents (up to approximately 400) will be enrolled, as follows:</p>\n <p style=\"margin-left: 13.1pt;\">\n <strong><u>Group 1</u></strong><strong>:</strong> Approximately 60 participants</p>\n <p style=\"margin-left: 13.1pt;\">\n <strong><u>Group 2</u></strong><strong>:</strong> Up to approximately 90 participants; enrollment begins with participant #61 and ends when the Group 3 dose has been selected from the Group 1 Analysis</p>\n <p style=\"margin-left: 13.1pt;\">\n <strong><u>Group 3</u></strong><strong>:</strong> At least 190 participants and up to 250 participants; enrollment begins when the Group 3 dose has been selected from the Group 1 Analysis</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 18.1%; height: 48px;\">\n <p>\n <strong>Treatment</strong></p>\n </td>\n <td style=\"width: 81.9%; height: 48px;\">\n <p style=\"margin-left: 12.95pt;\">\n <strong><u>Group 1</u></strong>: Participants will be randomized in a 1:1:1 ratio to receive GBT440 900 mg/day, GBT440 1500 mg/day, or matching placebo</p>\n <p style=\"margin-left: 12.95pt;\">\n <strong><u>Group 2</u></strong><strong>:</strong> Participants will be randomized in a 1:1:1 ratio to receive GBT440 900 mg/day, GBT440 1500 mg/day, or matching placebo</p>\n <p style=\"margin-left: 12.95pt;\">\n <strong><u>Group 3</u></strong><strong>:</strong> Participants will be randomized in a 1:1 ratio to receive GBT440 (900 mg/day or 1500 mg/day), or matching placebo</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 18.1%;\">\n <p>\n <strong>Objectives</strong></p>\n </td>\n <td style=\"width: 81.9%;\">\n <p style=\"margin-left: -0.4pt;\">\n <strong>Primary</strong></p>\n <p>\n The primary objective is to assess the efficacy of GBT440 in adolescents and adults with SCD as measured by improvement in anemia.</p>\n <p style=\"margin-left: -0.4pt;\">\n <strong>Secondary</strong></p>\n <p>\n The secondary objectives are to evaluate the effects of GBT440 compared to placebo on SCD symptom exacerbation and Total Symptom Score (TSS) from Patient Reported Outcome measurement (PRO), measures of anemia and hemolysis, and other clinical measures (e.g., vaso-occlusive crisis [VOC], Acute Chest Syndrome [ACS], hospitalization, red blood cell [RBC] transfusions, opioid use).</p>\n <p style=\"margin-left: -0.4pt;\">\n <strong>Exploratory</strong></p>\n <p>\n The exploratory objectives are to evaluate the effects of GBT440 compared to placebo on the EuroQol EQ-5D-5L health questionnaire (EQ-5D-5L™), days missed from work/school, and measures related to SCD pathophysiology and to evaluate measures predictive of response to GBT440.</p>\n <p>\n <strong>Safety</strong></p>\n <p>\n The safety objectives are to assess the safety of GBT440 compared to placebo based on adverse events (AEs), clinical laboratory tests, physical examinations, and other clinical measures (e.g., discontinuations due to AEs, dose reductions).</p>\n <p>\n <strong>Pharmacokinetics </strong></p>\n <p>\n The pharmacokinetic (PK) objective is to assess the PK of GBT440 as evaluated by population PK analysis.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 18.1%;\">\n <p>\n <strong>Study Design</strong></p>\n </td>\n <td style=\"width: 81.9%;\">\n <p>\n <strong>STUDY DESIGN</strong></p>\n <p>\n This study is a randomized, placebo-controlled, double blind, parallel group, multicenter study of participants, age 12 to 65 years, with SCD (HbSS, HbSC,HbSβ0 thalassaemia or other Sickle Cell Syndrome variants) conducted in three groups of study participants, Groups 1, 2, and 3. The key purposes for each group are:</p>\n <p style=\"margin-left: -0.4pt;\">\n <strong><u>Group 1</u>:</strong></p>\n <p style=\"margin-left: 36pt;\">\n ·      Dose selection: GBT440 dose (900 or 1500 mg) for further study.</p>\n <p style=\"margin-left: 36pt;\">\n ·      Final definition of endpoints for patient reported outcomes measure for the Main Population Analysis</p>\n <p style=\"margin-left: 36pt;\">\n ·      Electronic patient reported outcomes (ePRO) qualification for the Main Population Analysis</p>\n <p>\n <strong><u>Group 2</u>:</strong></p>\n <p style=\"margin-left: 36pt;\">\n ·      To allow for a seamless transition from Group 1 to Group 3 by continuing enrollment and data collection in the study during the Group 1 treatment period and data analysis (referred to as Group 1 Analysis).</p>\n <p>\n <strong><u>Group 3</u>:</strong></p>\n <p style=\"margin-left: 36pt;\">\n ·      Establish efficacy and safety of GBT440 at the selected dose. The final data analysis set ( referred to as the Main Population) will include</p>\n <p style=\"margin-left: 108pt;\">\n §  Group 2 participants</p>\n <p style=\"margin-left: 144pt;\">\n ·      Assigned to placebo</p>\n <p style=\"margin-left: 144pt;\">\n ·      Assigned to the selected dose and</p>\n <p style=\"margin-left: 108pt;\">\n §  All Group 3 participants.</p>\n <p style=\"margin-left: -0.4pt;\">\n <strong><u>Open Label Extension (under separate protocol)</u></strong></p>\n <p>\n Participants will be given the option to enroll in an open label extension study to receive GBT440 at the selected dose.</p>\n <p>\n The open label extension study will be available to eligible participants who:</p>\n <p style=\"margin-left: 22.1pt;\">\n ·      Were included in the Group 1 Analysis regardless of the treatment arm to which they were randomized.</p>\n <p style=\"margin-left: 22.1pt;\">\n ·      Were randomized in Group 2 to the dose not selected for Group 3.</p>\n <p style=\"margin-left: 22.1pt;\">\n ·      Were included in Group 3 and completed through end of treatment.</p>\n <p>\n The Study Schematic is provided in Figure 1, at the end of the Synopsis.</p>\n <p>\n <strong>Adolescent Participants </strong></p>\n <p>\n Initially only adult participants will be enrolled. Adolescent participants (12 to <18 years) will be included in enrollment/randomization when:</p>\n <p style=\"margin-left: 17.6pt;\">\n 1) Single dose PK data and modeling from Study GBT440-007 are available to confirm the appropriate dose for adolescent participants, and</p>\n <p style=\"margin-left: 17.6pt;\">\n 2) The Data Safety Monitoring Board (DSMB) has reviewed the safety data from at least 18 adults enrolled in this study of which at least 6 adults have received 1500 mg GBT440 for at least 4 weeks to confirm acceptable safety and tolerability before adolescents can be enrolled. Sites will be notified when adolescent participants can be enrolled in this study.</p>\n <p>\n At the time that these criteria are met, adolescents will begin to enroll (as early as in Group 1); a minimum of 50 adolescents will be included in the Main Population.</p>\n <p>\n <strong>Screening and Randomization</strong></p>\n <p>\n After signing the informed consent form (ICF), participant screening will include medical history, vital signs, electrocardiogram (ECG), complete physical exam (PE) including height and weight, blood chemistry including iron studies, hematology laboratory tests, serum pregnancy test for women, and urinalysis. The ePRO measure assessment must be completed for at least 75% of days of a 28-day Screening period. All screening procedures must be completed within 35 days before randomization. Laboratory tests will be performed by a central laboratory.</p>\n <p>\n <strong>Study DRUG INFORMATION</strong></p>\n <p>\n Participants receiving 1500 mg GBT440 will receive five 300 mg capsules or tablets, administered orally, once daily; participants receiving 900 mg GBT440 will receive three 300 mg capsules or tablets, and 2 placebo capsules or tablets administered orally, once daily. Participants randomized to placebo will receive 5 placebo capsules or tablets administered orally, once daily. Study drug may be taken with or without food. Participants in Group 1 must take their study drug in the mornings and must avoid high fat meals for 4 hours before and 4 hours after taking study drug. Group 2 and Group 3 participants may take study drug in the morning or evening, preferably at same time each day throughout the study ( Group 2 and Group 3 participants have no food restrictions/requirements).</p>\n <p>\n <strong>Dose Modifications</strong></p>\n <p>\n Guidelines for dose modification are provided in Table 1and Table 2at the end of the Synopsis. The Medical Monitor should be notified of all dose modifications within 72 hours. Details regarding study medication kit preparation and dispensation are provided in the Site Operations Manual.</p>\n <p>\n <strong>ANALYSIS GROUPS AND specifications </strong></p>\n <p>\n <strong>Analysis will be conducted on populations: </strong></p>\n <p style=\"margin-left: 36pt;\">\n ·      Group 1 Population</p>\n <p style=\"margin-left: 36pt;\">\n ·      Main Population: Group 2 (placebo and selected dose treatment arm only) and Group 3, combined</p>\n <p>\n <strong><u>Group 1</u>:  </strong></p>\n <p style=\"margin-left: 18pt;\">\n ·      When the 60^th participant reaches 12 weeks of treatment, data from the 60 participants will be unblinded, and a Group 1 Analysis will be conducted.</p>\n <p style=\"margin-left: 36pt;\">\n ·      The Group 1 Analysis will include PK, efficacy (primarily Hb response, ePRO endpoints, proportions of days with symptom exacerbation and change from Baseline in TSS), and safety endpoints, to inform the following for Group 3:</p>\n <p style=\"margin-left: 72pt;\">\n o   Dose selection will be performed: GBT440 dose (900 or 1500 mg) for further study.</p>\n <p style=\"margin-left: 72pt;\">\n o   Final definition of endpoints for patient reported outcomes measure for the Main Population Analysis</p>\n <p style=\"margin-left: 72pt;\">\n o   Electronic patient reported outcomes (ePRO) qualification for the Main Population Analysis.</p>\n <p style=\"margin-left: 72pt;\">\n o   Other potential modifications to the study: Allowable modifications will be to continue both doses if risk/benefit is unclear, to discontinue one of the doses if the second dose risk/benefit is clear, selection of intermediate dose (1200 mg) if the analysis suggests a better risk/benefit</p>\n <p style=\"margin-left: 36pt;\">\n ·      Data from Group 1 will not be combined with data from Groups 2 and 3 for the Main Population Analysis. </p>\n <p style=\"margin-left: 36pt;\">\n ·      The Sponsor may change or re-order the secondary endpoints for the Main Population Analysis based on the Group 1 Analysis and prior to unblinding of Main Population data.</p>\n <p style=\"margin-left: -0.4pt;\">\n <strong><u>Group 2</u>: </strong></p>\n <p style=\"margin-left: 36pt;\">\n ·      Group 2 includes study participants who enroll while the Group 1 Analysis is conducted.</p>\n <p style=\"margin-left: 36pt;\">\n ·      Randomization will continue 1:1:1 until a decision has been reached on the dose selected for use in Group 3.</p>\n <p style=\"margin-left: 36pt;\">\n ·      Once the GBT440 dose is selected for Group 3, participants who have received the non-selected GBT440 dose in Group 2 will be offered open label treatment under a separate protocol.</p>\n <p style=\"margin-left: 36pt;\">\n ·      Only participants in Group 2 assigned to placebo, and to the selected GBT440 dose for Group 3, will be included in the Main Population Analysis.</p>\n <p>\n <strong><u>Group 3</u>: </strong></p>\n <p style=\"margin-left: 36pt;\">\n ·      Group 3 participants will be randomized in a 1:1 ratio to receive the GBT440 selected dose or placebo. Group 3 will be included in the Main Population Analysis.</p>\n <p>\n <strong>BLINDING</strong></p>\n <p>\n This study is a double-blind study. The GBT440 and placebo capsules or tablets will be matched for shape, size, and color.</p>\n <p>\n For Group 1, with the exception of those noted below in Unblinding for Analysis, all individuals involved in the conduct of the study (i.e., site staff and study participants, contract research organization [CRO] personnel, Sponsor personnel) will be blinded to randomized treatment assignment.  </p>\n <p>\n For Groups 2 and 3, all individuals involved in the conduct of the study (i.e., site staff and study participants, Clinical CRO personnel, all Sponsor personnel) will be blinded to randomized treatment assignment. Drug Supply will remain unblinded throughout the study.</p>\n <p>\n <strong>Unblinding for Analysis</strong></p>\n <p style=\"margin-left: 13.1pt;\">\n <strong><u>Group 1</u></strong><strong>:</strong> To facilitate the Group 1 Analysis, certain Sponsor representatives and Sponsor designees will be unblinded to treatment assignments prior to and during the analysis (including the biostatistics CRO and external groups for bioanalytical PK/PD, and ePRO analyses). The blinded Sponsor study team members will be unblinded to the Group 1 Analysis results only after the Group 1 Analysis is complete.</p>\n <p style=\"margin-left: 13.1pt;\">\n <strong><u>Group 2</u>:</strong> Participants randomized to the non-selected dose will be unblinded and offered the option to enroll in an open label extension study. For the remaining Group 2 participants, unblinding to treatment assignment will occur after database lock for the Main Population Analysis.</p>\n <p style=\"margin-left: 12.95pt;\">\n <strong><u>Group 3</u>:</strong> Unblinding to treatment assignment will occur after database lock for the Main Population Analysis.</p>\n <p>\n <strong>Unblinding for Laboratory Test Assessment</strong></p>\n <p>\n Local laboratory tests including hematology laboratory tests may be used as needed per standard of care to manage AEs (such as hospitalization for VOC), and in these circumstances, the laboratory data may need to be unblinded.</p>\n <p>\n Because knowledge of certain laboratory assessments (Hb, hematocrit [Hct], RBC count, total and unconjugated bilirubin, and absolute and % reticulocyte count) may suggest the treatment assignment, these measurements will be redacted to the Investigator and monitored on a regular basis by the DSMB. Results of redacted laboratory tests will be communicated to the Investigator if a participant’s absolute reticulocyte count declines to <80 × 10⁸/L or Hb declines to <5.0 g/dL (but this does not require breaking of the treatment assignment blind). This is to ensure participant safety by allowing the Investigator to monitor for potential bone marrow suppression, as described in hydroxyurea (HU) monitoring guidelines (NHLBI 2014) (National Heart, Lung, and Blood Institute; NHLBI; 2014). All other laboratory assessments (not redacted) will be available to the Investigator. Anonymized laboratory results will be available to the Sponsor.</p>\n <p>\n <strong>Unblinding for Medical Need</strong></p>\n <p>\n If a medical condition should arise for which appropriate treatment cannot be decided without knowledge of the GBT440-031 study treatment assignment, the Investigator will contact the Sponsor to request permission to unblind. Pregnancy is considered a medical condition that requires unblinding. Upon written approval of the Sponsor, unblinding procedures will be followed as outlined in the Site Operations Manual and documented in the Investigator site file and the case report form (CRF).</p>\n <p>\n <strong>Data AND Safety Monitoring Board </strong></p>\n <p>\n An independent DSMB will monitor the safety and conduct of the trial. The DSMB will be comprised of medical and statistical representatives. The DSMB can provide recommendations to the Sponsor regarding stopping the study or discontinuing a treatment arm or otherwise modifying the study design or conduct.</p>\n <p>\n The DSMB will review:</p>\n <p style=\"margin-left: 36pt;\">\n ·       The Group 1 Analysis and provide an assessment of the benefit to risk ratio of the 900 mg and 1500 mg doses.</p>\n <p style=\"margin-left: 36pt;\">\n ·       Safety data from at least 18 adults enrolled in this study of which at least 6 adults have received 1500 mg GBT440 for at least 4 weeks to confirm acceptable safety and tolerability before adolescents can be enrolled. The sites will be notified when adolescent participants can be enrolled in this study.</p>\n <p style=\"margin-left: 36pt;\">\n ·       Safety data on a periodic basis as defined in the DSMB Charter.</p>\n <p>\n Sites will be informed of the DSMB recommendations only if the recommendations lead to changes in the study conduct.</p>\n <p>\n The composition, responsibilities, and other details of the DSMB will be described in the DSMB Charter.</p>\n <p>\n <strong>Safety Assessments </strong></p>\n <p>\n Participant safety and tolerability will be monitored during the study using standard measures, including physical examinations, vital signs (including blood pressure [BP] and pulse rate), 12 lead ECGs, safety laboratory tests, urinalysis, concomitant medication usage and AE monitoring. All laboratory tests (including during the screening period) will be performed through a central laboratory.</p>\n <p>\n Assessments will be performed at Screening, and prior to dosing (Baseline), and at defined times during the study. Assessments will include blood chemistry and hematology, GBT440 whole blood and plasma concentrations (for population PK analysis), erythropoietin levels, hemoglobin fetal (HbF) levels (Baseline, and End of Treatment [EOT]), physical examinations, ECGs, blood samples for biomarker testing, ePRO SCD Severity Measure (SCDSM), and eDiary. Once the participant initiates study drug treatment, assessments will be conducted every 2 weeks for the first 8 weeks, then every 4 weeks until end of study drug treatment. Safety assessments will be conducted at approximately 30 days after the last dose of study drug.</p>\n <p>\n Assessment of AEs will begin at the time of signing the ICF and will continue through the last study visit. AEs and laboratory values will be graded with National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 (v4.03: June 14, 2010).</p>\n <p>\n Participants enrolled will complete the EQ-5D-5L™ at defined times during the study. EQ-5D-5L™ is a standardized instrument for use as a measure of health outcome; it provides a simple descriptive profile and a single index value for health status.</p>\n <p>\n <strong>Restrictions Regarding Concomitant Medications </strong></p>\n <p>\n GBT440 should be used with caution with CYP3A4 substrates with a narrow therapeutic index.</p>\n <p>\n The use of strong inducers of CYP2B6, CYP2C9, CYP2C19, and CYP3A4/CYP3A5 is prohibited. The use of herbal medications (e.g., St. John’s Wort) is not allowed.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 18.1%; height: 48px;\">\n <p>\n <strong>Duration of Study Participation</strong></p>\n </td>\n <td style=\"width: 81.9%; height: 48px;\">\n <p>\n <strong>Duration of Treatment</strong></p>\n <p style=\"margin-left: 13.1pt;\">\n <strong><u>Group 1</u>:</strong> Minimum duration is 12 weeks, maximum duration is 72 weeks or up to the completion of the Group 1 Analysis, whichever comes first.</p>\n <p style=\"margin-left: 13.1pt;\">\n <strong><u>Group 2</u>:</strong> Minimum duration is 2 weeks, maximum duration is 72 weeks.</p>\n <p style=\"margin-left: 13.1pt;\">\n <strong><u>Group 3</u>:</strong> Minimum duration is 24 weeks, maximum duration is 72 weeks.</p>\n <p>\n <strong>Duration of Study</strong></p>\n <p>\n Duration of study for an individual participant includes Screening (at least 28 days, but up to 35 days to account for Screening window flexibility), treatment for a minimum of 12 weeks and a maximum of 72 weeks, and an End of Study (EOS) visit at 4 weeks (± 7 days) after the last dose of study drug. From Screening through follow-up, total participation in this study for an individual participant may last from approximately 22 weeks to up to 81weeks. The minimum study duration is approximately 10 weeks (for participants in Group 2 enrolled at a dose not selected for Group 3). Participants will continue to be followed for efficacy and safety through at least the endpoint visit (Week 12 for Group 1 and Week 24 for the Main Population) regardless of treatment discontinuation.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 18.1%;\">\n <p>\n <strong>Study Population</strong></p>\n </td>\n <td style=\"width: 81.9%;\">\n <p>\n <strong>Inclusion Criteria</strong></p>\n <p style=\"margin-left: 18pt;\">\n 1.     Male or female study participants with sickle cell disease</p>\n <p style=\"margin-left: 37.5pt;\">\n ·      Documentation of SCD genotype (HbSS, HbSC, HbSβthalassemia or other sickle cell syndrome variants) may be based on history of laboratory testing or must be confirmed by laboratory testing during screening</p>\n <p style=\"margin-left: 18pt;\">\n 2.     Participants have had at least 1 episode of VOC in the past 12 months. For study eligibility, VOC is defined as a previously documented episode of ACS or acute painful crisis <strong>(</strong>for which there was no explanation other than VOC<strong>)</strong> which required prescription or healthcare professional‑instructed use of analgesics for moderate to severe pain (documentation must exist in the patient medical record prior to Screening)</p>\n <p style=\"margin-left: 18pt;\">\n 3.     Age 12 to 65 years</p>\n <p style=\"margin-left: 18pt;\">\n 4.     Hemoglobin (Hb) ≥6.0 and ≤10.5 g/dL during Screening</p>\n <p style=\"margin-left: 18pt;\">\n 5.     Absolute reticulocyte count and % reticulocyte count must be >1.5 × upper limit of normal (ULN) during Screening</p>\n <p style=\"margin-left: 18pt;\">\n 6.     For participants taking HU, the dose of HU (mg/kg) must be stable for at least 3 months prior to signing the ICF and with no anticipated need for dose adjustments during the study, in the opinion of the Investigator</p>\n <p style=\"margin-left: 18pt;\">\n 7.     Participants must demonstrate 75% compliance with ePRO measure completion to be enrolled (participants will be given an ePRO device for at least 28 days during Screening; participants who are 60 to 74% compliant can re-screen once with Investigator approval; re‑screening is not allowed for participants who are <60% compliant)</p>\n <p style=\"margin-left: 18pt;\">\n 8.     Participants, who if female and of child bearing potential, are using highly effective methods of contraception from study start to 3 months after the last dose of study drug, and who if male are willing to use barrier methods of contraception, from study start to 3 months after the last dose of study drug</p>\n <p style=\"margin-left: 18pt;\">\n 9.     Participant has provided documented informed consent or assent (the ICF must be reviewed and signed by each participant; in the case of pediatric participants, both the consent of the participant’s legal representative or legal guardian, and the participant’s assent must be obtained)</p>\n <p>\n <strong>Exclusion Criteria</strong></p>\n <p style=\"margin-left: 18pt;\">\n 1.     More than 10 VOCs within the past 12 months that required a hospital, emergency room or clinic visit</p>\n <p style=\"margin-left: 18pt;\">\n 2.     Female who is breast feeding or pregnant</p>\n <p style=\"margin-left: 18pt;\">\n 3.     Patients who are receiving regularly scheduled blood (RBC) transfusion therapy (also termed chronic, prophylactic, or preventive transfusion) or have received a RBC transfusion for any reason within 28 days of signing the ICF</p>\n <p style=\"margin-left: 18pt;\">\n 4.     Hospitalized for sickle cell crisis or other vaso-occlusive event within 14 days of signing the ICF (i.e., a vaso-occlusive event cannot be within 14 days prior to ICF )</p>\n <p style=\"margin-left: 18pt;\">\n 5.     Hepatic dysfunction characterized by alanine aminotransferase (ALT) >4 × ULN</p>\n <p style=\"margin-left: 18pt;\">\n 6.     Participants with clinically significant bacterial, fungal, parasitic or viral infection which require therapy:</p>\n <p style=\"margin-left: 31.1pt;\">\n ·    Participants with acute bacterial infection requiring antibiotic use should delay screening/enrollment until the course of antibiotic therapy has been completed. 
</p>\n <p style=\"margin-left: 31.1pt;\">\n ·    Participants with known active hepatitis A, B, or C or who are known to be human immunodeficiency virus (HIV) positive</p>\n <p style=\"margin-left: 18pt;\">\n 6.     Severe renal dysfunction (estimated glomerular filtration rate at the Screening visit; calculated by the central laboratory) <30mL/min/1.73 m² or on chronic dialysis</p>\n <p style=\"margin-left: 18pt;\">\n 7.     History of malignancy within the past 2 years prior to treatment Day 1 requiring chemotherapy and/or radiation (with the exception of local therapy for non‑melanoma skin malignancy).</p>\n <p style=\"margin-left: 18pt;\">\n 8.     History of unstable or deteriorating cardiac or pulmonary disease within 6 months prior to consent including but not limited to the following:</p>\n <p style=\"margin-left: 31.1pt;\">\n ·    Unstable angina pectoris or myocardial infarction or elective coronary intervention</p>\n <p style=\"margin-left: 31.1pt;\">\n ·    Congestive heart failure requiring hospitalization</p>\n <p style=\"margin-left: 31.1pt;\">\n ·    Uncontrolled clinically significant arrhythmias</p>\n <p style=\"margin-left: 18pt;\">\n 10.  Any condition affecting drug absorption, such as major surgery involving the stomach or small intestine (prior cholecystectomy is acceptable).</p>\n <p style=\"margin-left: 18pt;\">\n 11.  Participated in another clinical trial of an investigational agent (or medical device) within 30 days or 5 half-lives of date of informed consent, whichever is longer, or is currently participating in another trial of an investigational agent (or medical device).</p>\n <p style=\"margin-left: 18pt;\">\n 12.  Inadequate venous access as determined by the Investigator/site staff.</p>\n <p style=\"margin-left: 18pt;\">\n 13.  Medical, psychological, or behavioral conditions, which, in the opinion of the Investigator, may confound study interpretation, interfere with compliance, or preclude informed consent.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 18.1%;\">\n <p>\n <strong>Statistical Methods</strong></p>\n </td>\n <td style=\"width: 81.9%;\">\n <p>\n <strong>Study Endpoints</strong></p>\n <p>\n The endpoints listed below are for the <strong><u>Main Population</u></strong><u> <strong>Analysis</strong></u><strong> (</strong>Groups 2 and 3). The same endpoints will be evaluated for Group 1 participants at the Week 12 visit. In addition, for the Group 1 population, the primary efficacy measure is evaluated as two endpoints (details are provided in Section 10.2).</p>\n <p>\n <strong>Primary Endpoint</strong></p>\n <p>\n Increase in Hb >1 g/dL from Baseline to Week 24. Participant is responder if Week 24 Hb is >1 g/dL compared to Baseline.</p>\n <p>\n <strong>Secondary Endpoints</strong></p>\n <p>\n The first four endpoints are alpha-controlled.</p>\n <p style=\"margin-left: 13.1pt;\">\n ·    Proportion of days with SCD symptom exacerbation during the first 24 weeks of treatment. This is the first-rank secondary endpoint.</p>\n <p style=\"margin-left: 13.1pt;\">\n •    Change from Baseline to Weeks 21–24 in the SCDSM TSS; for each participant, the TSS will be computed as follows: The Baseline TSS is the average of the score during the 28-day Screening period; during the treatment period, the TSS is the average score each 4-week period on treatment. The 4-week periods are Weeks 1–4, 5–8, 9–12, 13–16, 17–20, and 21–24 (and follows similarly for participants whose participation exceeds 24 weeks). This is the second-rank secondary endpoint.</p>\n <p style=\"margin-left: 13.1pt;\">\n •    Normalization of reticulocyte count at Week 24 (% reticulocytes <1.5 × ULN weeks)</p>\n <p style=\"margin-left: 13.1pt;\">\n ·    VOC during the treatment period is defined as:</p>\n <p style=\"margin-left: 13.1pt;\">\n A composite of acute painful crisis or ACS and includes the following:</p>\n <p style=\"margin-left: 35.6pt;\">\n o   Moderate to severe pain lasting at least 2 hours</p>\n <p style=\"margin-left: 35.6pt;\">\n o   No explanation other than VOC</p>\n <p style=\"margin-left: 36pt;\">\n o   Requires oral or parenteral opioids, ketorolac, or other analgesics prescribed or directed by a healthcare professional</p>\n <p style=\"margin-left: 36pt;\">\n o   Must be documented in patient medical record that the patient was seen, or contacted the physician, within 1 day of the event. The event may take place in a medical setting (hospital, clinic, emergency room)</p>\n <p style=\"margin-left: 36pt;\">\n o   May include episodes of ACS (ACS is defined as an acute illness characterized by fever and/or respiratory symptoms, accompanied by a new pulmonary infiltrate on a chest X-ray</p>\n <p style=\"margin-left: 15pt;\">\n ·     Rate of hospitalization for VOC during the treatment period</p>\n <p style=\"margin-left: 15pt;\">\n ·     Change from Baseline to 24 weeks in hemolysis and related measures: % reticulocytes, unconjugated bilirubin, Hb, dense RBCs</p>\n <p style=\"margin-left: 15pt;\">\n ·     Time to first ACS during the treatment period</p>\n <p style=\"margin-left: 15pt;\">\n ·     Time to first RBC transfusions during the treatment period</p>\n <p style=\"margin-left: 15pt;\">\n ·     Rate of opioid use, calculated as the proportion days that opioids were used each 4‑week period as recorded in an eDiary</p>\n <p style=\"margin-left: 15pt;\">\n ·     Length of hospitalization for VOC</p>\n <p>\n <strong>Exploratory Endpoints</strong></p>\n <p style=\"margin-left: 13.1pt;\">\n ·    Change in health status compared to Baseline utilizing the EQ-5D-5L™</p>\n <p style=\"margin-left: 13.1pt;\">\n ·    School and work attendance as measured in an eDiary. The rate of missed school and work days for each participant will be calculated as the proportion of days that school or work was missed every 4 weeks</p>\n <p style=\"margin-left: 13.1pt;\">\n ·    Change from Baseline to 24 weeks in measures related to SCD pathophysiology, including lactate dehydrogenase (LDH), carboxyhemoglobin, glycated Hb Soluble P‑selectin, VCAM, ICAM, E-Selectin (and other exploratory measures that may be related to disease activity), urine albumin to creatinine ratio, serum cystatin C, Hb distribution width, RBC deformability (to be assessed at select centers), RBC phosphatidylserine expression (to be assessed at select centers), and TR jet velocity as assessed by echocardiography (to be assessed at select centers)</p>\n <p style=\"margin-left: 13.1pt;\">\n ·    Resolution of jaundice at Week 24 (total bilirubin >2 × ULN at Baseline and ≤2 × ULN at 24 weeks)</p>\n <p>\n <strong>Safety Endpoint</strong></p>\n <p style=\"margin-left: 13.1pt;\">\n ·    AEs, clinical laboratory tests, physical examinations, and vital signs</p>\n <p>\n <strong>Pharmacokinetic Endpoint</strong></p>\n <p style=\"margin-left: 13.1pt;\">\n ·    PK of GBT440 as evaluated by population PK analysis using nonlinear mixed effects modeling</p>\n <p>\n <strong>Sample Size</strong></p>\n <p>\n The sample size for the study is estimated to be approximately 340 participants (up to approximately 400 participants).</p>\n <p style=\"margin-left: 13.1pt;\">\n <strong><u>Group 1</u></strong><strong>:</strong> Approximately 60 participants will be randomized 1:1:1 to GBT440 900 mg, 1500 mg, or placebo.</p>\n <p style=\"margin-left: 13.1pt;\">\n <strong><u>Group 2</u></strong><strong>:</strong> Up to approximately 90 participants will be randomized 1:1:1 to GBT440 900 mg, 1500 mg, or placebo.</p>\n <p style=\"margin-left: 13.1pt;\">\n <strong><u>Group 3</u>:</strong> At least 190 participants and up to 250 participants will be randomized 1:1 to GBT440 at the selected dose or placebo.</p>\n <p>\n <strong>Sample Size for Group 1</strong>:</p>\n <p>\n The primary efficacy measure , Hb, will be evaluated as 2 endpoints:</p>\n <p style=\"margin-left: 17.3pt;\">\n ·       as change from Week 12 to Baseline (primary)</p>\n <p style=\"margin-left: 17.3pt;\">\n ·       as a responder endpoint (change from Week 12 to Baseline >1 g/dL)</p>\n <p>\n For the endpoint of change from Baseline in Hb, power calculations assume a mean treatment effect of 0.8 g/dL (GBT440 at either dose, minus placebo), the placebo change from Baseline is equal to 0, a per-group standard deviation (SD) of 0.6 g/dL. With N = 20 participants per arm, the power exceeds 95% of detecting a difference between either GBT440 arm (900 mg or 1500 mg) versus placebo. Power is calculated for the t-test and assumes that the data are normally distributed. The estimates of 0.8 g/dL and 0.6 g/dL for the treatment effect and SD, respectively, are based on data at Day 90 from Cohorts 16 and 17 from the GBT440-001 study.</p>\n <p>\n For the responder endpoint at Week 12, the GBT440 dose arms will be pooled. Assuming responder proportions of 35% and 5% for GBT 440 (N = 40 after pooling data from the 900 and 1500 mg groups) and placebo (N = 20), respectively, the power with Fisher’s exact test at a two-sided alpha = 0.05 is 80%.</p>\n <p>\n <strong>Sample Size for the Main Population Analysis: </strong></p>\n <p>\n The Main Population Analysis consists of Group 2 participants (estimated to be approximately 60, which includes approximately 30 selected GBT440 dose and 30 placebo patients) and Group 3 participants (minimum 190 patients and maximum 250 patients) for a total of 250 (minimum) to 310 (maximum).</p>\n <p>\n For the Hb responder endpoint at Week 24, power exceeds 95% based on Fisher’s exact test and a two-sided alpha of 0.05, assuming a 35% and 5% response rate for GBT440 and placebo. A sample size larger than required for an adequately powered primary endpoint was selected for the safety database. The sample size for the primary and ePRO secondary endpoints for the Main Population Analysis will be re‑estimated from the Group 1 Analysis, and if necessary, will be increased up to a maximum of 310 participants to ensure adequate power for the first key secondary endpoint (proportion of days with SCD symptom exacerbation). The estimation will not require an alpha adjustment because data from the Group 1 Analysis will not be included in the Main Population Analysis .</p>\n <p>\n <strong>Stratification</strong></p>\n <p>\n At the time of randomization, participants will be stratified for HU use (yes/no), geographic region (US, Europe, Other), and age (adolescent, 12 to <18 years, and adults, 18 to 65 years).</p>\n <p>\n <strong>Efficacy Population and Analysis</strong></p>\n <p>\n For each population, efficacy analysis will be performed on the Intent to Treat (ITT) population which includes all randomized participants.</p>\n <p>\n The Group 1 Analysis will determine the GBT440 dose selected, and determine any further modifications to the study. There will no adjustment for multiplicity for the Group 1 population. If both GBT440 dose groups are selected in the Main Population Analysis, the comparisons will be of each GBT440 dose versus placebo, and will be adjusted for multiplicity via gatekeeping procedures outlined in the SAP.</p>\n <p>\n <strong>Group 1 and Main Population Analysis</strong></p>\n <p>\n <strong>Primary Endpoint:</strong></p>\n <p>\n Hb Week 12 change from Baseline will be analyzed with a mixed effect repeated measures model (MMRM). The model will include terms for treatment, time, and treatment by time interaction. An unstructured covariance matrix will be used.</p>\n <p>\n This analysis will be performed for the Group 1 Analysis: The comparison of treatments at Week 12 for each GBT440 dose versus placebo; the data beyond Week 12 will be presented descriptively.</p>\n <p>\n This analysis will be performed for the Group 1 Analysis and Main Population Analysis: The Hb responder endpoint will be analyzed by the Cochran‑Mantel‑Haenszel (CMH) test for each GBT440 dose versus placebo.</p>\n <p>\n <strong>Secondary Endpoints:</strong></p>\n <p>\n Where applicable, the Group 1 and Main Population will be analyzed with respect to their endpoint visit which is Week 12 for Group 1 and Week 24 for the Main Population. Analyses for Group 1 and the Main Population will be summarized beyond the endpoint visit. For example, for Group 1, proportion of days with SCD symptom exacerbation and change from Baseline in TSS will be summarized for visits after the endpoint visit, including Week 24.</p>\n <p>\n The proportion of days with SCD exacerbation during the first 12 weeks of treatment will be analyzed by a fixed effects linear model.</p>\n <p>\n Change from Baseline in the TSS will be analyzed with an MMRM.</p>\n <p>\n Normalization of reticulocyte count will be analyzed by the CMH test.</p>\n <p>\n The rate of VOC and rate of hospitalization due to VOC will be analyzed by the CMH row means scores test.</p>\n <p>\n The plan for the Main Population Analysis will be described in further detail in the Statistical Analysis Plan (SAP) after results from the Group 1 Analysis become available and before unblinding the Main Population Analysis.</p>\n <p>\n <strong>Missing Data:</strong> Proportion of participants with missing data for the primary and key secondary efficacy endpoints will be summarized by treatment group for study scheduled visits. Handling of missing data for analysis is described in the body of the protocol. The general rule is assigning a worst score for missing data due to hospitalization for VOC, and a worst score for RBC transfusions regardless of whether or not data are missing.</p>\n <p>\n <strong>Safety Population and Analysis (Group 1 and Main Population)</strong></p>\n <p>\n The Safety Population is defined as all randomized participants who have received at least one dose of study medication. Participants will be analyzed based on medication received.</p>\n <p>\n Data for participants who provide eDiary data but discontinue treatment will be included in the analysis. Descriptive statistics for healthcare utilization will be summarized in a separate report.</p>\n <p>\n The incidence of treatment-emergent adverse events (TEAEs) will be tabulated by System Organ Class (SOC), preferred term, severity, and relationship to study drug. AEs that are considered to be related to study drug by the Investigator will be summarized. Changes in laboratory parameters and vital signs over time will be summarized.</p>\n <p>\n Demographics (age, sex, ethnicity, and race) and Baseline characteristics (height and weight) will be summarized by treatment and overall medical history will be provided in a data listing.</p>\n <p>\n Descriptive summaries will be provided for AEs, laboratory tests (hematology, serum chemistry, and coagulation), and vital signs (BP and pulse rate).</p>\n <p>\n <strong>Pharmacokinetics Population and Analysis (Group 1 and Main Population)</strong></p>\n <p>\n The PK Population will consist of all participants who receive active study drug and have at least one measured concentration at a scheduled PK time point after the start of dosing. If any participants are found to be noncompliant with respect to dosing or have incomplete data, protocol violations, or clinical events that affect PK, a decision will be made on a case-by-case basis as to their inclusion in the analysis. Participants in this population will be used for all PK summaries.</p>\n <p>\n Population PK analyses using nonlinear mixed effects modeling will be performed to characterize GBT440 PK in plasma, if applicable, or whole blood. The influence of demographic covariates (such as body weight, age, gender) on GBT440 PK parameters (i.e., clearance [CL] and volume of distribution) will be investigated. If appropriate, the GBT440 PK data may be pooled with PK data from other studies.</p>\n <p>\n Summary statistics of PK parameters for whole blood, plasma, and RBCs will be presented including means, geometric means, SD, and coefficient of variation (CV), medians, and ranges.</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • study_title<p>\n A Phase 3, Double-blind, Randomized, Placebo-controlled, Multicenter Study of GBT440 Administered Orally to Patients With Sickle Cell Disease</p>\n
      • laymans_summary<div>\n Kindly find the attached document (C5341022 Plain Language Study Results Summary (PLSRS) Phase 2-4) for Laymans summary.</div>\n<p>\n  </p>\n
      • short_titleHOPE Sickle Cell Disease Clinical Study
      • protocol_noECCT/17/03/05
      • version_noAmendment 1
      • date_of_protocol09-11-2016
      • study_drugGBT440
      • disease_conditionSickle Cell Disease
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_nameGBT440
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressbernadette.kimotho@quintilesims.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter0
      • applicant_statement1
      • applicant_participating_countries1
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data0
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi0
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan0
      • applicant_contractual_agreement0
      • declaration_applicantBernadette Gathoni Kimotho (Clinical Researc Associate, Quinitles)
      • declaration_date120-03-2017
      • declaration_principal_investigatorProf Jessie Nyokabi Githanga
      • declaration_date216-03-2017
      • placebo_presentYes
      • study_objectives<div>\n Primary</div>\n<div>\n The primary objective is to assess the efficacy of GBT440 in adolescents and adults with SCD as measured by improvement in anemia.</div>\n<div>\n  </div>\n<div>\n Secondary</div>\n<div>\n The secondary objectives are to evaluate the effects of GBT440 compared to placebo on SCD symptom exacerbation and Total Symptom Score (TSS) from Patient</div>\n<div>\n Reported Outcome measurement (PRO), measures of anemia and hemolysis, and other clinical measures (e.g., vaso-occlusive crisis [VOC], Acute Chest Syndrome</div>\n<div>\n [ACS], hospitalization, red blood cell [RBC] transfusions, opioid use).</div>\n<div>\n  </div>\n<div>\n Exploratory</div>\n<div>\n The exploratory objectives are to evaluate the effects of GBT440 compared to placebo on the EuroQol EQ-5D-5L health questionnaire (EQ-5D-5L™), days missed</div>\n<div>\n from work/school, and measures related to SCD pathophysiology and to evaluate measures predictive of response to GBT440.</div>\n<div>\n  </div>\n<div>\n <div>\n Safety</div>\n <div>\n The safety objectives are to assess the safety of GBT440 compared to placebo based on adverse events (AEs), clinical laboratory tests, physical examinations, and other clinical measures (e.g., discontinuations due to AEs, dose reductions).</div>\n <div>\n  </div>\n <div>\n <div>\n Pharmacokinetics</div>\n <div>\n The pharmacokinetic (PK) objective is to assess the PK of GBT440 as evaluated by</div>\n <div>\n population PK analysis.</div>\n </div>\n <div>\n  </div>\n</div>\n<p>\n  </p>\n
      • principal_inclusion_criteria<p>\n <strong>Inclusion Criteria</strong></p>\n<p style=\"margin-left: 18pt;\">\n 1.     Male or female study participants with sickle cell disease</p>\n<p style=\"margin-left: 37.5pt;\">\n ·      Documentation of SCD genotype (HbSS, HbSC, HbSβthalassemia or other sickle cell syndrome variants) may be based on history of laboratory testing or must be confirmed by laboratory testing during screening</p>\n<p style=\"margin-left: 18pt;\">\n 2.     Participants have had at least 1 episode of VOC in the past 12 months. For study eligibility, VOC is defined as a previously documented episode of ACS or acute painful crisis <strong>(</strong>for which there was no explanation other than VOC<strong>)</strong> which required prescription or healthcare professional‑instructed use of analgesics for moderate to severe pain (documentation must exist in the patient medical record prior to Screening)</p>\n<p style=\"margin-left: 18pt;\">\n 3.     Age 12 to 65 years</p>\n<p style=\"margin-left: 18pt;\">\n 4.     Hemoglobin (Hb) ≥6.0 and ≤10.5 g/dL during Screening</p>\n<p style=\"margin-left: 18pt;\">\n 5.     Absolute reticulocyte count and % reticulocyte count must be >1.5 × upper limit of normal (ULN) during Screening</p>\n<p style=\"margin-left: 18pt;\">\n 6.     For participants taking HU, the dose of HU (mg/kg) must be stable for at least 3 months prior to signing the ICF and with no anticipated need for dose adjustments during the study, in the opinion of the Investigator</p>\n<p style=\"margin-left: 18pt;\">\n 7.     Participants must demonstrate 75% compliance with ePRO measure completion to be enrolled (participants will be given an ePRO device for at least 28 days during Screening; participants who are 60 to 74% compliant can re-screen once with Investigator approval; re‑screening is not allowed for participants who are <60% compliant)</p>\n<p style=\"margin-left: 18pt;\">\n 8.     Participants, who if female and of child bearing potential, are using highly effective methods of contraception from study start to 3 months after the last dose of study drug, and who if male are willing to use barrier methods of contraception, from study start to 3 months after the last dose of study drug</p>\n<p>\n  </p>\n<p style=\"margin-left: 18pt;\">\n 9.     Participant has provided documented informed consent or assent (the ICF must be reviewed and signed by each participant; in the case of pediatric participants, both the consent of the participant’s legal representative or legal guardian, and the participant’s assent must be obtained)</p>\n
      • principal_exclusion_criteria<p>\n <strong>Exclusion Criteria</strong></p>\n<p style=\"margin-left: 18pt;\">\n 1.     More than 10 VOCs within the past 12 months that required a hospital, emergency room or clinic visit</p>\n<p style=\"margin-left: 18pt;\">\n 2.     Female who is breast feeding or pregnant</p>\n<p style=\"margin-left: 18pt;\">\n 3.     Patients who are receiving regularly scheduled blood (RBC) transfusion therapy (also termed chronic, prophylactic, or preventive transfusion) or have received a RBC transfusion for any reason within 28 days of signing the ICF</p>\n<p style=\"margin-left: 18pt;\">\n 4.     Hospitalized for sickle cell crisis or other vaso-occlusive event within 14 days of signing the ICF (i.e., a vaso-occlusive event cannot be within 14 days prior to ICF )</p>\n<p style=\"margin-left: 18pt;\">\n 5.     Hepatic dysfunction characterized by alanine aminotransferase (ALT) >4 × ULN</p>\n<p style=\"margin-left: 18pt;\">\n 6.     Participants with clinically significant bacterial, fungal, parasitic or viral infection which require therapy:</p>\n<p style=\"margin-left: 31.1pt;\">\n ·    Participants with acute bacterial infection requiring antibiotic use should delay screening/enrollment until the course of antibiotic therapy has been completed. 
</p>\n<p style=\"margin-left: 31.1pt;\">\n ·    Participants with known active hepatitis A, B, or C or who are known to be human immunodeficiency virus (HIV) positive</p>\n<p style=\"margin-left: 18pt;\">\n 7.     Severe renal dysfunction (estimated glomerular filtration rate at the Screening visit; calculated by the central laboratory) <30mL/min/1.73 m² or on chronic dialysis</p>\n<p style=\"margin-left: 18pt;\">\n 8.     History of malignancy within the past 2 years prior to treatment Day 1 requiring chemotherapy and/or radiation (with the exception of local therapy for non‑melanoma skin malignancy).</p>\n<p style=\"margin-left: 18pt;\">\n 9.     History of unstable or deteriorating cardiac or pulmonary disease within 6 months prior to consent including but not limited to the following:</p>\n<p style=\"margin-left: 31.1pt;\">\n ·    Unstable angina pectoris or myocardial infarction or elective coronary intervention</p>\n<p style=\"margin-left: 31.1pt;\">\n ·    Congestive heart failure requiring hospitalization</p>\n<p style=\"margin-left: 31.1pt;\">\n ·    Uncontrolled clinically significant arrhythmias</p>\n<p style=\"margin-left: 18pt;\">\n 10.  Any condition affecting drug absorption, such as major surgery involving the stomach or small intestine (prior cholecystectomy is acceptable).</p>\n<p style=\"margin-left: 18pt;\">\n 11.  Participated in another clinical trial of an investigational agent (or medical device) within 30 days or 5 half-lives of date of informed consent, whichever is longer, or is currently participating in another trial of an investigational agent (or medical device).</p>\n<p style=\"margin-left: 18pt;\">\n 12.  Inadequate venous access as determined by the Investigator/site staff.</p>\n<p>\n  </p>\n<p style=\"margin-left: 18pt;\">\n 13.  Medical, psychological, or behavioral conditions, which, in the opinion of the Investigator, may confound study interpretation, interfere with compliance, or preclude informed consent.</p>\n
      • primary_end_points<p>\n  </p>\n<p>\n The primary objective is to assess the efficacy of GBT440 in adolescents and adults with SCD as measured by improvement in anemia.</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic1
      • scope_bioequivalence0
      • scope_dose_response1
      • scope_pharmacogenetic0
      • scope_pharmacogenomic1
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<table border=\"1\" cellpadding=\"1\" cellspacing=\"1\" style=\"width: 729px; height: 872px;\">\n <tbody>\n <tr>\n <td>\n SITE</td>\n <td>\n STAFF</td>\n <td>\n Facilities</td>\n <td>\n Experience</td>\n </tr>\n <tr>\n <td>\n Gertrude's Children's Hospital</td>\n <td>\n <p>\n PI - Prof Jessie Githanga (Mmed Path)</p>\n <p>\n Sub -I/SCC - Dr Jaspreet Gharial (Mmed Paeds)</p>\n <p>\n Pharmacist - Dr Monica Mirigo(Bpharm)</p>\n <p>\n Lab Technologist - Penina Chege</p>\n </td>\n <td>\n <p>\n Consultation Rooms</p>\n <p>\n Hospitalization facilities</p>\n <p>\n Air conditioned Pharmacy with temperature montoring</p>\n <p>\n Laboratory</p>\n <p>\n Emergency Trolley and ICU</p>\n <p>\n Phone and internet access</p>\n <p>\n  </p>\n </td>\n <td>\n <p>\n PI and Staff have experience conducting Randomized clinical trials in the sickle cell therapeutic area. The site has previously conducted two phase 3 clinical trials in sickle cell disease.</p>\n </td>\n </tr>\n <tr>\n <td>\n Strathmore University Medical Center</td>\n <td>\n <p>\n PI - Dr Bernhards Ogutu (MMed Paeds)</p>\n <p>\n Sub-I - Dr Anastacia Omoding (MBCHB)</p>\n <p>\n Investigator - Dr Elizabeth Juma (MBCHB)</p>\n <p>\n SCC - Amina Salim</p>\n </td>\n <td>\n <p>\n Consultation Rooms</p>\n <p>\n Emergency Trolley</p>\n <p>\n Pharmacy</p>\n <p>\n Laboratory</p>\n <p>\n Phone and internet access</p>\n </td>\n <td>\n <p>\n PI has over 10 years experience conducting clinical trials phase 1 to 4,and has experience in the similar sickle cell therapy trials, pharmacokinetic and pharmacogenomic studies.</p>\n </td>\n </tr>\n <tr>\n <td>\n KEMRI CRDR Research clinic at Chandaria Health Center</td>\n <td>\n <p>\n PI - Dr Videlis Nduba (MBCHB, MPH, PHD)</p>\n <p>\n Sub - I/SCC- Dr Grace Kiringa (MBCHB, Msc Clinical Trials)</p>\n <p>\n Pharmacist - Dr Tony Sang (BPharm)</p>\n <p>\n Lab Technician - Eric Njuki</p>\n </td>\n <td>\n <p>\n Consultation rooms</p>\n <p>\n Emergency Trolley</p>\n <p>\n Pharmacy</p>\n <p>\n Laboratory</p>\n <p>\n Phone and internet access</p>\n </td>\n <td>\n <p>\n PI has over 10 years experience conducting clinical trails phase 1 to 4. PI and site staff have experiece conducting sickle cell disease related trials including PK, PD and pharmacogenomic trials.</p>\n </td>\n </tr>\n <tr>\n <td>\n KEMRI Kondele Children's Hospital Center for Research</td>\n <td>\n <p>\n PI - Dr Bernhards Ogutu (MMed Paeds)</p>\n <p>\n Sub - I - Dr Godfrey Alan Otieno (MMed Paeds)</p>\n <p>\n SCC - Ishamel Sports</p>\n <p>\n  </p>\n </td>\n <td>\n <p>\n Consultation Rooms</p>\n <p>\n Hospitalization facilities</p>\n <p>\n Emergency Trolley, HDU</p>\n <p>\n Pharmacy</p>\n <p>\n Laboratory</p>\n <p>\n Phone and Internet access</p>\n </td>\n <td>\n <p>\n PI has over 10 years conducting clinical trials, phase 1 to 4 trials. PI , Sub-I and staff have previously conducted similar phase 3 Randomized Clinical Trials  in the sickle cell disease therapy area.</p>\n </td>\n </tr>\n <tr>\n <td>\n KEMRI Siaya Referral Hospital</td>\n <td>\n <p>\n PI - Dr Videlis Nduba (MBCHB. MPH, PHD)</p>\n <p>\n Sub - I - Dr Grace Kiringa(MBCHB, MSC. Clinical Trials)</p>\n <p>\n Pharmacist - Dr Tony Sang (Bpharm)</p>\n <p>\n SCC/Study Nurse - Elizabeth Akinyi</p>\n <p>\n Lab Technician  - Evans Ongesa</p>\n </td>\n <td>\n <p>\n Consultation rooms</p>\n <p>\n Hospitalization facilities</p>\n <p>\n Emergency Trolley</p>\n <p>\n Pharmacy</p>\n <p>\n Laboratory</p>\n <p>\n Phone and internet access</p>\n <p>\n  </p>\n </td>\n <td>\n <p>\n PI has over 10 years experience conducting Randomized clinical trials. PI and site staff have previously conducted similar phase 3 trials in the sickle cell therapy area. Site has experience in PK, PD and pharmacogenomic trials.</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • other_details_explanation<p>\n The trial will be conducted in the USA - the host country of the sponsor. There are 42 planned sites in United States.</p>\n
      • other_details_regulatory_notapproved<table border=\"1\" cellpadding=\"1\" cellspacing=\"1\" style=\"width: 500px;\">\n <tbody>\n <tr>\n <td>\n COUNTRY and RA</td>\n <td>\n DATE OF SUBMISSION</td>\n </tr>\n <tr>\n <td>\n Egypt, Egyptian MOH central directorate of research and health development</td>\n <td>\n 23 Feb 2017</td>\n </tr>\n <tr>\n <td>\n Italy, Agenzia Italiano del Farmaco</td>\n <td>\n 27 Feb 2017</td>\n </tr>\n <tr>\n <td>\n Jamaica</td>\n <td>\n 01 Dec 2016</td>\n </tr>\n <tr>\n <td>\n Netherlands CCMO</td>\n <td>\n 14 Mar 2017</td>\n </tr>\n <tr>\n <td>\n Turkey, Turkish Medicine and Medical Device Agency</td>\n <td>\n 30 Dec 2016</td>\n </tr>\n </tbody>\n</table>\n<p>\n *Lebanon and Oman - Only EC submission only.</p>\n
      • other_details_regulatory_approved<table border=\"1\" cellpadding=\"1\" cellspacing=\"1\" style=\"width: 500px;\">\n <tbody>\n <tr>\n <td>\n COUNTRY</td>\n <td>\n DATE OF APPROVAL</td>\n </tr>\n <tr>\n <td>\n UK, Medicines and Health Products Regulatory Authority</td>\n <td>\n 03 Feb 2017</td>\n </tr>\n <tr>\n <td>\n Canada, Health Canada</td>\n <td>\n 20 Jan 2017</td>\n </tr>\n <tr>\n <td>\n USA, Food and Drug Authority</td>\n <td>\n <p>\n Investigational New Drug submitted, Key elements of protocol - No Objection. FDA does not provide approval for ammendments.</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • other_details_regulatory_rejected<p>\n Not applicable</p>\n
      • other_details_regulatory_halted<p>\n Not applicable</p>\n
      • estimated_duration2 years (First site was opened in 29 Nov 2016. Study end is planned for Dec 2018)
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorPlacebo
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states15
      • number_of_sites5
      • multi_country_listCanada, Egypt, France, Ghana, Italy, Kenya, Nigeria, Jamaica, Lebanon, Netherlands, Oman, Qatar, Turkey, UK, USA
      • data_monitoring_committeeYes
      • total_enrolment_per_siteminimum 2 maximum 30
      • total_participants_worldwide400
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenYes
      • population_adolescentYes
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameJessie
      • investigator1_middle_nameNyokabi
      • investigator1_family_nameGithanga
      • investigator1_qualificationMBCHB, MMED (Path), FCPath
      • investigator1_professional_addressGertrude\'s Children\'s Hospital, Muthaiga Road, Off Thika Super Highway P.O Box 42325 - 00100, Nairobi, Kenya
      • investigator1_telephone+254721245721
      • investigator1_emailjgithanga3@gmail.com
      • organisations_transferred_Yes
      • number_participants100
      • notification<p>\n 1. Trial participants are adolescents from 12 - 17 years and adults 18 - 65 years.</p>\n<p>\n 2. The DSMB charter and Schedule of meetings is still under review. The draft document is attached.</p>\n<p>\n 3. The sites Budget is still not finalized. The breakdown of budget items is attached.</p>\n<p>\n 4. The scope of the study is the same at all sites. Same protocol through all sites globally.</p>\n
      • approval_date14-07-2017
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted28-06-2021
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report
      • implication_results
      • quantity_imported5477
      • quantity_dispensed4141
      • quantity_destroyed1573
      • quantity_exported17
      • balance_site0
      • final_date2025-07-31 13:24:00
      • modified2025-08-25 15:55:24
      • created2017-03-03 13:04:10
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id378
        • application_id598
        • given_nameVidelis
        • middle_name
        • family_nameNduba
        • qualificationMBCHB, MPH (epi), PHD (epi)
        • professional_addressKEMRI CRDR, KNH Complex P.O Box 47855, Nairobi, Kenya
        • telephone+254724522474
        • emailvnduba@gmail.com
        • created2017-03-03 13:17:32
        • modified2021-06-28 11:42:10
      • 1(array)
        • id379
        • application_id598
        • given_nameJessie
        • middle_nameNyokabi
        • family_nameGithanga
        • qualificationMBCHB, MMED (Path), FCPath
        • professional_addressGertrude\'s Children\'s Hospital, Muthaiga Rd, Off Thika super-highway, P.O BOX 42325 - 00100, Nairobi, Kenya
        • telephone+254721245721
        • emailjgithanga3@gmail.com
        • created2017-03-03 13:23:11
        • modified2021-06-28 11:42:10
    • SiteDetail(array)
      • 0(array)
        • id475
        • application_id598
        • county_id47
        • site_nameGertrude\'s Children\'s Hospital
        • physical_addressAlong Muthaiga Road, Off Thika superhighway
        • contact_detailsP.O Box 42325 - 00100, Nairobi, Kenya
        • contact_personProf. Jessie Nyokabi Githanga
        • site_capacity(null)
        • misc(null)
        • created2017-03-03 13:17:32
        • modified2021-06-28 11:42:10
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 1(array)
        • id476
        • application_id598
        • county_id47
        • site_nameStrathmore University Medical Center
        • physical_addressMadaraka Estate, Ole Sangale Road, off Langata road
        • contact_detailsP.O. Box 59857 - 00200 Nairobi, Kenya
        • contact_personDr Benhards Ogutu
        • site_capacity(null)
        • misc(null)
        • created2017-03-09 10:39:23
        • modified2021-06-28 11:42:10
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 2(array)
        • id477
        • application_id598
        • county_id47
        • site_nameKEMRI CRDR Clinical Research clinic at Chandaria Health Center
        • physical_addressThogoto Mutarakwa Road - Near Dagoretti Market
        • contact_detailsP.O. Box 43678 - 00200, Nairobi, Kenya
        • contact_personDr Videlis Nduba
        • site_capacity(null)
        • misc(null)
        • created2017-03-09 10:39:23
        • modified2021-06-28 11:42:10
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 3(array)
        • id478
        • application_id598
        • county_id42
        • site_nameKEMRI Kondele Childrens Hospital Center for Clinical Research
        • physical_addressWithin Jaramogi Oginga Odinga Teaching and Referral Hospital, Along Kisumu - Kakamega Highway
        • contact_detailsP.O. Box 54 - 40100 Kisumu, Kenya
        • contact_personDr Benhards Ogutu
        • site_capacity(null)
        • misc(null)
        • created2017-03-09 10:39:23
        • modified2021-06-28 11:42:10
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 4(array)
        • id479
        • application_id598
        • county_id41
        • site_nameKEMRI Clinical Research Center at Siaya County Referral Hospital
        • physical_addressKEMRI/CDC Research Building at Siaya County Referral Hospital, Siaya
        • contact_detailsP.O. Box 144 - Siaya, Kenya
        • contact_personDr Videlis Nduba
        • site_capacity(null)
        • misc(null)
        • created2017-03-09 10:39:23
        • modified2021-06-28 11:42:10
        • County(array)
          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
    • Sponsor(array)
      • 0(array)
        • id304
        • application_id598
        • sponsorGlobal Blood Therapeutics, inc.
        • sponsor_typeResearch Institution
        • contact_personAllison Intondi
        • address400 East Jamie Court, Suite 101 South San Francisco, CA 94080, USA
        • telephone_number+1650 351 4720
        • fax_number+1650 751 7716
        • cell_numberNot applicable
        • email_addressaintondi@globalbloodtx.com
        • created2017-03-03 13:17:32
        • modified2021-06-28 11:42:10
  • 1(array)
    • Application(array)
      • id1213
      • user_id263
      • trial_status_id4
      • abstract_of_study<p>\n COVID-19, also known as the coronavirus disease 2019, is a highly contagious respiratory illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It was first identified in December 2019 in Wuhan, China and has since become a pandemic, affecting people in more than 200 countries around the world. As of May 20, 2022, over 526 million cases of COVID-19 were reported worldwide, with over 6 million deaths (WHO Dashboard 2022). Infection with SARS-CoV-2 may be asymptomatic or it may cause a wide spectrum of illnesses, ranging from a mild upper respiratory tract infection to severe life-threatening sepsis and multiorgan failure (Wiersinga et al. 2020).</p>\n<p>\n The first of several effective COVID-19 vaccines was authorized in December 2020. However, despite large multi-national vaccination campaigns, as of July 2022, 63% of the global population have been fully vaccinated with rates less than 40%.in many low-income countries. Vaccination, apart from other public health measures such as hand hygiene and face masks, has been an important tool in reducing infection and complications. However, the durability of response after vaccination is not well understood, and there are increasing reports of breakthrough infections, including among fully vaccinated individuals, partly driven by the emergence of SARS-CoV-2 variants (Hacisuleyman et al. 2021).</p>\n<p>\n COVID-19 vaccines may also provide insufficient or incomplete protection due to both waning antibody responses post-vaccination along with the risk of emergence of viral variants, which further underscores the need for treatment options. There is also a need to evaluate therapies in the outpatient setting to prevent disease progression and reduce transmission. These efforts are particularly important in African countries, where access to effective therapies and vaccines may be limited.</p>\n<p>\n  </p>\n<p>\n COVID-19 Symptoms are typically thought to last 2 to 3 weeks, but many patients continue to experience symptoms for many weeks or develop new symptoms, which is now recognized as the post-acute COVID-19 syndrome, also called Long COVID (NIHR 2020). COVID-19 affects people of all age; however, people who are immunocompromised, elderly, or have certain underlying medical conditions (e.g. obesity, diabetes, chronic heart, lung and kidney disease, and cancer; and the immunocompromised) are at increased risk of mortality and poor outcomes (Carfi et al. 2020; CDC 2022; UK Health Security Agency 2021) and therefore have the greatest unmet need. There is therefore a continued urgent global need to develop effective drugs to make them available at scale and equitably across all countries including in Africa.</p>\n<p>\n <strong>Objectives:</strong> The primary objective of this study is to evaluate the efficacy of BEM compared with placebo in reducing all-cause hospitalization or all-cause death in COVID-19 outpatients receiving only supportive care.</p>\n<p>\n <strong>Methods:</strong> This is a Phase 3 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Bemnifosbuvir in High-Risk Outpatients with COVID-19.</p>\n<p>\n <strong>Study duration:</strong> The primary study period is up to 30 days, including up to 1 day for screening and 29 days from randomization. Extended follow-up data will be collected through Day 60 for mortality and medically attended visit assessment.</p>\n<p>\n <strong>Study Outcome</strong>: The efficacy of BEM compared with placebo in reducing all-cause hospitalization or all-cause death in COVID-19 outpatients receiving only supportive care. The antiviral activity of BEM compared with placebo on viral load rebound and the safety of BEM compared with placebo.</p>\n
      • study_title<p>\n A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Bemnifosbuvir in High-Risk Outpatients with COVID-19</p>\n
      • laymans_summary<p>\n <strong>Why should you do this study?</strong> The main aim of this study is to find out the performance of BEM compared with an inactive substance that looks the same as, and is given the same way as, BEM in reducing all-cause hospitalization or all-cause death in COVID-19 outpatients receiving only supportive care.</p>\n<p>\n Vaccination, apart from other public health measures such as hand hygiene and face masks, has been an important tool in reducing infection and complications. However, the durability of response after vaccination is not well understood, and there are increasing reports of infections after vaccination, including among fully vaccinated individuals.</p>\n<p>\n COVID-19(CORONA) affects people of all age; however, people who are Incapable of developing a normal immune response, elderly, or have certain underlying medical conditions (e.g., obesity, diabetes, chronic heart, lung and kidney disease, and cancer are at increased risk of death and poor outcomes (Carfi et al. 2020; CDC 2022; UK Health Security Agency 2021) and therefore have the greatest unmet need. There is therefore a continued urgent global need to develop effective drugs to make them available at scale and equitably across all countries including in Africa.</p>\n<p>\n <strong>Where is the study taking place?</strong> This study will take place at the Victoria Biomedical Research Institute VIBRI site at kisumu County Hospital in Kisumu, Kenya. This will be one of the sites around the world.</p>\n<p>\n <strong>How many participants does it involve?</strong> the Victoria Biomedical Research Institute VIBRI site will recruit about 100 participants for this study, although approximately 1500 participants should be recruited in other sites around the world.</p>\n<p>\n <strong>How will they be selected?</strong> Subject must be of age ≥80 years. Or age ≥18 years and age ≥65 years with underlying diseases as per the master protocol.</p>\n<p>\n <strong>What does the study involve for those taking part?</strong> The participants will be asked to come to the clinic for visits other visits will be done on phone as per the schedule of assessment in the protocol for the duration of the study period some laboratory tests will be done on blood samples and nasopharyngeal swab extracts. During the visits the participants will be assessed they will receive treatment and follow up visits will be done.</p>\n<p>\n <strong>When does the study start and end?</strong> The study will take: The primary study period is up to 30 days, including up to 1 day for screening and 29 days from randomization. Extended follow-up data will be collected through Day 60 for mortality and medically attended visit assessment.</p>\n<p>\n  </p>\n<p>\n  </p>\n
      • short_titleSunrise-3
      • protocol_noECCT/23/03/02
      • version_no1.0
      • date_of_protocol08-09-2022
      • study_drugBemnifosbuvir
      • disease_conditionCOVID-19
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals1
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressamina.salim@iqvia.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter0
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantAmina Salim
      • declaration_date101-03-2023
      • declaration_principal_investigatorDr Paul Yonga
      • declaration_date201-03-2023
      • placebo_presentYes
      • study_objectives<p>\n Primary Objective:</p>\n<p>\n To evaluate the efficacy of bemnifosbuvir (BEM) compared with placebo in reducing all-cause hospitalization or all-cause death in COVID-19 outpatients receiving only supportive care</p>\n<p>\n Secondary Objectives:</p>\n<p>\n To evaluate the efficacy of BEM compared with placebo on:</p>\n<p>\n • COVID-19 related hospitalization or all-cause death through Day 29</p>\n<p>\n • All-cause death through Day 29 and Day 60</p>\n<p>\n • COVID-19-related complications (e.g., death, hospitalization, radiologically confirmed pneumonia, acute respiratory failure, sepsis, coagulopathy, pericarditis/myocarditis, cardiac failure)</p>\n<p>\n • COVID-19-related medically attended visits (hospitalization, emergency room (ER) visit, urgent care visit, physician’s office visit, or telemedicine visit) or all-cause death through Day 29 and Day 60</p>\n<p>\n • COVID-19 symptom relapse To evaluate the antiviral activity of BEM compared with placebo on viral load rebound To evaluate the safety of BEM compared with placebo</p>\n<p>\n Exploratory Objectives:</p>\n<p>\n To evaluate the efficacy of BEM compared with placebo on:</p>\n<p>\n • Alleviation or improvement of individual COVID-19 symptoms</p>\n<p>\n • Return to usual (pre-COVID-19) health</p>\n<p>\n • Requirement for post-randomization rescue therapy</p>\n<p>\n • The antiviral activity of BEM compared with placebo To assess plasma concentrations of AT-511 (free base form of AT-527 [BEM]) and its metabolites</p>\n
      • principal_inclusion_criteria<p>\n 1. Willing and able to provide informed consent.</p>\n<p>\n 2. Positive SARS-CoV-2 diagnostic test (RT-PCR or validated rapid antigen test) conducted ≤ 5 days prior to randomization. Note: The test may be obtained locally. A documented historical record of positive result (RT-PCR or validated rapid antigen test) from test conducted ≤ 5 days prior to randomization is acceptable.</p>\n<p>\n 3. Mild or moderate COVID-19 with symptom onset ≤ 5 days before randomization and at least one COVID-19 related symptom present at time of screening: • Mild COVID-19: − Symptoms of mild illness with COVID-19, which could include fever, cough, sore throat, malaise, headache, muscle pain, nausea, vomiting, diarrhea, and loss of taste or smell, without shortness of breath or dyspnea − No clinical signs indicative of moderate, severe, or critical illness severity • Moderate COVID-19: − Symptoms of moderate illness with COVID-19, which could include any symptom of mild illness or shortness of breath with exertion − Clinical signs suggestive of moderate illness with COVID-19, such as respiratory rate ≥ 20 breaths per minute, heart rate ≥ 90 beats per minute; with saturation of oxygen (SpO2) > 93% on room air at sea level − No clinical signs indicative of severe or critical illness severity</p>\n<p>\n 4. For females of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use adequate contraception during the treatment period and for 30 days after the final dose of study drug.</p>\n<p>\n 5. Females of childbearing potential must have a negative pregnancy test prior to initiation of study drug.</p>\n<p>\n 6. Subject must be able to take oral tablet medications. 7. Subject is, in the opinion of the investigator, willing and able to comply with the study drug regimen and all other study requirements. 8. Subject must be high risk, defined below. • Age ≥80 years OR • Age ≥65 years with one of the following:</p>\n<p>\n − Obesity (body mass index [BMI] ≥30 kg/m2)</p>\n<p>\n − Diabetes mellitus</p>\n<p>\n − Cardiovascular disease (including congenital heart disease) or hypertension (with at least one medication recommended or prescribed)</p>\n<p>\n − Chronic lung disease requiring routine therapy (e.g., chronic obstructive pulmonary disease [COPD], moderate-to-severe asthma, interstitial lung disease, cystic fibrosis, pulmonary hypertension)</p>\n<p>\n OR</p>\n<p>\n • Age ≥18 years with one of the following:</p>\n<p>\n − Down syndrome, sickle cell disease, dementia, Parkinson’s disease, or care home residents</p>\n<p>\n − One of the following immunocompromising conditions or immunosuppressive treatment:</p>\n<p>\n o Receiving chemotherapy or other therapies for cancer</p>\n<p>\n o Hematologic malignancy (active or in remission)</p>\n<p>\n o Being within 2 years from receiving a hematopoietic stem cell or at any time following a solid organ transplant</p>\n<p>\n o Human immunodeficiency virus (HIV) infection untreated or with CD4+ T lymphocyte count <350 cells per cubic millimeter (mm3 ) within the past 6 months</p>\n<p>\n o Combined primary immunodeficiency disorder o Taking immunosuppressive medications (e.g., drugs to suppress rejection of transplanted organs or to treat rheumatologic and gastrointestinal conditions such as anti-tumor necrosis factor (TNF) agents, mycophenolate, or rituximab)</p>\n
      • principal_exclusion_criteria<p>\n 1. Female subject is pregnant or breastfeeding.</p>\n<p>\n 2. Clinical signs or symptoms indicative of severe or critical COVID-19 illness, including any of the following: shortness of breath at rest, respiratory rate ≥ 30 breaths per minute, heart rate ≥ 125 beats per minute, SpO2 ≤ 93% on room air at sea level, partial pressure of oxygen/ fraction of inspired oxygen (PaO2/FiO2) <300, shock (defined by systolic blood pressure < 90 mm Hg or diastolic blood pressure < 60 mm Hg or requiring vasopressors), multi-organ dysfunction/failure, respiratory distress, respiratory failure; requirement of endotracheal intubation, mechanical ventilation, oxygen delivered by high-flow nasal cannula, noninvasive positive pressure ventilation, extracorporeal membrane oxygenation (ECMO).</p>\n<p>\n 3. Admitted to a hospital within 90 days prior to randomization due to COVID-19 or is hospitalized (inpatient) at randomization due to COVID-19. Note: If local policyrequires COVID-19 isolation or internment in a hospital or similar facility, but subjects otherwise meet criteria, this exclusion may not apply.</p>\n<p>\n 4. In the opinion of the investigator, is likely to experience imminent deterioration and require hospitalization within 24 hours.</p>\n<p>\n 5. Use of other investigational drugs within 30 days prior to planned dosing, or plans to enroll in another clinical trial of an investigational agent while participating in the present study, except for unblinded protocols that don’t include direct acting antivirals for COVID-19 (e.g., open-label oncological regimen variations or biologic studies). Note: Prior to enrolling subjects that are on other open-label studies, it is the site’s responsibility to ensure that the study criteria for that study allow for enrollment into this study.</p>\n<p>\n 6. Initiation or planned initiation of remdesivir for treatment of the current SARS-CoV-2 infection.</p>\n<p>\n 7. Requirement of any prohibited medications, as described in Section 5.7, including either hydroxychloroquine or amiodarone within 3 months prior to screening. Note: Subjects who had already initiated any COVID-19 drug with antiviral effects intended to treat symptomatic SARS-CoV-2 infection (≥ 24 hours prior to randomization) will be excluded. During screening (or within 24 hours prior to or after randomization), locally available COVID-19 drugs with antiviral effects (including but not limited to Paxlovid, molnupiravir, favipiravir, mAbs) will be permitted, as long as there are no concerns for DDIs (e.g., remdesivir would not be permitted).</p>\n<p>\n 8. Other known active viral or bacterial infection at the time of screening, such as influenza (i.e., as verified by a locally available rapid flu test at screening_ and respiratory syncytial virus (RSV). Note: This exclusion does not apply to subjects with stable chronic viral infections, such as chronic HCV or HIV providing other eligibility criteria are met.</p>\n<p>\n 9. Receiving dialysis or have known moderate to severe renal impairment [i.e. estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2 within 6 months of the screening visit, using the serum creatinine-based CKD-EPI formula]. Note: If the investigator suspects the subject may have eGFR <45 mL/min/1.73 m2 , a confirmatory test should be performed at screening to confirm eligibility before the first dose of study drug.</p>\n<p>\n 10. History of severe hepatic impairment (Child-Pugh Class C)</p>\n<p>\n 11. Known allergy or hypersensitivity to components of study drug.</p>\n<p>\n 12. Malabsorption syndrome or other condition that would interfere with enteral absorption.</p>\n<p>\n 13. Any clinically significant medical condition or known laboratory abnormality that, in the opinion of the investigator, could jeopardize the safety of the subject or impact subject compliance or safety/efficacy observations in the study</p>\n
      • primary_end_points<p>\n The primary efficacy endpoint is the proportion of subjects in the supportive-care-only population who are hospitalized for any cause or who died due to any cause through Day 29.</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 1.Fountain Projects and Research Office - Clinical Research Centre (FOPRO-CRC) PI-Dr. Paul Yonga </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Dr. Anthony Akoto (Investigator), Mr. Jairus Kipyego (Investigator), Dr. Damaris Sertoi (Investigator and Study Coordinator)</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <span font-size:=\"\" style=\"font-family: \" trebuchet=\"\">Fountain Projects and Research Office Clinical Research Centre (FOPRO-CRC) will be one of four sites in Kenya undertaking the trial. FOPRO-CRC is the research unit of Fountain Health Care Hospital, a level 5 hospital located in Eldoret, Uasin-Gishu County, Kenya. It is staffed by six principal investigators, each of whom is supported by a team of study coordinators, research clinicians, a pharmacist on record, a laboratory scientist, and a data manager. FOPRO-CRC is collaborating with a number of academic and research institutions (University of Oxford, UK; Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand; KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya; and Kenya Cardiac Society/World Heart Federation) as well as industry (Sanofi Pasteur, GSK, and AstraZeneca) in undertaking a number of interventional and observational studies in infectious diseases, cardiovascular diseases, and diabetes mellitus type II.</span></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 2. Kenyatta National Hospital (PI Dr John Kinuthia)</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n This will be a hospital-based study conducted at Kenyatta National Hospital, a level 6 tertiary teaching and referral hospital in Nairobi County. It is the largest public teaching and referral facility in Kenya. The hospital has a 2000 bed capacity, including a 60-bed COVID-19 unit and a six-bed critical care COVID-19 unit. The hospital provides integrated services for all its COVID patients. As a national referral facility, it has a diverse and multidisciplinary team of HCWs including infectious disease specialists, consultant physicians, medical doctors and nursing staff who can review and manage both simple and complicated COVID patients from the greater Nairobi area and throughout the country. Moreover, it also serves as the training hospital for the College of Health Sciences at the University of Nairobi (UoN) and the main campus for the Kenya Medical Training College (KMTC).</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 3. VIBRI (PI: Dr Lucas Otieno Tina):</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Victoria Biomedical Research Institute (VIBRI) is a non-profit providing pharmaceutical, academic research, and non-profit organizations with a network of clinical sites and expertise focusing on accelerating transformative therapeutics, vaccines, and devices research for major global health diseases in Kenya. VIBRI is located at the Kisumu County Referral Hospital in Kisumu County, western Kenya.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Kisumu County is one of 47 counties in the Republic of Kenya. Its headquarters is <a href=\"https://en.wikipedia.org/wiki/Kisumu\" style=\"color: rgb(51, 51, 51); text-decoration-line: none;\">Kisumu </a>City which is the third largest city in <a href=\"https://en.wikipedia.org/wiki/Kenya\" style=\"color: rgb(51, 51, 51); text-decoration-line: none;\">Kenya</a>. It has a population of 1,155,574 (Kenya National Bureau of Statistics, 2019). The land area of Kisumu County totals 2085.9 km<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; top: -0.5em;\">2</span>. The county has a shoreline on <a href=\"https://en.wikipedia.org/wiki/Lake_Victoria\" style=\"color: rgb(51, 51, 51); text-decoration-line: none;\">Lake Victoria</a>, occupying northern, western and a part of the southern shores of the <a href=\"https://en.wikipedia.org/wiki/Winam_Gulf\" style=\"color: rgb(51, 51, 51); text-decoration-line: none;\">Winam Gulf</a>. The city of Kisumu has historically functioned as a major center of Western Kenya commerce. Health in Kisumu County is provided by several institutions that are either private or government funded. There is one teaching and referral hospital, 5 County referral hospitals, 14 sub-county hospitals, 74 dispensaries and 18 health centres in the county.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n VIBRI was established to conduct biomedical research including clinical trials, bioequivalence studies, basic science research studies, epidemiology and population health studies,implementation science studies, build a strong foundation in data science, conduct training and capacity building on clinical research in Kenya. VIBRI has experienced and accomplished clinical research scientists who have designed and conducted GCP compliant phase 1b to phase IV paediatric and adult clinical trials on vaccines and drugs for different indications including malaria, HIV, tuberculosis, diarrhea, sickle cell disease, ebola, pneumonia, polio among many others. The VIBRI Clinical Trials Program will conduct trial activities out of the Kisumu County Referral Hospital and surrounding health facilities. The staff and infrastructure can serve several satellite sites for reaching high-risk populations from Kisumu City.</p>\n
      • other_details_explanation<p>\n <span class=\"normaltextrun\"><span lang=\"EN-US\" style=\"font-size: 9pt; font-family: Arial, sans-serif; color: black; background-image: initial; background-position: initial; background-size: initial; background-repeat: initial; background-attachment: initial; background-origin: initial; background-clip: initial;\">This is trial is being conducted in the host country of the Sponsor (USA)</span></span></p>\n
      • other_details_regulatory_notapproved<p>\n Argentina-Administracion Nacional de Alimentos, Medicamentos y Tecnología Médica (ANMAT)</p>\n<p>\n Egypt-Egypt Drug Authority (EDA)</p>\n<p>\n India-Central Drugs Standard and Control Organization</p>\n<p>\n Latvia-State Agency of Medicines</p>\n<p>\n Romania-National Agency for Medicines and Medical Devices</p>\n<p>\n South Africa-South African Health Products Regulatory Authority</p>\n<p>\n Spain-Agencia Española del Medicamento y Productos Sanitarios (AEMPS)</p>\n<p>\n Tunisia-Direction de la Pharmacie et du Médicament (DPM)</p>\n<p>\n Turkey-Türkiye Ä°laç ve Tıbbi Cihaz Kurumu (TITCK)</p>\n<p>\n United Kingdom-edicines & Healthcare products regulatory agency (MHRA)</p>\n<p>\n United States-Food and Drug Administration</p>\n<p>\n  </p>\n<p>\n  </p>\n
      • other_details_regulatory_approved<p>\n Brazil-Agencia Nacional De Vigilancia Sanitaria (ANVISA)</p>\n<p>\n Canada-Health Canada</p>\n<p>\n Netherlands-De Centrale Commissie Mensgebonden Onderzoek (CCMO)</p>\n<p>\n Germany-Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM - Federal Institute for Drugs and Medical Devices)</p>\n<p>\n Sweden-Läkemedelsverket</p>\n
      • other_details_regulatory_rejected<p>\n none</p>\n
      • other_details_regulatory_halted<p>\n None</p>\n
      • estimated_duration1 year
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparator Matching BEM-placebo tab
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states24
      • number_of_sites3
      • multi_country_listArgentina\nBrazil\nCanada\nColombia\nEgypt\nGermany\nGhana\nIndia\nJapan\nKenya\nLatvia\nMexico\nMorocco\nNetherlands\nPakistan\nPhilippines\nRomania\nSouth Africa\nSpain\nSweden\nTunisia\nTurkey\nUnited Kingdom\nUnited States
      • data_monitoring_committeeYes
      • total_enrolment_per_siteThe study is competitive enrollment and there is no minimum or maximum cap per site.
      • total_participants_worldwide1500
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyYes
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameDr. Paul
      • investigator1_middle_name
      • investigator1_family_nameYonga
      • investigator1_qualificationMBChB, MSPH, FRCP Edin
      • investigator1_professional_addressFountain Health Care Hospital, off Uganda Road (next to Lion’s School), Eldoret, KENYA
      • investigator1_telephone+254723149249
      • investigator1_emailpaul.yonga@fhc.co.ke
      • organisations_transferred_Yes
      • number_participants33
      • notification
      • approval_date09-08-2023
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted01-03-2023
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonAll reviewer comments have been responded to.
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-04-11 15:10:15
      • created2023-01-19 13:28:35
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id883
        • application_id1213
        • given_nameDr. Paul
        • middle_name
        • family_nameYonga
        • qualificationMBChB, MSPH, FRCP Edin
        • professional_addressFountain Health Care Hospital, off Uganda Road (next to Lion’s School), Eldoret, KENYA
        • telephone+254723149249
        • emailpaul.yonga@fhc.co.ke
        • created2023-01-19 14:42:47
        • modified2023-03-01 15:55:53
      • 1(array)
        • id885
        • application_id1213
        • given_nameDr John
        • middle_name
        • family_nameKinuthia
        • qualificationMBChB, MMed, MPH
        • professional_addressP.O. Box 20723-00202, Nairobi
        • telephone+254722799052
        • email_ kinuthia@uw.edu
        • created2023-01-20 14:22:49
        • modified2023-03-01 15:55:53
      • 2(array)
        • id886
        • application_id1213
        • given_nameDR LUCAS
        • middle_nameOTIENO
        • family_nameTINA
        • qualificationMBChB MPH
        • professional_addressVictoria Biomedical Research Institute (VIBRI),P.O. Box 7180, Postal Code 4010
        • telephone+254 720 597654
        • emailltina@vibriafrica.org
        • created2023-01-20 14:30:02
        • modified2023-03-01 15:55:53
    • SiteDetail(array)
      • 0(array)
        • id1395
        • application_id1213
        • county_id42
        • site_nameFountain Projects and Research Office, Clinical Research Centre (FOPRO-CRC)
        • physical_addressFountain Health Care Hospital, off Uganda Road (next to Lion’s School), Eldoret, KENYA
        • contact_details+254723149249
        • contact_personDr Paul Yonga
        • site_capacity(null)
        • misc(null)
        • created2023-01-19 14:42:47
        • modified2023-03-01 15:55:53
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 1(array)
        • id1410
        • application_id1213
        • county_id47
        • site_nameKENYATTA NATIONAL HOSPITAL
        • physical_addressP.O. Box 20723-00202, Nairobi
        • contact_details+254722 799052
        • contact_personDr John Kinuthia
        • site_capacity(null)
        • misc(null)
        • created2023-01-20 22:39:37
        • modified2023-03-01 15:55:53
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 2(array)
        • id1412
        • application_id1213
        • county_id42
        • site_nameVictoria Biomedical Research Institute (VIBRI)
        • physical_addressKisumu County Referral Hospital, P. O. Box 7180, Postal Code 40100
        • contact_details+254714421248
        • contact_personDr Lucas Otieno Tina
        • site_capacity(null)
        • misc(null)
        • created2023-01-21 11:23:44
        • modified2023-03-01 15:55:53
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
    • Sponsor(array)
      • 0(array)
        • id630
        • application_id1213
        • sponsorAtea Pharmaceuticals, Inc.
        • sponsor_typeIndustry
        • contact_personKristen Perkins
        • address225 Franklin Street Suite 2100 Boston, MA 02110 USA
        • telephone_number+1 (857) 284-8891
        • fax_number
        • cell_number+1 (857) 284-8891
        • email_addressperkins.kristen@ateapharma.com
        • created2023-01-19 14:42:47
        • modified2023-03-01 15:55:53
  • 2(array)
    • Application(array)
      • id905
      • user_id360
      • trial_status_id5
      • abstract_of_study<p>\n PATH and GlaxoSmithKline (GSK) are committed to developing a malaria vaccine to help reduce the burden of malaria disease in children and contribute to malaria elimination. GSK has developed a candidate vaccine against malaria caused by Plasmodium falciparum, RTS,S/AS01. The vaccine has been shown to be safe in multiple trials and efficacy data in pediatric populations has led to a pilot implementation program in three African countries including Kenya. The RTS,S/AS01 vaccine mechanism of action is presumed to work on the initial sporozoite and liver stages of P. falciparum infection through neutralization of the circumsporozoite (CS) antigen on parasites invading after a mosquito bite in individuals immunized with the RTS,S/AS01 vaccine. In order to inform whether a vaccine such as RTS,S/AS01 may have a future role in malaria elimination, it will be important to establish vaccine efficacy in adults in Sub-Saharan Africa who are reservoirs of parasites and who contribute to ongoing malaria transmission. However, in previous trials, the vaccine has been less effective in adults in endemic regions compared to challenge studies. While the cause of this is likely multi-factorial, there is a degree of immunologic hypo-responsiveness that occurs in endemic regions that may impede the development of a protective immune response following immunization that is presumed to be related to chronic infection. This study postulates that treatment of infection prior to immunization can reset the immune response leading to an improved vaccine efficacy. To evaluate this hypothesis, the study will recruit 5 groups. Groups 1 and 4 will have asymptomatic infection with P. falciparum as measured by a highly sensitive PCR assay (planned assay is an RNA-based PCR though the backup utilizes both RNA and DNA PCR, see protocol for details) and will be treated with antimalarial medications prior to immunization with RTS,S/AS01 or the comparator rabies vaccine, respectively, with the primary objective of evaluating the vaccine efficacy of RTS,S/AS01 relative to the rabies vaccine in this context. Groups 2 and 5 will be negative for asymptomatic infection with P. falciparum as measured by a highly sensitive PCR assay and will be treated with antimalarial medications prior to immunization with RTS,S/AS01 or the comparator rabies vaccine, respectively, with the secondary objective of evaluating the vaccine efficacy of RTS,S/AS01 relative to the rabies vaccine in this context. Group 3 will have asymptomatic infection with P. falciparum as measured by a highly sensitive PCR assay but will not be treated with antimalarial medications prior to immunization with the RTS,S/AS01 vaccine; the immunological profile (including anti-CS and cell-mediated immune responses) of this group and groups 1 and 2 will be evaluated as part of secondary and exploratory objectives. Other secondary objectives include safety assessments and other exploratory objectives defined in this protocol. A total of 619 subjects will be enrolled (164 in groups 1 and 4, 128 in groups 2 and 5, and 35 in group 3) over a period of 6 months and will participate in the study for an initial immunization period (vaccine given on 0, 1, and 7 month schedule with the final dose being 1/5 of the dose of the first two immunizations) followed by 6-12 months of follow-up (varying based on the number of events), with the primary and secondary efficacy endpoints of time to first malaria infection by PCR. Total duration expected to be 20.5-26.5 months. Those groups receiving antimalarial medications (1, 2, 3, 4) will receive either dihydroartemisinin-piperaquine or artemether/lumefantrine and low-dose primaquine as described in the protocol.</p>\n
      • study_title<p>\n A Phase 2b randomized, open-label, controlled, single center study in Plasmodium falciparum-infected and uninfected adults age 18-55 years old in Kenya to evaluate the efficacy of the delayed, fractional dose RTS,S/AS01E malaria vaccine in subjects treated with artemisinin combination therapy plus primaquine</p>\n
      • laymans_summary<p>\n PATH and GlaxoSmithKline (GSK) are committed to developing a malaria vaccine to help reduce the burden of malaria disease in children and contribute to malaria elimination. GSK has developed a candidate vaccine called RTS,S/AS01 which helps the immune system of people vaccinated with RTS,S/AS01 prevent infection with the parasite that causes malaria. The RTS,S/AS01 vaccine has been shown to be safe in multiple studies around the world and is currently beginning a pilot implementation program in children in sub-Saharan Africa. The vaccine has been shown to be effective in adults who have never had malaria when they are challenged with malaria infection in the United States, but has been less effective when given to adults in Africa who have had malaria before. There are probably multiple reasons for this, but one possible reason that is probably very important is that prior infection with malaria or an infection with malaria for long periods, even without symptoms of the disease, can prevent the vaccine from working properly. This study is testing the question that if we treat individuals with antimalarial medications before giving the vaccine, will that make it more effective in people who have a history of malaria infection. The RTS,S/AS01 malaria vaccine will be compared to a rabies vaccine to see if this will improve the effectiveness. We will also be looking at the safety of the vaccine and the response of the immune system to this vaccine.</p>\n
      • short_titleCVIA078
      • protocol_noECCT/20/06/03
      • version_no2.0
      • date_of_protocol14-05-2020
      • study_drugRTS,S/AS01E vaccine
      • disease_conditionMalaria
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines1
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorYes
      • comparator_nameAbhayrab rabies vaccine
      • comparator_registeredYes
      • comparator_countriesAbhayrab rabies vaccine
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressdotigondi3@gmail.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter0
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum0
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter0
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan0
      • applicant_contractual_agreement0
      • declaration_applicantNathanial Copeland
      • declaration_date112-06-2020
      • declaration_principal_investigatorNathanial Copeland
      • declaration_date212-06-2020
      • placebo_presentNo
      • study_objectives<p>\n Primary Objective: To assess vaccine efficacy assessed by time to first P. falciparum infection in RTS,S/AS01E vaccinated adults (Group 1) positive for P. falciparum by PCR at baseline and treated to clear parasites compared to adults administered a comparator vaccine (Group 4) positive for P. falciparum by PCR at baseline and treated to clear parasites. Secondary Objectives: Efficacy: To assess vaccine efficacy by time to first P. falciparum infection by PCR in RTS,S/AS01E vaccinated adults (Group 2) negative for P. falciparum at baseline and provided anti-malarial chemo-prophylaxis versus comparator group (Group 5) negative for P. falciparum at baseline and provided anti-malarial chemo-prophylaxis. Safety: • To assess the safety of RTS,S/AS01E in terms of serious adverse events (SAEs) during the whole study period (from Dose 1 to study conclusion) • To assess the safety and reactogenicity of RTS,S/AS01E in terms solicited local and systemic adverse events within 7 days after each vaccination in the first 50 subjects in groups 1 and 2, and in all 35 subjects from Group 3. • To assess the safety of RTS,S/AS01E in terms of unsolicited adverse events within 28 days after each vaccination Immunogenicity: To assess anti-circumsporozoite (CS) antibody titers & avidity, hepatitis B surface antibody (HBsAb) titres, from groups 1, 2 and 3 as detailed in Appendix E. Exploratory Objectives: • To assess in subjects immunized with RTS,S/AS01E the relationship between HLA Class 1 and Class 2 alleles with protection against P. falciparum infection. • To assess anti-rabies titers in subset of subjects at time points from groups 4 and 5 as shown in Appendix E. • To assess cell-mediated immune responses and transcriptomes in Groups 1 – 3. • Other immunological assays evaluating the immune response to CS and HBsAg might be performed.</p>\n
      • principal_inclusion_criteria<p>\n • Provision of signed or thumb printed and dated informed consent form • Stated willingness to comply with all study procedures and availability for the duration of the study • Male or female between 18 and 55 years of age, inclusive • In good general health as evidenced by medical history and clinical examination before entering the study • Ability to take oral medication and be willing to adhere to the medication regimen • For females, she must be of non-childbearing potential or use appropriate measures to prevent pregnancy for 30 days prior to vaccination through 2 months after completion of the vaccine series. Non-childbearing potential means she is surgically sterilized or at least one year post-menopausal. Appropriate measures to prevent pregnancy include abstinence or adequate contraceptive precautions (i.e. intrauterine contraceptive device; oral contraceptives; diaphragm or condom in combination with contraceptive jelly, cream or foam; Norplant or Depo-Provera). Kombewa clinical staff will assist with provision of acceptable birth control for study entry and will discuss with volunteer at screening visit.</p>\n
      • principal_exclusion_criteria<p>\n • Planned administration/administration of a vaccine not foreseen by the study protocol from within 30 days before the first dose of study vaccine until 30 days after the last dose of study vaccine. • Any prior receipt of any rabies vaccine or experimental malaria vaccine. • Confirmed or suspected significant immunosuppressive or immunodeficient condition as determined by the investigator, including clinical stage 3 or 4 human immunodeficiency virus (HIV) infection (Appendix G). • A family history of congenital or hereditary immunodeficiency. • History of allergic reactions, significant IgE-mediated events or anaphylaxis to previous immunizations. • History of any neurologic disorders. • Acute disease (defined as the presence of a moderate or severe illness with or without fever), including acute malaria, at the time of enrolment. All vaccines can be administered to persons with a minor illness, such as diarrhea or mild upper respiratory infection without fever, i.e. Oral temperature < 37.5°C. Individuals excluded with acute disease, including acute malaria, can become eligible again after complete recovery of the illness, including appropriate treatment as applicable, and can be rescreened at a later date. • Acute or chronic, clinically significant pulmonary, cardiovascular (including cardiac arrythmias) , hepatic or renal functional abnormality, as determined by medical history, physical examination or laboratory screening tests. • History of homozygous sickle cell disease (Hgb SS). • Any clinically significant laboratory abnormalities as determined by the investigator on screening labs (site reference ranges, Appendix F). • History of splenectomy. • Administration of immunoglobulins, blood transfusions or other blood products within the three months preceding the first dose of study vaccine or planned administration during the study period. • Pregnant (i.e. a positive pregnancy test) or lactating female during immunization phase of the study (refer to section 2.3 for rationale). If a woman becomes pregnant after all vaccinations are complete, she will not be excluded from the remainder of the study. • Female planning to become pregnant or planning to discontinue contraceptive precautions during the vaccination phase. • History of chronic alcohol consumption and/or drug abuse. • Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose (for corticosteroids, this will mean prednisone, or equivalent, ≥ 0.5 mg/kg/day. Inhaled and topical steroids are allowed). • Major congenital defects or serious chronic illness. • Simultaneous participation in any other clinical trial (apart from participation in the HDSS network). • Any other findings that the investigator feels would increase the risk of having an adverse outcome from participation in the trial.</p>\n
      • primary_end_points<p>\n The primary endpoint is defined as the time to first PCR-detectable malaria infection in Groups 1 and 4 during the ADI phase of the study. Vaccine efficacy in African adults (Group 1) administered RTS,S with sub-clinical PCR-positive parasitemia at baseline and treated to clear parasites before immunization will be compared to volunteers in Group 4 with sub-clinical PCR-positive parasitemia at baseline and treated to clear parasites before immunization with a comparator rabies vaccine.</p>\n
      • scope_diagnosis0
      • scope_prophylaxis1
      • scope_therapy0
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other1
      • trial_other_specifyOther: Prevention/Vaccine exploratory (Phase II)
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n The site has adequate staff and facilities to conduct the trial.</p>\n
      • other_details_explanation<p>\n The applicant is employed by the US Army and is stationed in Kisumu, Kenya as part of a >50 year collaboration between the US Army and KEMRI. The sponsor is an international nonprofit organization focused on improving health for all. They are headquartered in Seattle, WA, USA, but work globally, with multiple prior projects in Kenya. Malaria is a focus area for PATH and as such they have partnered with multiple Kenyan organizations over the year in efforts to better understand and prevent this disease.</p>\n
      • other_details_regulatory_notapproved<p>\n None</p>\n
      • other_details_regulatory_approved<p>\n 1)KEMRI Centre for Clinical Research’s Centre Scientific Committee, approved 25 Feb 2020, approved for single site in Kenya. 2) KEMRI Scientific and Ethics Review Unit, approved 26 May 2020, approved for single site in Kenya.</p>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n None</p>\n
      • estimated_duration26.5 months
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorrabies vaccine
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKombewa Clinical Research Centre
      • single_site_physical_addressOff Kisumu Bondo Road. Opposite Kombewa County Hopital
      • single_site_contact_personNathanial Copeland
      • single_site_telephone+254 705 251782
      • multiple_sites_member_stateNo
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites
      • multi_country_list
      • data_monitoring_committeeNo
      • total_enrolment_per_siteN/A
      • total_participants_worldwide619
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersYes
      • subjects_others_specifysubset of participants asymptomatically infected with malaria parasite
      • investigator1_given_nameNathanial
      • investigator1_middle_nameKelsey
      • investigator1_family_nameCopeland
      • investigator1_qualificationMedical Doctor (MD), Master in Tropical Medicine and Hygiene
      • investigator1_professional_addressP.O. Box 606, 00621 Village Market, Nairobi
      • investigator1_telephone+254 0705 251 782
      • investigator1_emailnathanial.copeland@usamru-k.org
      • organisations_transferred_Yes
      • number_participants619
      • notification
      • approval_date19-08-2020
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted29-10-2020
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonThe application has been approved by PPB ECCT
      • final_report<div>\n A total of 1191 participants were screened for enrolment, and 620 participants were randomized. Overall, 605 participants from these randomized participants were administered study vaccine. Reasons for randomized participants not receiving study vaccine mainly included pregnancy, potential issues of noncompliance, withdrawal of consent, alcohol abuse and personal reasons. One hundred sixty participants were allocated to Group 1, 124 participants were allocated to Group 2, 35 participants were allocated to Group 3, 159 participants were allocated to Group 4, and 127 participants were allocated to Group 5.</div>\n<div>\n Of the 605 participants who received study vaccine, 582 (93.9%) participants received all scheduled vaccinations, and 539 (89.1%) participants completed the study. Sixty-six (10.9%) participants discontinued the study. Reasons for discontinuation of participants included: lost to follow-up for 49 (8.1%) participants; Investigator decision for 3 (0.5%) participants; withdrawal by participant for 7 (1.2%) participants; and other reasons for 6 (1.0%) participants. One (0.2%) participant died during the study.</div>\n<div>\n •</div>\n<div>\n The primary objective of the study was completed. The persons-years at risk (PYAR) was 59.53 for Group 1 and 53.67 for Group 4. The crude estimated vaccine efficacy was 34.8% (p-value = 0.012; 95% CI: 8.9-53.4 %).</div>\n<div>\n •</div>\n<div>\n The PYAR for Group 2 was 49.63 years compared to 54.88 years for Group 5. The secondary objective of the study was completed.</div>\n<div>\n •</div>\n<div>\n Overall, 799 unsolicited AEs were reported for 412 (68.1% [64.2-71.8]) participants, 124 systemic solicited AEs were reported for 50 (38.2% [29.8-47.1]) participants, and 142 local systemic solicited AEs were reported for 64 (48.9) [40.0-57.7] participants. Most AEs were mild, and none were considered related to the study treatment.</div>\n<div>\n •</div>\n<div>\n A total of 13 SAEs were reported in 10 participants. One SAE resulted in death, and one led to discontinuation.</div>\n<div>\n •</div>\n<div>\n There were no AESIs reported in the study.</div>\n<div>\n •</div>\n<div>\n The RTS,S/AS01E vaccine was immunogenic in all groups based on titers/avidity measured at different timepoints. Regardless of baseline parasitemia status, the clearance of parasite with anti-malarial chemotherapy or chemoprevention of malaria, there was a similar antibody profile in all RTS,S/AS01E vaccinated groups.</div>\n<div>\n •</div>\n<div>\n  </div>\n
      • implication_results<p>\n There was no impact of baseline parasitemia, chemoprevention or clearance of parasites with anti-malarial chemotherapy on HbsAb levels.</p>\n
      • quantity_imported37540
      • quantity_dispensed29814
      • quantity_destroyed7726
      • quantity_exported0
      • balance_site0
      • final_date0000-00-00
      • modified2025-03-11 17:34:08
      • created2020-06-12 11:15:56
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id560
        • application_id905
        • given_nameNathanial
        • middle_nameKelsey
        • family_nameCopeland
        • qualificationMedical Doctor (MD), Master in Tropical Medicine and Hygiene,
        • professional_addressP.O. Box 606, 00621 Village Market, Nairobi
        • telephone+254 0705 251 782
        • emailnathanial.copeland@usamru-k.org
        • created2020-06-12 11:22:45
        • modified2020-10-29 14:59:14
    • SiteDetail(array)
      • 0(array)
        • id782
        • application_id905
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2020-06-12 11:22:45
        • modified2020-10-29 14:59:14
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id435
        • application_id905
        • sponsorPATH
        • sponsor_typeResearch Institution
        • contact_personKaren Ivinson
        • addressRue de Varembe 7, 1202, Geneva, Switzerland
        • telephone_number+41 791 024 175
        • fax_numberN/A
        • cell_number+41 791 024 175
        • email_addresskivinson@path.org
        • created2020-06-12 11:22:45
        • modified2020-10-29 14:59:14
  • 3(array)
    • Application(array)
      • id481
      • user_id229
      • trial_status_id5
      • abstract_of_study<p>\n Shigellosis remains a major health problem in developing countries with approximately 100 million cases per year mostly in children ≤5 years. Antibiotic resistance of Shigella is increasing and no vaccine is currently available against shigellosis.</p>\n<p>\n The purpose of H03_04TP study is to evaluate the safety and the immunogenicity of two different doses (25 μg and 100 μg) of the GVGH S. sonnei 1790GAHB vaccine in healthy adults and represents the first step towards testing of the GMMA vaccine in the vaccine target population of children from developing countries where shigellosis is endemic.</p>\n
      • study_title<p>\n A Phase 2a, observer blind, randomized, controlled, Single Center Study to evaluate the Safety, Reactogenicity and Immunogenicity of 2 doses of the GVGH 1790GAHB Vaccine against <em>Shigella sonnei</em>, administered intramuscularly in Adult Subjects from a country endemic for shigellosis [GVGH study H03_04TP]</p>\n
      • laymans_summary(null)
      • short_titleA study of the safety and immune response of 2 doses of a new Shigella vaccine in Kenyan adults.
      • protocol_noECCT/16/02/06
      • version_no2.0
      • date_of_protocol04-11-2015
      • study_drugShigella sonnei 1790GAHB vaccine
      • disease_conditionShigellosis
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals1
      • product_type_vaccines1
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparator(null)
      • comparator_name(null)
      • comparator_registered(null)
      • comparator_countries(null)
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressgodfrey.m.nyakaya@gsk.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries1
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd(null)
      • applicant_prev_data(null)
      • applicant_stability_data(null)
      • applicant_analysis_cert(null)
      • applicant_pictorial_sample(null)
      • applicant_gcp_training(null)
      • applicant_dsmb_charter(null)
      • applicant_detailed_budget(null)
      • applicant_indemnity_pi(null)
      • applicant_practice_license(null)
      • applicant_registration_ctr(null)
      • applicant_pan_african(null)
      • applicant_hard_copies(null)
      • applicant_signed_checklist(null)
      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantFrancis Karanja
      • declaration_date115-02-2016
      • declaration_principal_investigatorFrancis Karanja
      • declaration_date215-02-2016
      • placebo_presentNo
      • study_objectives(null)
      • principal_inclusion_criteria<p>\n 1) Individuals ≥18 years to ≤45 years of age on the day of informed consent who are resident in the study area and are not planning to leave during the study period.</p>\n<p>\n 2) Individuals who, after the nature of the study has been explained, have voluntarily given written consent according to local regulatory requirements, prior to study entry.</p>\n<p>\n 3) Individuals who can comply with study procedures including follow-up.</p>\n<p>\n 4) Individuals in good health as determined by the outcome of medical history, physical examination, hematology, renal function, and liver function tests, urine dipstick/urinalysis and the clinical judgment of the investigator.</p>\n<p>\n 5) Males</p>\n<p>\n Or</p>\n<p>\n Females of childbearing potential who are using an effective birth control method which they intend to use for the duration of the study</p>\n<p>\n Or</p>\n<p>\n Females without childbearing potential (i.e. irrespective of birth control method).</p>\n
      • principal_exclusion_criteria<p>\n 1) Individuals with behavioral or cognitive impairment or psychiatric disease that, in the opinion of the investigator, may interfere with the subject's ability to participate in the study.</p>\n<p>\n 2) Individuals with any progressive or severe neurological disorder, seizure disorder or previous Guillain-Barré syndrome.</p>\n<p>\n 3) Individuals who, in the judgment of the investigator, may not be able to comply with all the required study procedures.</p>\n<p>\n 4) Individuals with history of any illness that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the subjects due to participation in the study.</p>\n<p>\n 5) Individuals with history of reactive arthritis.</p>\n<p>\n 6) Individuals with known HIV or hepatitis B virus infection or HIV related disease, history of an autoimmune disorder or any other known or suspected impairment /alteration of the immune system. Individuals under systemic administration of corticosteroids (PO/IV/IM) for more than 14 consecutive days within 90 days prior to screening.</p>\n<p>\n 7) Individuals with a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time.</p>\n<p>\n 8) Individuals with a neutrophil count lower than 1.8 x 109/L (applicable to the initial 18 subjects) or lower than 1.0 x 109/L (applicable to the additional subjects if approved by DSMB) at screening.</p>\n<p>\n 9) Individuals with any serious chronic or progressive disease according to judgment of the investigator (e.g., neoplasm, insulin dependent diabetes, Type 2 diabetes mellitus, hypertension, cardiac, renal or hepatic disease and tuberculosis).</p>\n<p>\n 10) Individuals who have any malignancy or lymphoproliferative disorder.</p>\n<p>\n 11) Individuals with history of allergy to vaccines components or any other allergies deemed by the investigator to increase the risk of an adverse event if they were to participate in the trial.</p>\n<p>\n 12) Individuals participating in any clinical trial with another investigational product within 28 days prior to the screening study visit or intent to participate in another clinical study at any time during the conduct of this study.</p>\n<p>\n 13) Individuals who received vaccines containing meningococcal A, C, W, Y or tetanus, diphtheria or pertussis antigens within 12 months before screening, or any other vaccines within 4 weeks prior to screening in this study or who are planning to receive any vaccine within the entire study duration.</p>\n<p>\n 14) Individuals who have received blood, blood products, and/or plasma derivatives including parenteral immunoglobulin preparations in the 12 weeks prior to the first dose of the study vaccine.</p>\n<p>\n 15) Individuals who are study personnel or immediate family members (parents, children, spouse and brothers/sisters) to the personnel conducting this study.</p>\n<p>\n 16) Individuals with body temperature > 38.0â—¦C within 3 days of intended study vaccination is a reason for delay of vaccination.</p>\n<p>\n 17) Individuals with Body Mass Index (BMI)> 30 kg/m2</p>\n<p>\n 18) Individuals with history of substance or alcohol abuse within the past 2 years.</p>\n<p>\n 19) Women who are pregnant or are breast-feeding, or are of childbearing age who have not used (for the two months preceding the 1st vaccination) and are not willing to use acceptable contraceptive measures, for the duration of the study. If subjects are women of childbearing potential, they must have a negative pregnancy test at screening visit and prior to enrollment (visit 1). For the purposes of this study acceptable methods of contraception are oral, injected or implantable contraceptives.</p>\n<p>\n 20) Individuals who have a previously laboratory confirmed case of disease caused by S. sonnei.</p>\n<p>\n 21) Any condition which, in the opinion of the investigator, may pose an increased and unreasonable safety risk to the subject if they participated in the study.</p>\n
      • primary_end_points<p>\n <strong>1) Primary Safety Endpoint(s) </strong></p>\n<p>\n The safety profile of the two vaccine doses and control(s) will be assessed through measurement of the following:</p>\n<p>\n a. Number and percentage of subjects with solicited local and systemic adverse reactions during 7 days following each vaccination.</p>\n<p>\n b. Numbers and percentage of subjects with deviations from normal ranges of safety laboratory data after each vaccination.</p>\n<p>\n c. Number and percentage of subjects with reported unsolicited adverse events during 28 days following each vaccination.</p>\n<p>\n d. Number and percentage of subjects with reported SAEs throughout the study duration.</p>\n<p>\n e. Number and percentage of subjects with reported reactive arthritis (AESIs).</p>\n<p>\n <strong>2) Primary Efficacy Endpoint(s) </strong></p>\n<p>\n The study does not have primary efficacy endpoint(s).</p>\n<p>\n <strong>3) Primary Immunogenicity Endpoint(s) </strong></p>\n<p>\n The study does not have primary immunogenicity endpoint(s).</p>\n
      • scope_diagnosis0
      • scope_prophylaxis1
      • scope_therapy0
      • scope_safety1
      • scope_efficacy0
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response1
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others1
      • scope_others_specifyImmunogenicity
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory1
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n Number of staff, names, qualifications, experience -- including study co-ordinators, site facilities, emergency facilities, other relevant infrastructure)</p>\n<p>\n <strong>Number of staff:</strong></p>\n<p>\n The KEMRI Wellcome Trust Research Programme in Kilifi currently has 650 staff including 27 clinical officers, 23 nurses, 1 pharmacist, 4 counselors, and 102 field workers.</p>\n<p>\n <strong>Name</strong>s: ï‚·</p>\n<ul>\n <li>\n Prof. Philip Bejon: KEMRI Wellcome Trust Research Programme Executive Director (and co-PI for study H03_04TP) ï‚·</li>\n <li>\n Dr. Christina Obiero: Principal Investigator (PI) of study H03_04TP ï‚·</li>\n <li>\n Dr. Patricia Njuguna: co-PI for study H03_04TP</li>\n</ul>\n<p>\n <strong>Qualifications/experience </strong></p>\n<p>\n The site staff has previous experience in conducting clinical research on: ï‚·</p>\n<p>\n Infectious Disease (malaria, HIV, pneumococcal infection, Ebola) ï‚·</p>\n<p>\n Vaccines (malaria, Ebola) ï‚·</p>\n<p>\n General fields: behavioral, malnutrition, anemia</p>\n<p>\n A GCP training (done by a member of the monitoring team) is organized every two years and a refresh training is performed in between. The investigators also perform an on-line training on the ethical aspects of clinical trials.</p>\n<p>\n <strong>Site facilities, emergency facilities, other relevant infrastructure: </strong></p>\n<p>\n The clinical site is located within the Kilifi campus in a wide area, close to the Kilifi County Hospital. It is secured with a perimeter wall and 24-hour security. The Kilifi County Hospital (adjacent to KEMRI-WT) is the main government health facility serving residents of Kilifi County and includes a HIV clinic and care service (CCRC) in which the clinical site cooperates in providing care (including patients and people who take part in clinical research). In case of SAE (e.g. in case the study participant needs to be hospitalized), study subjects are referred to this hospital. If the condition becomes worse the subject is transported to the hospital of Mombasa (ambulance is available).</p>\n<p>\n The pharmacy is located within the hospital and provides dedicated staff and service for clinical trials.</p>\n<p>\n The clinical site can count on a number of laboratories that perform both research activities (microbiology, blood cultures, immunology, entomology, cellular immunology, blood culture, DNA sequencing, etc.) and laboratory services for the Kilifi County Hospital. The access to the labs is secured with the use of badges. The labs have a quality assurance system in place and GCLP accreditation. The site can also refer to a dedicated Clinical Trial Laboratory (the safety lab) for hematology, biochemistry, microbiology testing, parasitology, part of microbiology testing, urinalysis and malaria.</p>\n<p>\n The clinical site has an on-site archive dedicated to clinical trials. The site usually refers to an off-site company (G4S) for long-term storage.</p>\n<p>\n In addition to the clinical trials facility, the KEMRI Wellcome Trust Research Programme includes an Epidemiology and Demography department, a Socio-behavioral department, a Data Management department and a Training facility and it is also involved in an ongoing Vaccine Monitoring Surveillance.</p>\n
      • other_details_explanation<p>\n The GSK Vaccines Institute for Global Health develops vaccines against neglected diseases for impoverished communities. Shigellosis remains a major public health problem around the world. It is one of the leading causes of diarrheal disease in low and middle income countries with the majority of these cases occuring in children less than 5 years of age. The Global Enteric Multicenter Study (GEMS) was aimed to evaluate the incidence of moderate & severe diarrhea (MSD) in children aged less than 5 years of age in sub-Saharan Africa and South Asia, with study sites in Gambia, Kenya, Mali, Mozambique, India, Bangladesh, and Pakistan. The results of this study have consistently indicated that shigellosis is one of the top 5 causes of MSD in each of the three age sub groups being considered: 0-11 months, 12-23 months and 24-59 months, respectively.</p>\n<p>\n The Shigella sonnei vaccine has been developed by GVGH and the first-in-human clinical Phase 1 studies have been performed in Europe at two trial sides, one in France (dose escalation up to 100 μg of protein) and one in the UK (different routes of administration). The clinical Phase 2a study is designed to evaluate the safety profile of two injections of S. sonnei 1790GAHB vaccine in healthy adults in Kenya, a Shigella endemic country.</p>\n
      • other_details_regulatory_notapproved<p>\n Not applicable.</p>\n
      • other_details_regulatory_approved<p>\n Not applicable.</p>\n
      • other_details_regulatory_rejected<p>\n Not applicable.</p>\n
      • other_details_regulatory_halted<p>\n Not applicable.</p>\n
      • estimated_duration5 months (anticipated start date: 2016-03-01; anticipated end date: 2016-07-30)
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindYes
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherYes
      • design_controlled_specifyObserver blind
      • design_controlled_comparatorMenveo and Boostrix
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherYes
      • design_controlled_medicinal_specifyGAHB-Placebo is used to dilute 1790GAHB vaccine at clinical site to prepare 25 μg dose (as protein) in support of dose response evaluation.
      • single_site_member_stateYes
      • location_of_areaKenya Medical Research Institute (KEMRI) -Wellcome Trust Research Programme
      • single_site_physical_addressP.O.Box 230 - 80108, Kilifi, Kenya
      • single_site_contact_personDr Christina Obiero
      • single_site_telephone(+254) 417 522535/522063/525043
      • multiple_sites_member_stateNo
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites
      • multi_country_list
      • data_monitoring_committeeYes
      • total_enrolment_per_site72
      • total_participants_worldwide72
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameChristina
      • investigator1_middle_nameWesonga
      • investigator1_family_nameObiero
      • investigator1_qualificationBachelor of Medicine and Bachelor of Surgery (MBChB); Master of Public Health (MPH)
      • investigator1_professional_addressKenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme, P.O.Box 230, 801080 Kilifi, Kenya
      • investigator1_telephone+254 721889581
      • investigator1_emailcobiero@kemri-wellcome.org
      • organisations_transferred_Yes
      • number_participants72
      • notification
      • approval_date15-04-2016
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted19-02-2016
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonYour study is now approved
      • final_reportDISCUSSION AND OVERALL CONCLUSIONS\nThe present report evaluated the safety and immunogenicity profile of 2 different doses of 1790GAHB vaccine in healthy adults at 28 days after first and second vaccination by measuring the anti-S sonnei LPS serum IgG.\nThe immunogenicity results show a baseline antibody concentration much higher than previously observed in European subjects. This is likely due to a persistent natural exposure to S sonnei in endemic countries. Overall, across all the vaccine groups, a very good immunogenicity response was observed after each vaccination, despite high baseline concentrations. Immunogenicity after the first vaccination was higher in the 5.9/100MCG_SHI group, reached plateau and did not show any significant variation after the second vaccination. By contrast, after the second vaccination, a further increase in antibody concentration was recorded in the 1.5/25MCG_SHI group. As expected, no change in antibody levels was observed in the control group. All the investigational vaccine groups achieved high seroresponses rates and all subjects in these groups achieved anti-S sonnei LPS IgG ≥121 EU/mL.\nAll vaccines were well tolerated. The most commonly reported local AE was injection site pain. Most of the solicited AEs were mild to moderate in severity and limited in duration. The most commonly reported systemic AE was headache, followed by arthralgia, chills, fatigue, malaise and myalgia.\n\nDuring the trial, 10 episodes of neutropenia fulfilling the protocol definition of AESI\nwere reported in 2 (9%), 3 (12%) and 1 (4%) participants in the 1.5/25 μg, 5.9/100 μg,\nand control groups, respectively. These episodes were all considered probably or possibly related to vaccination; 2 of them occurred in the 1.5/25 μg group (1 mild and 1 moderate),5 in the 5.9/100 μg group (4 mild and 1 moderate) and 3 in the control group (1 mild, 1 moderate and 1 severe). Two subjects in the 5.9/100 μg group were withdrawn from 2nd\nvaccination due to neutropenia; a 3rd should have been withdrawn but inadvertently was\nnot and experienced moderate neutropenia at day 57. All cases were transient (recovering\nwithin 7 days and recovered at study end) and, except for one subject in the 5.9/100 μg\ngroup who experienced upper respiratory tract infection (D1) and 38.1°C fever (D8), were\nalso asymptomatic, as confirmed by daily home visits during the 7 days post\nvaccination. Eight of these episodes occurred in 5 of the 18 individuals from the first\ncohort (screened and monitored using the ANC Western threshold of 1.8*109/L), While\nthe remaining 2 episodes occurred in one of the 54 participants in the second cohort\n(screened and monitored using the local threshold of 1.0*109/L). No SAEs occurred in the\nstudy. However, as defined in the study protocol the AESIs were reported as SAEs. There\nwas no case of reactive arthritis recorded.\n
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2019-07-19 10:25:13
      • created2016-02-14 22:12:10
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id321
        • application_id481
        • given_nameChristina
        • middle_nameWesonga
        • family_nameObiero
        • qualificationBachelor of Medicine and Bachelor of Surgery (MBChB); Master of Public Health (MPH)
        • professional_addressKenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme, P.O.Box 230, 801080 Kilifi, Kenya
        • telephone+254 721889581
        • emailcobiero@kemri-wellcome.org
        • created2016-02-14 22:57:03
        • modified2016-02-15 18:49:17
    • SiteDetail(array)
      • 0(array)
        • id382
        • application_id481
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2016-02-14 22:57:03
        • modified2016-02-15 18:49:17
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id254
        • application_id481
        • sponsorGSK Vaccines Institute for Global Health (GVGH)
        • sponsor_type(null)
        • contact_personAudino Podda
        • addressVia Fiorentina, 53100 Siena, Italy
        • telephone_number0039 0577 24 3496
        • fax_number0039 0577 24 9114
        • cell_number0039 335 7026 950
        • email_addressaudino.p.podda@gsk.com
        • created2016-02-14 22:57:03
        • modified2016-02-15 18:49:17
  • 4(array)
    • Application(array)
      • id1342
      • user_id263
      • trial_status_id6
      • abstract_of_study<p>\n <strong>Protocol Title:</strong></p>\n<p>\n A Phase 2a, Multicenter, Open-label, Dose-finding, Dose escalation Study of Meplazumab in Adult Patients diagnosed with Uncomplicated <em>Plasmodium falciparum</em> Malaria.</p>\n<p>\n <strong>Rationale</strong><strong>:</strong></p>\n<p>\n Meplazumab, an erythrocytic stage-macromolecular antibody drug, has the potential to control clinical occurrence of falciparum malaria. Meplazumab is a humanized anti-CD147 immunoglobulin G subclass 2 (IgG2) monoclonal antibody with strong affinity to CD147. CD147 is expressed on erythrocyte lineage cells throughout erythroid development, including mature erythrocytes and is the target for Plasmodium merozoites to allow reorientation and subsequent invasion of the erythrocytes. Nonclinical studies have demonstrated that meplazumab binding to CD147 interferes with the receptor‑ligand interaction between CD147 and rhoptry-associated protein 2 (RAP2) of the <em>P. falciparum</em> merozoite and inhibits the formation of parasitophorous vacuoles of <em>P. falciparum</em> thus preventing the invasion of <em>P. falciparum</em> into human erythrocytes. Furthermore, the therapeutic and prophylactic effects of meplazumab were demonstrated in vivo using a human erythrocyte chimeric NOG mouse model, which is considered as an optimal choice for in vivo inhibition efficacy study for human-hosted <em>P. falciparum</em>.</p>\n<p>\n Meplazumab has previously been studied in healthy participants in two Phase 1 studies and has also been evaluated for activity in 2 completed clinical trials in patients diagnosed with coronavirus disease 2019 (COVID‑19). In the safety, tolerability, and pharmacokinetics study in healthy participants, MPZ‑I-01, results demonstrated a high and prolonged receptor occupancy (RO%) of meplazumab at CD147.</p>\n<p>\n This Phase 2a study is designed as a dose escalation trial to assess safety of meplazumab in the target population and to evaluate whether meplazumab is efficacious in treating malaria. The data obtained in this study will be used to determine a recommended meplazumab dose for future Phase 2b and 3 efficacy trials.</p>\n<p>\n <strong>Protocol Title:</strong></p>\n<p>\n A Phase 2a, Multicenter, Open-label, Dose-finding, Dose escalation Study of Meplazumab in Adult Patients diagnosed with Uncomplicated <em>Plasmodium falciparum</em> Malaria.</p>\n<p>\n <strong>Rationale</strong><strong>:</strong></p>\n<p>\n Meplazumab, an erythrocytic stage-macromolecular antibody drug, has the potential to control clinical occurrence of falciparum malaria. Meplazumab is a humanized anti-CD147 immunoglobulin G subclass 2 (IgG2) monoclonal antibody with strong affinity to CD147. CD147 is expressed on erythrocyte lineage cells throughout erythroid development, including mature erythrocytes and is the target for Plasmodium merozoites to allow reorientation and subsequent invasion of the erythrocytes. Nonclinical studies have demonstrated that meplazumab binding to CD147 interferes with the receptor‑ligand interaction between CD147 and rhoptry-associated protein 2 (RAP2) of the <em>P. falciparum</em> merozoite and inhibits the formation of parasitophorous vacuoles of <em>P. falciparum</em> thus preventing the invasion of <em>P. falciparum</em> into human erythrocytes. Furthermore, the therapeutic and prophylactic effects of meplazumab were demonstrated in vivo using a human erythrocyte chimeric NOG mouse model, which is considered as an optimal choice for in vivo inhibition efficacy study for human-hosted <em>P. falciparum</em>.</p>\n<p>\n Meplazumab has previously been studied in healthy participants in two Phase 1 studies and has also been evaluated for activity in 2 completed clinical trials in patients diagnosed with coronavirus disease 2019 (COVID‑19). In the safety, tolerability, and pharmacokinetics study in healthy participants, MPZ‑I-01, results demonstrated a high and prolonged receptor occupancy (RO%) of meplazumab at CD147.</p>\n<p>\n This Phase 2a study is designed as a dose escalation trial to assess safety of meplazumab in the target population and to evaluate whether meplazumab is efficacious in treating malaria. The data obtained in this study will be used to determine a recommended meplazumab dose for future Phase 2b and 3 efficacy trials.</p>\n<p>\n <strong>Objectives and Endpoints</strong><strong>:</strong></p>\n<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" title=\"Synopsis\">\n <thead>\n <tr>\n <th style=\"width:264px;\">\n <p>\n <strong>Objectives</strong></p>\n </th>\n <th style=\"width:342px;\">\n <p>\n <strong>Endpoints</strong></p>\n </th>\n </tr>\n </thead>\n <tbody>\n <tr>\n <td colspan=\"2\" style=\"width:606px;\">\n <p>\n <strong>Primary</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:264px;\">\n <ul>\n <li>\n To evaluate the safety of meplazumab in an adult population with uncomplicated, symptomatic <em>P. falciparum</em> infection</li>\n </ul>\n </td>\n <td style=\"width:342px;\">\n <ul>\n <li>\n Incidence and severity of AE</li>\n <li>\n Incidence of (number of participants with):\n <ul>\n <li>\n Drug-related SAE</li>\n <li>\n All-cause SAE</li>\n <li>\n Drug-related AESI</li>\n <li>\n All-cause AESI</li>\n <li>\n Participants discontinuation/ withdrawals due to AE</li>\n </ul>\n </li>\n </ul>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:606px;\">\n <p>\n <strong>Secondary</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:264px;height:50px;\">\n <ul>\n <li>\n To evaluate the efficacy of meplazumab as defined by:\n <ul>\n <li>\n Early treatment failure</li>\n <li>\n Late clinical failure</li>\n <li>\n Late parasitological failure</li>\n <li>\n Uncorrected ACPR</li>\n </ul>\n </li>\n </ul>\n </td>\n <td style=\"width:342px;height:50px;\">\n <ul>\n <li>\n Incidence (number of participants with) of early treatment failure</li>\n <li>\n Incidence of late clinical failure</li>\n <li>\n Incidence of late parasitological failure</li>\n <li>\n Incidence of uncorrected ACPR at Day 28</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td style=\"width:264px;\">\n <ul>\n <li>\n To evaluate PRR</li>\n </ul>\n </td>\n <td style=\"width:342px;\">\n <ul>\n <li>\n PRR at 72h</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td style=\"width:264px;\">\n <ul>\n <li>\n To determine the recrudescence (see Section 9.3.7) and re-infection (see Section 9.3.7)</li>\n </ul>\n </td>\n <td style=\"width:342px;\">\n <ul>\n <li>\n Incidence of (number of participants with) recrudescence and re-infection at Week 4</li>\n <li>\n Time to recrudescence and re-infection at Week 4</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td style=\"width:264px;\">\n <ul>\n <li>\n To determine the time to relief of fever</li>\n </ul>\n </td>\n <td style=\"width:342px;\">\n <ul>\n <li>\n FCT at 72h</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td style=\"width:264px;\">\n <ul>\n <li>\n To determine the dose-response trend relationship between 3 dose  levels of meplazumab by evaluation of safety, efficacy and ACPR outcomes</li>\n </ul>\n </td>\n <td style=\"width:342px;\">\n <ul>\n <li>\n Dose-response trend relationship between the 3 dose levels of meplazumab, based on change from baseline in the summary of the safety and efficacy outcomes to Week 4</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td style=\"width:264px;\">\n <ul>\n <li>\n To evaluate the pharmacokinetics of meplazumab in serum</li>\n </ul>\n </td>\n <td style=\"width:342px;\">\n <ul>\n <li>\n Meplazumab serum concentration-time profiles and PK parameters including but not limited to C_max, t_max, AUC_(0-last), AUC_(0-inf), t_½, CL, V_z, and V_ss</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td style=\"width:264px;\">\n <ul>\n <li>\n To evaluate immunogenicity following meplazumab administration</li>\n </ul>\n </td>\n <td style=\"width:342px;\">\n <ul>\n <li>\n Frequency of confirmed anti-drug antibody (ADA) response, ADA titers, and neutralizing activity</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:606px;\">\n <p>\n <strong>Exploratory</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:264px;height:45px;\">\n <ul>\n <li>\n To evaluate the efficacy of meplazumab by PCR-corrected ACPR</li>\n </ul>\n </td>\n <td style=\"width:342px;height:45px;\">\n <ul>\n <li>\n Incidence of (number of participants with) PCR‑corrected ACPR at Week 4</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td style=\"width:264px;\">\n <ul>\n <li>\n To evaluate RO (%) of meplazumab in red blood cells following single dose administration</li>\n </ul>\n </td>\n <td style=\"width:342px;\">\n <ul>\n <li>\n Meplazumab RO%-time profiles, pharmacodynamic parameters determined for RO including but not limited to maximum RO% and duration RO% (RO% half-life)</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td style=\"width:264px;\">\n <ul>\n <li>\n To quantify the levels of complement regulatory proteins, the deposition of complement on  erythrocytes, and serum complement activation in human subjects treated with meplazumab.</li>\n </ul>\n </td>\n <td style=\"width:342px;\">\n <ul>\n <li>\n Cell-surface expression of complement regulatory proteins and presence of complement products measured by flow cytometry; and complement activation measured by ELISA kit</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td style=\"width:264px;\">\n <ul>\n <li>\n To evaluate the relationship between exposure to meplazumab and key efficacy and/or safety parameters</li>\n </ul>\n </td>\n <td style=\"width:342px;\">\n <ul>\n <li>\n Graphical (and statistical, if appropriate) display of exposure versus response</li>\n </ul>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n Abbreviations: ACPR=adequate clinical & parasitological response; ADA=anti-drug antibodies; AE=adverse event; AESI =adverse event of special interest; AUC_{(0‑inf)}=area under the concentration‑time curve extrapolated to infinity; AUC_{(0‑last)}=area under the concentration‑time curve to the last quantifiable concentration; CL=systemic clearance; C_max=maximum concentration; FCT=fever clearance time; polymerase chain reaction PCR=polymerase chain reaction; <em>P. falciparum</em>=<em>Plasmodium falciparum</em>; PRR=parasite reduction rate; RO=receptor occupancy; SAE=serious adverse event; t_½=elimination half‑life; t_max=time to C_max; V_z=volume of distribution; V_ss=volume at steady state.</p>\n<p>\n <strong>Overall Design:</strong></p>\n<p>\n This is a Phase 2a multicenter, open-label, dose-finding, dose escalation study. The study will recruit participants with confirmed <em>P. falciparum</em> infection. Up to 60 participants will be enrolled into 1 of 3 meplazumab dose levels (20 participants /dose level).</p>\n<p>\n <strong>Number of Participants:</strong></p>\n<p>\n Up to 60 participants will be enrolled into 1 of 3 meplazumab dose levels (20 participants/dose level).</p>\n<p>\n <strong>Intervention Groups and Duration</strong><strong>:</strong></p>\n<p>\n Participants will be administered a single intravenous (IV) infusion dose of meplazumab 120±5 minutes on Day 0 and hospitalized for 72 hours after dosing (up to Day 3) to monitor for safety and tolerability of therapy, and to ensure treatment response. During hospitalization, blood sampling for safety, pharmacokinetic (PK), and RO pharmacodynamic (PD) testing at predefined times will be collected as specified per the Schedule of Assessment (SoA). Furthermore, in a subset of first 10 participants/dose level, additional (serial) PK and PD samples will be collected at 1, 2, 4 and 8 hours post end-of-infusion. Up to 3 additional samples may be added to the Day 0-3 serial sample collection period.</p>\n<p>\n If clinically well, participants may be discharged from the clinical unit on Day 3 at the Investigator’s discretion. Participants will return to the study center for follow-up visits on Days 28±2, 56±7, 84±7 and 182±7 (End of Study) for safety, tolerability, PK, PD (RO rate), and immunogenicity assessments as per the SoA (Weeks 4, 8, 12 and 26).</p>\n<p>\n <strong>Data Monitoring/Other Committee: </strong>Yes</p>\n<p>\n  </p>\n
      • study_title<p>\n A Phase 2a, Multicenter, Open-label, Dose-finding, Dose Escalation Study of Meplazumab in Adult Patients Diagnosed with Uncomplicated <em>Plasmodium falciparum</em> Malaria</p>\n
      • laymans_summary<p>\n <span class=\"ui-provider ee bir bis bit biu biv biw bix biy biz bja bjb bjc bjd bje bjf bjg bjh bji bjj bjk bjl bjm bjn bjo bjp bjq bjr bjs bjt bju bjv bjw bjx bjy\" dir=\"ltr\">Open-Label Study to evaluate the safety of meplazumab in an adult population with uncomplicated, symptomatic P. falciparum infection. Malaria is caused by Plasmodium, a parasite which is transmitted to humans by infected female anopheles mosquitoes (malaria vector). When infected anopheles bites a human, Plasmodium sporozoites in the mosquito’s saliva enter the bloodstream and migrate to the liver, followed by the merozoites reproduction within the hepatocytes. This stage is known as exoerythrocytic phase. Merozoites reproduce and form schizonts, which contain several thousands of merozoites. After the schizonts mature and rupture, merozoites are released into the blood and invade erythrocytes, hence initiating the merozoites reproduction in the erythrocytic phase. Current methods toward malaria elimination usually involve the combination of prevention and treatment. Artemisinin-based combination therapies (ACTs) are currently recommended by the World Health Organization for the treatment of malaria. Antimalarial drugs mainly include drugs to eliminate Plasmodium during the erythrocytic or exoerythrocytic phase. From the 1950s, falciparum malaria has developed general resistance to antimalarial drugs such as chloroquine, and sulfadoxine-pyrimethamine, leading to ineffective malaria control. Plasmodium developed higher resistance to the drugs used in combination in ACTs. Therefore, new antimalarial therapies and drugs are imperative due to the recurrent drug resistance of Plasmodium. Meplazumab, an erythrocytic stage-macromolecular antibody drug, has the potential to control clinical occurrence of falciparum malaria. Meplazumab is a humanized anti-CD147 immunoglobulin G subclass 2 (IgG2) monoclonal antibody with strong affinity to CD147. CD147 is expressed on erythrocyte lineage cells throughout erythroid development, including mature erythrocytes and is the target for Plasmodium merozoites to allow reorientation and subsequent invasion of the erythrocytes.</span></p>\n
      • short_titleMPZ-MAL-01
      • protocol_noECCT/23/11/01
      • version_noAmendment 1
      • date_of_protocol27-07-2023
      • study_drugMeplazumab
      • disease_conditionUncomplicated Plasmodium falciparum Malaria
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals1
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressamina.salim@iqvia.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter0
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum1
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      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
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      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
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      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantQuinter Atieno
      • declaration_date103-11-2023
      • declaration_principal_investigatorDr Lucas Tina Otieno
      • declaration_date203-11-2023
      • placebo_presentNo
      • study_objectives<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" title=\"Synopsis\">\n <thead>\n <tr>\n <th style=\"width:264px;\">\n <p>\n <strong>Objectives</strong></p>\n </th>\n <th style=\"width:342px;\">\n <p>\n <strong>Endpoints</strong></p>\n </th>\n </tr>\n </thead>\n <tbody>\n <tr>\n <td colspan=\"2\" style=\"width:606px;\">\n <p>\n <strong>Primary</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:264px;\">\n <ul>\n <li>\n To evaluate the safety of meplazumab in an adult population with uncomplicated, symptomatic <em>P. falciparum</em> infection</li>\n </ul>\n </td>\n <td style=\"width:342px;\">\n <ul>\n <li>\n Incidence and severity of AE</li>\n <li>\n Incidence of (number of participants with):\n <ul>\n <li>\n Drug-related SAE</li>\n <li>\n All-cause SAE</li>\n <li>\n Drug-related AESI</li>\n <li>\n All-cause AESI</li>\n <li>\n Participants discontinuation/ withdrawals due to AE</li>\n </ul>\n </li>\n </ul>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:606px;\">\n <p>\n <strong>Secondary</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:264px;height:50px;\">\n <ul>\n <li>\n To evaluate the efficacy of meplazumab as defined by\n <ul>\n <li>\n Early treatment failure</li>\n <li>\n Late clinical failure</li>\n <li>\n Late parasitological failure</li>\n <li>\n Uncorrected ACPR</li>\n </ul>\n </li>\n </ul>\n </td>\n <td style=\"width:342px;height:50px;\">\n <ul>\n <li>\n Incidence (number of participants with) of early treatment failure</li>\n <li>\n Incidence of late clinical failure</li>\n <li>\n Incidence of late parasitological failure</li>\n <li>\n Incidence of uncorrected ACPR at Day 28</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td style=\"width:264px;\">\n <ul>\n <li>\n To evaluate PRR</li>\n </ul>\n </td>\n <td style=\"width:342px;\">\n <ul>\n <li>\n PRR at 72h</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td style=\"width:264px;\">\n <ul>\n <li>\n To determine the recrudescence (see Section 9.3.7) and re-infection (see Section 9.3.7)</li>\n </ul>\n </td>\n <td style=\"width:342px;\">\n <ul>\n <li>\n Incidence of (number of participants with) recrudescence and re-infection at Week 4</li>\n <li>\n Time to recrudescence and re-infection at Week 4</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td style=\"width:264px;\">\n <ul>\n <li>\n To determine the time to relief of fever</li>\n </ul>\n </td>\n <td style=\"width:342px;\">\n <ul>\n <li>\n FCT at 72h</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td style=\"width:264px;\">\n <ul>\n <li>\n To determine the dose-response trend relationship between 3 dose levels of meplazumab by evaluation of safety, efficacy and ACPR outcomes</li>\n </ul>\n </td>\n <td style=\"width:342px;\">\n <ul>\n <li>\n Dose-response trend relationship between the 3 dose levels of meplazumab, based on change from baseline in the summary of the safety and efficacy outcomes to Week 4</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td style=\"width:264px;\">\n <ul>\n <li>\n To evaluate the pharmacokinetics of meplazumab in serum</li>\n </ul>\n </td>\n <td style=\"width:342px;\">\n <ul>\n <li>\n Meplazumab serum concentration-time profiles and PK parameters including but not limited to C_max, t_max, AUC_(0-last), AUC_(0-inf), t_½, CL, V_z, and V_ss</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td style=\"width:264px;\">\n <ul>\n <li>\n To evaluate immunogenicity following meplazumab administration</li>\n </ul>\n </td>\n <td style=\"width:342px;\">\n <ul>\n <li>\n Frequency of confirmed ADA response, ADA titers, and neutralizing activity</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:606px;\">\n <p>\n <strong>Exploratory</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:264px;height:45px;\">\n <ul>\n <li>\n To evaluate the efficacy of meplazumab by PCR-corrected ACPR</li>\n </ul>\n </td>\n <td style=\"width:342px;height:45px;\">\n <ul>\n <li>\n Incidence of (number of participants with) PCR‑corrected ACPR at Week 4</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td style=\"width:264px;\">\n <ul>\n <li>\n To evaluate RO (%) of meplazumab in red blood cells following single dose administration</li>\n </ul>\n </td>\n <td style=\"width:342px;\">\n <ul>\n <li>\n Meplazumab RO%-time profiles, pharmacodynamic parameters determined for RO including but not limited to maximum RO% and duration RO% (RO% half-life)</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td style=\"width:264px;\">\n <ul>\n <li>\n To quantify the levels of complement regulatory proteins, the deposition of complement on  erythrocytes, and serum complement activation in human subjects treated with meplazumab.</li>\n </ul>\n </td>\n <td style=\"width:342px;\">\n <ul>\n <li>\n Cell-surface expression of complement regulatory proteins and presence of complement products measured by flow cytometry; and complement activation measured by ELISA kit</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td style=\"width:264px;\">\n <ul>\n <li>\n To evaluate the relationship between exposure to meplazumab and key efficacy and/or safety parameters</li>\n </ul>\n </td>\n <td style=\"width:342px;\">\n <ul>\n <li>\n Graphical (and statistical, if appropriate) display of exposure versus response</li>\n </ul>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n Abbreviations: ACPR=adequate clinical & parasitological response; ADA=anti-drug antibodies; AE=adverse event; AESI=adverse event of special interest; AUC_{(0‑inf)}=area under the concentration‑time curve extrapolated to infinity; AUC_{(0‑last)}=area under the concentration‑time curve to the last quantifiable concentration; CL=systemic clearance; C_max=maximum concentration; FCT=fever clearance time; polymerase chain reaction PCR=polymerase chain reaction; <em>P. falciparum</em>=<em>Plasmodium falciparum</em>; PRR=parasite reduction rate; RO=receptor occupancy; SAE=serious adverse event; t_½=elimination half‑life; t_max=time to C_max; V_z=volume of distribution; V_ss=volume at steady state.</p>\n<p>\n  </p>\n
      • principal_inclusion_criteria<p>\n Participants are eligible to be included in the study only if all of the following criteria apply:</p>\n<ol>\n <li>\n Ability to provide informed consent signed by the study participant or legally authorized representative</li>\n <li>\n Adults 18 to 55 years at the time of signing the informed consent form (ICF)</li>\n <li>\n Female participants are eligible to participate if they do not qualify as a woman of childbearing potential (WOCBP), as defined in Section 10.4.</li>\n <li>\n Male participants who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception as described in Section 10.4.</li>\n <li>\n BMI ≥18 to ≤30 kg/m²</li>\n <li>\n Mono-infection with <em>P. falciparum</em> documented by:</li>\n</ol>\n<ul>\n <li>\n Microscopically confirmed parasite infection using Giemsa-stained thick film (refer to the laboratory manual for details) consisting of 1000 – 100,000 asexual parasites /µL of blood <strong><u>and</u></strong></li>\n <li>\n Documented fever (≥38.0°C oral, rectal or tympanic; ≥37.5°C axillary) or documented history of fever in previous 24 hours</li>\n</ul>\n<p>\n  </p>\n
      • principal_exclusion_criteria<p>\n Participants are NOT eligible to be included in the study if any of the following exclusion criteria apply:</p>\n<ol>\n <li>\n Presence of severe malaria (as defined by World Health Organization Guidelines for Malaria 16 February 2021).</li>\n</ol>\n<ul>\n <li>\n Severe falciparum malaria is defined as one or more of the following, occurring in the absence of an identified alternative cause and in the presence of <em>P. falciparum</em> asexual parasitemia.\n <ul>\n <li>\n Impaired consciousness: A Glasgow coma score <11 in adults</li>\n <li>\n Prostration: Generalized weakness so that the person is unable to sit, stand or walk without assistance</li>\n <li>\n Multiple convulsions: More than 2 episodes within 24 h</li>\n <li>\n Acidosis: A base deficit of >8 mEq/L or, if not available, a plasma bicarbonate level of <15 mmol/L or venous plasma lactate ≥5 mmol/L. Severe acidosis manifests clinically as respiratory distress (rapid, deep, labored breathing).</li>\n <li>\n Hypoglycemia: Blood or plasma glucose <2.2 mmol/L (<40 mg/dL)</li>\n <li>\n Severe malarial anemia: Hemoglobin concentration ≤7 g/dL or a hematocrit of ≤20% in adults with a parasite count >10,000/μL</li>\n <li>\n Renal impairment: Plasma or serum creatinine >265 μmol/L (3 mg/dL) or blood urea >20 mmol/L</li>\n <li>\n Jaundice: Plasma or serum bilirubin >50 μmol/L (3 mg/dL) with a parasite count >100,000/ μL</li>\n <li>\n Pulmonary edema: Radiologically confirmed or oxygen saturation <92% on room air with a respiratory rate >30/min, often with chest indrawing and crepitations on auscultation</li>\n <li>\n Significant bleeding: Including recurrent or prolonged bleeding from the nose, gums or venepuncture sites; hematemesis or melena</li>\n <li>\n Shock: Compensated shock is defined as capillary refill ≥3 s or temperature gradient on leg (mid to proximal limb), but no hypotension. Decompensated shock is defined as systolic blood pressure <80 mmHg in adults, with evidence of impaired perfusion (cool peripheries or prolonged capillary refill).</li>\n <li>\n Hyperparasitemia: <em>P. falciparum</em> parasitemia >10%</li>\n </ul>\n </li>\n</ul>\n<ol>\n <li value=\"2\">\n Antimalarial treatment (alone or in combination) during the following periods before Screening:</li>\n</ol>\n<ul>\n <li>\n Piperaquine, mefloquine, naphthoquine or sulfadoxine-pyrimethamine within 6 weeks prior to Screening.</li>\n <li>\n Amodiaquine, chloroquine within 4 weeks prior to Screening.</li>\n <li>\n Any artemisinin derivative (artesunate, artemether or dihydroartemisinin), quinine, lumefantrine or any other antimalarial treatment or antibiotic with antimalarial activity (including cotrimoxazole, tetracyclines, quinolones and fluoroquinolones and azithromycin) within 14 days prior to Screening.</li>\n <li>\n Any herbal products or traditional medicines, within the past 7 days.</li>\n</ul>\n<ol>\n <li value=\"3\">\n Previous participation in any malaria vaccine study or received malaria vaccine within 3 months of Screening Visit.</li>\n <li value=\"4\">\n Known allergy to any study medication, including allergy to any component of protocol prescribed rescue treatment i.e., country-specific ACT regimen.</li>\n <li value=\"5\">\n Any clinically important illness as judged by the investigator, including but not limited to a history of clinically significant chronic respiratory disease (eg, chronic obstructive pulmonary disease [COPD] or asthma), medical/surgical procedure, or trauma within 4 weeks of the first administration of investigational product.</li>\n <li value=\"6\">\n Participants participate in another clinical study. There will be a need for washout with 5 half-lives depending on the study treatment or 30 days, whichever is longer.</li>\n <li value=\"7\">\n Use of anti-cancer, anti-transplant rejection, or immunomodulatory biological drug or kinase inhibitor (e.g., tocilizumab, sarilumab) or Janus kinase inhibitors (within 30 days of enrollment or 5 times the half-life [whichever is longer]).</li>\n <li value=\"8\">\n  Systemic administration of corticosteroids (PO/IV/IM) at a dose of ≥20 mg/day of prednisone or equivalent for more than 14 consecutive days within 90 days prior to informed consent. Topical, inhaled, and intranasal corticosteroids are permitted. Intermittent use (one dose in 30 days) of intra-articular corticosteroids are also permitted.</li>\n <li value=\"9\">\n Live (live-attenuated) vaccines are not permitted within 2 weeks prior to study treatment or during the study treatment and safety follow-up periods.</li>\n <li value=\"10\">\n Presence of Hepatitis A IgM, Hepatitis B surface antigen, or Hepatitis C antibody, or Anti-HIV1 and/or HIV2 antibody , or Rapid Plasma Reagin test positive for syphilis..</li>\n <li value=\"11\">\n TBL >1.5 × ULN, ALT >2 × ULN, or AST >2 × ULN.</li>\n <li value=\"12\">\n Hematocrit <20%, hemoglobin <70 g/L (<7 g/dL), or white blood count >15,000/μL.</li>\n <li value=\"13\">\n Creatinine >1.5 × ULN.</li>\n</ol>\n<p>\n  </p>\n
      • primary_end_points<p style=\"margin-left:18.0pt;\">\n ·       Incidence and severity of AE</p>\n<p style=\"margin-left:18.0pt;\">\n ·       Incidence of (number of participants with):</p>\n<p style=\"margin-left:54.0pt;\">\n o   Drug-related SAE</p>\n<p style=\"margin-left:54.0pt;\">\n o   All-cause SAE</p>\n<p style=\"margin-left:54.0pt;\">\n o   Drug-related AESI</p>\n<p style=\"margin-left:54.0pt;\">\n o   All-cause AESI</p>\n<p style=\"margin-left:54.0pt;\">\n o  Participants discontinuation/ withdrawals due to AE</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response1
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory1
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledNo
      • site_capacity(null)
      • staff_numbers<p style=\"margin: 0px;\">\n  </p>\n<p style=\"margin-bottom: 8px;\">\n <span style=\"font-family:arial,helvetica,sans-serif;\"><span style=\"font-size:12px;\"><span class=\"ui-provider ee bir bis bit biu biv biw bix biy biz bja bjb bjc bjd bje bjf bjg bjh bji bjj bjk bjl bjm bjn bjo bjp bjq bjr bjs bjt bju bjv bjw bjx bjy\" dir=\"ltr\"><span style=\"white-space-collapse: preserve;\">VIBRI  is located at Kisumu County Referral Hospital. Kisumu County, Kenya, has  a population of about  1,155,574 (Kenya National Bureau of Statistics, 2019). The  land  area of Kisumu County totals 2085.9 km2. The county has  a shoreline on Lake Victoria, occupying northern, western and a part  of the southern shores of the Winam Gulf. Several institutions that </span></span></span></span><span style=\"font-family: arial, helvetica, sans-serif;\"><span class=\"ui-provider ee bir bis bit biu biv biw bix biy biz bja bjb bjc bjd bje bjf bjg bjh bji bjj bjk bjl bjm bjn bjo bjp bjq bjr bjs bjt bju bjv bjw bjx bjy\" dir=\"ltr\"><span style=\"white-space-collapse: preserve;\">are either private or government funded provide health services in Kisumu County. There is one  teaching and referral hospital, 5 County referral hospitals, 14 sub-county hospitals, 74 dispensaries and 18 health centers in the county. Given that  VIBRI  has  access </span></span></span><span style=\"white-space-collapse: preserve; font-family: arial, helvetica, sans-serif;\">to a well-developed health system coupled with  a strong  collaborative network with  the county ministries of health as well  as easy accessibility of patients through the hospital networks in Kisumu County and other  nearby counties, it is anticipated that the study will be able  to screen and enroll  participants into the study with  minimal challenges.</span><span style=\"white-space-collapse: preserve; font-family: arial, helvetica, sans-serif;\"> </span></p>\n<p>\n <span style=\"font-family:arial,helvetica,sans-serif;\"><span style=\"font-size:12px;\">Laboratory procedures are described in the main protocol section 8 and appendix 2. Study samples will be collected at the VIBRI site at the Kisumu County Referral Hospital for processing, analysis and/or storage. These samples include Blood for Malaria Microscopy, Hematology, Chemistry, Pregnancy Testing, Blood for PCR Genotyping, Pharmacokinetics, Pharmacodynamics (Receptor Occupancy Assay), Immunogenicity Assessments, etc. Urine pregnancy tests will be done on site.All labs are qualified according to SOPs from the sponsor.</span></span></p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">The  trial  site  has  the capacity to conduct this  trial  to the highest international standards in accordance with  Good Clinical Practice (GCP) and Human Subjects Protection requirements. </span></span><span style=\"font-family: arial, helvetica, sans-serif;\">The trial site has the human resources, pharmacy and laboratory infrastructure, clinical examination  rooms, data  entry rooms  withgood </span><span style=\"font-family: arial, helvetica, sans-serif;\">internet services, monitoring space and office  space for work  and meetings</span><span style=\"font-family: arial, helvetica, sans-serif;\">.</span></p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\"><span class=\"ui-provider ee bir bis bit biu biv biw bix biy biz bja bjb bjc bjd bje bjf bjg bjh bji bjj bjk bjl bjm bjn bjo bjp bjq bjr bjs bjt bju bjv bjw bjx bjy\" dir=\"ltr\">Principal Investigator - Dr. Lucas Otieno  Tina, MBChB  MSc. DLSHTM </span></span></span></p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\"><span class=\"ui-provider ee bir bis bit biu biv biw bix biy biz bja bjb bjc bjd bje bjf bjg bjh bji bjj bjk bjl bjm bjn bjo bjp bjq bjr bjs bjt bju bjv bjw bjx bjy\" dir=\"ltr\">Sub-Investigators:</span></span></span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Dr. Walter Otieno, MBChB, M. Med, PhD</span></span><span segoe=\"\" style=\"font-size:7.5pt;font-family:\"><o:p></o:p></span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Dr. Antony Oindo, MBChB</span></span><span segoe=\"\" style=\"font-size:7.5pt;font-family:\"><o:p></o:p></span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Fredrick O. Oluoch, BSc. MSc. Public Health</span></span><span segoe=\"\" style=\"font-size:7.5pt;font-family:\"><o:p></o:p></span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Dr. Irene Diana Odhiambo, MBChB, MBA, MPH</span></span><span segoe=\"\" style=\"font-size:7.5pt;font-family:\"><o:p></o:p></span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Dr. Kenson K. Nyolmo, MBChB</span></span><span segoe=\"\" style=\"font-size:7.5pt;font-family:\"><o:p></o:p></span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Dr. Millicent Melanie Miruka, BPHARM </span></span><span segoe=\"\" style=\"font-size:7.5pt;font-family:\"><o:p></o:p></span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Dr. Anne Rogena, B. Pharm, MBA</span></span></p>\n<p style=\"margin:0cm\">\n  </p>\n<p style=\"margin:0cm\">\n <span segoe=\"\" style=\"font-size:7.5pt;font-family:\"><o:p></o:p></span>Study Coordinators and site  staff: </p>\n<p style=\"margin:0cm\">\n  </p>\n<p style=\"margin:0cm\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">David Ogolla - Project Manager</span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">George Awino - Study Coordinator</span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Beatrice Nyagol – Clinical Research Coordinator</span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Eunice Oyola – Clinical Research Coordinator/Clinician</span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Geoffrey Olado - Clinical Research Coordinator</span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Brenda Okuba - Clinical Research Coordinator</span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Vincent Omondi - Lab Coordinator </span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Tom Nyamira Jogoo - Lab Coordinator</span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Pinto Okatch - Lab Technician</span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Nickanor Pande - Lab Technician</span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">David Agengo - Lab Technician</span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Elvis Tawa - Lab Technician</span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Finch Odhach - Clinician</span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Leah Martha Atieno - Clinician </span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Josephine Mulera - Clinician</span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Paul Ogai - Clinician</span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Annette Imojong Onyamasi - Nurse/QC</span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Roseline Orimbo - Nurse</span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Irene Adera - Nurse</span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Immaculate Ochieng - Nurse</span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Gaudensia Oyugi Nyauke - Nurse</span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Jane Atieno Oriato - Nurse</span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Mercy John - Nurse</span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Pamela Ombewa - Nurse</span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Basil Okumu - Nurse</span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Lydiah Otitah - Data Clerk</span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Franciscah Awino - Data Clerk</span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Alfred Ochieng - Data Clerk</span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Mercy Opondo - Data Clerk</span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Samson Ndori - Data Clerk</span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Mercy Munene - Data Clerk</span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Linda Atieno - QC/HTS</span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Maurice Opiyo - Field Coordinator</span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Merab Magak - Community Liaison Officer</span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Serphine Wamboga - Field Assistant</span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Edith Aluoch - Field Assistant</span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Paul Osodo - Field Assistant/HTS provider</span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Ezekiel Onditi - Field Assistant</span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Beverlyne Joy Atieno - Front Office</span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Sharon Omollo - Supply Chain Officer</span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Josephine Akinyi - Administrative Officer</span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Jeremiah Kuja - Admin/Procurement Assistant</span></p>\n<p style=\"margin:0cm\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Carlos Agwera - Finance Officer</span></p>\n
      • other_details_explanation<p>\n No</p>\n
      • other_details_regulatory_notapproved<p>\n Rwanda Food and Drug Authority-3 November 2023</p>\n<p>\n Ghana Food and Drug Authority-17 October 2023</p>\n
      • other_details_regulatory_approved<p>\n No Approvals recived yet.</p>\n
      • other_details_regulatory_rejected<p>\n Not Applicable</p>\n
      • other_details_regulatory_halted<p>\n Not Applicable</p>\n
      • estimated_duration2 years
      • design_controlled_randomised
      • design_controlled_open
      • design_controlled_single_blind
      • design_controlled_double_blind
      • design_controlled_parallel_group
      • design_controlled_cross_over
      • design_controlled_other
      • design_controlled_specify
      • design_controlled_comparator
      • design_controlled_other_medicinal
      • design_controlled_placebo
      • design_controlled_medicinal_other
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states4
      • number_of_sites3
      • multi_country_listRwanda\nGhana\nGabon
      • data_monitoring_committeeYes
      • total_enrolment_per_siteRecruitment is competitive between sites and countries. There are no minimum or maximum number per site.
      • total_participants_worldwide60
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsNo
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameLucas
      • investigator1_middle_nameOtieno
      • investigator1_family_nameTina
      • investigator1_qualificationMedical Doctor
      • investigator1_professional_addressKisumu County Referral Hospital, off Ang’awa Avenue, P O Box 7180-40100, Kisumu, Kenya
      • investigator1_telephone+254 720 597654
      • investigator1_emailltina@vibriafrica.org
      • organisations_transferred_Yes
      • number_participants9 participants
      • notification
      • approval_date20-02-2024
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted03-11-2023
      • is_child0
      • unsubmitted1
      • initial_date_submitted03-11-2023
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonThe reviewer comments have been addressed
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-05-28 14:33:20
      • created2023-10-31 11:08:16
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id993
        • application_id1342
        • given_name Lucas
        • middle_nameOtieno
        • family_nameTina
        • qualificationMedical Doctor
        • professional_addressKisumu County Referral Hospital, off Ang’awa Avenue, P O Box 7180-40100, Kisumu, Kenya
        • telephone+254 720 597654
        • emailltina@vibriafrica.org
        • created2023-11-01 09:38:37
        • modified2024-07-08 10:48:09
    • SiteDetail(array)
      • 0(array)
        • id1619
        • application_id1342
        • county_id42
        • site_nameVictoria Biomedical Research Institute (VIBRI)
        • physical_addressKisumu County Referral Hospital, off Ang’awa Avenue, P O Box 7180-40100, Kisumu, Kenya
        • contact_details+254 720 597654
        • contact_personDr Lucas Otieno Tina
        • site_capacity(null)
        • misc(null)
        • created2023-11-01 09:38:37
        • modified2024-07-08 10:48:09
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 1(array)
        • id1620
        • application_id1342
        • county_id42
        • site_nameAHERO CLINICAL TRIALS UNIT
        • physical_addressHOUSED WITHIN AHERO COUNTY HOSPITAL, PO BOX 54,40100 KISUMU, ALONG KISUMU NAIROBI HIGHWAY FIELD SITE FOR CENTRE FOR RESEARCH IN THERAPEUATIC SCIENCES
        • contact_details +254733812613
        • contact_personDr. Bernhards Ogutu
        • site_capacity(null)
        • misc(null)
        • created2023-11-01 10:39:17
        • modified2024-07-08 10:48:09
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 2(array)
        • id1621
        • application_id1342
        • county_id41
        • site_nameKenya Medical Research Institute(KEMRI):Siaya Clinical Research Annex
        • physical_addressKEMRI Clinical Research Annex, Within Siaya County Referral Hospital Ground. P.O BOX 144-40600 ,Siaya, Keny
        • contact_details+254724522474
        • contact_personDr Videlis Nduba
        • site_capacity(null)
        • misc(null)
        • created2023-11-01 10:39:17
        • modified2024-07-08 10:48:09
        • County(array)
          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
    • Sponsor(array)
      • 0(array)
        • id705
        • application_id1342
        • sponsorJiangsu Pacific Meinuoke Biopharmaceutical Co. Ltd.(PMBP)
        • sponsor_typeIndustry
        • contact_personXiaochun Chen
        • addressNo. 128 Hehai West Road, Xinbei District, Changzhou, 213022, Jiangsu People’s Republic of China
        • telephone_number+86 15851999825
        • fax_number
        • cell_number0519-68889888
        • email_addresscxc@pmbp.cn
        • created2023-11-01 09:38:37
        • modified2024-07-08 10:48:09
• page_options(array)
  • 55
  • 1010
• redir
• $request->data(array)
  • Application(empty)
• $this->validationErrors(array)
  • Permission(empty)
  • Aro(empty)
  • Aco(empty)
  • Application(empty)
  • User(empty)
  • TrialStatus(empty)
  • InvestigatorContact(empty)
  • Sponsor(empty)
  • SiteDetail(empty)
  • County(empty)
• Loaded Helpers(array)
  • 0Html
  • 1Form
  • 2Session
  • 3Text
  • 4Number
  • 5SimpleGraph
  • 6Paginator
  • 7DebugTimer
  • 8Toolbar
  • 9HtmlToolbar

App Constants

CakePHP Constants

PHP Environment

Included Files

Include Paths

• 0/var/www/html/ctr/app/Plugin/Media/Lib/mm/src
• 1/var/www/html/ctr/lib
• 3/usr/share/php
• 4-> /var/www/html/ctr/lib/Cake/

Included Files

• core(array)
  • Behavior(array)
    • 0CORE/Model/Behavior/TreeBehavior.php
    • 1CORE/Model/Behavior/ContainableBehavior.php
    • 2CORE/Model/Behavior/AclBehavior.php
  • Cache(array)
    • 0CORE/Cache/Cache.php
    • 1CORE/Cache/Engine/FileEngine.php
    • 2CORE/Cache/CacheEngine.php
  • Component(array)
    • 0CORE/Controller/Component/AclComponent.php
    • 1CORE/Controller/Component/Acl/DbAcl.php
    • 2CORE/Controller/Component/Acl/AclInterface.php
    • 3CORE/Controller/Component/AuthComponent.php
    • 4CORE/Controller/Component/RequestHandlerComponent.php
    • 5CORE/Controller/Component/SessionComponent.php
    • 6CORE/Controller/Component/PaginatorComponent.php
  • Config(array)
    • 0CORE/Config/routes.php
    • 1CORE/Config/config.php
  • Controller(array)
    • 0CORE/Controller/Controller.php
    • 1CORE/Controller/ComponentCollection.php
    • 2CORE/Controller/Component.php
  • Datasource(array)
    • 0CORE/Model/Datasource/CakeSession.php
    • 1CORE/Model/Datasource/Database/Mysql.php
    • 2CORE/Model/Datasource/DboSource.php
    • 3CORE/Model/Datasource/DataSource.php
  • Error(array)
    • 0CORE/Error/exceptions.php
    • 1CORE/Error/ErrorHandler.php
  • I18n(array)
    • 0CORE/I18n/I18n.php
    • 1CORE/I18n/L10n.php
  • Log(array)
    • 0CORE/Log/CakeLog.php
    • 1CORE/Log/LogEngineCollection.php
    • 2CORE/Log/Engine/FileLog.php
    • 3CORE/Log/Engine/BaseLog.php
    • 4CORE/Log/CakeLogInterface.php
  • Model(array)
    • 0CORE/Model/ConnectionManager.php
    • 1CORE/Model/Permission.php
    • 2CORE/Model/Model.php
    • 3CORE/Model/BehaviorCollection.php
    • 4CORE/Model/Aro.php
    • 5CORE/Model/AclNode.php
    • 6CORE/Model/Aco.php
    • 7CORE/Model/ModelBehavior.php
  • Network(array)
    • 0CORE/Network/CakeRequest.php
    • 1CORE/Network/CakeResponse.php
  • Other(array)
    • 0CORE/bootstrap.php
    • 1CORE/basics.php
    • 2CORE/Core/App.php
    • 3CORE/Core/Configure.php
    • 4CORE/Core/CakePlugin.php
    • 5CORE/Event/CakeEventListener.php
    • 6CORE/Event/CakeEvent.php
    • 7CORE/Event/CakeEventManager.php
    • 8CORE/Core/Object.php
  • Routing(array)
    • 0CORE/Routing/Dispatcher.php
    • 1CORE/Routing/Filter/AssetDispatcher.php
    • 2CORE/Routing/DispatcherFilter.php
    • 3CORE/Routing/Filter/CacheDispatcher.php
    • 4CORE/Routing/Router.php
    • 5CORE/Routing/Route/CakeRoute.php
    • 6CORE/Routing/Route/PluginShortRoute.php
  • Utility(array)
    • 0CORE/Utility/Hash.php
    • 1CORE/Utility/Inflector.php
    • 2CORE/Utility/ObjectCollection.php
    • 3CORE/Utility/Debugger.php
    • 4CORE/Utility/String.php
    • 5CORE/Utility/ClassRegistry.php
    • 6CORE/Utility/Set.php
    • 7CORE/Utility/Sanitize.php
  • View(array)
    • 0CORE/View/HelperCollection.php
• app(array)
  • Behavior(array)
    • 0APP/Model/Behavior/SoftDeleteBehavior.php
  • Config(array)
    • 0APP/Config/core.php
    • 1APP/Config/bootstrap.php
    • 2APP/Config/routes.php
    • 3APP/Config/database.php
  • Controller(array)
    • 0APP/Controller/ApplicationsController.php
    • 1APP/Controller/AppController.php
  • Model(array)
    • 0APP/Model/AppModel.php
    • 1APP/Model/Application.php
    • 2APP/Model/User.php
    • 3APP/Model/TrialStatus.php
    • 4APP/Model/InvestigatorContact.php
    • 5APP/Model/Sponsor.php
    • 6APP/Model/SiteDetail.php
    • 7APP/Model/County.php
  • Other(array)
    • 0APP/webroot/index.php
• plugins(array)
  • CakePdf(array)
    • Config(array)
      • 0CakePdf/Config/bootstrap.php
      • 1CakePdf/Config/routes.php
  • CakeResque(array)
    • Config(array)
      • 0CakeResque/Config/bootstrap.php
    • Plugin(array)
      • 0CakeResque/Lib/CakeResque.php
      • 1CakeResque/vendor/kamisama/php-resque-ex/lib/Resque.php
      • 2CakeResque/vendor/kamisama/php-resque-ex/lib/Resque/Event.php
      • 3CakeResque/vendor/kamisama/php-resque-ex/lib/Resque/Exception.php
  • DebugKit(array)
    • Component(array)
      • 0DebugKit/Controller/Component/ToolbarComponent.php
    • Plugin(array)
      • 0DebugKit/Lib/DebugMemory.php
      • 1DebugKit/Lib/Panel/HistoryPanel.php
      • 2DebugKit/Lib/DebugPanel.php
      • 3DebugKit/Lib/Panel/SessionPanel.php
      • 4DebugKit/Lib/Panel/RequestPanel.php
      • 5DebugKit/Lib/Panel/SqlLogPanel.php
      • 6DebugKit/Lib/Panel/TimerPanel.php
      • 7DebugKit/Lib/Panel/LogPanel.php
      • 8DebugKit/Lib/Log/Engine/DebugKitLog.php
      • 9DebugKit/Lib/Panel/VariablesPanel.php
      • 10DebugKit/Lib/Panel/EnvironmentPanel.php
      • 11DebugKit/Lib/Panel/IncludePanel.php
      • 12DebugKit/Lib/DebugTimer.php
  • Media(array)
    • Config(array)
      • 0Media/Config/bootstrap.php
    • Plugin(array)
      • 0Media/Lib/mm/src/Mime/Type.php
      • 1Media/Lib/mm/src/Mime/Type/Magic/Adapter/Fileinfo.php
      • 2Media/Lib/mm/src/Mime/Type/Magic/Adapter.php
      • 3Media/Lib/mm/src/Mime/Type/Glob/Adapter/Memory.php
      • 4Media/Lib/mm/src/Mime/Type/Glob/Adapter.php
      • 5Media/Lib/mm/src/Media/Process.php
      • 6Media/Lib/mm/src/Media/Info.php
  • Search(array)
    • Component(array)
      • 0Search/Controller/Component/PrgComponent.php
    • Behavior(array)
      • 0Search/Model/Behavior/SearchableBehavior.php
  • Shim(array)
    • Config(array)
      • 0Shim/Config/bootstrap.php
  • Tools(array)
    • Config(array)
      • 0Tools/Config/bootstrap.php