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      • id1178
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      • abstract_of_study<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>B</strong><strong>a</strong><strong>c</strong><strong>k</strong><strong>g</strong><strong>r</strong><strong>o</strong><strong>und</strong><strong>:</strong></p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Sickle cell disease (SCD) is a serious and life-threatening inherited hemoglobin (Hb) disorder caused by a single amino acid substitution in the beta (β)-globin gene (β s c.20A>T; rs334). Sickle cell disease affects millions of people worldwide. The homozygous form (HbSS) occurs in most cases and represents approximately 88% to 96% in certain areas of Africa. Preliminary data indicate that mitapivat may reduce Hemoglobin S polymerization, sickling, and hemolysis. Therefore, in this study mitapivat is a therapeutic candidate for the treatment of adult patients with SCD with the potential to provide clinical benefit by both improvement of anemia and reduction in sickle cell pain crises (SCPCs).</p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n The only current curative treatment approach for some patients with SCD is bone marrow transplant. However, a lack of histocompatible donors, concerns about transplantrelated morbidity and mortality, and pre-existing conditions (organ dysfunction or alloimmunization) often preclude patients from pursuing this treatment option. For decades, hydroxyurea was the only disease-modifying therapy available for patients with SCD. Hydroxyurea is indicated to reduce the frequency of painful crises; however, its use  is limited by its safety profile, which includes myelosuppression (neutropenia and thrombocytopenia) and gastrointestinal toxicity. Reduced fertility has been reported as a longterm adverse effect.</p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>J</strong><strong>u</strong><strong>s</strong><strong>t</strong><strong>i</strong><strong>f</strong><strong>i</strong><strong>c</strong><strong>a</strong><strong>t</strong><strong>i</strong><strong>o</strong><strong>n</strong><strong>/</strong><strong>R</strong><strong>a</strong><strong>t</strong><strong>i</strong><strong>o</strong><strong>n</strong><strong>a</strong><strong>l</strong><strong>e</strong><strong>:</strong></p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n The use  of curative options for SCD is currently limited to a small subgroup of patients who are deemed fit for bone marrow transplantation and have available donors. The treatment options for SCD are not universally effective or globally available, tend to address only a single component of the disease, or are limited by their safety profile. Therefore, a significant unmet medical need exists for safe and effective therapies for the treatment of SCD that result in both an improvement in anemia and reduction in sickle cell–related crises.</p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Mitapivat is a small molecule, oral activator of wild-type (WT) and mutant forms of the RBC-specific form of pyruvate kinase (PKR). Activation of PKR has potential application in the treatment of hemolytic anemias, including SCD, which are characterized by increased metabolic demands or by defects in glycolysis that contribute to the shortened life span of the RBC. Decreases in PKR function, exemplified in patients with pyruvate kinase deficiency, leads to dysfunctional RBCs that are characterized by defective glycolysis, including a build-up of 2,3-DPG and PEP with decreased levels of ATP. However, there is evidence that the activation of the normal (WT) PKR enzyme can play a role in other hemolytic anemias such  as SCD.</p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>Main Objectives: Phase 2:</strong></p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n 1. To determine the recommended Phase 3 dose of mitapivat by evaluating the effect of 2 dose levels of mitapivat versus placebo on:</p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n • Anemia in subjects with sickle cell disease (SCD)</p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n • Safety</p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Phase 3: 1. To determine the effect of mitapivat versus placebo on:</p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n • Anemia in subjects with sickle cell disease (SCD)</p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n • Sickle cell pain crises (SCPCs) in subjects with SCD</p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>Secondary objectives:</strong></p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>Pha</strong><strong>se </strong><strong>2</strong><strong>:</strong></p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n 1. To evaluate the effect of 2 doses of mitapivat versus placebo on:</p>\n<ul>\n <li style=\"margin: 0px 0px 10px 29.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <img height=\"4\" src=\"file:///C:/Users/kimettjc/AppData/Local/Temp/msohtmlclip1/01/clip_image001.gif\" style=\"height: auto; max-width: 100%; vertical-align: middle; border: 0px;\" width=\"4\" />Anemia</li>\n <li style=\"margin: 0px 0px 10px 29.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <img height=\"4\" src=\"file:///C:/Users/kimettjc/AppData/Local/Temp/msohtmlclip1/01/clip_image002.gif\" style=\"height: auto; max-width: 100%; vertical-align: middle; border: 0px;\" width=\"4\" />Markers of hemolysis and erythropoiesis</li>\n <li style=\"margin: 0px 0px 10px 29.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <img height=\"4\" src=\"file:///C:/Users/kimettjc/AppData/Local/Temp/msohtmlclip1/01/clip_image003.gif\" style=\"height: auto; max-width: 100%; vertical-align: middle; border: 0px;\" width=\"4\" />Patient-reported fatigue</li>\n <li style=\"margin: 0px 0px 10px 29.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <img height=\"4\" src=\"file:///C:/Users/kimettjc/AppData/Local/Temp/msohtmlclip1/01/clip_image004.gif\" style=\"height: auto; max-width: 100%; vertical-align: middle; border: 0px;\" width=\"4\" />Sickle cell pain crises (SCPCs)</li>\n</ul>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n 2. To evaluate the pharmacokinetic and pharmacodynamic effects of mitapivat.</p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>Pha</strong><strong>se </strong><strong>3</strong><strong>:</strong></p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n 1. To evaluate the effect of mitapivat versus placebo on:</p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n • Anemia in subjects with SCD</p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n • Markers of hemolysis</p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n • Markers of erythropoiesis</p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n • Patient-reported fatigue</p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n • Additional clinical efficacy measures related to SCPC</p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>Methods:</strong></p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>Ove</strong><strong>rall Study </strong><strong>d</strong><strong>e</strong><strong>s</strong><strong>i</strong><strong>g</strong><strong>n</strong></p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n This is a Phase 2/3, double-blind, randomized, placebo-controlled, global, multicenter study evaluating the efficacy and safety of mitapivat versus placebo in subjects with SCD using an operationally seamless design. The Phase 2 portion is a double-blind, randomized, placebo-controlled, dose-finding study evaluating 2 dose levels of mitapivat (50 mg BID and 100 mg BID) versus placebo to select the dose of mitapivat to be evaluated in the Phase 3 portion. The Phase 3 portion is a double-blind, randomized, placebo-controlled study evaluating the efficacy and safety of mitapivat at the selected Phase 3 dose versus placebo. Subjects who complete the Double-blind Period in eitherthe Phase 2 or Phase 3 portion will have the option to receive mitapivat in the Open-label Extension Period. A total of 267 subjects (69 in Phase 2 and 198 in Phase 3)</p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n will be randomized in this study. The initiation of the Phase 3 portion will be based on prespecified go/no-go criteria and dose selection criteria. Subjects who participate in the</p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Phase 2 portion of the study are not eligible to participate in the Phase 3 portion of the study.</p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>Study outcomes:</strong></p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n The primary outcome, or endpoint, for the phase 2 study is hemoglobin (Hb) response, defined as a ≥1.0 g/dL increase in average Hb concentration from Week 10 through Week 12 compared with baseline and safety defined as adverse events (AEs) and serious adverse events (SAEs). The primary outcome for the phase 3 study is Hemoglobin (Hb) response, defined as a ≥1.0 g/dL increase in average Hb concentration from Week 24 through Week 52 compared with baseline and annualized rate of sickle cell pain crises (SCPCs) in subjects with SCD.</p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>S</strong><strong>tudy </strong><strong>du</strong><strong>r</strong><strong>a</strong><strong>t</strong><strong>i</strong><strong>o</strong><strong>n</strong><strong>:</strong></p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n The duration of participation of a subject in the Phase 2 portion is up to 4.5 years (236 weeks). The duration of participation of a subject in the Phase 3 portion is up to 5.3 years (276 weeks). The end of the study is defined as the time at which all subjects complete all study visits, are lost to follow-up, have withdrawn consent for further participation in the study, or when the Sponsor terminates the study.</p>\n
      • study_title<p>\n <span style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">A Phase 2/3, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Mitapivat in Subjects With Sickle Cell Disease. Mitapivat - AG348-C-020</span></p>\n
      • laymans_summary<table class=\"table table-condensed\" style=\"max-width: 100%; border-collapse: collapse; border-spacing: 0px; width: 915.271px; margin-bottom: 20px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <thead>\n <tr>\n <th class=\"table-label required\" style=\"padding: 4px 15px 4px 5px; line-height: 20px; text-align: left; vertical-align: bottom; border-top: 0px; color: rgb(0, 112, 0); width: 895.271px;\">\n <h5 style=\"margin: 10px 0px; font-family: inherit; line-height: 20px; color: inherit; text-rendering: optimizelegibility; font-size: 14px; text-align: center;\">\n Laymans Summary: <span class=\"sterix\" style=\"color: red;\">*</span></h5>\n </th>\n </tr>\n </thead>\n <tbody>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221);\">\n <p style=\"margin: 0px 0px 10px;\">\n Sickle cell disease (SCD) is an inherited blood disorder where the red blood cells, which carry oxygen around the body, develop abnormally and become rigid and shaped like a crescent (sickle shape). Sickle cell disease affects millions of people worldwide and is very common in certain areas of Africa. This study will look at a possible drug for treatment of Sickle cell disease called Mitapivat. Results from earlier studies with mitapivat shows that it may reduce the change of shape in red blood cells which makes them look like a sickle and causes the red blood cells to be destroyed resulting in a person with sickle cell disease getting low blood level (anemia). Therefore, in this study mitapivat is a drug candidate for the treatment of adult patients with sickle cell disease with the potential to provide clinical benefit by both improvement of anemia and reduction in sickle cell pain crisis.</p>\n <p style=\"margin: 0px 0px 10px;\">\n  </p>\n <p style=\"margin: 0px 0px 10px;\">\n This study has both a Phase 2 and a Phase 3. The main aim of the Phase 2 portion of the study is to define how mitapivat works in the short term, how safe it is and the right dose which will be selected for the Phase 3 portion of the study. The aim of the Phase 3 portion of the study is to assess the how well the selected dose of mitapivat works for treatment and how safe it when used in patients with sickle cell disease. This portion of the study is intended to show the extent to which mitapivat treatment reduces painful crisis because of blocked blood vessels and reduces anemia in sickle cell disease. In this Phase2/3 study, both the participant and most study staff including the doctors don’t know which treatment has been given to the participant (referred to as doubleblind). One group of study participants called the treatment group will receive the mitapivat and another group called the control group will receive a study treatment with no active ingredient called a placebo.</p>\n <p style=\"margin: 0px 0px 10px;\">\n  </p>\n <p style=\"margin: 0px 0px 10px;\">\n The study is being done in different countries around the world, in multiple study centers in participants with SCD. The Phase 2 portion dose-finding study will assess 2 dose levels of mitapivat (50 mg twice a day and 100 mg twice a day) versus placebo to select the dose of mitapivat to be evaluated in the Phase 3 portion. The Phase 3 portion is a double-blind, randomized, placebo-controlled study evaluating how effective and safe mitapivat is at the selected Phase 3 dose versus placebo. Participants who complete the Double-blind Period in the Phase 2/3 portion will have the option to receive mitapivat in the non-blinded (Open label) Extension Period. Approximately 267 participants (69 in Phase 2 and 198 in Phase 3) are planned to be enrolled in this study worldwide. In Kenya there are 7 sites ,3 sites in Nairobi,1 in western and 3 in Nyanza. Enrollment is competitive world wide.</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • short_titleAgios Study
      • protocol_noECCT/22/10/05
      • version_noAmendment 1 (V1.0)
      • date_of_protocol09-03-2022
      • study_drugMitavpivat Dr Nduba Siaya and Nairobi site
      • 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_nameMitapivat
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressPPDSubmissionsMembers.SM@ppd.com
      • applicant_covering_letter1
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      • applicant_indemnity_cover1
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      • applicant_participating_countries(null)
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      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantMillicent.Aketch
      • declaration_date128-10-2022
      • declaration_principal_investigatorDr Ogutu Bernhards
      • declaration_date228-10-2022
      • placebo_presentYes
      • study_objectives<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Main objective:</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Phase 2:</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 1. To determine the recommended Phase 3 dose of mitapivat by evaluating the effect of 2 dose levels of mitapivat versus placebo on</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n : • Anemia in subjects with sickle cell disease (SCD). and</p>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n Safety </li>\n</ul>\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 <strong>Safety Phase 3:</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 1. To determine the effect of mitapivat versus placebo on</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n : • Anemia in subjects with sickle cell disease (SCD)</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n • Sickle cell pain crises (SCPCs) in subjects with SCD</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Secondary objectives:</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Phase 2</strong>:</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 1. To evaluate the effect of 2 doses of mitapivat versus placebo on:</p>\n<ul>\n <li font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51);\" trebuchet=\"\">\n Anemia</li>\n <li font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51);\" trebuchet=\"\">\n Markers of hemolysis and erythropoiesis</li>\n <li font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51);\" trebuchet=\"\">\n Patient-reported fatigue</li>\n <li font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51);\" trebuchet=\"\">\n Sickle cell pain crises (SCPCs)</li>\n</ul>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 2. To evaluate the pharmacokinetic and pharmacodynamic effects of mitapivat.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Phase 3</strong>:</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 1. To evaluate the effect of mitapivat versus placebo on:</p>\n<ul>\n <li font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51);\" trebuchet=\"\">\n Anemia in subjects with SCD</li>\n <li font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51);\" trebuchet=\"\">\n Markers of hemolysis Markers of erythropoiesis</li>\n <li font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51);\" trebuchet=\"\">\n Patient-reported fatigue</li>\n <li font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51);\" trebuchet=\"\">\n Additional clinical efficacy measures related to SCPC</li>\n</ul>\n
      • principal_inclusion_criteria<p font-size:=\"\" style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 1. Age ≥16 years; subjects age 16 or 17 years must physically have completed puberty.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 2. Documented diagnosis of SCD (HbSS, HbSC, HbS/β0-thalassemia, HbS/β+ thalassemia, or other sickle cell syndrome variants).</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  3. At least 2 sickle cell pain crises (SCPCs) and no more than 10 SCPCs in the past 12 months.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  4. Hemoglobin ≥5.5 and ≤10.5 g/dL.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  5. If taking hydroxyurea, the hydroxyurea dose must be stable for at least 90 days before starting study drug.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  6. Women capable of becoming pregnant and men with partners who are women that are capable of becoming pregnant must agree to use  2 forms of contraception.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 7. Other protocol-defined inclusion criteria may apply</p>\n
      • principal_exclusion_criteria<p font-size:=\"\" style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 1. Pregnant or breastfeeding.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 2. Receiving regularly scheduled transfusions.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  3. Hepatobiliary disorders including but not limited to significant liver disease or gallbladder disease.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  4. Severe kidney disease.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  5. Prior exposure to gene therapy or prior bone marrow or stem cell transplantation.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  6. Currently receiving treatment for SCD (eg, voxelotor, crizanlizumab, L glutamine), with the exception of hydroxyurea. The last dose of such  therapies must have been administered at least 90 days before starting study drug.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  7. Currently receiving treatment with hematopoietic stimulating agents; the last dose must have been administered at least 90 days before starting study drug.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  8. Received treatment on another investigational trial within 90 days prior to start of study drug or plans to participate in another investigational drug trial.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  9. Taking medications that are strong inhibitors of CYP3A4/5 or strong inducers of CYP3A4 that cannot be stopped in an acceptable timeframe before starting study drug (timeframe will be discussed with your doctor).</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 10. Other protocol defined exclusion criteria may apply</p>\n
      • primary_end_points<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Phase 2 Primary Endpoints</strong>:</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 1. Percentage of participants with hemoglobin (Hb) response</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 2. Percentage of participants with treatment emergent adverse events (AEs) and treatment emergent serious adverse events (SAEs)</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Timepoint(s) of evaluation of this end point:</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Phase 2 primary endpoint of percentage of participants with Hb response: Week 12</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Phase 2 primary endpoint of percentage of participants with treatment emergent AEs and treatment emergent SAEs: Up to Week 12</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Phase 3 Primary Endpoints</strong>:</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 1. Percentage of participants with hemoglobin (Hb) response</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 2. Annualized rate of Sickle Cell Pain Crises (SCPCs)</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Timepoint(s) of evaluation of this end point</strong>:</p>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n Phase 3 primary endpoint of percentage of participants with Hb response: Week 52</li>\n <li style=\"line-height: 20px;\">\n Phase 3 primary endpoint of annualized rate of sickle cell pain crises:Up to Week 52</li>\n</ul>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic1
      • 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_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n <strong>KEMRI/CRDR clinical research Site</strong></p>\n<p>\n Site activities will take place within the KEMRI/CRDR clinical research annex. This facility has several clinical rooms available for consenting, nursing procedures, clinical exams and dosing. There are also additional facilities that include an inpatient ward, staff work areas and a monitoring space, a pharmacy, laboratory and kitchen for preparing participant meals.</p>\n<p>\n Site staff include the principal investigator, 4 medical officers, 2 pharmacists, 1 pharmtech, 5 nurses, 5 quality assurance officers, 3 clinical officers and 6 community health workers.</p>\n<p>\n <strong>Kisumu/SiayaSite</strong></p>\n<p>\n Site activities are located in Kisumu/Siaya and Nairobi Counties. Kisumu hosts the main IP storage site, administrative offices of the PI and co-investigators, procurement and Human Resource functions are housed at theKEMRI Kisian Campus. Recruitment, follow-up of study participants will occur in Siaya. KEMRI has a modern research annex at the Siaya county hospital with capacity to conduct phase I to Phase III studies. After community mobilization, screening and enrollment, IP dispensation will occur at the Siaya Clinical Research Annexe.</p>\n<p>\n Site investigators responsible for day to day running of the project include: Medical Officer 2, Pharmacist 1, Pharm tech 2, Nurses 5, Quality Assurance Officer 2, Quality Control 1, Clinical Officer 2, Community Interviewers 4.</p>\n<p>\n N/A</p>\n<p>\n All the 5 sites have been submitted.</p>\n
      • other_details_explanation<p>\n <strong font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">N/A</strong><span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">, trial is being conducted in the USA</span></p>\n
      • other_details_regulatory_notapproved<table border=\"0\" cellpadding=\"0\" cellspacing=\"0\" font-size:=\"\" style=\"max-width: 100%; border-collapse: collapse; border-spacing: 0px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <tbody>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 186px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px;\">\n  </p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 153px; height: 13px;\">\n <table border=\"1\" cellpadding=\"1\" cellspacing=\"1\" style=\"width:500px;\">\n <tbody>\n <tr>\n <td>\n Country </td>\n <td>\n Date submited </td>\n <td>\n status </td>\n <td>\n  </td>\n </tr>\n <tr>\n <td>\n kenya </td>\n <td>\n 01 Sep 2022_ 2 sites </td>\n <td>\n Pending approval </td>\n <td>\n  </td>\n </tr>\n <tr>\n <td>\n Kenya </td>\n <td>\n 14 Oct  2022 _ 1 site </td>\n <td>\n Pending Apprval</td>\n <td>\n  </td>\n </tr>\n <tr>\n <td>\n Egypt </td>\n <td>\n 13 Jun 2022</td>\n <td>\n Pending  Approval</td>\n <td>\n  </td>\n </tr>\n </tbody>\n </table>\n <p>\n  </p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 61px; height: 13px;\">\n  </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • other_details_regulatory_approved<p>\n  </p>\n<table class=\"table table-condensed\" font-size:=\"\" style=\"max-width: 100%; border-collapse: collapse; border-spacing: 0px; width: 915.271px; margin-bottom: 20px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <tbody>\n <tr>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221);\">\n <table border=\"0\" cellpadding=\"0\" cellspacing=\"0\" style=\"max-width: 100%; background-color: transparent; border-collapse: collapse; border-spacing: 0px;\">\n <tbody>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 110px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n Regualtory</p>\n </td>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 103px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n Approval Date</p>\n </td>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 186px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n Number of site per Country</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 110px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n Canada</p>\n </td>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 103px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n 16 Nov  2021</p>\n </td>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 186px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n 4</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 110px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n United Kingdom</p>\n </td>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 103px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n 13 Sep 2021</p>\n </td>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 186px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n 7</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 110px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n Belgium</p>\n </td>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 103px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n 16 Feb 2022</p>\n </td>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 186px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n 8</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 110px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n France</p>\n </td>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 103px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n 27 Jan 2022</p>\n </td>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 186px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n 6</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 110px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n Germany</p>\n </td>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 103px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n 07 Apr 2022</p>\n </td>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 186px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n 4</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 110px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n Italy</p>\n </td>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 103px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n 23 Feb 2022</p>\n </td>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 186px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n 8</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 148px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n Regulatory Authority</p>\n </td>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 90px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n Approved Date</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 161px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n Number of site per country</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 148px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n Netherlands</p>\n </td>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 90px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n 23 Dec 2021</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 161px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n 1</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 148px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n Brazil</p>\n </td>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 90px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n 21 Jan 2022</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 161px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n 8</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 148px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n Israel</p>\n </td>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 90px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n 09 Aug 2021</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 161px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n 4</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 148px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n United States of America</p>\n </td>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 90px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n 26 May 2022</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 161px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n 23</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 148px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Turkey</p>\n </td>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 90px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 04 Jul 2022 </p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 161px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 5</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 148px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Saudia Arabia</p>\n </td>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 90px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 06Sep 2022</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 161px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 3</p>\n </td>\n </tr>\n </tbody>\n </table>\n <p style=\"margin: 0px 0px 10px;\">\n Nigeria _ 22 Aug 2022 - sites _6 </p>\n <p style=\"margin: 0px 0px 10px;\">\n Kenya _ 06 Sep  2022 _ sites approved 2 out of 7 .</p>\n <div>\n  </div>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • other_details_regulatory_rejected<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">No Regulatory authority nor Ethics Committee has rejected this trial</span></p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration9 years 10 months 0 days
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherYes
      • design_controlled_specifyThere is an open label extension period following completion of the double blind period.
      • 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_states17
      • number_of_sites7
      • multi_country_listBelgium Brazil Canada Egypt France Germany Israel Italy Kenya Lebanon Netherlands Nigeria Oman Saudi Arabia Turkey\nUnited Kingdom United States
      • data_monitoring_committeeYes
      • total_enrolment_per_siteNo maximum nor minimum enrolment per site as enrolment is competitive world wide
      • total_participants_worldwide267 for both phases(69 in Phase 2 and 198 in Phase 3)
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentYes
      • population_above_18Yes
      • population_adultYes
      • population_elderlyYes
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
      • subjects_specifyFor subjects under 18 Years of age written informed assent/consent will be obtained from parents and child assent. It must be obtained before any study-related procedures are conducted
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameBernhards
      • investigator1_middle_nameRagama
      • investigator1_family_nameOgutu
      • investigator1_qualificationMedical Doctor
      • investigator1_professional_addressStrathmore University Medical Centre_CREATES Madaraka Estate, Ole Sangale Road P.O Box 59857-00200 Nairobi
      • investigator1_telephone+254 733812613
      • investigator1_emailogutu6@gmail.com
      • organisations_transferred_Yes
      • number_participantsEnrolment is competitive world wide
      • notification
      • approval_date26-02-2023
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted16-12-2022
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonThe Approval is based on review of a similar study ECCT/22/10/02, alongside response of PI to reviewer comments.\n
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-11-17 21:19:23
      • created2022-10-14 11:33:51
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id853
        • application_id1178
        • given_nameVidelis
        • middle_nameN
        • family_nameNduba
        • qualificationMedical Doctor
        • professional_addressKEMRI-CRDR , Kenyata National Hospital
        • telephone+254724522474
        • emailvnduba@gmail.com
        • created2022-10-14 11:35:08
        • modified2022-12-16 22:48:30
    • SiteDetail(array)
      • 0(array)
        • id1322
        • application_id1178
        • county_id47
        • site_nameKEMRI/CRDR
        • physical_addressKenyatta National Hospital Off Hospital Road, CRDR
        • contact_detailsTel:+254790484654, P.O Box 47855-00100
        • contact_personProf. Videlis Nduba
        • site_capacity(null)
        • misc(null)
        • created2022-10-14 11:35:08
        • modified2022-12-16 22:48:30
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 1(array)
        • id1324
        • application_id1178
        • county_id41
        • site_nameKEMRI Siaya Clinical Research Annex
        • physical_addressKEMRI Clinical research Annex,Siaya County Hospital,
        • contact_detailsTel: +254722205901, P.O Box 144-40600
        • contact_personProf. Videlis Nduba
        • site_capacity(null)
        • misc(null)
        • created2022-10-31 08:28:02
        • modified2022-12-16 22:48:30
        • County(array)
          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
    • Sponsor(array)
      • 0(array)
        • id607
        • application_id1178
        • sponsorAgios Pharmaceuticals, Inc.
        • sponsor_typeIndustry
        • contact_personJamie Cohen
        • address88 Sidney Street Cambridge, MA 02139-4169 USA
        • telephone_number+1 617-844-6657
        • fax_number+1 617-588-0455
        • cell_number+1 617-844-6657
        • email_addressJamie.cohen@agios.com
        • created2022-10-14 11:35:08
        • modified2022-12-16 22:48:30
  • 1(array)
    • Application(array)
      • id1555
      • user_id799
      • trial_status_id2
      • abstract_of_study<div>\n Increasing antimicrobial resistance (AMR) threatens to undermine the effectiveness of World Health Organization (WHO) recommended antibiotic treatments for neonatal sepsis in most low- and middle-income country (LMIC) settings where disease burden is high. The key threat is multidrug-resistant (MDR) Gram-negative bacteria, where there are limited well established neonatal treatment options and a wide use of meropenem, driving carbapenem resistance. Accumulating data show that these MDR Gram-negative bacteria are now the dominant cause of neonatal sepsis in many high-burden settings. Current WHO guidelines, however, continue to recommend empiric first- and second-line regimens for neonatal sepsis that have remained unchanged for nearly 20 years, despite considerably higher observed rates of AMR. There is therefore an urgent need to re-evaluate guidance for empiric treatment and develop updated first-line empiric and second-line regimens with improved efficacy in the context of increasing MDR sepsis in neonates. It is critically important to directly compare suitable novel regimens, including off-patent drugs with a neonatal licence but not currently widely used for the treatment of neonatal sepsis, to currently recommended and used regimens given the lack of evidence supporting use. Although large pragmatic randomised controlled trials are needed, study designs with either two or multiple arms are not feasible for various reasons, and novel trial designs are crucial to allow for multiple parallel group comparisons from sites randomising different sub-populations of neonates across different sets of clinically relevant regimens for their site and specific sub-population.</div>\n<div>\n  </div>\n<div>\n <div>\n NeoSep1 trial, will test three novel dual combinations of three existing, off-patent drugs, namely fosfomycin + amikacin, flomoxef + amikacin and fosfomycin + flomoxef, and compare these to WHO recommended and other currently used broad spectrum antibiotic combinations. Reflecting that they have been infrequently used in neonatal populations, we will perform a run-in non-randomised pharmacokinetic (PK) study of the fosfomycin and flomoxef when given with amikacin or each other to confirm plasma drug levels at the proposed doses based on other studies and collect safety data (Part 1) before the start of the main randomised trial (Part 2). Part 1 of the NeoSep1 trial aimed to confirm that the recommended doses of fosfomycin and flomoxef, in combination with each other or with amikacin, provided adequate drug exposure and were safe in neonates with suspected sepsis. Three sites participated in Part 1: Kilifi County Hospital (Kenya), (Tygerberg Hospital (South Africa), and Chris Hani Baragwanath Hospital (South Africa). Sixty-five neonates (52 from South Africa; 13 from Kenya) were enrolled March-November 2023; 62 received trial antibiotics. At baseline, 48/62 (77%) were preterm, and 48 (77%) were ≤7 days PNA. The early, middle, and late median concentrations after the first dose were 195, 164 and 98 μg/mL for fosfomycin; and 117, 103 and 50 μg/mL for flomoxef, respectively. Eighteen (29%) neonates had 22 Serious Adverse Events (SAEs), all unrelated to study drugs. Prolonged jaundice occurred in 1 neonate, was possibly related to fosfomycin and flomoxef, and resolved spontaneously. Seven neonates (11.6%; 95%CI: 5.7–22.8) died by day 28 (all unrelated). In this predominately preterm population, fosfomycin and flomoxef exposures shortly after birth were therefore similar to previously published studies, although with substantial variability, supporting the planned dosing for Part 2.</div>\n <div>\n  </div>\n <div>\n In Part 2 of the trial, approximately 3,000 neonates (approximately 600 participants across the 3 sites in Kenya, approximately 200 per site) hospitalised with clinical signs of neonatal sepsis will be randomised across trial sited located in sub-Saharan Africa and Asia, including Kenya and South Africa, to locally relevant first- and second-line antibiotic regimens and followed up for 90 days for safety and efficacy outcomes. In Kenya, 3 sites (Kilifi County Hospital in Kilifi, Coast General Teaching and Referral Hospital in Mombasa, and Mbagathi Hospital in Nairobi) will participate in Part 2. First-line treatment is expected to continue for 7±2 days based on clinician’s judgement of the baby’s condition for babies with culture negative sepsis and 10 days (-3 +4) for culture positive sepsis. If antibiotics are switched to second-line treatment, the total duration of antibiotic treatment including first- and second-line is 14 ±7 days depending on the neonate’s condition. Assessment of safety (Part 1 and 2) and efficacy (Part 2 only) will include blood investigations (C-reactive protein, full blood count, kidney and liver function tests) and clinical assessment using a recovery score respectively. Peri-rectal swabs will be taken at baseline and at the end of treatment to assay carriage of commensal organisms and antimicrobial resistance genes in Part 2. Healthcare-related costs will be measured in Part 2 of the trial. Results obtained from this trial will inform treatment guidelines and improve survival of neonates hospitalised with sepsis.</div>\n</div>\n<p>\n  </p>\n
      • study_title<p>\n <span style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px; background-color: rgb(249, 249, 249);\">An open-label randomised controlled trial comparing novel combination and currently used antibiotic regimens for the empiric treatment of neonatal sepsis with a run-in confirmatory pharmacokinetic phase.</span></p>\n
      • laymans_summary<p>\n <strong>A study comparing new and currently used antibiotic combinations for treatment of newborn babies hospitalised with infection.</strong></p>\n<div>\n <strong>What is the problem/background?</strong></div>\n<div>\n Babies admitted to hospital with a severe infection of the blood are treated with medicines called “antibiotics.” In many countries, these antibiotics are those recommended by the World Health Organisation (WHO). Other countries use different antibiotics based on local policies but unfortunately these are not always easily available. The use of different antibiotics also varies from baby to baby and between countries and hospitals.</div>\n<div>\n More infections are now being caused by bacteria which are “resistant” to commonly used antibiotics. This means these antibiotics will not kill the bacteria and therefore will not cure the infection. These bacteria are often called multidrug resistant, as they are not killed by most antibiotics. We need to find new ways of treating these infections – using combinations of existing antibiotics is one possibility. Fosfomycin, flomoxef and amikacin are three antibiotics that could be combined into different two drug combinations. Another option is to give stronger antibiotics at the start of treatment. The problem with doing this is that not all babies will need these antibiotics – and the more we use them, the more resistance will develop to these antibiotics. So, using stronger antibiotics in lots of babies now, who don’t need them, may mean that in future we will not be able to use them in any babies who might need them.</div>\n<div>\n  </div>\n<div>\n <strong>What questions are we trying to answer?</strong></div>\n<div>\n The NeoSep1 study will test how well giving fosfomycin and amikacin, OR flomoxef and amikacin OR fosfomycin and flomoxef works to treat babies 28 days old or younger who are in hospital with severe infection of the blood. It will also test how well these new combinations work compared to other antibiotics or combinations of antibiotics that are currently used globally.</div>\n<div>\n  </div>\n<div>\n <strong>Where is the study taking place, how many people does it involve and how are they selected?</strong></div>\n<div>\n The study will take place across sites selected in several countries particularly in low- and middle-income countries (LMICs) including Kenya, and South Africa and other countries in Africa and Southeast Asia. Babies aged 28 days or below hospitalised with severe infection requiring intravenous (IV) antibiotics will be screened at admission to check if they fulfil criteria required for study participation. During screening, clinicians will obtain medical history, perform physical examination, and obtain blood samples for baseline/routine investigations which include full blood count (FBC), kidney function tests, and blood culture. Written informed consent will be obtained from parents/guardians before enrolment. Verbal assent will be obtained from parents/guardians of seriously ill babies, and this will be followed up by written informed consent. In addition to routine investigations at admission, blood samples to measure liver function and C-reactive Protein (CRP), a marker of infection in blood, will be done after obtaining consent. Each of these tests will require about 0.5-1 ml (a few drops) of blood.</div>\n<div>\n We have worked out the right doses of fosfomycin, amikacin and flomoxef to use in an earlier part of this study by measuring levels of these drugs in babies’ blood. We will check how well these three combinations, as well as other antibiotics that are used routinely to treat severe infection in newborn babies, treat bacterial infections and stop babies from dying. Approximately 3000 babies (approximately 600 participants across the 3 sites in Kenya, approximately 200 per site) hospitalised with a severe infection of the blood will be enrolled in several countries in Africa and South East Asia, including Kenya and South Africa. In Kenya, 3 sites i.e., Kilifi County Hospital in Kilifi, Coast General Teaching and Referral Hospital in Mombasa and Mbagathi Hospital in Nairobi will participate.</div>\n<div>\n  </div>\n<div>\n <strong>What does the study involve for those who are in it?</strong></div>\n<div>\n A computer programme will assign antibiotic treatments at random (like the flip of a coin) and babies will generally get antibiotics for about 7-10 days in the first instance (their “first line” treatment). If a baby’s condition gets worse during this time, or doesn’t get better as would be expected, doctors will be able to give them a different antibiotic (also known as “second-line” treatment) to see if they do better with different antibiotics. Which specific second-line antibiotics each baby gets will also be chosen at random from a set of combinations that doctors would use after each first-line treatment. Babies will get different second-line antibiotic treatments to those they already had as first-line.</div>\n<div>\n CRP will be repeated on Days 3 and 7. FBC, kidney and liver function tests will be done at baseline and if abnormal, repeated on Day 3, Day 7, Day 14, end of treatment (if not Day 7 or 14), Day 28, and Day 90 after starting treatment. Blood culture will be repeated in case of clinical deterioration and before switching to second-line antibiotics. Additional safety blood tests or investigations will be performed to investigate symptoms or monitor laboratory test abnormalities as clinically indicated following routine clinical practice. We will collect data on any side-effects from Day 0 to Day 28. Babies will have their bottoms/nappies swabbed or a fresh stool sample collected on Day 0 and at the end of treatment to test presence of bacteria resistant to antibiotics. We will collect information of treatment costs from all parents/guardians (e.g. transport costs, family information such as parental age, education level and data on socio-economic status, and information on clinic and hospital visits) and healthcare providers (e.g. costs of medication and procedures, overhead costs and staff costs). Babies will be followed up for 90 days, with a visit or telephone call 28 and 90 days after entering the study to see if the baby is still doing well.</div>\n<div>\n  </div>\n<div>\n <strong>What are the benefits and risks/costs of the study for those involved?</strong></div>\n<div>\n All babies will receive comprehensive medical care while in the ward (including a daily structured review to check progress) and during follow-up. Additional clinical and nursing staff will be recruited and will undertake study duties and assist in general care in the ward, adding to the staff available. Training will be enhanced for all paediatric ward staff on treatment of sick babies. Following discharge from the ward, parents/guardians will have continued access to the study staff via telephone contact and will be advised to bring their babies to the study clinic for review in case of illness while at home.</div>\n<div>\n Drawing a blood sample carries the risks of damage to the vein and infection. However, the study staff will be trained on careful procedures including cleaning the skin to help prevent these. Blood sample volumes obtained for investigation will be minimal, based the baby’s body weight/percentage total blood volume. Swabs of baby’s bottom are minimally invasive and can be taken in a standardised manner independent of passing stools using a soft swab. The risks of swabbing a baby’s bottom are minimal and our study sites have experience in obtaining these samples. Side effects that may be associated with the antibiotics include changes in the level of salts/sodium in blood following administration of fosfomycin. Babies will be monitored for side effects and treated appropriately in case they occur. Parents/guardians will receive transport reimbursement (during scheduled and unscheduled sick visits) and an out-of-pocket allowance (during scheduled visits) for clinic visits. However, costs related to hospitalisation will not be reimbursed.</div>\n<div>\n  </div>\n<div>\n <strong>How will the study benefit society?</strong></div>\n<div>\n The study will enable us to measure the doses of new antibiotics and confirm optimal doses that can be used to treat babies with infection. We will compare different antibiotic combinations, including new ones and those already used in hospitals to see which ones are safe and the best in treating babies with infection. Knowledge of safe and effective antibiotic combinations in sick babies will help decision-making about the first antibiotics to give babies who have infection when they are admitted to hospital to improve their outcomes. This will also help to minimise chances of development and spread of bacteria that are resistant to the antibiotics in use. Knowledge of how bacteria resistant to antibiotics spreads in hospitalised babies will help in finding ways to prevent emergence and spread of resistance and inform development and use of effective antibiotics. Knowledge of individual and provider healthcare costs will guide policymakers on planning and allocation of limited resources to meet the population’s health needs.</div>\n<div>\n  </div>\n<div>\n <strong>When does the study start and finish?</strong></div>\n<div>\n The first part of the study started as soon as scientific and ethical approval was granted. The study is expected to continue for about 5 years until follow-up of participants is completed and the results are available.</div>\n
      • short_titleNeosep1
      • protocol_noECCT/25/06/01
      • version_no4.0
      • date_of_protocol01-11-2024
      • study_drugAntibiotics of interest are: Fosfomycin, Amikacin and Flomoxef. Other antibiotics are: Ampicillin/ amoxicillin, Benzylpenicillin, Cefotaxime, Ceftazidime, Ceftriaxone, Cloxacillin, Flucloxacillin, Gentamicin, Meropenem, Piperacillin/tazobactam
      • disease_conditionNeonatal Sepsis
      • 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_nameFosfomycin, Amikacin and Flomoxef
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressneosep1@pharmalys.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_countries(null)
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      • applicant_impd1
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      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
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      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantKamaljot Hunjan, Main Local Contact - Pharmalys
      • declaration_date103-06-2025
      • declaration_principal_investigatorDr Christina Obiero, National Principal Investigator
      • declaration_date203-06-2025
      • placebo_presentNo
      • study_objectives<p>\n <strong><span font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">Primary objectives</span></strong></p>\n<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">To provide a ranking of eight different clinically relevant antibiotic regimens for first-line empiric and second-line (after lack of response/deterioration) treatment of neonatal sepsis, in terms of 28-day mortality as the primary outcome measure.</span></p>\n<p>\n <strong><span font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">Secondary objective(s)</span></strong></p>\n<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">1. To provide a ranking of clinically relevant antibiotic regimens based on other efficacy and safety secondary outcomes, as well as on health economic measures and the potential selection of resistance at an individual neonate and neonatal unit level.</span></p>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">\n 2. To determine efficacy of antibiotic treatment regimen used based on:</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); margin-left: 40px;\" trebuchet=\"\">\n • Clinical status at days 3, 7, 14 and 28 after randomisation</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); margin-left: 40px;\" trebuchet=\"\">\n • Clinically appropriate need for additional antibiotics beyond the first randomised treatment</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); margin-left: 40px;\" trebuchet=\"\">\n • Clinically appropriate need for additional antibiotics beyond the first randomised and second (for failure) treatment</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">\n <div style=\"margin-left: 40px;\">\n • Cure, defined as clinical improvement and no need for further antibiotic treatment for the original sepsis episode, at test of cure (TOC) visit (day 14 ± 3 days after randomisation).</div>\n <div style=\"margin-left: 40px;\">\n • Length of stay during the index hospitalisation</div>\n <div style=\"margin-left: 40px;\">\n • Systemic antibiotic exposure (days on antibiotics) during the index hospitalisation</div>\n <div style=\"margin-left: 40px;\">\n • 90-day mortality</div>\n <div style=\"margin-left: 40px;\">\n • Change in C-reactive protein from baseline to day 3 and day 7</div>\n <div>\n 3. To collect safety data on different antibiotic treatment regimens</div>\n <div>\n 4. To determine antibiotic resistance development in neonates treated with different first- and second-line antibiotic regimens</div>\n <div>\n 5. To investigate health economic outcomes in neonates treated with different first- and second-line antibiotic regimens</div>\n</div>\n<p>\n  </p>\n
      • principal_inclusion_criteria<p>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">1. Currently admitted to hospital</span></p>\n<p>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">2. Aged <span font-size:=\"\" style=\"font-family: \" trebuchet=\"\">≤28</span> days (post-natal age)</span></p>\n<p>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">3. Weight <span font-size:=\"\" style=\"font-family: \" trebuchet=\"\">≥</span>1000g</span></p>\n<p>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">4. Clinical diagnosis of a new episode of sepsis with two or more of the following clinical signs together with planned treatment with IV antibiotics</span></p>\n<p style=\"margin-left: 40px;\">\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">a. Abnormal temperature (<35.5°C Or ≥38°C)</span></p>\n<p style=\"margin-left: 40px;\">\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">b. Chest indrawing or increase in oxygen requirement or increase of respiratory support</span></p>\n<p style=\"margin-left: 40px;\">\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">c. Abdominal distension</span></p>\n<p style=\"margin-left: 40px;\">\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">d. Difficulty in feeding or feeding intolerance</span></p>\n<p style=\"margin-left: 40px;\">\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">e. Evidence of shock including cold peripheries</span></p>\n<p style=\"margin-left: 40px;\">\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">f. Lethargy, or reduced or no spontaneous movement</span></p>\n<p style=\"margin-left: 40px;\">\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">g. Cyanosis</span></p>\n<p style=\"margin-left: 40px;\">\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">h. Abnormal heart rate (bradycardia <80 bpm; tachycardia >180 bpm)</span></p>\n<p style=\"margin-left: 40px;\">\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">i. Convulsions</span></p>\n<p style=\"margin-left: 40px;\">\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">j. Irritability For making the diagnosis of significant sepsis, the neonate should have no alternative primary explanation for these criteria (such as Hypoxic Ischaemic Encephalopathy, hypothermia, hypoglycemia, prematurity etc)</span></p>\n<p>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">5. At moderate to high risk of death from this episode of sepsis, based on a neonatal sepsis severity score (NeoSep Severity Score) :. This was adapted from the WHO pSBI based scores for the hospital setting and developed using baseline clinical information and subsequent mortality from the NeoOBS study; specifically, a NeoSep Severity Score of 5 or higher at presentation for this episode of sepsis (which may be before formal screening)</span></p>\n<p>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">6. Can receive all potential treatment options on the relevant randomisation list for this neonate at their site, ensuring randomisation is possible (see country-specific appendices)</span></p>\n<p>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">7. IV antibiotics about to be started OR not received more than 24 hours of IV antibiotics for this episode of neonatal sepsis at the point of randomisation</span></p>\n<p>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">8. Parent/guardian willing and able to provide consent (written or, if their neonate is severely ill, verbal consent which must be confirmed by written consent as soon as possible and wherever possible within 48 hours after the first trial specific procedure). Verbal consent allows for administration of first-line antibiotics at no or minimal delay </span></p>\n
      • principal_exclusion_criteria<p>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">1. A known serious, non-infective co-morbidity anticipated to cause death within this admission (including major congenital abnormalities anticipated to cause death within this admission other than prematurity, e.g. known large ventricular septal defect)</span></p>\n<p>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">2. Previously enrolled in this trial</span></p>\n<p>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">3. Current participation in any other clinical study of an Investigational Medicinal Product (IMP) that is a systemic drug, unless it has received prior approval by the NeoSep1 Trial Management Group (TMG)</span></p>\n<p>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">4. Known contraindication to any of the trial antibiotics on the randomisation list for the relevant neonatal sub-population in that site </span></p>\n
      • primary_end_points<p>\n <strong><span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">PRIMARY END POINT</span></strong></p>\n<ul>\n <li>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">28-day mortality</span></li>\n</ul>\n<p>\n <strong><span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">SECONDARY ENDPOINTS </span></strong></p>\n<p>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">Efficacy</span></p>\n<ul>\n <li>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">Clinical status, assessed daily after randomisation through to the earlier of discharge from a trial site or Day 28, using a clinical recovery score based on data from the NeoOBS observational study  </span></li>\n <li>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">Additional systemic antibiotics beyond the first randomised treatment through Day 28</span></li>\n <li>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">Additional systemic antibiotics beyond the first randomised and second (for failure) treatment through Day 28</span></li>\n <li>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">Length of stay during the index hospitalisation</span></li>\n <li>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">Systemic antibiotic exposure (days on antibiotics) during the index hospitalisation</span></li>\n <li>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">90-day mortality</span></li>\n <li>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">Change in C-reactive protein from baseline to Day 3 and Day 7</span></li>\n <li>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">Re-admission by Day 90 (all-cause)</span></li>\n</ul>\n<p>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">Safety (all graded using combined LMIC relevant adapted DAIDS and NAESS):</span></p>\n<ul>\n <li>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">Grade 3/4 adverse events (AEs) through Day 28</span></li>\n <li>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">AEs of any grade related to antibiotics through Day 28</span></li>\n <li>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">Modification (including discontinuation) of antibiotics for adverse reactions through Day 28</span></li>\n <li>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">Neurodevelopment as assessed by the WHO Global Scale for Early Development (GSED) package at Day 28 and Day 90</span></li>\n</ul>\n
      • scope_diagnosis1
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others1
      • scope_others_specify- Health Economics\n- Microbiology
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other1
      • trial_other_specifyPharmacokinetics
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use1
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n Please refer to the site specific addendum form attached.</p>\n
      • other_details_explanation<p>\n <span style=\"color: rgb(51, 51, 51);\">The choice of the countries participating to this study and specifically Kenya is mainly because the high mortality rate due to neonetal sepsis which is not the case in Switzerland.</span></p>\n
      • other_details_regulatory_notapproved<p>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">Initial application to GHANA FDA Date of application: 14th January 2025</span></p>\n<p>\n <span font-size:=\"\" style=\"background-color: rgb(249, 249, 249); color: rgb(51, 51, 51);\" trebuchet=\"\">Initial application to UGANDA NDA Date of application: 19th May 2025</span></p>\n
      • other_details_regulatory_approved<p>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">Amendment made to SOUTH AFRICA SAPHRA- Date of approval: 07th November 2024 - Number of sites: 02</span></p>\n<p>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">Amendment made to KENYA PPB - </span><span font-size:=\"\" style=\"background-color: rgb(249, 249, 249); color: rgb(51, 51, 51);\" trebuchet=\"\">Date of approval: 06th May 2025 - Number of sites: 1 - New application requested for 2 additional sites</span></p>\n
      • other_details_regulatory_rejected<p>\n Not applicable</p>\n
      • other_details_regulatory_halted<p>\n Not applicable</p>\n
      • estimated_duration4 years
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherYes
      • design_controlled_specifyPersonalised RAndomised Controlled Trial (PRACTical), comparing multiple different novel combination and currently used antibiotic regimens, including a Sequential Multiple Assignment Randomised Trial (SMART) design
      • design_controlled_comparatorAmikacin, Gentamicin
      • design_controlled_other_medicinalYes
      • design_controlled_placeboNo
      • 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_states9 countries
      • number_of_sites3
      • multi_country_list8 sites in Africa have been confirmed in Uganda (2 sites), Kenya (3 sites), Ghana (1 site), and South Africa (2 sites). \n8 sites have been selected in South-East Asia in Bangladesh (2 sites), India (3 sites), Malaysia (1 site), Pakistan (1 site), and Vietnam (1 site)
      • data_monitoring_committeeYes
      • total_enrolment_per_site200 (A minimum of 50 and a maximum of 400 per site will be randomised)
      • total_participants_worldwide3000
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornYes
      • population_newbornYes
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18No
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
      • subjects_specifyNeonates
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameChristina
      • investigator1_middle_nameWesonga
      • investigator1_family_nameObiero
      • investigator1_qualificationMBCHB, MPH
      • investigator1_professional_addressP.O Box 230-80108 Kilifi, Kenya
      • investigator1_telephone+254 721 889 581
      • investigator1_emailcobiero@kemri-wellcome.org
      • organisations_transferred_Yes
      • number_participants600 across 3 sites (Kilifi County Hospital in Kilifi, Coast General Teaching and Referral Hospital in Mombasa, and Mbagathi Hospital in Nairobi)
      • notification
      • approval_date02-10-2025
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted03-06-2025
      • is_child0
      • unsubmitted1
      • initial_date_submitted03-06-2025
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonFeedback on evaluation comments from applicant satisfactory
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-11-12 15:55:50
      • created2025-05-28 18:31:50
      • total_sites1
      • ecitizen_invoice374415
    • InvestigatorContact(array)
      • 0(array)
        • id1301
        • application_id1555
        • given_nameChristine
        • middle_nameNafula
        • family_nameManyasi
        • qualificationMBCHB, MMED, Dip. Neonatology
        • professional_addressP.O. Box 40205-00200 Nairobi, Kenya
        • telephone+254 722384594
        • emailnmanyasi@gmail.com
        • created2025-05-31 09:17:54
        • modified2025-07-09 17:18:41
    • SiteDetail(array)
      • 0(array)
        • id1937
        • application_id1555
        • county_id47
        • site_nameMbagathi County Referral Hospital
        • physical_addressMbagathi Road, Off Raila Odinga Way (former Mbagathi way)
        • contact_detailsP.O. Box 40205-00200 Nairobi
        • contact_personDr. Christine Nafula Manyasi
        • site_capacity(null)
        • misc(null)
        • created2025-05-31 09:17:54
        • modified2025-07-09 17:18:41
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
    • Sponsor(array)
      • 0(array)
        • id846
        • application_id1555
        • sponsorGlobal Antibiotic Research and Development Partnership (GARDP)
        • sponsor_typeResearch Institution
        • contact_personSally Ellis
        • addressGlobal Antibiotic Research and Development Partnership (GARDP) 15 Chemin Camille-Vidart 1202 Geneva, Switzerland
        • telephone_number+41 22 5551990
        • fax_number
        • cell_number+44 7727 596296
        • email_addresssellis@gardp.org
        • created2025-05-31 09:17:54
        • modified2025-07-09 17:18:41
  • 2(array)
    • Application(array)
      • id1556
      • user_id799
      • trial_status_id2
      • abstract_of_study<div>\n Increasing antimicrobial resistance (AMR) threatens to undermine the effectiveness of World Health Organization (WHO) recommended antibiotic treatments for neonatal sepsis in most low- and middle-income country (LMIC) settings where disease burden is high. The key threat is multidrug-resistant (MDR) Gram-negative bacteria, where there are limited well established neonatal treatment options and a wide use of meropenem, driving carbapenem resistance. Accumulating data show that these MDR Gram-negative bacteria are now the dominant cause of neonatal sepsis in many high-burden settings. Current WHO guidelines, however, continue to recommend empiric first- and second-line regimens for neonatal sepsis that have remained unchanged for nearly 20 years, despite considerably higher observed rates of AMR. There is therefore an urgent need to re-evaluate guidance for empiric treatment and develop updated first-line empiric and second-line regimens with improved efficacy in the context of increasing MDR sepsis in neonates. It is critically important to directly compare suitable novel regimens, including off-patent drugs with a neonatal licence but not currently widely used for the treatment of neonatal sepsis, to currently recommended and used regimens given the lack of evidence supporting use. Although large pragmatic randomised controlled trials are needed, study designs with either two or multiple arms are not feasible for various reasons, and novel trial designs are crucial to allow for multiple parallel group comparisons from sites randomising different sub-populations of neonates across different sets of clinically relevant regimens for their site and specific sub-population.</div>\n<div>\n  </div>\n<div>\n <div>\n NeoSep1 trial, will test three novel dual combinations of three existing, off-patent drugs, namely fosfomycin + amikacin, flomoxef + amikacin and fosfomycin + flomoxef, and compare these to WHO recommended and other currently used broad spectrum antibiotic combinations. Reflecting that they have been infrequently used in neonatal populations, we will perform a run-in non-randomised pharmacokinetic (PK) study of the fosfomycin and flomoxef when given with amikacin or each other to confirm plasma drug levels at the proposed doses based on other studies and collect safety data (Part 1) before the start of the main randomised trial (Part 2). Part 1 of the NeoSep1 trial aimed to confirm that the recommended doses of fosfomycin and flomoxef, in combination with each other or with amikacin, provided adequate drug exposure and were safe in neonates with suspected sepsis. Three sites participated in Part 1: Kilifi County Hospital (Kenya), (Tygerberg Hospital (South Africa), and Chris Hani Baragwanath Hospital (South Africa). Sixty-five neonates (52 from South Africa; 13 from Kenya) were enrolled March-November 2023; 62 received trial antibiotics. At baseline, 48/62 (77%) were preterm, and 48 (77%) were ≤7 days PNA. The early, middle, and late median concentrations after the first dose were 195, 164 and 98 μg/mL for fosfomycin; and 117, 103 and 50 μg/mL for flomoxef, respectively. Eighteen (29%) neonates had 22 Serious Adverse Events (SAEs), all unrelated to study drugs. Prolonged jaundice occurred in 1 neonate, was possibly related to fosfomycin and flomoxef, and resolved spontaneously. Seven neonates (11.6%; 95%CI: 5.7–22.8) died by day 28 (all unrelated). In this predominately preterm population, fosfomycin and flomoxef exposures shortly after birth were therefore similar to previously published studies, although with substantial variability, supporting the planned dosing for Part 2.</div>\n <div>\n  </div>\n <div>\n In Part 2 of the trial, approximately 3,000 neonates (approximately 600 participants across the 3 sites in Kenya, approximately 200 per site) hospitalised with clinical signs of neonatal sepsis will be randomised across trial sited located in sub-Saharan Africa and Asia, including Kenya and South Africa, to locally relevant first- and second-line antibiotic regimens and followed up for 90 days for safety and efficacy outcomes. In Kenya, 3 sites (Kilifi County Hospital in Kilifi, Coast General Teaching and Referral Hospital in Mombasa, and Mbagathi Hospital in Nairobi) will participate in Part 2. First-line treatment is expected to continue for 7±2 days based on clinician’s judgement of the baby’s condition for babies with culture negative sepsis and 10 days (-3 +4) for culture positive sepsis. If antibiotics are switched to second-line treatment, the total duration of antibiotic treatment including first- and second-line is 14 ±7 days depending on the neonate’s condition. Assessment of safety (Part 1 and 2) and efficacy (Part 2 only) will include blood investigations (C-reactive protein, full blood count, kidney and liver function tests) and clinical assessment using a recovery score respectively. Peri-rectal swabs will be taken at baseline and at the end of treatment to assay carriage of commensal organisms and antimicrobial resistance genes in Part 2. Healthcare-related costs will be measured in Part 2 of the trial. Results obtained from this trial will inform treatment guidelines and improve survival of neonates hospitalised with sepsis.</div>\n</div>\n<p>\n  </p>\n
      • study_title<p>\n <span style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px; background-color: rgb(249, 249, 249);\">An open-label randomised controlled trial comparing novel combination and currently used antibiotic regimens for the empiric treatment of neonatal sepsis with a run-in confirmatory pharmacokinetic phase.</span></p>\n
      • laymans_summary<p>\n <strong>A study comparing new and currently used antibiotic combinations for treatment of newborn babies hospitalised with infection.</strong></p>\n<div>\n <strong>What is the problem/background?</strong></div>\n<div>\n Babies admitted to hospital with a severe infection of the blood are treated with medicines called “antibiotics.” In many countries, these antibiotics are those recommended by the World Health Organisation (WHO). Other countries use different antibiotics based on local policies but unfortunately these are not always easily available. The use of different antibiotics also varies from baby to baby and between countries and hospitals.</div>\n<div>\n More infections are now being caused by bacteria which are “resistant” to commonly used antibiotics. This means these antibiotics will not kill the bacteria and therefore will not cure the infection. These bacteria are often called multidrug resistant, as they are not killed by most antibiotics. We need to find new ways of treating these infections – using combinations of existing antibiotics is one possibility. Fosfomycin, flomoxef and amikacin are three antibiotics that could be combined into different two drug combinations. Another option is to give stronger antibiotics at the start of treatment. The problem with doing this is that not all babies will need these antibiotics – and the more we use them, the more resistance will develop to these antibiotics. So, using stronger antibiotics in lots of babies now, who don’t need them, may mean that in future we will not be able to use them in any babies who might need them.</div>\n<div>\n  </div>\n<div>\n <strong>What questions are we trying to answer?</strong></div>\n<div>\n The NeoSep1 study will test how well giving fosfomycin and amikacin, OR flomoxef and amikacin OR fosfomycin and flomoxef works to treat babies 28 days old or younger who are in hospital with severe infection of the blood. It will also test how well these new combinations work compared to other antibiotics or combinations of antibiotics that are currently used globally.</div>\n<div>\n  </div>\n<div>\n <strong>Where is the study taking place, how many people does it involve and how are they selected?</strong></div>\n<div>\n The study will take place across sites selected in several countries particularly in low- and middle-income countries (LMICs) including Kenya, and South Africa and other countries in Africa and Southeast Asia. Babies aged 28 days or below hospitalised with severe infection requiring intravenous (IV) antibiotics will be screened at admission to check if they fulfil criteria required for study participation. During screening, clinicians will obtain medical history, perform physical examination, and obtain blood samples for baseline/routine investigations which include full blood count (FBC), kidney function tests, and blood culture. Written informed consent will be obtained from parents/guardians before enrolment. Verbal assent will be obtained from parents/guardians of seriously ill babies, and this will be followed up by written informed consent. In addition to routine investigations at admission, blood samples to measure liver function and C-reactive Protein (CRP), a marker of infection in blood, will be done after obtaining consent. Each of these tests will require about 0.5-1 ml (a few drops) of blood.</div>\n<div>\n We have worked out the right doses of fosfomycin, amikacin and flomoxef to use in an earlier part of this study by measuring levels of these drugs in babies’ blood. We will check how well these three combinations, as well as other antibiotics that are used routinely to treat severe infection in newborn babies, treat bacterial infections and stop babies from dying. Approximately 3000 babies (approximately 600 participants across the 3 sites in Kenya, approximately 200 per site) hospitalised with a severe infection of the blood will be enrolled in several countries in Africa and South East Asia, including Kenya and South Africa. In Kenya, 3 sites i.e., Kilifi County Hospital in Kilifi, Coast General Teaching and Referral Hospital in Mombasa and Mbagathi Hospital in Nairobi will participate.</div>\n<div>\n  </div>\n<div>\n <strong>What does the study involve for those who are in it?</strong></div>\n<div>\n A computer programme will assign antibiotic treatments at random (like the flip of a coin) and babies will generally get antibiotics for about 7-10 days in the first instance (their “first line” treatment). If a baby’s condition gets worse during this time, or doesn’t get better as would be expected, doctors will be able to give them a different antibiotic (also known as “second-line” treatment) to see if they do better with different antibiotics. Which specific second-line antibiotics each baby gets will also be chosen at random from a set of combinations that doctors would use after each first-line treatment. Babies will get different second-line antibiotic treatments to those they already had as first-line.</div>\n<div>\n CRP will be repeated on Days 3 and 7. FBC, kidney and liver function tests will be done at baseline and if abnormal, repeated on Day 3, Day 7, Day 14, end of treatment (if not Day 7 or 14), Day 28, and Day 90 after starting treatment. Blood culture will be repeated in case of clinical deterioration and before switching to second-line antibiotics. Additional safety blood tests or investigations will be performed to investigate symptoms or monitor laboratory test abnormalities as clinically indicated following routine clinical practice. We will collect data on any side-effects from Day 0 to Day 28. Babies will have their bottoms/nappies swabbed or a fresh stool sample collected on Day 0 and at the end of treatment to test presence of bacteria resistant to antibiotics. We will collect information of treatment costs from all parents/guardians (e.g. transport costs, family information such as parental age, education level and data on socio-economic status, and information on clinic and hospital visits) and healthcare providers (e.g. costs of medication and procedures, overhead costs and staff costs). Babies will be followed up for 90 days, with a visit or telephone call 28 and 90 days after entering the study to see if the baby is still doing well.</div>\n<div>\n  </div>\n<div>\n <strong>What are the benefits and risks/costs of the study for those involved?</strong></div>\n<div>\n All babies will receive comprehensive medical care while in the ward (including a daily structured review to check progress) and during follow-up. Additional clinical and nursing staff will be recruited and will undertake study duties and assist in general care in the ward, adding to the staff available. Training will be enhanced for all paediatric ward staff on treatment of sick babies. Following discharge from the ward, parents/guardians will have continued access to the study staff via telephone contact and will be advised to bring their babies to the study clinic for review in case of illness while at home.</div>\n<div>\n Drawing a blood sample carries the risks of damage to the vein and infection. However, the study staff will be trained on careful procedures including cleaning the skin to help prevent these. Blood sample volumes obtained for investigation will be minimal, based the baby’s body weight/percentage total blood volume. Swabs of baby’s bottom are minimally invasive and can be taken in a standardised manner independent of passing stools using a soft swab. The risks of swabbing a baby’s bottom are minimal and our study sites have experience in obtaining these samples. Side effects that may be associated with the antibiotics include changes in the level of salts/sodium in blood following administration of fosfomycin. Babies will be monitored for side effects and treated appropriately in case they occur. Parents/guardians will receive transport reimbursement (during scheduled and unscheduled sick visits) and an out-of-pocket allowance (during scheduled visits) for clinic visits. However, costs related to hospitalisation will not be reimbursed.</div>\n<div>\n  </div>\n<div>\n <strong>How will the study benefit society?</strong></div>\n<div>\n The study will enable us to measure the doses of new antibiotics and confirm optimal doses that can be used to treat babies with infection. We will compare different antibiotic combinations, including new ones and those already used in hospitals to see which ones are safe and the best in treating babies with infection. Knowledge of safe and effective antibiotic combinations in sick babies will help decision-making about the first antibiotics to give babies who have infection when they are admitted to hospital to improve their outcomes. This will also help to minimise chances of development and spread of bacteria that are resistant to the antibiotics in use. Knowledge of how bacteria resistant to antibiotics spreads in hospitalised babies will help in finding ways to prevent emergence and spread of resistance and inform development and use of effective antibiotics. Knowledge of individual and provider healthcare costs will guide policymakers on planning and allocation of limited resources to meet the population’s health needs.</div>\n<div>\n  </div>\n<div>\n <strong>When does the study start and finish?</strong></div>\n<div>\n The first part of the study started as soon as scientific and ethical approval was granted. The study is expected to continue for about 5 years until follow-up of participants is completed and the results are available.</div>\n
      • short_titleNeosep1
      • protocol_noECCT/25/06/02
      • version_no4.0
      • date_of_protocol01-11-2024
      • study_drugAntibiotics of interest are: Fosfomycin, Amikacin and Flomoxef. Other antibiotics are: Ampicillin/ amoxicillin, Benzylpenicillin, Cefotaxime, Ceftazidime, Ceftriaxone, Cloxacillin, Flucloxacillin, Gentamicin, Meropenem, Piperacillin/tazobactam
      • disease_conditionNeonatal Sepsis
      • 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_nameFosfomycin, Amikacin and Flomoxef
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressneosep1@pharmalys.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_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_applicantKamaljot Hunjan, Main Local Contact - Pharmalys
      • declaration_date103-06-2025
      • declaration_principal_investigatorDr Christina Obiero, National Principal Investigator
      • declaration_date203-06-2025
      • placebo_presentNo
      • study_objectives<p>\n <strong><span font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">Primary objectives</span></strong></p>\n<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">To provide a ranking of eight different clinically relevant antibiotic regimens for first-line empiric and second-line (after lack of response/deterioration) treatment of neonatal sepsis, in terms of 28-day mortality as the primary outcome measure.</span></p>\n<p>\n <strong><span font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">Secondary objective(s)</span></strong></p>\n<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">1. To provide a ranking of clinically relevant antibiotic regimens based on other efficacy and safety secondary outcomes, as well as on health economic measures and the potential selection of resistance at an individual neonate and neonatal unit level.</span></p>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">\n 2. To determine efficacy of antibiotic treatment regimen used based on:</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); margin-left: 40px;\" trebuchet=\"\">\n • Clinical status at days 3, 7, 14 and 28 after randomisation</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); margin-left: 40px;\" trebuchet=\"\">\n • Clinically appropriate need for additional antibiotics beyond the first randomised treatment</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">\n <div style=\"margin-left: 40px;\">\n • Clinically appropriate need for additional antibiotics beyond the first randomised and second (for failure) treatment</div>\n <div style=\"margin-left: 40px;\">\n • Cure, defined as clinical improvement and no need for further antibiotic treatment for the original sepsis episode, at test of cure (TOC) visit (day 14 ± 3 days after randomisation).</div>\n <div style=\"margin-left: 40px;\">\n • Length of stay during the index hospitalisation</div>\n <div style=\"margin-left: 40px;\">\n • Systemic antibiotic exposure (days on antibiotics) during the index hospitalisation</div>\n <div style=\"margin-left: 40px;\">\n • 90-day mortality</div>\n <div style=\"margin-left: 40px;\">\n • Change in C-reactive protein from baseline to day 3 and day 7</div>\n <div>\n 3. To collect safety data on different antibiotic treatment regimens</div>\n <div>\n 4. To determine antibiotic resistance development in neonates treated with different first- and second-line antibiotic regimens</div>\n <div>\n 5. To investigate health economic outcomes in neonates treated with different first- and second-line antibiotic regimens</div>\n</div>\n<p>\n  </p>\n<p>\n  </p>\n
      • principal_inclusion_criteria<p>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">1. Currently admitted to hospital</span></p>\n<p>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">2. Aged <span font-size:=\"\" trebuchet=\"\">≤28</span> days (post-natal age)</span></p>\n<p>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">3. Weight <span font-size:=\"\" trebuchet=\"\">≥</span>1000g</span></p>\n<p>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">4. Clinical diagnosis of a new episode of sepsis with two or more of the following clinical signs together with planned treatment with IV antibiotics</span></p>\n<p style=\"margin-left: 40px;\">\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">a. Abnormal temperature (<35.5°C Or ≥38°C)</span></p>\n<p style=\"margin-left: 40px;\">\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">b. Chest indrawing or increase in oxygen requirement or increase of respiratory support</span></p>\n<p style=\"margin-left: 40px;\">\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">c. Abdominal distension</span></p>\n<p style=\"margin-left: 40px;\">\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">d. Difficulty in feeding or feeding intolerance</span></p>\n<p style=\"margin-left: 40px;\">\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">e. Evidence of shock including cold peripheries</span></p>\n<p style=\"margin-left: 40px;\">\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">f. Lethargy, or reduced or no spontaneous movement</span></p>\n<p style=\"margin-left: 40px;\">\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">g. Cyanosis</span></p>\n<p style=\"margin-left: 40px;\">\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">h. Abnormal heart rate (bradycardia <80 bpm; tachycardia >180 bpm)</span></p>\n<p style=\"margin-left: 40px;\">\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">i. Convulsions</span></p>\n<p style=\"margin-left: 40px;\">\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">j. Irritability For making the diagnosis of significant sepsis, the neonate should have no alternative primary explanation for these criteria (such as Hypoxic Ischaemic Encephalopathy, hypothermia, hypoglycemia, prematurity etc)</span></p>\n<p>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">5. At moderate to high risk of death from this episode of sepsis, based on a neonatal sepsis severity score (NeoSep Severity Score) :. This was adapted from the WHO pSBI based scores for the hospital setting and developed using baseline clinical information and subsequent mortality from the NeoOBS study; specifically, a NeoSep Severity Score of 5 or higher at presentation for this episode of sepsis (which may be before formal screening)</span></p>\n<p>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">6. Can receive all potential treatment options on the relevant randomisation list for this neonate at their site, ensuring randomisation is possible (see country-specific appendices)</span></p>\n<p>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">7. IV antibiotics about to be started OR not received more than 24 hours of IV antibiotics for this episode of neonatal sepsis at the point of randomisation</span></p>\n<p>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">8. Parent/guardian willing and able to provide consent (written or, if their neonate is severely ill, verbal consent which must be confirmed by written consent as soon as possible and wherever possible within 48 hours after the first trial specific procedure). Verbal consent allows for administration of first-line antibiotics at no or minimal delay </span></p>\n
      • principal_exclusion_criteria<p>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">1. A known serious, non-infective co-morbidity anticipated to cause death within this admission (including major congenital abnormalities anticipated to cause death within this admission other than prematurity, e.g. known large ventricular septal defect)</span></p>\n<p>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">2. Previously enrolled in this trial</span></p>\n<p>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">3. Current participation in any other clinical study of an Investigational Medicinal Product (IMP) that is a systemic drug, unless it has received prior approval by the NeoSep1 Trial Management Group (TMG)</span></p>\n<p>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">4. Known contraindication to any of the trial antibiotics on the randomisation list for the relevant neonatal sub-population in that site </span></p>\n
      • primary_end_points<p>\n <strong><span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">PRIMARY END POINT</span></strong></p>\n<ul>\n <li>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">28-day mortality</span></li>\n</ul>\n<p>\n <strong><span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">SECONDARY ENDPOINTS</span></strong></p>\n<p>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">Efficacy</span></p>\n<ul>\n <li>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">Clinical status, assessed daily after randomisation through to the earlier of discharge from a trial site or Day 28, using a clinical recovery score based on data from the NeoOBS observational study  </span></li>\n <li>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">Additional systemic antibiotics beyond the first randomised treatment through Day 28</span></li>\n <li>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">Additional systemic antibiotics beyond the first randomised and second (for failure) treatment through Day 28</span></li>\n <li>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">Length of stay during the index hospitalisation</span></li>\n <li>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">Systemic antibiotic exposure (days on antibiotics) during the index hospitalisation</span></li>\n <li>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">90-day mortality</span></li>\n <li>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">Change in C-reactive protein from baseline to Day 3 and Day 7</span></li>\n <li>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">Re-admission by Day 90 (all-cause)</span></li>\n</ul>\n<p>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">Safety (all graded using combined LMIC relevant adapted DAIDS and NAESS):</span></p>\n<ul>\n <li>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">Grade 3/4 adverse events (AEs) through Day 28</span></li>\n <li>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">AEs of any grade related to antibiotics through Day 28</span></li>\n <li>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">Modification (including discontinuation) of antibiotics for adverse reactions through Day 28</span></li>\n <li>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51);\" trebuchet=\"\">Neurodevelopment as assessed by the WHO Global Scale for Early Development (GSED) package at Day 28 and Day 90</span></li>\n</ul>\n
      • scope_diagnosis1
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others1
      • scope_others_specify- Health Economics\n- Microbiology
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other1
      • trial_other_specifyPharmacokinetics
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use1
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n Please refer to the site specific addendum attached</p>\n
      • other_details_explanation<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">The choice of the countries participating to this study and specifically Kenya is mainly because the high mortality rate due to neonetal sepsis which is not the case in Switzerland.</span></p>\n
      • other_details_regulatory_notapproved<p>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">Initial application to GHANA FDA Date of application: 14th January 2025</span></p>\n<p>\n <span font-size:=\"\" style=\"background-color: rgb(249, 249, 249); color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">Initial application to UGANDA NDA Date of application: 19th May 2025</span></p>\n
      • other_details_regulatory_approved<p>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">Amendment made to SOUTH AFRICA SAPHRA- Date of approval: 07th November 2024 - Number of sites: 02</span></p>\n<p>\n <span background-color:=\"\" font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">Amendment made to KENYA PPB - </span><span font-size:=\"\" style=\"background-color: rgb(249, 249, 249); color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">Date of approval: 06th May 2025 - Number of sites: 1 - New application requested for 2 additional sites</span></p>\n
      • other_details_regulatory_rejected<p>\n Not applicable</p>\n
      • other_details_regulatory_halted<p>\n Not applicable</p>\n
      • estimated_duration4 years
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherYes
      • design_controlled_specifyPersonalised RAndomised Controlled Trial (PRACTical), comparing multiple different novel combination and currently used antibiotic regimens, including a Sequential Multiple Assignment Randomised Trial (SMART) design
      • design_controlled_comparatorAmikacin, Gentamicin
      • design_controlled_other_medicinalYes
      • design_controlled_placeboNo
      • 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_states9 countries
      • number_of_sites3
      • multi_country_list8 sites in Africa have been confirmed in Uganda (2 sites), Kenya (3 sites), Ghana (1 site), and South Africa (2 sites).\n8 sites have been selected in South-East Asia in Bangladesh (2 sites), India (3 sites), Malaysia (1 site), Pakistan (1 site), and Vietnam (1 site).
      • data_monitoring_committeeYes
      • total_enrolment_per_site200 (A minimum of 50 and a maximum of 400 per site will be randomised)
      • total_participants_worldwide3000
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornYes
      • population_newbornYes
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18No
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
      • subjects_specifyNeonates
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameChristina
      • investigator1_middle_nameWesonga
      • investigator1_family_nameObiero
      • investigator1_qualificationMBCHB, MPH
      • investigator1_professional_addressP.O Box 230-80108 Kilifi, Kenya
      • investigator1_telephone+254 721 889 581
      • investigator1_emailcobiero@kemri-wellcome.org
      • organisations_transferred_Yes
      • number_participants600 across 3 sites (Kilifi County Hospital in Kilifi, Coast General Teaching and Referral Hospital in Mombasa, and Mbagathi Hospital in Nairobi)
      • notification
      • approval_date02-10-2025
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted04-06-2025
      • is_child0
      • unsubmitted1
      • initial_date_submitted04-06-2025
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonFeedback on evaluation comments from applicant satisfactory
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-11-12 16:28:03
      • created2025-05-28 18:52:45
      • total_sites1
      • ecitizen_invoice374418
    • InvestigatorContact(array)
      • 0(array)
        • id1299
        • application_id1556
        • given_nameNayirat
        • middle_nameMohamed
        • family_nameDormohamed
        • qualificationMBCHB, MMed, MPhil
        • professional_addressPO Box 85639-80100, Mombasa, Kenya
        • telephone+254 723311339
        • emailnayiratdor@gmail.com
        • created2025-05-28 20:01:29
        • modified2025-07-07 18:44:05
    • SiteDetail(array)
      • 0(array)
        • id1935
        • application_id1556
        • county_id1
        • site_nameCoast General Teaching and Referral Hospital
        • physical_addressKisauni Road, Mombasa
        • contact_detailsPO Box 90231-80100 Mombasa
        • contact_personNayirat Mohamed Dormohamed
        • site_capacity(null)
        • misc(null)
        • created2025-05-28 20:01:29
        • modified2025-07-07 18:44:05
        • County(array)
          • id1
          • county_nameMombasa
          • created2012-05-31 16:15:11
          • modified2012-07-09 13:06:23
    • Sponsor(array)
      • 0(array)
        • id844
        • application_id1556
        • sponsorGlobal Antibiotic Research and Development Partnership (GARDP)
        • sponsor_typeResearch Institution
        • contact_personSally Ellis
        • addressGlobal Antibiotic Research and Development Partnership (GARDP) 15 Chemin Camille-Vidart 1202 Geneva, Switzerland
        • telephone_number+41 22 5551990
        • fax_number
        • cell_number+44 7727 596296
        • email_addresssellis@gardp.org
        • created2025-05-28 20:01:29
        • modified2025-07-07 18:44:05
  • 3(array)
    • Application(array)
      • id1257
      • user_id81
      • trial_status_id7
      • abstract_of_study<p>\n SARS-C-oV-2 infection driven COVID-19 cases and associated deaths continue to be reported around the world, indicating a persistent risk for waves of increased transmission, previously characterised by high levels of hospitalisations with severe disease, and death. SARS-CoV-2 virus also continues to evolve, with the Omicron (and it’s sub-lineages), now being the dominant variant globally. The sequential changes in SARS-CoV-2 virus are associated with structural modifications that confer the newly evolved variants the ability for immune escape from vaccine induced immunity. Indeed, there is now evidence that Omicron variants and their sub-lineages can escape from neutralisation of antibodies induced from either prior immunisation with the original BNT162b2 (Pfizer-BioNTech) vaccine, implying a causal link with a reduction in vaccine effectiveness. Furthermore, the original BNT162b2 (similar with other COVID-19) vaccine(s) induced protection is also short-lived, necessitating the sequential administrations of additional vaccine doses (now called “booster immunisations”) to extend and broaden protection from the primary vaccination series. One way to overcome these challenges of the reducing vaccine efficacy associated with either SARS-CoV-2 evolution, and/or a rapidly decaying immune response, is to add components of the current dominant Omicron variant to the original vaccine, as this would extend the initial protection to last longer, whilst also broadening it to cover more SARS-CoV-2 variants. Therefore, the new generation of COVID-19 vaccines are bivalent: combining components of the original Wuhan-Hu-1 and at least one or more of the current Omicron variants. The Pfizer bivalent BNT162b2 COVID-19 vaccine (containing components of the Wuhan-Hu-1 and Omicrons BA.4 and BA.5), being tested here, is currently approved for booster vaccinations in high income countries. However, it has not been formerly tested in unvaccinated individuals. While there are many regional variations in COVID-19 epidemiology, most of Africans are seropositive for SARS-CoV-2 owing to natural infection rather than vaccination. Concurrently, COVID-19 vaccination coverage remains very low in Africa. It is unclear if one dose of the bivalent vaccine will be sufficient to provide protection against Omicron variants and their sub-lineages in sub–Saharan African populations. We propose a clinical trial comparing safety and immunogenicity of the bivalent BNT162b2 COVID-19 vaccine with the corresponding original BNT162b2 (monovalent) COVID-19 vaccine in previously unvaccinated sub-Saharan Africa adults. The evidence generated will guide policies for the rational use of bivalent and the original mRNA vaccines in COVID-19 control. </p>\n
      • study_title<p>\n <span class=\"NormalTextRun SCXW36608480 BCX8\" data-ccp-parastyle=\"Title\" style=\"margin: 0px; padding: 0px; user-select: text; -webkit-user-drag: none; -webkit-tap-highlight-color: transparent; font-family: "Times New Roman", "Times New Roman_EmbeddedFont", "Times New Roman_MSFontService", serif; font-size: 16px; font-variant-ligatures: none; font-weight: 700; white-space: pre-wrap;\">A randomised, controlled clinical trial to assess and compare the immunogenicity, safety and reactogenicity of the bivalent</span><span class=\"NormalTextRun SCXW36608480 BCX8\" data-ccp-parastyle=\"Title\" style=\"margin: 0px; padding: 0px; user-select: text; -webkit-user-drag: none; -webkit-tap-highlight-color: transparent; font-family: "Times New Roman", "Times New Roman_EmbeddedFont", "Times New Roman_MSFontService", serif; font-size: 16px; font-variant-ligatures: none; font-weight: 700; white-space: pre-wrap;\"> </span><span class=\"NormalTextRun SCXW36608480 BCX8\" data-ccp-parastyle=\"Title\" style=\"margin: 0px; padding: 0px; user-select: text; -webkit-user-drag: none; -webkit-tap-highlight-color: transparent; font-family: "Times New Roman", "Times New Roman_EmbeddedFont", "Times New Roman_MSFontService", serif; font-size: 16px; font-variant-ligatures: none; font-weight: 700; white-space: pre-wrap;\">Omicron </span><span class=\"NormalTextRun SCXW36608480 BCX8\" data-ccp-parastyle=\"Title\" style=\"margin: 0px; padding: 0px; user-select: text; -webkit-user-drag: none; -webkit-tap-highlight-color: transparent; font-family: "Times New Roman", "Times New Roman_EmbeddedFont", "Times New Roman_MSFontService", serif; font-size: 16px; font-variant-ligatures: none; font-weight: 700; white-space: pre-wrap;\">BA.4/BA.5</span><span class=\"NormalTextRun SCXW36608480 BCX8\" data-ccp-parastyle=\"Title\" style=\"margin: 0px; padding: 0px; user-select: text; -webkit-user-drag: none; -webkit-tap-highlight-color: transparent; font-family: "Times New Roman", "Times New Roman_EmbeddedFont", "Times New Roman_MSFontService", serif; font-size: 16px; font-variant-ligatures: none; font-weight: 700; white-space: pre-wrap;\"> </span><span class=\"NormalTextRun SCXW36608480 BCX8\" data-ccp-parastyle=\"Title\" style=\"margin: 0px; padding: 0px; user-select: text; -webkit-user-drag: none; -webkit-tap-highlight-color: transparent; font-family: "Times New Roman", "Times New Roman_EmbeddedFont", "Times New Roman_MSFontService", serif; font-size: 16px; font-variant-ligatures: none; font-weight: 700; white-space: pre-wrap;\">adapted</span><span class=\"NormalTextRun SCXW36608480 BCX8\" data-ccp-parastyle=\"Title\" style=\"margin: 0px; padding: 0px; user-select: text; -webkit-user-drag: none; -webkit-tap-highlight-color: transparent; font-family: "Times New Roman", "Times New Roman_EmbeddedFont", "Times New Roman_MSFontService", serif; font-size: 16px; font-variant-ligatures: none; font-weight: 700; white-space: pre-wrap;\">,</span><span class=\"NormalTextRun SCXW36608480 BCX8\" data-ccp-parastyle=\"Title\" style=\"margin: 0px; padding: 0px; user-select: text; -webkit-user-drag: none; -webkit-tap-highlight-color: transparent; font-family: "Times New Roman", "Times New Roman_EmbeddedFont", "Times New Roman_MSFontService", serif; font-size: 16px; font-variant-ligatures: none; font-weight: 700; white-space: pre-wrap;\"> and the </span><span class=\"NormalTextRun SCXW36608480 BCX8\" data-ccp-parastyle=\"Title\" style=\"margin: 0px; padding: 0px; user-select: text; -webkit-user-drag: none; -webkit-tap-highlight-color: transparent; font-family: "Times New Roman", "Times New Roman_EmbeddedFont", "Times New Roman_MSFontService", serif; font-size: 16px; font-variant-ligatures: none; font-weight: 700; white-space: pre-wrap;\">original </span><span class=\"NormalTextRun SCXW36608480 BCX8\" data-ccp-parastyle=\"Title\" style=\"margin: 0px; padding: 0px; user-select: text; -webkit-user-drag: none; -webkit-tap-highlight-color: transparent; font-family: "Times New Roman", "Times New Roman_EmbeddedFont", "Times New Roman_MSFontService", serif; font-size: 16px; font-variant-ligatures: none; font-weight: 700; white-space: pre-wrap;\">Wuhan-Hu-1-strain</span><span class=\"NormalTextRun SCXW36608480 BCX8\" data-ccp-parastyle=\"Title\" style=\"margin: 0px; padding: 0px; user-select: text; -webkit-user-drag: none; -webkit-tap-highlight-color: transparent; font-family: "Times New Roman", "Times New Roman_EmbeddedFont", "Times New Roman_MSFontService", serif; font-size: 16px; font-variant-ligatures: none; font-weight: 700; white-space: pre-wrap;\">,</span><span class=\"NormalTextRun SCXW36608480 BCX8\" data-ccp-parastyle=\"Title\" style=\"margin: 0px; padding: 0px; user-select: text; -webkit-user-drag: none; -webkit-tap-highlight-color: transparent; font-family: "Times New Roman", "Times New Roman_EmbeddedFont", "Times New Roman_MSFontService", serif; font-size: 16px; font-variant-ligatures: none; font-weight: 700; white-space: pre-wrap;\"> BNT162b2 COVID-19 vaccine</span><span class=\"NormalTextRun SCXW36608480 BCX8\" data-ccp-parastyle=\"Title\" style=\"margin: 0px; padding: 0px; user-select: text; -webkit-user-drag: none; -webkit-tap-highlight-color: transparent; font-family: "Times New Roman", "Times New Roman_EmbeddedFont", "Times New Roman_MSFontService", serif; font-size: 16px; font-variant-ligatures: none; font-weight: 700; white-space: pre-wrap;\"> formulations</span><span class=\"NormalTextRun SCXW36608480 BCX8\" data-ccp-parastyle=\"Title\" style=\"margin: 0px; padding: 0px; user-select: text; -webkit-user-drag: none; -webkit-tap-highlight-color: transparent; font-family: "Times New Roman", "Times New Roman_EmbeddedFont", "Times New Roman_MSFontService", serif; font-size: 16px; font-variant-ligatures: none; font-weight: 700; white-space: pre-wrap;\"> in healthy unvaccinated East African </span><span class=\"NormalTextRun SCXW36608480 BCX8\" data-ccp-parastyle=\"Title\" style=\"margin: 0px; padding: 0px; user-select: text; -webkit-user-drag: none; -webkit-tap-highlight-color: transparent; font-family: "Times New Roman", "Times New Roman_EmbeddedFont", "Times New Roman_MSFontService", serif; font-size: 16px; font-variant-ligatures: none; font-weight: 700; white-space: pre-wrap;\">adults.</span></p>\n
      • laymans_summary<p align=\"left\">\n COVID-19 virus infections and cases continue to be reported from most regions around the world, including Africa. Thus, waves of increased COVID-19 virus spreading, which are often characterised by high levels of hospitalisations with severe disease and deaths will remain a major risk for now, and in the future. Besides the large numbers of COVID-19 attributable hospitalisations and deaths that occurred in large cities like Nairobi and Dar es Salaam in 2020 and 2021, data from the Kilifi Demographic Surveillance show increased mortality among older adults since the beginning of the pandemic suggesting that increased vaccination coverage in rural areas may enhance their protection, as well as those with underlying chronic diseases.</p>\n<address>\n COVID-19 virus also continues to evolve, with the Omicron variant now being the dominant strain globally. Sequential changes (over time) in the virus makeup are associated with structural modifications that increase its transmissibility, and in the case of Omicron, immune escape from vaccine induced immunity. Because the currently available COVID-19 vaccines were optimized for protection against the originally described (ancestral) COVID-19 virus strain, it is likely that they will be rendered less effective against COVID-19 associated with Omicron and other future variants.  Furthermore, the vaccine induced protection also wanes with time, necessitating the administrations of additional vaccine doses to fully vaccinated people to extend the protection afforded by the primary immunisation series.</address>\n<address>\n One way to overcome the challenges of waning vaccine efficacy, owing to the introduction of new COVID-19 virus variants and passage of time, is to add components of the Omicron variant to the original vaccines, so that the new generation of “bivalent” vaccines are also optimised to protect against the more recently evolved COVID-19 virus variants. Vaccine manufacturers are now making these bivalent vaccines, and the one from Pfizer-BioNTech is already approved for use in some countries, and already in the market for COVID-19 control.  Until now, this vaccine has only been tested in previously COVID-19 vaccinated individuals, as additional booster vaccine doses.</address>\n<address>\n For now, it also unclear if two doses of the new bivalent vaccines are necessary to provide sufficient protection against Omicron variants in populations where exposure to COVID-19 virus infection has been very high but with very low vaccine coverage, like in Kenya and Tanzania. Thus, this study will generate data indicating whether unvaccinated, but SARS-CoV-2 exposed adults can be sufficiently protected by single doses of the new vaccine. Importantly, if the new bivalent vaccines can be used as a single dose, this information may encourage increased vaccine use and coverage in regions with low vaccine uptake, as a simplified vaccination programme relying on a single dose will likely be more acceptable than the current two doses for a primary series. Thus, results from the trial will guide local policy recommendations for the rational use of available vaccines, outside of high-income countries.</address>\n<address>\n We would now like to compare the performance and safety profiles of the Pfizer-BioNTech Omicron-adapted bivalent COVID-19 vaccine, with that of the corresponding original Pfizer-BioNTech vaccine in previously COVID-19 unvaccinated adults in East African adults, to determine whether it induces a bigger immune response, while retaining a similar safety profile. The present trial is planned in Kilifi, Kenya and in Dar es Salaam, Tanzania.</address>\n<address>\n <p>\n  </p>\n <address>\n <p>\n <br />\n <!-- /--></p>\n <p align=\"left\">\n  </p>\n </address>\n <p>\n  </p>\n</address>\n
      • short_titleBiMVaC01
      • protocol_noECCT/23/04/05
      • version_noV.1.0
      • date_of_protocol06-03-2023
      • study_drugBivalent BNT162b2 COVID-19 vaccine
      • disease_conditionCOVID-19
      • product_type_biologicals0
      • product_type_proteins1
      • product_type_immunologicals0
      • product_type_vaccines1
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_nameBivalent BNT162b2
      • product_type_medical_device_name
      • comparatorYes
      • comparator_nameOriginal BNT162b2 COVID-19 vaccine
      • comparator_registeredyes
      • comparator_countriesWHO emergency use approval -world wide
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressCGMRCCSC@kemri-wellcome.org
      • 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_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_applicantStella Mwakio
      • declaration_date118-04-2023
      • declaration_principal_investigatorProf. Francis Ndungu
      • declaration_date218-04-2023
      • placebo_presentNo
      • study_objectives<p>\n To determine superiority of the immune response against the Omicron BA.4/BA.5 sub lineage of SARS-CoV-2, measured as day 28 neutralising antibodies (Nabs) GMT in previously COVID-19 unvaccinated healthy East African adults following vaccinations with two doses of the Omicron BA.4/BA.5 adapted Bivalent BNT162b2 COVID-19 vaccine (28 days apart), versus two doses of the Original BNT162b2 COVID-19 vaccine.</p>\n<p>\n To determine non-inferiority of the immune response against the Omicron BA.4/BA.5 sublinage of SARS-CoV-2, measured as day 28 NAbs GMT in previously COVID-19 unvaccinated healthy adults following vaccinations with one dose of the Bivalent BNT162b2 COVID-19 vaccine, versus two doses (28 days apart) of the Original BNT162b2 COVID-19 vaccine.</p>\n<p>\n To assess and compare the safety and reactogenicity between the two trial vaccination arms following each of two successive doses of the Bivalent BNT162b2 and the Original BNT162b2vaccines in previously COVID-19 unvaccinated adults.</p>\n
      • principal_inclusion_criteria<p>\n 1) Adult (18 years of age) males, or non-pregnant females.</p>\n<p>\n 2) Able and willing to comply with trial requirements.</p>\n<p>\n 3) For females only, a negative pregnancy test within 24 hours prior to administration of each of the two vaccine doses and willing to take contraception till 28 days after the second vaccine dose.</p>\n<p>\n 4) Provide written informed consent.</p>\n
      • principal_exclusion_criteria<p>\n 1) Documented history of any COVID-19 vaccination.</p>\n<p>\n 2) Prior receipt of an investigational, or licensed vaccine within the last 30 days.</p>\n<p>\n 3) Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the first vaccine dose.</p>\n<p>\n 4) Any confirmed, or suspected immunosuppressive, or immunodeficient state, including HIV infection; asplenia; recurrent severe infections and use of immunosuppressant medication within the past 6 months, except topical steroids or short-term oral steroids (course lasting <14 days).</p>\n<p>\n 5) History of allergic disease, or reactions that could be exacerbated by any component of study vaccine.</p>\n<p>\n 6) Any history of angioedema or anaphylaxis.</p>\n<p>\n 7) Any history of myocarditis and pericarditis.</p>\n<p>\n 8) Pregnancy or lactation at the time of screening</p>\n
      • primary_end_points<p>\n Primary</p>\n<p>\n • Geometric mean titres (GMTs) of Omicron-specific NAbs at 28 days following 2 doses of Bivalent BNT162b2 COVID-19 vaccine and 2 doses of Original BNT162b2COVID-19 vaccine.</p>\n<p>\n Secondary immunogenicity</p>\n<p>\n • GMTs of Omicron specific NAbs at 28 days following 1 dose of Omicroncontaining COVID-19 vaccine and 1 dose of original BNT162b2 monovalent COVID-19 vaccine.</p>\n<p>\n • GMTs of BAbs at 28 days following each dose of bivalent Omicron-containing COVID-19 vaccine and each dose of original BNT162b2 monovalent COVID19 vaccine.</p>\n<p>\n • GMTs of Omicron-specific NAbs at 6 months following last vaccine dose in each treatment arm.</p>\n<p>\n • GMTs of BAbs at 6 months following the last vaccine dose in each treatment arm. • GMTs of NAbs against ancestral strain of SARS-CoV-2 at 28 days following each vaccine dose in each treatment arm.</p>\n<p>\n • GMTs of NAbs against ancestral strain of SARS-CoV-2 at 6 months following last vaccine dose in each treatment arm.</p>\n<p>\n • Geometric mean fold rise (GMFR) of BAbs, Omicron-specific NAb and NABs against ancestral strain of SARS-CoV-2 at</p>\n<p>\n -28 days post dose 1 as compared to baseline titres for each treatment arm.</p>\n<p>\n -28 days post dose 2 as compared to baseline and pre-dose 2 titres for each treatment arm.</p>\n
      • scope_diagnosis0
      • scope_prophylaxis1
      • scope_therapy0
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence1
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study1
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<div ccp_infra_copy_id=\"e22fa8c7-c0eb-4ca0-a3ca-408b47b3bb2d\" ccp_infra_timestamp=\"1681799652268\" ccp_infra_user_hash=\"211019686\" ccp_infra_version=\"3\" data-ccp-timestamp=\"1681799652268\">\n <table style=\"border-collapse: collapse; width: 414pt;\" width=\"552\">\n <colgroup>\n <col style=\"width: 179pt;\" width=\"238\" />\n <col style=\"width: 236pt;\" width=\"314\" />\n </colgroup>\n <tbody>\n <tr height=\"21\" style=\"height: 15.75pt;\">\n <td class=\"xl139\" height=\"21\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 15.75pt;\" width=\"238\">\n Principal Investigator (Francis Ndungu)</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204); width: 236pt;\" width=\"314\">\n Overal Trial supervision</td>\n </tr>\n <tr height=\"21\" style=\"height: 15.75pt;\">\n <td class=\"xl139\" height=\"21\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 15.75pt;\" width=\"238\">\n Medical officer(Makobu Kimani)</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204);\">\n Principal assitant to P.I and head clinical section</td>\n </tr>\n <tr height=\"21\" style=\"height: 15.75pt;\">\n <td class=\"xl139\" height=\"21\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 15.75pt;\" width=\"238\">\n Project Manager (Stella Mwakio)</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204);\">\n Day-to-day Project supervision</td>\n </tr>\n <tr height=\"21\" style=\"height: 15.75pt;\">\n <td class=\"xl139\" height=\"21\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 15.75pt;\" width=\"238\">\n Grant manager (Keith Kipoto</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204);\">\n project accountant </td>\n </tr>\n <tr height=\"21\" style=\"height: 15.75pt;\">\n <td class=\"xl139\" height=\"21\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 15.75pt;\" width=\"238\">\n Clinical officer (Two)</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204);\">\n Provide clinical services including vaccine administration </td>\n </tr>\n <tr height=\"21\" style=\"height: 15.75pt;\">\n <td class=\"xl139\" height=\"21\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 15.75pt;\" width=\"238\">\n Nurse (five)</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204);\">\n Clinical Services and Emergence care</td>\n </tr>\n <tr height=\"21\" style=\"height: 15.75pt;\">\n <td class=\"xl139\" height=\"21\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 15.75pt;\" width=\"238\">\n Pharmacist (Mwaganyuma Mwatasa)</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204);\">\n Vaccine handling management </td>\n </tr>\n <tr height=\"21\" style=\"height: 15.75pt;\">\n <td class=\"xl139\" height=\"21\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 15.75pt;\" width=\"238\">\n Pharmaceutical technologist (Two)</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204);\">\n Vaccine prepration (Unblinded)</td>\n </tr>\n <tr height=\"21\" style=\"height: 15.75pt;\">\n <td class=\"xl139\" height=\"21\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 15.75pt;\" width=\"238\">\n Research counselor (one)</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204);\">\n HIV testing and counselling </td>\n </tr>\n <tr height=\"21\" style=\"height: 15.75pt;\">\n <td class=\"xl139\" height=\"21\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 15.75pt;\" width=\"238\">\n Community facilitator (one)</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204);\">\n Link between clinical and community teams </td>\n </tr>\n <tr height=\"21\" style=\"height: 15.75pt;\">\n <td class=\"xl139\" height=\"21\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 15.75pt;\" width=\"238\">\n Research officer (Post Doc Entry)</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204);\">\n Principal assitant to P.I on immunology work </td>\n </tr>\n <tr height=\"21\" style=\"height: 15.75pt;\">\n <td class=\"xl139\" height=\"21\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 15.75pt;\" width=\"238\">\n Laboratory Technician (two)</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204);\">\n Day-to-day sample handling </td>\n </tr>\n <tr height=\"42\" style=\"height: 31.5pt;\">\n <td class=\"xl139\" height=\"42\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 31.5pt;\" width=\"238\">\n Assistant Research officer (Jennifer Musyoki's)</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204);\">\n Supervision of lab technitians</td>\n </tr>\n <tr height=\"21\" style=\"height: 15.75pt;\">\n <td class=\"xl139\" height=\"21\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 15.75pt;\" width=\"238\">\n Field Supervisor (Juliana)</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204);\">\n Supervision of field teams</td>\n </tr>\n <tr height=\"21\" style=\"height: 15.75pt;\">\n <td class=\"xl139\" height=\"21\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 15.75pt;\" width=\"238\">\n Data Manager (Stanely Cheriot)</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204);\">\n Data quality assurance </td>\n </tr>\n <tr height=\"21\" style=\"height: 15.75pt;\">\n <td class=\"xl139\" height=\"21\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 15.75pt;\" width=\"238\">\n Data Clerk (four)</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204);\">\n Data entry</td>\n </tr>\n <tr height=\"21\" style=\"height: 15.75pt;\">\n <td class=\"xl139\" height=\"21\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 15.75pt;\" width=\"238\">\n Field Worker (six)</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204);\">\n Recruitment of volunteers </td>\n </tr>\n <tr height=\"21\" style=\"height: 15.75pt;\">\n <td class=\"xl139\" height=\"21\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 15.75pt;\" width=\"238\">\n Administrative Assistant (one)</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204);\">\n General administration of the project</td>\n </tr>\n <tr height=\"21\" style=\"height: 15.75pt;\">\n <td class=\"xl139\" height=\"21\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 15.75pt;\" width=\"238\">\n Lab Archivist (One)</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204);\">\n Store samples & Maintain sample data</td>\n </tr>\n <tr height=\"21\" style=\"height: 15.75pt;\">\n <td class=\"xl139\" height=\"21\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 15.75pt;\" width=\"238\">\n Biostatician (Benedict Orinid)</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204);\">\n Data analaysis </td>\n </tr>\n <tr height=\"42\" style=\"height: 31.5pt;\">\n <td class=\"xl139\" height=\"42\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 31.5pt;\" width=\"238\">\n Monitors (two: Maureen Gacemba, Siti Ndaa)</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204);\">\n Internal monitoring of study procedures </td>\n </tr>\n <tr height=\"21\" style=\"height: 15.75pt;\">\n <td class=\"xl139\" height=\"21\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 15.75pt;\" width=\"238\">\n Grants Officer Oxford</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204);\">\n post award management</td>\n </tr>\n </tbody>\n </table>\n</div>\n<p>\n <strong>Site Facility</strong></p>\n<p>\n Clinical Trial facility located within the KEMRI-CGMRC Kilifi is well equiped with Offices for Clinical Trials Staff and Principal investiagtors.</p>\n<p>\n It is well equiped with Resources and personnel for Data management, clinical trial laboartory, clinical trial Phamacy and the Clinical areas.</p>\n<p>\n <strong>Emergency Preparedness</strong></p>\n<p>\n <span class=\"ui-provider gz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Individual vaccinees will be closely monitored for symptoms and signs including chest pain, fatigue, swelling of the legs, ankles and feet, unexplained shortness of breath, light-headedness and flu-like symptoms during the 30 minutes following each vaccination at the clinic and will be monitored closely by the study staff via daily phone calls for the subsequent 7 days for such occurrences. KEMRI-CGMR-C has the capacity to diagnose and refer such cases to specialists like the Kilifi County, and the Aga Khan and Premier Hospitals at the coast of Kenya</span></p>\n
      • other_details_explanation<p>\n <span class=\"ui-provider gz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">The sponsor (Oxford University), has sub-contracted the KWTRP as one of two sites to conduct the study. There currently is no data on the bivalent vaccine in African populations. The vaccine manufacturer (Pfizer), will soon discontinue production of the original monovalent vaccine. Consequently, it is imperative that data on the bivalent vaccine from African populations are availed.</span></p>\n
      • other_details_regulatory_notapproved<p>\n TMDA TANZANIA</p>\n
      • other_details_regulatory_approved<p>\n None</p>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n none</p>\n
      • estimated_duration16months
      • 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_comparatorstandard of care arm
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKEMRI-CGMRC Kilifi
      • single_site_physical_address230
      • single_site_contact_personKimani Makobu
      • single_site_telephone+254722258102
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states2
      • number_of_sites
      • multi_country_listKenya \nTanzania
      • data_monitoring_committeeYes
      • total_enrolment_per_site290 each site
      • total_participants_worldwide580
      • 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_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_nameMac
      • investigator1_middle_nameMakobu
      • investigator1_family_nameKimani
      • investigator1_qualificationMBChB
      • investigator1_professional_address230
      • investigator1_telephone+254722258102
      • investigator1_emailKMakobu@kemri-wellcome.org
      • organisations_transferred_No
      • number_participants580
      • notification<p>\n None</p>\n
      • approval_date06-07-2023
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted06-07-2023
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonThe reviewer comments have been addressed.
      • final_report<p>\n This was a phase 3 multicounty, randomized controlled, double blind, trial is with two arms</p>\n<p>\n -  arm 1: randomized to receive the monovalent Pfizer COVID-19 vaccine; optimized for the ancestral Wuhan strain of SARS-CoV-2. Containing 30µg of the S protein from the ancestral Wuhan-Hu-1 strain </p>\n<p>\n -  arm 2: randomized to receive the bivalent Pfizer vaccine; optimized against the Omicron BA4/5 and Wuhan strains of SARS-CoV-2. mRNA vaccine containing 15/15 µg (each) of the S-protein from the ancestral strain & Omicron BA.4/BA.5 sub-lineages.</p>\n<p>\n The study was designed to demonstrate the non-inferiority of the Bivalent vaccine compared to the monovalent one. Non-inferiority was compared for safety, reactogenicity and immunogenicity.</p>\n<p>\n Participants were randomized in a 1:1 ration to either study arm. They each received two (2) doses of either vaccine. The dosing schedules were identical (28 days apart).</p>\n<p>\n Two hundred and ninety (290) were enrolled from the Kilifi Health and Demographic Surveillance System (HDSS). Enrollment began on 26^th September 2023 and the last participant received their last vaccine dose on 29^th December 2023.</p>\n<p>\n There was one withdrawal just prior to administration of the second vaccine dose. The participant opted not to have the vaccine administered out of personal choice. He did not exit the study, however.  There were also four (4) participants who were lost to follow-up despite all efforts to locate them. One of the participants is in legal custody while three moved outside the study area for work. The last participant last visit (LPLV) was on the 31^st of August 2024.  Participants made a total of seven study visits including screening, enrollment, vaccination, safety and reactogenicity visits, booster vaccination visit, repeat safety, immunogenicty and reactogenicity visits. Additionally, study staff had virtual contact with participants in the seven days following a vaccination visit. </p>\n<p>\n Safety profile of both vaccine regimens was evaluated through the collection and reporting of both solicited and unsolicited adverse reaction in the three months subsequent to administration of the investigational products. Information and follow-up for serious adverse events (SAE’s) was collected for the entire duration of a participant’s study involvement.</p>\n<p>\n There were two SAEs at the Kenyan site and a SUSAR (resulting in death of a participant), reported at the Tanzanian site. Neither the SAEs nor the SUSAR were related to study procedures or participation. All safety reports were submitted to the respective ethical and regulatory authorities as well as the DSMB.</p>\n<p>\n There was one substantive protocol amendment made in May 2024. The amendment sought to set up an additional cohort that would receive a vaccine optimized against the Omicron XBB 1.5 variant of SARS-CoV-2. However, this arm of the study did not proceed as the funder opted not to continue with that study arm.  The the declaration by WHO that COVID-19 was no longer a public health emergency of international concern, informed the decision by the funder.  There was one pregnancy reported and resulted in a positive outcome with a healthy child delivered with no congenital anomalies.</p>\n<p>\n The data safety monitoring board (DSMB) had three meetings and recommended the study procced without any changes.</p>\n<p>\n All protocol deviations and violation that occurred in the study were reported and uploaded onto the PPB portal. Response letters were received from SERU for all reported protocol deviations /violation.</p>\n<p>\n In conclusion, both the original monovalent and the bivalent studied vaccine were well tolerated. Preliminary data point to a robust humoral immune response against the vaccine antigens. Unblinded data will soon be available to compare the immune responses of each vaccine</p>\n
      • implication_results<p>\n <span data-teams=\"true\">The safety profile for both vaccines is comparable. There were no safety signals in the entire cohort. As soon as immunogenicity data are available we will update on the impact to policy around vaccination against COVID-19. </span></p>\n
      • quantity_imported500 BNT162B2 Monovalent,687 BNT162b2 Bivalent,250 XBB1.5
      • quantity_dispensed293 Monovalent,288 Bivalent ,0 XXB
      • quantity_destroyedAwaiting Feedback from the PPB Inspector
      • quantity_exported0
      • balance_site207 Monovalent,399 bivalent and 250 XBB
      • final_date0000-00-00
      • modified2025-07-13 18:29:26
      • created2023-04-14 11:56:10
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id925
        • application_id1257
        • given_nameNDUNGU
        • middle_name
        • family_nameFRANCIS
        • qualificationPh.D.in immunology
        • professional_address230
        • telephone+254715279268
        • emailFNdungu@kemri-wellcome.org
        • created2023-04-14 14:02:21
        • modified2023-07-06 12:01:13
      • 1(array)
        • id926
        • application_id1257
        • given_nameSaid
        • middle_name
        • family_nameJongo
        • qualificationMMed,PHD
        • professional_address78373
        • telephone+255714939831
        • emailSaid Jongo <sjongo@ihi.or.tz>
        • created2023-04-18 08:21:23
        • modified2023-07-06 12:01:13
    • SiteDetail(array)
      • 0(array)
        • id1486
        • application_id1257
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2023-04-14 14:02:21
        • modified2023-07-06 12:01:13
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id660
        • application_id1257
        • sponsorUniversity of Oxford
        • sponsor_typeResearch Institution
        • contact_personProf. Phillip Bejon
        • address230
        • telephone_number+254 709 983 549
        • fax_number
        • cell_number+254 709 983 549
        • email_addresspbejon@kemri-wellcome.org
        • created2023-04-14 14:02:21
        • modified2023-07-06 12:01:13
  • 4(array)
    • Application(array)
      • id387
      • user_id32
      • trial_status_id5
      • abstract_of_study<div>\n  </div>\n<div>\n Short Title: IVERMAL study</div>\n<div>\n  </div>\n<div>\n Background and rationale: In western Kenya the prevalence of malaria in <5 year olds has fallen from 70% in 1997 to 40% in 2008, where it has now stagnated. Innovative approaches are needed to continue towards elimination. Ivermectin is a broad spectrum antiparasitic endectocide widely used for the control of onchocerciasis and lymphatic filariasis at a dose of 150-200 mcg/kg. Ivermectin at this dose has a potent, but short-lived effect for 6-11 days on mosquito survival, egg-laying, and parasite sporogony. Higher doses are needed to prolong its mosquitocidal effects. Regulatory studies have shown ivermectin is very well tolerated and safe even up to 2,000 mcg/kg. We will conduct dose finding studies to evaluate the transmission blocking effect of high-dose ivermectin to define the optimal dose for future use of ivermectin in combination with artemisinin-based combination therapy (ACT) for mass drug administration (MDA) for malaria in Kenya. This study explores a research question of global relevance. A prolonged transmission blocking effect of ivermectin could have substantial consequences for malaria control in the next decades. We expect the results to inform the national regulator in Kenya, national malaria control programs in malaria endemic countries, to inform WHO guidelines, and to contribute to the regulatory process.</div>\n<div>\n  </div>\n<div>\n Primary objective: To determine the safety and efficacy of ivermectin 0, 300, 600 mcg/kg/day for 3 days, when provided with a standard 3-day course of dihydroartemisinin-piperaquine (DP) for uncomplicated malaria, on 14-day mosquito survival after feeding experiment performed at 7 days after treatment.</div>\n<div>\n Hypothesis: High dose ivermectin at 600 mcg/kg daily for 3 days is well tolerated and safe and will have a longer lasting mosquitocidal effect and a greater potential impact on malaria transmission.</div>\n<div>\n  </div>\n<div>\n Overview Study Design: Double-blind placebo-controlled, parallel-group, 3-arm, superiority trial to determine the effect of different doses of ivermectin on mosquito survival. The unit of randomization will be the patient, and the unit of analysis will be the mosquito. The primary endpoint will be mosquito survival 14 days after a feed on blood from a patient who has started ivermectin 7 days earlier (i.e. about 5 days after the last dose of ivermectin with a 3-day regimen administering ivermectin at 0, 24, and 48 hours [days 0, 1 and 2]). Because mosquito feeding involves approximately 100 mosquitoes per feed, the study will use a cluster randomized design with the patient as the cluster unit. The study will have a nested rich pharmacokinetic component in the first 12 patients per study arm, and a sparse sampling population pharmacokinetic component in the remaining patients. The study will also compare the potential modifying effect of the method of feeding by comparing the mosquitocidal effect of ivermectin with membrane versus direct skin feeding.</div>\n<div>\n Sites: The study will be conducted in the Provincial Hospital in Kisumu, western Kenya recently renamed to the Jaramogi Oginga Odinga Teaching and Referral Hospital (JOOTRH). Dependent on the recruitment rate, enrolment will be expanded to up to 3 other hospitals in Kisumu and Siaya counties.</div>\n<div>\n Study Population: Adults with uncomplicated falciparum malaria attending out-patient clinics.</div>\n<div>\n  </div>\n<div>\n Study Interventions: 1. Dihydroartemisinin-piperaquine (DP) alone, DP plus ivermectin 0 mcg/kg/day for 3 days (“placebo” arm); 2. DP plus ivermectin 300 mcg/kg/day plus 300 mcg/kg/day ivermectin-placebo for 3 days (“300 mcg/kg” arm); 3. DP plus ivermectin 600 mcg/kg/day (“600 mcg/kg” arm).</div>\n<div>\n Outcome Measures: Primary efficacy outcome: Mosquito survival: Survival of mosquitoes at 14 days after feeding on blood taking from study participants who started the 3-day ivermectin and DP regimen 7 days earlier. Primary safety outcome measure: Mydriasis quantitated by pupillometry. Key secondary safety outcome: QTc(F) prolongation by ECG.</div>\n<div>\n  </div>\n<div>\n Follow-up procedures: Treatment visits on day 1 and 2. Post-treatment follow-up at day 2 (+4 hours after last dose of ivermectin), days 7, 10, 14, 21, and 28.</div>\n<div>\n Sample size: Main trial: 141 participants (47 per arm); Rich pharmacokinetic study: 36 participants (12 per arm); direct feeding vs membrane feeding 27 participants (9 per arm, day 7 post ivermectin only).</div>\n<div>\n  </div>\n<div>\n Data Analysis: Primary outcomes will be summarised by number (%) of events and analysed using a Generalized Estimating Equations (GEE) model with binomial distribution and log link function that includes treatment as a single predictor taking the cluster design into account, which will generate risk ratios together with their 95% confidence intervals of having a primary endpoint between two active dose groups and the placebo group. Exchangeable covariance structure will be used. The primary endpoint analysis will be based on the ITT population.</div>\n<div>\n  </div>\n<div>\n Partner institutions: KEMRI and CDC Collaboration, Kisumu, western Kenya; Kenya Ministry of Health, Liverpool School of Tropical Medicine; US Centers for Disease Control and Prevention</div>\n<div>\n  </div>\n<div>\n Funding: Malaria Eradication Scientific Alliance (MESA) which is funded through a grant from the Bill and Melinda Gates Foundation.</div>\n
      • study_title<p>\n <font face=\"Arial, sans-serif\"><span style=\"line-height: 18.3999996185303px;\"><b>Efficacy and safety of high-dose Ivermectin for reducing malaria transmission: A dose finding study</b></span></font></p>\n
      • laymans_summary<p>\n --</p>\n
      • short_titleIVERMAL study
      • protocol_noECCT/15/02/03
      • version_no1.4
      • date_of_protocol27-01-2015
      • study_drugIvermectin
      • disease_conditionMalaria
      • 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_nameIvermectin
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addresstsang@kemricdc.org
      • applicant_covering_letter1
      • applicant_protocol1
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      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries0
      • applicant_addendum0
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      • applicant_complete_form(null)
      • applicant_impd0
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      • applicant_gcp_training1
      • applicant_dsmb_charter0
      • applicant_detailed_budget1
      • applicant_indemnity_pi0
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      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist0
      • statistical_analysis_plan1
      • applicant_contractual_agreement0
      • declaration_applicantTony Sang
      • declaration_date116-02-2015
      • declaration_principal_investigatorMenno Smit
      • declaration_date216-02-2015
      • placebo_presentYes
      • study_objectives<div>\n The overall aim of the study is to compare the effect of 3-day courses with ivermectin 0, 300, 600 mcg/kg/day when given in combination with standard 3-day course of dihydroartemisinin-piperaquine, on mosquito survival.</div>\n<div>\n  </div>\n<div>\n PRIMARY OBJECTIVE</div>\n<div>\n  </div>\n<div>\n To determine the safety and efficacy of ivermectin 0, 300, 600 mcg/kg/day for 3 days, when provided with a standard 3-day course of dihydroartemisinin-piperaquine (DP) for uncomplicated malaria, on 14-day mosquito survival after feeding experiment performed at 7 days after treatment (i.e. 5 days after the last dose of ivermectin).</div>\n<div>\n  </div>\n<div>\n SECONDARY OBJECTIVES</div>\n<div>\n  </div>\n<div>\n 1. To determine the effect of different doses of ivermectin on oocyst and sporozoite rates.</div>\n<div>\n 2. To determine the effect of different doses of ivermectin on other ectoparasites (e.g. head lice, scabies).</div>\n<div>\n 3. To determine the pharmacokinetic profile of the different ivermectin regimens</div>\n<div>\n 4. To determine if ivermectin interacts with the pharmacokinetics of piperaquine</div>\n<div>\n 5. To determine whether the addition of ivermectin to DP interacts with the ability of DP to clear asexual and sexual stage parasites</div>\n<div>\n 6. To determine the role of genetic variants of CYP3A4 activity in metabolizing ivermectin</div>\n<div>\n 7. To determine the effect of direct feeding versus membrane feeding on mosquito surviv</div>\n
      • principal_inclusion_criteria<div>\n •<span class=\"Apple-tab-span\" style=\"white-space: pre;\"> </span>Asymptomatic, uncomplicated Plasmodium falciparum infection</div>\n<div>\n •<span class=\"Apple-tab-span\" style=\"white-space:pre\"> </span>Positive malaria microscopy or malaria RDT (pLDH)</div>\n<div>\n •<span class=\"Apple-tab-span\" style=\"white-space:pre\"> </span>Age: 18-50 years</div>\n<div>\n •<span class=\"Apple-tab-span\" style=\"white-space:pre\"> </span>Provide written informed consent</div>\n<div>\n •<span class=\"Apple-tab-span\" style=\"white-space:pre\"> </span>Agree to be able to travel to clinic on days: 1, 2, 7, 10, 14, 21, and 28</div>\n<div>\n  </div>\n<div>\n  </div>\n<p>\n  </p>\n
      • principal_exclusion_criteria<div>\n  </div>\n<p>\n •<span class=\"Apple-tab-span\" style=\"white-space:pre\"> </span>Signs or symptoms of severe malaria</p>\n<div>\n •<span class=\"Apple-tab-span\" style=\"white-space:pre\"> </span>Unable to provide written informed consent</div>\n<div>\n •<span class=\"Apple-tab-span\" style=\"white-space:pre\"> </span>For women: pregnancy or lactation</div>\n<div>\n •<span class=\"Apple-tab-span\" style=\"white-space:pre\"> </span>Hypersensitivity to ivermectin or DP</div>\n<div>\n •<span class=\"Apple-tab-span\" style=\"white-space:pre\"> </span>Qtc > 460 ms on ECG</div>\n<div>\n •<span class=\"Apple-tab-span\" style=\"white-space:pre\"> </span>Body Mass Index (BMI) below 16 or above 32 kg/m2</div>\n<div>\n •<span class=\"Apple-tab-span\" style=\"white-space:pre\"> </span>Haemoglobin concentration below 9 g/dL</div>\n<div>\n •<span class=\"Apple-tab-span\" style=\"white-space:pre\"> </span>Taken ivermectin in the last month</div>\n<div>\n •<span class=\"Apple-tab-span\" style=\"white-space:pre\"> </span>Taken dihydroartemisinin-piperaquine in the last 12 weeks</div>\n<div>\n •<span class=\"Apple-tab-span\" style=\"white-space:pre\"> </span>Loa loa as assessed by travel history to Angola, Cameroon, Chad, Central African Republic, Congo, DR Congo, Equatorial Guinea, Ethiopia, Gabon, Nigeria and Sudan</div>\n<div>\n •<span class=\"Apple-tab-span\" style=\"white-space:pre\"> </span>History and/or symptoms indicating chronic illness</div>\n<div>\n •<span class=\"Apple-tab-span\" style=\"white-space:pre\"> </span>Current use of tuberculosis or anti-retroviral medication</div>\n<div>\n •<span class=\"Apple-tab-span\" style=\"white-space:pre\"> </span>Previously enrolled in the same study</div>\n<div>\n  </div>\n
      • primary_end_points<ul>\n <li>\n Mosquito survival: Survival of mosquitoes at 14 days after feeding on blood taking from study participants who started the 3-day ivermectin and DP regimen 7 days earlier</li>\n</ul>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic1
      • scope_bioequivalence0
      • scope_dose_response1
      • scope_pharmacogenetic1
      • 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<div>\n Study Coordinator, Menno Smit</div>\n<div>\n Project manager, Elizabeth Nyothach</div>\n<div>\n Pharmacist, Tony Sang</div>\n<div>\n Regulatory Officer, Juliana Kisakye</div>\n<div>\n Clinical Officer 1, name TBC</div>\n<div>\n Clinical Officer 2, name TBC</div>\n<div>\n Clinical Officer 3, name TBC</div>\n<div>\n Microscopist 1, name TBC</div>\n<div>\n Microscopist 2, name TBC</div>\n<div>\n Phlebotomist 1, name TBC</div>\n<div>\n Laboratory technician 1, TBC</div>\n<div>\n Entomology laboratory assistant 1, TBC</div>\n<div>\n Entomology laboratory assistant 2, TBC</div>\n<div>\n Data manager, TBC</div>\n<div>\n Data clerk, TBC</div>\n<div>\n  </div>\n<div>\n The study will be conducted in the Provincial Hospital in Kisumu, western Kenya recently renamed to the Jaramogi Oginga Odinga Teaching and Referral Hospital (JOOTRH). JOOTRH is a major tertiary care hospital with self-contained paediatric, medical, and obstetric wards, as well as an intensive care unit with mechanical ventilators and telemetry capabilities. Almost 25,000 outpatients are treated for clinical malaria at JOOTRH annually, of which one-third are laboratory confirmed. Approximately 20% of these patients are 18-50 years old. On a daily basis around 4.6 adults (18–50 years old) test positive for malaria in JOOTRH’s outpatient clinic.</div>\n<div>\n  </div>\n
      • other_details_explanation<p>\n The study involves patients with malaria.</p>\n
      • other_details_regulatory_notapproved<p>\n None</p>\n
      • other_details_regulatory_approved<div style=\"margin-left: 40px;\">\n KEMRI  SSC- 12 Feb 2015</div>\n<div style=\"margin-left: 40px;\">\n  </div>\n<div style=\"margin-left: 40px;\">\n Liverpool School of Tropical Medicine  -   23-Jan-2015</div>\n<div>\n  </div>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n None</p>\n
      • estimated_duration4-6 months
      • 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_countriesNo
      • multiple_member_states
      • number_of_sitesOne main site and three potential expansion sites
      • multi_country_list
      • data_monitoring_committeeYes
      • total_enrolment_per_siteJaramogi Oginga Odinga Teaching & Referral Hospital : 0-141\nKisumu District Hospital : 0-141\nSiaya District Hospital : 0-141\nV District Hospital: 0-141
      • total_participants_worldwide141
      • 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_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • 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_nameMenno
      • investigator1_middle_nameRoderick
      • investigator1_family_nameSmit
      • investigator1_qualificationMD, MPH
      • investigator1_professional_addressKEMRI/CDC, P.O. Box 1578, Kisumu 40100, Kenya
      • investigator1_telephone+254 703 991513
      • investigator1_emailmenno.smit@liverpool.ac.uk
      • organisations_transferred_Yes
      • number_participants141
      • notification
      • approval_date26-03-2015
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted26-01-2021
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonThe study has now been approved
      • final_report<div>\n <strong>Summary</strong></div>\n<div>\n Background Ivermectin is being considered for mass drug administration for malaria due to its ability to kill mosquitoes feeding on recently treated individuals. However, standard, single doses of 150–200 μg/kg used for onchocerciasis and lymphatic filariasis have a short-lived mosquitocidal effect (<7 days). Because ivermectin is well tolerated up to 2000 μg/kg, we aimed to establish the safety, tolerability, and mosquitocidal efficacy of 3 day courses of high-dose ivermectin, co-administered with a standard malaria treatment.</div>\n<div>\n  </div>\n<div>\n <strong>Methods</strong> We did a randomised, double-blind, placebo-controlled, superiority trial at the Jaramogi Oginga Odinga Teaching and Referral Hospital (Kisumu, Kenya). Adults (aged 18–50 years) were eligible if they had confirmed symptomatic uncomplicated Plasmodium falciparum malaria and agreed to the follow-up schedule. Participants were randomly assigned (1:1:1) using sealed envelopes, stratified by sex and body-mass index (men: <21 vs ≥21 kg/m²; women: <23 vs ≥23 kg/m²), with permuted blocks of three, to receive 3 days of ivermectin 300 μg/kg per day, ivermectin 600 μg/kg per day, or placebo, all co-administered with 3 days of dihydroartemisinin-piperaquine. Blood of patients taken on post-treatment days 0, 2 + 4 h, 7, 10, 14, 21, and 28 was fed to laboratory-reared Anopheles gambiae sensu stricto mosquitoes, and mosquito survival was assessed daily for 28 days after feeding. The primary outcome was 14-day cumulative mortality of mosquitoes fed 7 days after ivermectin treatment (from participants who received at least one dose of study medication). The study is registered with ClinicalTrials.gov, number NCT02511353.</div>\n<div>\n  </div>\n<div>\n <strong>Findings</strong> Between July 20, 2015, and May 7, 2016, 741 adults with malaria were assessed for eligibility, of whom 141 were randomly assigned to receive ivermectin 600 μg/kg per day (n=47), ivermectin 300 μg/kg per day (n=48), or placebo (n=46). 128 patients (91%) attended the primary outcome visit 7 days post treatment. Compared with placebo, ivermectin was associated with higher 14 day post-feeding mosquito mortality when fed on blood taken 7 days post treatment (ivermectin 600 μg/kg per day risk ratio [RR] 2·26, 95% CI 1·93–2·65, p<0·0001; hazard ratio [HR] 6·32,</div>\n<div>\n 4·61–8·67, p<0·0001; ivermectin 300 μg/kg per day RR 2·18, 1·86–2·57, p<0·0001; HR 4·21, 3·06–5·79, p<0·0001). Mosquito mortality remained significantly increased 28 days post treatment (ivermectin 600 μg/kg per day RR 1·23, 1·01–1·50, p=0·0374; and ivermectin 300 μg/kg per day 1·21, 1·01–1·44, p=0·0337). Five (11%) of 45 patients receiving ivermectin 600 μg/kg per day, two (4%) of 48 patients receiving ivermectin 300 μg/kg per day, and none of 46 patients receiving placebo had one or more treatment-related adverse events.</div>\n<div>\n  </div>\n<div>\n <strong>Interpretation </strong>Ivermectin at both doses assessed was well tolerated and reduced mosquito survival for at least 28 days</div>\n<div>\n after treatment. Ivermectin 300 μg/kg per day for 3 days provided a good balance between efficacy and tolerability, and</div>\n<div>\n this drug shows promise as a potential new tool for malaria elimination.</div>\n
      • implication_results(null)
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      • modified2021-01-26 12:43:18
      • created2015-02-13 17:23:59
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        • id261
        • application_id387
        • given_nameMenno
        • middle_nameRoderick
        • family_nameSmit
        • qualificationMD, MPH
        • professional_addressKEMRI/CDC, P.O. Box 1578, Kisumu 40100, Kenya
        • telephone+254 703 991513
        • emailmenno.smit@liverpool.ac.uk
        • created2015-02-13 17:33:17
        • modified2021-01-26 12:43:18
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        • site_nameJaramogi Oginga Odinga Teaching and Referral Hospital (JOOTRH)
        • physical_addressKakamega Road, Kisumu, Kenya
        • contact_detailsKEMRI/CDC-CRC, P.O. Box 1578, Kisumu 40100, Kenya
        • contact_personMenno Smit
        • site_capacity(null)
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        • created2015-02-13 17:33:17
        • modified2021-01-26 12:43:18
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          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 1(array)
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        • application_id387
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        • site_nameKisumu District Hospital (KDH),
        • physical_addressKisumu
        • contact_detailsP. O. Box 4685, Kisumu
        • contact_personMenno Smit
        • site_capacity(null)
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        • created2015-02-17 17:10:55
        • modified2021-01-26 12:43:18
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          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
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        • site_capacity(null)
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        • created2015-02-17 17:10:55
        • modified2021-01-26 12:43:18
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          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
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        • application_id387
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        • site_nameVihiga District Hospital
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        • contact_detailsP.O. Box 1069, Vihiga
        • contact_personMenno Smit
        • site_capacity(null)
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        • created2015-02-17 17:10:55
        • modified2021-01-26 12:43:18
        • County(array)
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          • created2012-06-15 10:26:37
          • modified2012-06-15 10:26:37
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        • id201
        • application_id387
        • sponsorLiverpool School of Tropical Medicine
        • sponsor_typeResearch Institution
        • contact_personMenno Smit
        • addressKEMRI/CDC, P.O. Box 1578, Kisumu 40100, Kenya
        • telephone_number+254 703 991513
        • fax_number
        • cell_number+254 703 991513
        • email_addressmenno.smit@liverpool.ac.uk
        • created2015-02-13 17:33:17
        • modified2021-01-26 12:43:18
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    • 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