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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
      • applicant_opinion_letter1
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      • applicant_participating_countries(null)
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      • applicant_complete_form(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
      • 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)
      • modified2024-10-11 21:38:40
      • 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)
      • id1175
      • user_id693
      • trial_status_id2
      • abstract_of_study<p align=\"center\" style=\"margin-left:224.7pt;\">\n <strong>Ab</strong><strong>stract of </strong><strong>the  study: </strong></p>\n<p style=\"margin-left:5.9pt;\">\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-left:5.9pt;\">\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-left:5.9pt;\">\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-left:5.9pt;\">\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-left:5.9pt;\">\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-left:5.9pt;\">\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-left:5.9pt;\">\n <strong>Ma</strong><strong>in </strong><strong>O</strong><strong>b</strong><strong>j</strong><strong>e</strong><strong>c</strong><strong>t</strong><strong>i</strong><strong>v</strong><strong>e</strong><strong>s</strong>: <strong>Pha</strong><strong>se </strong><strong>2</strong><strong>:</strong></p>\n<p style=\"margin-left:5.9pt;\">\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-left:5.9pt;\">\n • Anemia in subjects with sickle cell disease (SCD)</p>\n<p style=\"margin-left:5.9pt;\">\n • Safety</p>\n<p style=\"margin-left:5.9pt;\">\n Phase 3: 1. To determine the effect of mitapivat versus placebo on:</p>\n<p style=\"margin-left:5.9pt;\">\n • Anemia in subjects with sickle cell disease (SCD)</p>\n<p style=\"margin-left:5.9pt;\">\n • Sickle cell pain crises (SCPCs) in subjects with SCD</p>\n<p style=\"margin-left:5.9pt;\">\n Secondary objectives:</p>\n<p style=\"margin-left:5.9pt;\">\n <strong>Pha</strong><strong>se </strong><strong>2</strong><strong>:</strong></p>\n<p style=\"margin-left:5.9pt;\">\n 1. To evaluate the effect of 2 doses of mitapivat versus placebo on:</p>\n<p style=\"margin-left:29.9pt;\">\n <img height=\"4\" src=\"file:///C:/Users/kimettjc/AppData/Local/Temp/msohtmlclip1/01/clip_image001.gif\" width=\"4\" />Anemia</p>\n<p style=\"margin-left:29.9pt;\">\n <img height=\"4\" src=\"file:///C:/Users/kimettjc/AppData/Local/Temp/msohtmlclip1/01/clip_image002.gif\" width=\"4\" />Markers of hemolysis and erythropoiesis</p>\n<p style=\"margin-left:29.9pt;\">\n <img height=\"4\" src=\"file:///C:/Users/kimettjc/AppData/Local/Temp/msohtmlclip1/01/clip_image003.gif\" width=\"4\" />Patient-reported fatigue</p>\n<p style=\"margin-left:29.9pt;\">\n <img height=\"4\" src=\"file:///C:/Users/kimettjc/AppData/Local/Temp/msohtmlclip1/01/clip_image004.gif\" width=\"4\" />Sickle cell pain crises (SCPCs)</p>\n<p style=\"margin-left:5.9pt;\">\n 2. To evaluate the pharmacokinetic and pharmacodynamic effects of mitapivat.</p>\n<p style=\"margin-left:5.9pt;\">\n <strong>Pha</strong><strong>se </strong><strong>3</strong><strong>:</strong></p>\n<p style=\"margin-left:5.9pt;\">\n 1. To evaluate the effect of mitapivat versus placebo on:</p>\n<p style=\"margin-left:5.9pt;\">\n • Anemia in subjects with SCD</p>\n<p style=\"margin-left:5.9pt;\">\n • Markers of hemolysis</p>\n<p style=\"margin-left:5.9pt;\">\n • Markers of erythropoiesis</p>\n<p style=\"margin-left:5.9pt;\">\n • Patient-reported fatigue</p>\n<p style=\"margin-left:5.9pt;\">\n • Additional clinical efficacy measures related to SCPC</p>\n<p style=\"margin-left:5.9pt;\">\n <strong>M</strong><strong>e</strong><strong>t</strong><strong>h</strong><strong>o</strong><strong>d</strong><strong>s</strong><strong>:</strong></p>\n<p style=\"margin-left:5.9pt;\">\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-left:5.9pt;\">\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-left:5.9pt;\">\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-left:5.9pt;\">\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-left:5.9pt;\">\n <strong>S</strong><strong>tudy </strong><strong>o</strong><strong>u</strong><strong>tc</strong><strong>o</strong><strong>m</strong><strong>e</strong><strong>s</strong><strong>:</strong></p>\n<p style=\"margin-left:5.9pt;\">\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-left:5.9pt;\">\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-left:5.9pt;\">\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<p>\n  </p>\n
      • study_title<p>\n 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</p>\n
      • laymans_summary<p>\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>\n  </p>\n<p>\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>\n  </p>\n<p>\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. Abstract</p>\n
      • short_titleAgios Study
      • protocol_noECCT/22/10/02
      • version_noAmendment 1 (V1.0)
      • date_of_protocol09-03-2022
      • study_drugMitapivat _ Dr Oyieko Janet
      • 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
      • 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_applicantMillicent Aketch
      • declaration_date114-10-2022
      • declaration_principal_investigatorDr Ogutu Bernhards
      • declaration_date214-10-2022
      • placebo_presentYes
      • study_objectives<p>\n * Main objective:</p>\n<p>\n <strong>Phase 2:</strong></p>\n<p>\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>\n : • Anemia in subjects with sickle cell disease (SCD). and</p>\n<ul>\n <li>\n Safety </li>\n</ul>\n<p>\n  </p>\n<p>\n <strong>Safety Phase 3:</strong></p>\n<p>\n 1. To determine the effect of mitapivat versus placebo on</p>\n<p>\n : • Anemia in subjects with sickle cell disease (SCD)</p>\n<p>\n • Sickle cell pain crises (SCPCs) in subjects with SCD</p>\n<p>\n <strong>Secondary objectives:</strong></p>\n<p>\n <strong>Phase 2</strong>:</p>\n<p>\n 1. To evaluate the effect of 2 doses of mitapivat versus placebo on:</p>\n<p>\n Anemia</p>\n<p>\n Markers of hemolysis and erythropoiesis</p>\n<p>\n Patient-reported fatigue</p>\n<p>\n Sickle cell pain crises (SCPCs)</p>\n<p>\n 2. To evaluate the pharmacokinetic and pharmacodynamic effects of mitapivat.</p>\n<p>\n <strong>Phase 3</strong>:</p>\n<p>\n 1. To evaluate the effect of mitapivat versus placebo on:</p>\n<p>\n Anemia in subjects with SCD</p>\n<p>\n Markers of hemolysis Markers of erythropoiesis</p>\n<p>\n Patient-reported fatigue</p>\n<p>\n Additional clinical efficacy measures related to SCPC</p>\n
      • principal_inclusion_criteria<p style=\"margin-left:5.9pt;\">\n 1. Age ≥16 years; subjects age 16 or 17 years must physically have completed puberty.</p>\n<p style=\"margin-left:5.9pt;\">\n 2. Documented diagnosis of SCD (HbSS, HbSC, HbS/β0-thalassemia, HbS/β+ thalassemia, or other sickle cell syndrome variants).</p>\n<p>\n  3. At least 2 sickle cell pain crises (SCPCs) and no more than 10 SCPCs in the past 12 months.</p>\n<p>\n  4. Hemoglobin ≥5.5 and ≤10.5 g/dL.</p>\n<p>\n  5. If taking hydroxyurea, the hydroxyurea dose must be stable for at least 90 days before starting study drug.</p>\n<p>\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>\n 7. Other protocol-defined inclusion criteria may apply</p>\n
      • principal_exclusion_criteria<p style=\"margin-left:5.9pt;\">\n 1. Pregnant or breastfeeding.</p>\n<p style=\"margin-left:5.9pt;\">\n 2. Receiving regularly scheduled transfusions.</p>\n<p>\n  3. Hepatobiliary disorders including but not limited to significant liver disease or gallbladder disease.</p>\n<p>\n  4. Severe kidney disease.</p>\n<p>\n  5. Prior exposure to gene therapy or prior bone marrow or stem cell transplantation.</p>\n<p>\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>\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>\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>\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>\n 10. Other protocol defined exclusion criteria may apply</p>\n
      • primary_end_points<p>\n <strong>Phase 2 Primary Endpoints</strong>:</p>\n<p>\n 1. Percentage of participants with hemoglobin (Hb) response</p>\n<p>\n 2. Percentage of participants with treatment emergent adverse events (AEs) and treatment emergent serious adverse events (SAEs)</p>\n<p>\n <strong>Timepoint(s) of evaluation of this end point:</strong></p>\n<p>\n Phase 2 primary endpoint of percentage of participants with Hb response: Week 12</p>\n<p>\n Phase 2 primary endpoint of percentage of participants with treatment emergent AEs and treatment emergent SAEs: Up to Week 12</p>\n<p>\n <strong>Phase 3 Primary Endpoints</strong>:</p>\n<p>\n 1. Percentage of participants with hemoglobin (Hb) response</p>\n<p>\n 2. Annualized rate of Sickle Cell Pain Crises (SCPCs)</p>\n<p>\n <strong>Timepoint(s) of evaluation of this end point</strong>:</p>\n<ul>\n <li>\n Phase 3 primary endpoint of percentage of participants with Hb response: Week 52</li>\n <li>\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_bioequivalence1
      • 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 Kombewa Clinical Research Centre</p>\n<p>\n The KEMRI/WRP Kombewa Clinical Research Center (KCRC) is designed for large clinical trials and has a full clinical laboratory including microbiology capability. KCRC is part of The Walter Reed Project (WRP), which is a 40-year collaboration between the Kenya Medical Research Institute, (KEMRI) and the Walter Reed Army Institute of Research (WRAIR).</p>\n<p>\n The US Army Medical Research Unit in Kenya (USAMRU-K) is a WRAIR attachment stationed in Kenya with headquarters in Nairobi and field stations in Kericho and Kisumu. WRP-Kisumu conducts a wide spectrum of field and laboratory work including numerous clinical research trials. The study will be conducted at the KCRC and recruitment will occur at the Kombewa County hospital as well as in the surrounding health facilities. </p>\n<p>\n The KEMRI/WRP Clinical Research Centre in Kombewa is staffed by KEMRI/WRP qualified research personnel, some of whom will be involved with recruitment of study subjects and conduct of the study. The KCRC is located opposite the Kombewa County Hospital in Kisumu West District of Nyanza Province in Western Kenya. It is located about 40 kilometres west of Kisumu town and has previously been used as a site for many clinical trials and epidemiological studies involving both adults and children on malaria, trypanosomiasis, leishmaniasis, entomology, HIV/AIDS and arboviruses.</p>\n<p>\n INVESTIGATORS AND COORDINATORS: ROLES AND RESPONSIBILITIES</p>\n<p>\n Dr. Janet Oyieko, Principal Investigator Kombewa Clinical Research Centre: will be responsible for the overall conduct of the trial at this study site, administrative actions between WRP, Institutional Review Boards, and the sponsor, oversight of field activities and care accorded to participants. She contributed to the site protocol addendum development and may contribute to the writing of the scientific report(s). </p>\n<p>\n Dr. Jack Hutter, Associate Investigator: will be responsible for the site administrative conduct of the trial, oversight of field activities. He contributed to the protocol addendum development and may contribute to writing of scientific report(s).</p>\n<p>\n Dr. Walter Otieno, Associate Investigator: will be responsible for the clinical conduct of the trial, the care provided to participants, oversight of field activities. He contributed to the protocol addendum development and may contribute to the writing of scientific report(s).</p>\n<p>\n Dr. Valentine Sing’oei, Associate Investigator: will be responsible for the clinical conduct of the trial, the care provided to participants, oversight of field activities. She may contribute to the writing of scientific report(s).</p>\n<p>\n Dr. Michal Ohaga, Associate Investigator: will be responsible for the clinical conduct of the trial, the care provided to participants, oversight of field activities. She may contribute to the writing of scientific report(s).</p>\n<p>\n Irene Onyango- Regulatory Affairs oversight will be responsible for communication with IRBs and ECs.</p>\n<p>\n Millicent Achola - Clinical Research Coordinator; responsible for overall study coordination while working in a team environment under the direction of the investigators. Coordinating the recruiting, screening, and enrolling of study participants; arranging follow-up visits; completing and ensuring the accuracy of CRFs and regulatory documents; and ensuring the adherence to GCP guidelines.</p>\n
      • other_details_explanation<p>\n <strong>N/A</strong>, trial is being conducted in the USA</p>\n
      • other_details_regulatory_notapproved<table border=\"0\" cellpadding=\"0\" cellspacing=\"0\">\n <tbody>\n <tr>\n <td style=\"width:186px;height:13px;\">\n <p>\n Kenya </p>\n </td>\n <td style=\"width:153px;height:13px;\">\n <p>\n 01 Sep  2022 </p>\n </td>\n <td style=\"width:61px;height:13px;\">\n <p>\n 2 additional sites submitted </p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • other_details_regulatory_approved<table border=\"0\" cellpadding=\"0\" cellspacing=\"0\">\n <tbody>\n <tr>\n <td style=\"width:110px;height:13px;\">\n <p style=\"margin-left:.55pt;\">\n Regualtory</p>\n </td>\n <td colspan=\"2\" style=\"width:103px;height:13px;\">\n <p style=\"margin-left:.55pt;\">\n Approval Date</p>\n </td>\n <td colspan=\"2\" style=\"width:186px;height:13px;\">\n <p style=\"margin-left:.55pt;\">\n Number of site per Country</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:110px;height:13px;\">\n <p style=\"margin-left:.55pt;\">\n Canada</p>\n </td>\n <td colspan=\"2\" style=\"width:103px;height:13px;\">\n <p style=\"margin-left:.55pt;\">\n 16 Nov  2021</p>\n </td>\n <td colspan=\"2\" style=\"width:186px;height:13px;\">\n <p style=\"margin-left:.55pt;\">\n 4</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:110px;height:13px;\">\n <p style=\"margin-left:.55pt;\">\n United Kingdom</p>\n </td>\n <td colspan=\"2\" style=\"width:103px;height:13px;\">\n <p style=\"margin-left:.55pt;\">\n 13 Sep 2021</p>\n </td>\n <td colspan=\"2\" style=\"width:186px;height:13px;\">\n <p style=\"margin-left:.55pt;\">\n 7</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:110px;height:13px;\">\n <p style=\"margin-left:.55pt;\">\n Belgium</p>\n </td>\n <td colspan=\"2\" style=\"width:103px;height:13px;\">\n <p style=\"margin-left:.55pt;\">\n 16 Feb 2022</p>\n </td>\n <td colspan=\"2\" style=\"width:186px;height:13px;\">\n <p style=\"margin-left:.55pt;\">\n 8</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:110px;height:13px;\">\n <p style=\"margin-left:.55pt;\">\n France</p>\n </td>\n <td colspan=\"2\" style=\"width:103px;height:13px;\">\n <p style=\"margin-left:.55pt;\">\n 27 Jan 2022</p>\n </td>\n <td colspan=\"2\" style=\"width:186px;height:13px;\">\n <p style=\"margin-left:.55pt;\">\n 6</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:110px;height:13px;\">\n <p style=\"margin-left:.55pt;\">\n Germany</p>\n </td>\n <td colspan=\"2\" style=\"width:103px;height:13px;\">\n <p style=\"margin-left:.55pt;\">\n 07 Apr 2022</p>\n </td>\n <td colspan=\"2\" style=\"width:186px;height:13px;\">\n <p style=\"margin-left:.55pt;\">\n 4</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:110px;height:13px;\">\n <p style=\"margin-left:.55pt;\">\n Italy</p>\n </td>\n <td colspan=\"2\" style=\"width:103px;height:13px;\">\n <p style=\"margin-left:.55pt;\">\n 23 Feb 2022</p>\n </td>\n <td colspan=\"2\" style=\"width:186px;height:13px;\">\n <p style=\"margin-left:.55pt;\">\n 8</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:148px;height:13px;\">\n <p style=\"margin-left:.55pt;\">\n Regulatory Authority</p>\n </td>\n <td colspan=\"2\" style=\"width:90px;height:13px;\">\n <p style=\"margin-left:.55pt;\">\n Approved Date</p>\n </td>\n <td style=\"width:161px;height:13px;\">\n <p style=\"margin-left:.55pt;\">\n Number of site per country</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:148px;height:13px;\">\n <p style=\"margin-left:.55pt;\">\n Netherlands</p>\n </td>\n <td colspan=\"2\" style=\"width:90px;height:13px;\">\n <p style=\"margin-left:.55pt;\">\n 23 Dec 2021</p>\n </td>\n <td style=\"width:161px;height:13px;\">\n <p style=\"margin-left:.55pt;\">\n 1</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:148px;height:13px;\">\n <p style=\"margin-left:.55pt;\">\n Brazil</p>\n </td>\n <td colspan=\"2\" style=\"width:90px;height:13px;\">\n <p style=\"margin-left:.55pt;\">\n 21 Jan 2022</p>\n </td>\n <td style=\"width:161px;height:13px;\">\n <p style=\"margin-left:.55pt;\">\n 8</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:148px;height:13px;\">\n <p style=\"margin-left:.55pt;\">\n Israel</p>\n </td>\n <td colspan=\"2\" style=\"width:90px;height:13px;\">\n <p style=\"margin-left:.55pt;\">\n 09 Aug 2021</p>\n </td>\n <td style=\"width:161px;height:13px;\">\n <p style=\"margin-left:.55pt;\">\n 4</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:148px;height:13px;\">\n <p style=\"margin-left:.55pt;\">\n United States of America</p>\n </td>\n <td colspan=\"2\" style=\"width:90px;height:13px;\">\n <p style=\"margin-left:.55pt;\">\n 26 May 2022</p>\n </td>\n <td style=\"width:161px;height:13px;\">\n <p style=\"margin-left:.55pt;\">\n 23</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:148px;height:13px;\">\n <p>\n Turkey</p>\n </td>\n <td colspan=\"2\" style=\"width:90px;height:13px;\">\n <p>\n 04 Jul 2022 </p>\n </td>\n <td style=\"width:161px;height:13px;\">\n <p>\n 5</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:148px;height:13px;\">\n <p>\n Saudia Arabia</p>\n </td>\n <td colspan=\"2\" style=\"width:90px;height:13px;\">\n <p>\n 06Sep 2022</p>\n </td>\n <td style=\"width:161px;height:13px;\">\n <p>\n 3</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n Nigeria _ 22 Aug 2022 - sites _6 </p>\n<p>\n Kenya _ 06 Sep  2022 _ sites approved 2 out of 7 .</p>\n
      • other_details_regulatory_rejected<p style=\"margin-left:5.9pt;\">\n No Regulatory authority nor Ethics Committee has rejected this trial</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\n
      • 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_date10-02-2023
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted14-10-2022
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonThe reviewer comments have been reviewed internally and considered adequate.
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2024-10-11 21:39:39
      • created2022-09-27 09:23:19
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id852
        • application_id1175
        • given_nameJanet
        • middle_nameN
        • family_nameOyieko
        • qualificationPediatrician
        • professional_addressKEMRI_CCR
        • telephone+254721996988
        • emailJanet.Oyieko@gmail.com
        • created2022-09-27 09:24:50
        • modified2022-10-14 14:51:43
    • SiteDetail(array)
      • 0(array)
        • id1315
        • application_id1175
        • county_id42
        • site_name Kombewa Clinical Research Centre
        • physical_addressKombewa, Opposite Kombewa Sub-County Hospital
        • contact_details +254721996988
        • contact_personDr Janet Oyieko
        • site_capacity(null)
        • misc(null)
        • created2022-09-27 09:24:50
        • modified2022-10-14 14:51:43
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 1(array)
        • id1316
        • application_id1175
        • county_id42
        • site_nameVictoria Biomedical Research Institute
        • physical_addressButere County Hospital, Postal Code 40100, Kisumu, Kenya
        • contact_detailsTel: +254 720 597654 P.O. Box 7180
        • contact_personDr. Lucas Otieno Tina
        • site_capacity(null)
        • misc(null)
        • created2022-09-27 12:42:07
        • modified2022-10-14 14:51:43
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 2(array)
        • id1317
        • application_id1175
        • county_id47
        • site_nameKEMRI/CRDR
        • physical_address Kenyatta National Hospital Off Hospital Road, CRDR
        • contact_detailsTel:+254790484654, P.O Box 47855-00100
        • contact_personProf. Videlis Nduba
        • site_capacity(null)
        • misc(null)
        • created2022-09-27 12:42:07
        • modified2022-10-14 14:51:43
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 3(array)
        • id1318
        • application_id1175
        • county_id41
        • site_nameKEMRI Siaya Clinical Research Annex
        • physical_address KEMRI Clinical research Annex,Siaya County Hospital,
        • contact_detailsTel: +254722205901, P.O Box 144-40600
        • contact_personProf. Videlis Nduba
        • site_capacity(null)
        • misc(null)
        • created2022-09-27 12:42:07
        • modified2022-10-14 14:51:43
        • County(array)
          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
      • 4(array)
        • id1319
        • application_id1175
        • county_id47
        • site_nameGertrude’s Children’s Hospital
        • physical_addressGertrude’s Children’s Hospital, 34 Muthaiga Road
        • contact_details+254 721245721
        • contact_personProf. Jessie Githanga
        • site_capacity(null)
        • misc(null)
        • created2022-09-27 12:42:07
        • modified2022-10-14 14:51:43
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 5(array)
        • id1320
        • application_id1175
        • county_id42
        • site_nameKEMRI Kondele Children\'s Hospital
        • physical_addressKondele Children\'s Hospital
        • contact_details+254714481488
        • contact_personDr Godfrey Allan Otieno
        • site_capacity(null)
        • misc(null)
        • created2022-09-27 12:42:07
        • modified2022-10-14 14:51:43
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 6(array)
        • id1321
        • application_id1175
        • county_id47
        • site_nameStrathmore University Medical Centre
        • physical_addressStrathmore University Medical Centre, Ole Sangale Rd
        • contact_details+254733813613
        • contact_personDr Bernhards Ogutu
        • site_capacity(null)
        • misc(null)
        • created2022-09-27 12:42:07
        • modified2022-10-14 14:51:43
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
    • Sponsor(array)
      • 0(array)
        • id606
        • application_id1175
        • 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
        • created2022-09-27 09:24:50
        • modified2022-10-14 14:51:43
  • 2(array)
    • Application(array)
      • id1172
      • user_id781
      • trial_status_id(null)
      • abstract_of_study<p>\n <strong>Introduction - </strong>birth asphyxia remain a leading cause of neonatal mortality and morbidity in Kenya. The primary cause of birth asphyxia is poor perfusion of the fetus by the placenta during labor, which may lead to non-reassuring fetal status (fetal distress), hypoxic injury, or death.  Currently, there are no evidence-based therapies to improve fetal perfusion during labor in cases of severe fetal compromise.  In low-resource settings, intrapartum fetal monitoring may not be available to detect fetal distress and access to urgent operative delivery to relieve distress may be limited.  Feasible therapies for use in low-resource settings to reduce deaths from birth asphyxia are urgently needed.  Sildenafil citrate is a novel approach to reduce fetal distress during labor.  Sildenafil citrate is a phosphodiesterase type-5 inhibitor that acts as a vasodilator that is known to increase uteroplacental blood flow. It is unknown if intrapartum sildenafil citrate would be feasible or effective in low-resource settings. We hypothesize that treatment with sildenafil citrate during labor will decrease stillbirth and early neonatal mortality in low-resource settings, but, first, a feasibility trial to inform the design of a definitive trial appropriate for low-resource settings is necessary.  The specific aims correspond to feasibility objectives that will inform the design and implementation of a large randomized controlled trial of intrapartum sildenafil citrate.</p>\n<p>\n <strong>Objective</strong>: To assess the feasibility of drug administration during early labor, patient acceptance of the intervention, and to confirm the safety of sildenafil citrate in pregnant women in a low-resource setting</p>\n<p>\n <strong>Study design</strong>: Double blinded, placebo-controlled randomized feasibility trial</p>\n<p>\n <strong>Study Setting</strong>; Nakuru county and referral hospital in the Mother and Baby unit</p>\n<p>\n <strong>Methods: </strong>Pregnant women aged 18 to 50years who present to the study health care facilities in early labor will be screened for study eligibility. Eligible women who consent  and if husbands are available have consented for the study will be randomized to receive sildenafil 50 mg orally every 8 hours up to a total of 3 doses or a placebo every 8 hours up to a total of 3 doses during the course of labor. All additional care of the mother and infant will provided according to the local standard of care.  The number and timing of sildenafil doses as well as length of labor in participants will be reported.  The intervention will be considered acceptable if 50% of eligible women enroll.  All enrolled women will be monitored by clinical treatment team for symptoms presenting potential side effects of sildenafil occurring from the time of dose administration to 8 hours following the last dose.  All enrolled neonates will be monitored for neonatal hypoxemia. NICU admission rates in all participants will also be recorded and features of hypoxic ischemic injury will be determined using Sarnat examination. Data will be analyzed using SPSS version 24</p>\n
      • study_title<p align=\"center\">\n <strong>Sildenafil citrate to improve maternal and neonatal outcomes in low-resource settings: </strong></p>\n<p align=\"center\">\n <strong>a randomized feasibility trial</strong></p>\n
      • laymans_summary<p>\n Birth asphyxia, defined by the WHO as failure to establish spontaneous breathing at birth, accounts for nearly 1 million neonatal deaths annually.^1,2  Birth asphyxia is the second most common cause of neonatal mortality worldwide.^1,2The primary cause of birth asphyxia is poor perfusion of the fetus by the placenta during labor, which may lead to non-reassuring fetal status (fetal distress), hypoxic injury, or death.  Currently, there are no evidence-based therapies to improve fetal perfusion during labor in cases of severe fetal compromise.  Urgent operative delivery is the only option to restore gas exchange to the baby.  In low-resource settings, intrapartum fetal monitoring may not be available to detect fetal distress and access to urgent operative delivery to relieve distress may be limited.  Thus, a high burden of death due to birth asphyxia is carried in the developing world. </p>\n<p>\n Feasible therapies for use in low-resource settings to reduce deaths from birth asphyxia are urgently needed.  Sildenafil citrate is a novel approach to reduce fetal distress during labor</p>\n
      • short_titleSildenafil citrate to improve
      • protocol_noECCT/23/05/06
      • version_no1
      • date_of_protocol07-02-2022
      • study_drugSildenafil Citrate
      • disease_conditionBirth asphyxia
      • 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_nameSildenafil citrate
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressamosotara@yahoo.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
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      • applicant_signed_declaration1
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      • applicant_indemnity_cover1
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      • applicant_detailed_budget1
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      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
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      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantAMOS MAGEMBE OTARA
      • declaration_date129-03-2023
      • declaration_principal_investigatorAMOS MAGEMBE OTARA
      • declaration_date229-03-2023
      • placebo_presentYes
      • study_objectives<p>\n <strong>1: To describe the current practices and baseline healthcare provider knowledge regarding fetal heart rate monitoring and indications for operative delivery in a low-resource settings.</strong></p>\n<p>\n <strong>2: To determine the incidence of key maternal and neonatal outcomes that may be targeted in a large definitive trial of intrapartum sildenafil citrate. </strong></p>\n<p>\n <strong>3:To assess the feasibility of drug administration during early labor, patient acceptance of the intervention, and to confirm safety of sildenafil citrate in pregnant women in a low-resource setting.  </strong></p>\n<p>\n  </p>\n
      • principal_inclusion_criteria<ul>\n <li>\n Pregnant women presenting in early labor with a term pregnancy (≥37 weeks gestation)\n <ul>\n <li>\n Early labor will be defined as cervical dilation less than or equal to 6 cm</li>\n <li>\n Gestational age will be calculated from the most reliable variable using the following hierarchy of reliability: 1) gestational dating ultrasound completed at any time during the pregnancy (with preference to the earliest exam), 2) date of last menstrual period if menses are regular</li>\n </ul>\n </li>\n <li>\n Planned vaginal delivery </li>\n <li>\n Maternal age 18-50 years or an emancipated minor according to local standards</li>\n <li>\n A single, live fetus in cephalic presentation confirmed prior to randomization</li>\n</ul>\n
      • principal_exclusion_criteria<ul>\n <li>\n Unknown gestational age</li>\n <li>\n Maternal history of more than 1 prior caesarian delivery</li>\n <li>\n Planned cesarean delivery</li>\n <li>\n Maternal contraindication to sildenafil therapy such as hypersensitivity to nitrates or nitrites</li>\n <li>\n Recognized major fetal anomaly (neurologic, cardiac or pulmonary malformation) or known genetic condition (trisomy)</li>\n <li>\n Any maternal medical condition or status that precludes informed consent</li>\n</ul>\n
      • primary_end_points<p>\n Results of this feasibility trial are an essential first step in the study of sildenafil citrate as a novel treatment to improve fetal status during labor and thus reduce birth asphyxia.  This study, therefore, has the potential to impact one of the most common causes of neonatal mortality worldwide and may alter standard of care of women in labor.   </p>\n<p>\n If this study demonstrates feasibility of intrapartum sildenafil citrate, our team will use the data generated to design a definitive trial.  This study will help to identify the appropriate study outcomes for a trial of sildenafil citrate in a low-resource settings as well as identify any skill or knowledge gaps that require intervention prior to a large trial. </p>\n
      • scope_diagnosis1
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory1
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n <strong>The study facility</strong></p>\n<p>\n The 250-bed capacity Margaret Kenyatta Mother Baby Wing at Nakuru Level Five opened by First Lady Margaret Kenyatta in 2018.The Sh450 million state-of-the-art maternity wing is the biggest in the larger Rift Valley region, the largest after Nairobi County’s Pumwani Hospital. It also serves Bomet, Baringo, Narok, Kericho, Samburu, Laikipia and Nyandarua counties. It’s one of the busiest unit in the county with about 1200 deliveries per month. The facility has 3 sections accommodating obstetric cases and one section is been occupied by the gynaecology cases. The unit also has a maternity theatre with two operating and a 24 hour laboratory providing services to the patients in the unit.The facility has a newborn unit with a bed capacity of 50 with facilities to provide continuous positive pressure to neonates with respiratory challenges.</p>\n<p>\n On human resource the maternal   section has 9 obstetrician & gynecologist that man the unit in both the gynecology, obstetric wards and theatre, it has 9 medical officers and at least 4 medical officers interns and 4 clinical officers interns. The newborn units are run by two Paediatricians, one medical officer and at least two medical officers’ interns and two clinical officers’ interns. The whole unit has over 100 nurses with majority of them in the labour ward</p>\n<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\">\n <tbody>\n <tr>\n <td style=\"width:60px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:107px;\">\n <p>\n <strong>Name</strong></p>\n </td>\n <td style=\"width:86px;\">\n <p>\n <strong>Project Role</strong></p>\n </td>\n <td style=\"width:116px;\">\n <p>\n <strong>Qualification</strong></p>\n </td>\n <td style=\"width:138px;\">\n <p>\n <strong>Career</strong></p>\n </td>\n <td style=\"width:116px;\">\n <p>\n <strong>Experience</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:60px;\">\n <p>\n 1</p>\n </td>\n <td style=\"width:107px;\">\n <p>\n Dr Amos Otara Magembe</p>\n </td>\n <td style=\"width:86px;\">\n <p>\n Site Coordinator</p>\n </td>\n <td style=\"width:116px;\">\n <p>\n MBChB 1994</p>\n <p>\n M.Med (Obstetrics and Gynaecology) 2000</p>\n </td>\n <td style=\"width:138px;\">\n <p>\n Senior lecturer, Egerton University, Department of Reproductive Health</p>\n <p>\n  </p>\n <p>\n Consultant Obstetrician-Gynaecologist Nakuru County Referral Teaching Hospital</p>\n <p>\n  </p>\n </td>\n <td style=\"width:116px;\">\n <p>\n WHO clinical trial among pregnant women in the county referral hospital e.g.</p>\n <p>\n  </p>\n <p>\n WOMAN Trial 2014</p>\n <p>\n  </p>\n <p>\n Multi-county survey on Maternal and New-born Health 2012</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:60px;\">\n <p>\n 2</p>\n </td>\n <td style=\"width:107px;\">\n <p>\n Dr Elizabeth Gathoni Kibaru</p>\n </td>\n <td style=\"width:86px;\">\n <p>\n Site Investigator</p>\n </td>\n <td style=\"width:116px;\">\n <p>\n MBChB 2001</p>\n <p>\n  </p>\n <p>\n M. Med degree (Pediatrics and child health )2009.</p>\n </td>\n <td style=\"width:138px;\">\n <p>\n Lecturer, Egerton University, Department of Child Health</p>\n <p>\n  </p>\n <p>\n Consultant Pediatrician –Nakuru County and Referral hospital in the Newborn Unit Nakuru.</p>\n <p>\n  </p>\n </td>\n <td style=\"width:116px;\">\n <p>\n Involved in multiple policy implementation studies and WHO clinical trials in Kenya aimed at improving newborn outcome in Nakuru County</p>\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:60px;\">\n <p>\n 3</p>\n </td>\n <td style=\"width:107px;\">\n <p>\n Dr. Rose Jerono Keter</p>\n </td>\n <td style=\"width:86px;\">\n <p>\n Study Pharmacist</p>\n </td>\n <td style=\"width:116px;\">\n <p>\n BPharm</p>\n <p>\n M.Pharm(Clinical Pharmacy)</p>\n </td>\n <td style=\"width:138px;\">\n <p>\n Clinical Pharmacist Nakuru County and Referral hospital in the Newborn Unit Nakuru</p>\n </td>\n <td style=\"width:116px;\">\n <p>\n Studies on Antibiotic Use at NCRH</p>\n <p>\n  </p>\n <p>\n  </p>\n <p>\n  </p>\n <p>\n  </p>\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:60px;\">\n <p>\n 4</p>\n </td>\n <td style=\"width:107px;\">\n <p>\n Jeremia Orina</p>\n </td>\n <td style=\"width:86px;\">\n <p>\n Study Nurse</p>\n </td>\n <td style=\"width:116px;\">\n <p>\n KRCHN</p>\n </td>\n <td style=\"width:138px;\">\n <p>\n Nurse Midwive</p>\n </td>\n <td style=\"width:116px;\">\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:60px;\">\n <p>\n 5</p>\n </td>\n <td style=\"width:107px;\">\n <p>\n Hellen Nafula</p>\n </td>\n <td style=\"width:86px;\">\n <p>\n Study Nurse</p>\n </td>\n <td style=\"width:116px;\">\n <p>\n KRCHN</p>\n <p>\n Kenya registered Neonatal nurse</p>\n </td>\n <td style=\"width:138px;\">\n <p>\n Neonatology Nurse</p>\n </td>\n <td style=\"width:116px;\">\n <p>\n Working in NBU for the last 11 years</p>\n <p>\n CPAP trainer</p>\n <p>\n Trainer and mentor in NEST project</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:60px;\">\n <p>\n 6</p>\n </td>\n <td style=\"width:107px;\">\n  </td>\n <td style=\"width:86px;\">\n  </td>\n <td style=\"width:116px;\">\n  </td>\n <td style=\"width:138px;\">\n  </td>\n <td style=\"width:116px;\">\n <p>\n  </p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • other_details_explanation<p>\n The goal of the trial is to determine the impact of sildeafil citrate in resource limited environment.  The sponsors home country, USA, does not meet these criteria.  </p>\n
      • other_details_regulatory_notapproved<p>\n NONE</p>\n
      • other_details_regulatory_approved<p>\n University of Alabama at Birmingham Institutional Review Board, April 2022</p>\n<div>\n  </div>\n<div>\n EGERTON UNIVERSITY ETHICS REVIEW COMMITTEE (EUREC), August 2022</div>\n<p>\n  </p>\n
      • other_details_regulatory_rejected<p>\n n/a</p>\n
      • other_details_regulatory_halted<p>\n n/a</p>\n
      • estimated_duration3-6 MONTHS
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorSILDENAFIL AND PLACEBO
      • design_controlled_other_medicinalYes
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaNAKURU COUNTY REFERRAL AND TEACHING HOSPITAL
      • single_site_physical_addressNAKURU COUNTY REFERAL AND TEACHING HOSPITAL
      • single_site_contact_personAMOS OTARA
      • single_site_telephone+254722747470
      • multiple_sites_member_stateNo
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites
      • multi_country_list
      • data_monitoring_committeeYes
      • total_enrolment_per_site500
      • total_participants_worldwide1000
      • 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_male0
      • subjects_healthyNo
      • subjects_patientsNo
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenYes
      • subjects_nursing_womenYes
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameAmos
      • investigator1_middle_nameMagembe
      • investigator1_family_nameOtara
      • investigator1_qualificationMMED. Obstetrics ang Gynaecology
      • investigator1_professional_addressEGERTON UNIVERSITY
      • investigator1_telephone+254722747470
      • investigator1_emailamosotara@yahoo.com
      • organisations_transferred_Yes
      • number_participants500
      • notification
      • approval_date05-07-2024
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted20-09-2023
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonThe reviewer comments have been addressed.
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2024-07-05 10:47:03
      • created2022-09-08 15:44:06
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id850
        • application_id1172
        • given_nameNora
        • middle_name
        • family_nameSwitchenko
        • qualificationMD, Assistant Professor Department of Pediatrics Division of Neonatology
        • professional_address Universityof Alabama at Birmingham
        • telephone860-798-1557
        • emailnswitchenko@uabmc.edu
        • created2022-09-08 16:10:59
        • modified2023-09-20 17:27:32
    • SiteDetail(array)
      • 0(array)
        • id1313
        • application_id1172
        • county_id(null)
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        • site_capacity(null)
        • misc(null)
        • created2022-09-08 16:10:59
        • modified2023-09-20 17:27:32
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id604
        • application_id1172
        • sponsorUAB MARY HEERSINK INSTITUTE FOR GLOBAL HEALTH
        • sponsor_typeResearch Institution
        • contact_personPATRICIA M SMITH
        • addressMARY HEERSINK INSTITUTE OF GLOBAL HEALTH AT UAB
        • telephone_number+19024395214
        • fax_number
        • cell_number+19024395214
        • email_addresspmsmith@uabmc.edu
        • created2022-09-08 16:10:59
        • modified2023-09-20 17:27:32
  • 3(array)
    • Application(array)
      • id1165
      • user_id642
      • trial_status_id4
      • abstract_of_study<p>\n Background The outbreak of SARS-CoV-2 infection has rapidly become a global epidemic, causing heavy economic stress, medical burden and a serious threat to human survival and health for people worldwide. SARS-CoV2 is transmitted primarily by respiratory droplets and close contact. Based on current epidemiological investigations, the incubation period for the onset of SARS-CoV-2 infection is 1-14 days, mostly 3-7 days. Fever, dry cough and malaise are the main manifestations. In the current absence of effective treatments, effective vaccination plays a crucial role in preventing and controlling the spread of COVID-19. LVRNA009 is a SARS-CoV-2 mRNA vaccine obtained by using recombinant gene technology to construct and produce linearized vectors, synthesizing mRNA molecules through in vitro enzyme-catalyzed technology, purification, and formulation process. Objective To evaluate the protective efficacy of LVRNA009 (50μg) in the prevention of first episodes of virologically-confirmed symptomatic cases of COVID-19 of any severity occurring from 14 days after 2nd dose in the initial set of vaccination in SARS-CoV-2 naive participants. Methodology This is a global Phase2/3, multi-center, randomized, blinded, placebo-controlled study followed by blinded crossover vaccination, to evaluate the efficacy, safety, and immunogenicity of SARS-CoV-2 mRNA vaccine (LVRNA009) against COVID-19 in participants aged 18 years and older. Participants will be randomized in a 1:1 ratio to receive 1 dose of the study vaccine or placebo on Day 0 and Day 28. Site Activities will be conducted in Siaya at the Siaya Referral Hospital grounds; Siaya Clinical Research Annex.. This is a global study that plans to enroll 300 participants for Phase 2 and about 33,700 participants aged 18 years and older will be included in “Phase 3” portion, and about 10%-20% of participants aged 60 years and older will be included. The Siaya Clinical Research Annex is targeting to recruit at least 1000 Participants. Expected Application of Results The study vaccine will provide protection against symptomatic COVID-19 in healthy adults aged 18 years and older.</p>\n
      • study_title<p>\n A Global Multi-center, Randomized, Blinded, Placebo-controlled Phase 2/3 Clinical Study to Evaluate the Efficacy, Safety and Immunogenicity of SARS-CoV-2 mRNA Vaccine (LVRNA009) for the Prevention of COVID-19 in Participants Aged 18 Years and Olde</p>\n
      • laymans_summary<p>\n The existence of a severe respiratory illness in Wuhan City, Hubei Province, China in December 2019 led to the discovery of a unique type of germs called coronavirus. This type of germs is a virus which causes a flu-like illness called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) or COVID-19 in the human population. The outbreak led to its announcement on 30 January 2020 by the World Health Organization (WHO) as a Public Health Emergency of International Concern and later declared on 11 March 2020 as a pandemic. It presents as a mild illness in most cases and some individuals may be asymptomatic. The symptoms include cough and shortness of breath, diarrhoea and nausea, loss of smell and taste. More severe symptoms include sudden onset and severe difficulty in breathing` requiring assisted breathing while in some cases it causes death. Most symptoms resolve on their own, such as fatigue and difficulty breathing but may appear to persist for up to 2 months after illness onset despite clearance of the virus. Research shows that adults over 50 years of age and individuals with chronic medical conditions are at a higher risk of bad outcomes and even death. As of July 19th 2022, The Ministry of Health, Kenya reported that a total of 19,148,223 vaccines had been administered across the country. Of these, 16,944,531 were doses administered to the adult population (18 years and above). Another 1,575,736 were doses administered to those between 15 to 17 years, 48,415 were below 15 years but above 12 years while 579,541 were booster doses. Proportion of adults fully vaccinated was 32.3%. The Government was working towards vaccinating a targeted population of 27,246,033.Despite measures of isolation, quarantine, social distancing, community containment, mask wearing, hand washing and sanitization, and the rapid development and global deployment of multiple authorized COVID-19 vaccines, the worldwide burden of COVID-19 infections and associated disease remains large. </p>\n
      • short_titleAIM-LVRNA009-II_III-01
      • protocol_noECCT/22/08/02
      • version_noV 1.2
      • date_of_protocol02-04-2022
      • study_drugSARS-CoV-2 mRNA Vaccine (LVRNA009)
      • disease_conditionCOVID-19
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines1
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressclinops@africa-cts.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
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      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter0
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
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      • applicant_stability_data1
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      • applicant_detailed_budget1
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      • applicant_registration_ctr(null)
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      • declaration_applicantDr. Videlis Nduba
      • declaration_date105-08-2022
      • declaration_principal_investigatorDr. Videlis Nduba
      • declaration_date205-08-2022
      • placebo_presentYes
      • study_objectives<p>\n Primary efficacy objective: To evaluate the protective efficacy of LVRNA009 (50 μg) in the prevention of first episodes of virologically-confirmed symptomatic cases of COVID-19 of any severity occurring from 14 days after 2 nd dose in the initial set of vaccination in SARS-CoV-2 naive participant</p>\n<p>\n Secondary efficacy objectives: 1. To evaluate the protective efficacy of LVRNA009 (50 μg) in the prevention of first episodes of virologically-confirmed moderate to severe cases of COVID-19 from 14 days after 2 nd dose in the initial set of vaccination in SARS-CoV-2 naive participants. 2. To evaluate the protective efficacy of LVRNA009 (50 μg) in the prevention of first episodes of virologically-confirmed severe cases of COVID-19 from 14 days after 2 nd dose in the initial set of vaccination in SARS-CoV-2 naive participants. 3. To evaluate the protective efficacy of LVRNA009 (50 μg) in the prevention of first episodes of virologically-confirmed cases of COVID-19 leading to death from 14 days after 2 nd dose in the initial set of vaccination in SARS-CoV-2 naive participants. 4. To evaluate the protective efficacy of LVRNA009 (50 μg) in the prevention of first episodes of virologically-confirmed symptomatic cases of COVID-19 of any severity occurring from 14 days after 2 nd dose in the initial set of vaccination in SARS-CoV-2 naive participants in different age strata (18-59 years old and ≥ 60 years old). 5. To evaluate the protective efficacy of LVRNA009 (50 μg) in the prevention of first episodes of virologically-confirmed symptomatic cases of COVID-19 of any severity occurring from 14 days after 2 nd dose in the initial set of vaccination in SARS-CoV-2 non-naive participants. 6. To evaluate the protective efficacy of LVRNA009 (50 μg) in the prevention of first episodes of virologically-confirmed severe cases of COVID-19 from 14 days after 2 nd dose in the initial set of vaccination in SARS-CoV-2 non-naive participants. 7. To evaluate the protective efficacy of LVRNA009 (50 μg) in the prevention of first episodes of virologically-confirmed symptomatic cases COVID-19 of any severity occurring from 14 days after 2 nd dose in the initial set of vaccination regardless of evidence of prior SARS-CoV-2 infection. 8. To evaluate the protective efficacy of LVRNA009 (50 μg) in the prevention of first episodes of virologically-confirmed symptomatic cases of COVID-19 of any severity occurring from the day of the 1 st dose in the initial set of vaccination. 9. To evaluate the protective efficacy of LVRNA009 (50 μg) in the prevention of first episodes of virologically-confirmed symptomatic cases of COVID-19 of any severity occurring from 7 days after the 2 nd dose in the initial set of vaccination. 10. To evaluate the protective efficacy of LVRNA009 (50 μg) in the prevention of first episodes of virologically-confirmed moderate to severe cases of COVID-19 from 14 days after the 2 nd dose in the crossover set of vaccination in SARS-CoV-2 naive participants. 11. To evaluate the protective efficacy of LVRNA009 (50 μg) in the prevention of first episodes of virologically-confirmed severe cases of COVID-19 from 14 days after the 2 nd dose in the crossover set of vaccination in SARS-CoV-2 naive participants. 12. To evaluate the protective efficacy of LVRNA009 (50 μg) in the prevention of first episodes of virologically-confirmed cases of COVID-19 leading to death from 14 days after the 2 nd dose in the crossover set of vaccination regardless of evidence of prior SARS-CoV-2 infection</p>\n<p>\n Secondary safety objectives: 1. To assess the solicited AEs (local and systemic) occurring 0-14 days post each dose in the reactogenicity subgroup in the initial set of vaccination. 2. To assess the AEs occurring 0-28 days post each dose in all participants of each set of vaccinations (initial and crossover). 3. To assess SAE, AESI, pregnancy events from 1 st dose in the initial set of vaccination to 12 months after the the 2 nd dose in the crossover set of vaccination </p>\n<p>\n Secondary immunogenicity objectives (for immunogenicity subgroup): 1. To assess the SARS-CoV-2 virus neutralizing antibody responses and S-protein IgG antibodies responses 14 days, 28 days, 3 months and 6 months after the 2nddose of initial set of vaccination or the day of crossover vaccination (whichever come earlier), 28 days, 3 months, 6 months and 12 months after the the 2 nd dose in the crossover set of vaccination. 2. To assess the seroconversion of SARS-CoV-2 virus neutralizing antibody and S-protein IgG antibodies in seronegative participants at baseline, 14 days, 28 days, 3 months and 6 months after 2 nd dose of initial set of vaccination or the day of crossover vaccination (whichever comes earlier), and 28 days, 3 months, 6 months and 12 months after the the 2 nd dose in the crossover set of vaccination. 3. To assess the 4-fold rise response of SARS-CoV-2 virus neutralizing antibody and S-protein IgG antibodies in seropositive participants at baseline, 14 days, 28 days, 3 months and 6 months after 2 nd dose of initial set of vaccination or the day of crossover vaccination (whichever comes earlier), and 28 days, 3 months, 6 months and 12 months after the 2 nd dose in the crossover set of vaccination</p>\n<p>\n Exploratory efficacy objectives: 1. To evaluate the protective efficacy of LVRNA009 (50 μg) in the prevention of first episodes of virologically-confirmed symptomatic cases of COVID-19 of any severity occurring from 14 days after the 2 nd dose in the crossover set of vaccination in SARS-CoV-2 naive participants. 2. To evaluate the protective efficacy of LVRNA009 (50 μg) in the prevention of first episodes of virologically-confirmed symptomatic cases of COVID-19 of any severity occurring from 14 days after the 2 nd dose in the crossover set of vaccination in SARS-CoV-2 non-naive participants. 3. To demonstrate the efficacy of LVRNA009 (50 μg) in the prevention of first episodes of virologically-confirmed cases of COVID-19 of any severity from 14 days after the 2 nd dose caused by individual VOCs in the initial set of vaccination</p>\n<p>\n Exploratory immunogenicity objectives (for immunogenicity subgroup): 1. To assess the specific cellular immune response 7 days, 14 days, 28 days after the 2 nd dose of initial set of vaccination in the cellular immune subgroup. 2. To assess the cross-neutralizing ability of serum neutralizing antibodies collected 14 days and 28 days after the the 2 nd dose of initial set of vaccination.in cross-neutralization subgroup. 3. To evaluate the immunological correlation of risk and protection against symptomatic COVID-19 and SARS-CoV-2 infection after the initial set of vaccination.</p>\n
      • principal_inclusion_criteria<p>\n 1. Adults aged 18 years and older. 2. Understand the content of the ICF, and voluntarily sign the ICF (If the participant is unable to sign the ICF on his/her own due to illiteracy, an impartial witness is needed). 3. Participants who are willing and able to comply with study requirements, including all scheduled visits, vaccinations, laboratory tests, and other study procedures. 4. Female participants of childbearing potential or partners of male participants: voluntarily agree to use effective contraception with their partners prior to the first vaccination and must agree to continue such precautions during the study until 3 months after full vaccination (including the initial set of vaccination and crossover set of vaccination). [Effective contraception includes oral contraceptives, injectable or implantable contraception, extended-release topical contraceptives, hormonal patches, intrauterine devices (IUDs), sterilization, abstinence, condoms (for male), diaphragms, cervical caps, etc.]. 5. For female participants: without childbearing potential (amenorrhea for at least 1 year or documented surgical sterilization) or have used effective contraception with a negative pregnancy test before each vaccination in this study. 6. During the screening period and 72 hours prior to vaccination, axillary temperatures <37.3°C/99.1°F. 7. Healthy participants or participants with mild underlying disease [in a stable state without exacerbation (no admission to hospital or no major adjustment to treatment regimen, etc.) for at least 3 months prior to enrollment in this study]</p>\n
      • principal_exclusion_criteria<p>\n Participants meeting any of the following criteria will be excluded from the study. 1. History of Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), or other coronavirus infections. 2. Individuals using prescription medications for prophylaxis or treatment of SARS-CoV-2 (including vaccination of licensed COVID-19 vaccines). 3. History of a previous laboratory-confirmed diagnosis of SARS-CoV-2 infection or COVID-19. 4. History of allergy to any component of the study vaccine or history of severe allergic reaction to vaccine or drug (including but not limited to anaphylaxis, allergic laryngeal edema, anaphylactic purpura, thrombocytopenic purpura, or localized allergic necrosis (Arthus reaction)). 5. Positive nucleic acid for SARS-CoV-2 in nasopharyngeal/oropharyngeal swab specimens. 6. Positive HIV test results. 7. A history or family history of convulsions, epilepsy, encephalopathy and psychosis. 8. Malignant tumors in the active phase, malignant tumors not receiving adequate treatment, malignant tumors at potential risk of recurrence during the study period. 9. Asplenia or functional asplenia, complete or partial splenectomy from any cause. 10. Prolonged (defined as more than 14 days) use of immunosuppressive or other immunomodulatory drugs (e.g., corticosteroids, ≥20 mg/d prednisone or equivalent; however, inhaled and topical steroids are permitted) within 6 months prior to the 1 st dose of investigational vaccine 11. Any other licensed vaccines given within 28 days prior to the study vaccination, or planned administration of vaccine(s) within 28 days after the 2 nd dose in the blinded crossover vaccination. 12. Have received immunoglobulin or other blood products within 3 months prior to enrollment or plan to receive them during the study period. 13. Blood donation or blood loss ≥ 450 mL within 1 month prior to enrollment or planned to donate blood during the study period. 14. Participants who have received any other investigational product within 1 month prior to enrollment or intent to participate in another clinical study at any time during the conduct of this study 15. Women who are pregnant or breastfeeding. 16. Participants deemed unsuitable for participation in this study based on the investigator's assessment.</p>\n
      • primary_end_points<p>\n Efficacy endpoints: Primary efficacy endpoint: The person-year incidence density of first episodes of virologically-confirmed symptomatic cases of COVID-19 of any severity meeting the case definition for the primary efficacy analysis occurring from 14 days after the 2 nd dose in the initial set of vaccination in SARS-CoV-2 naive participants in the LVRNA009 (50 μg) dose group.</p>\n<p>\n Secondary efficacy endpoints: 1. The person-year incidence density of first episodes of virologically-confirmed moderate to severe cases of COVID-19 from 14 days after the 2 nd dose of the initial set of vaccination meeting the case definition for the primary efficacy analysis for SARS-CoV-2 naive participants in the LVRNA009 (50 μg) dose group. 2. The person-year incidence density of first episodes of virologically-confirmed severe cases of COVID-19 from 14 days after the 2 nd dose of the initial set of vaccination meeting the case definition for the primary efficacy analysis for SARS-CoV-2 naive participants in the LVRNA009 (50 μg) dose group. 3. The person-year incidence density of first episodes of virologically-confirmed cases of COVID-19 leading to death from 14 days after the 2 nd dose of the initial set of vaccination meeting the case definition for the primary efficacy analysis for SARS-CoV-2 naive participants in the LVRNA009 (50 μg) dose group. 4. The person-year incidence density of first episodes of virologically-confirmed symptomatic cases of COVID-19 of any severity occurring from 14 days after the 2 nd dose in the initial set of vaccination for SARS-CoV-2 naive participants at different age strata (18-59 years, ≥ 60 years) in the LVRNA009 (50 μg) dose group. 5. The person-year incidence density of first episodes of virologically-confirmed symptomatic cases of COVID-19 of any severity occurring from 14 days after the 2 nd dose in the initial set of vaccination for SARS-CoV-2 non-naive participants in the LVRNA009 (50 μg) dose group. 6. The person-year incidence density of first episodes of virologically-confirmed severe cases of COVID-19 from 14 days after the 2 nd dose in the initial set of vaccination for SARS-CoV-2 non-naive participants in the LVRNA009 (50 μg) dose group. 7. The person-year incidence density of first episodes of virologically-confirmed symptomatic cases of COVID-19 of any severity occurring from 14 days after the 2 nd dose in the initial set of vaccination regardless prior SARS-CoV-2 infection in the LVRNA009 (50 μg) dose group. 8. The person-year incidence density of first episodes of virologically-confirmed symptomatic cases of COVID-19 of any severity occurring from the 1 st dose in the initial set of vaccination in the LVRNA009 (50 μg) dose group. 9. The person-year incidence density of first episodes of virologically-confirmed symptomatic cases of COVID-19 of any severity occurring from 7 days after the 2 nd dose in the initial set of vaccination in the LVRNA009 (50 μg) dose group. 10. The person-year incidence density of first episodes of virologically-confirmed moderate to severe cases of COVID-19 from 14 days after the 2 nd dose in the crossover set of vaccination for SARS-CoV-2 naive participants in the LVRNA009 (50 μg) dose group. 11. The person-year incidence density of first episodes of virologically-confirmed severe cases of COVID-19 from 14 days after the 2 nd dose in the crossover set of vaccination for SARS-CoV-2 naive participants in the LVRNA009 (50 μg) dose group. 12. The person-year incidence density of first episodes of virologically-confirmed cases of COVID-19 leading to death from 14 days after the 2 nd dose in the crossover set of vaccination regardless prior SARS-CoV-2 infection in the LVRNA009 (50 μg) dose group</p>\n<p>\n Exploratory efficacy endpoints: 1. The person-year incidence density of first episodes of virologically-confirmed symptomatic cases of COVID-19 of any severity occurring from 14 days after the 2 nd dose in the crossover set of vaccination for SARS-CoV-2 naive participants in the LVRNA009 (50 μg) dose group. 2. The person-year incidence density of first episodes of virologically-confirmed symptomatic cases of COVID-19 of any severity occurring from 14 days after the 2 nd dose in the crossover set of vaccination for SARS-CoV-2 non-naive participants in the LVRNA009 (50 μg) dose group. 3. The person-year incidence density of first episodes of virologically-confirmed cases of COVID-19 of any severity from 14 days after the the 2 nd dose caused by individual VOCs in the initial set of vaccination in the LVRNA009 (50 μg) dose group</p>\n<p>\n Secondary safety endpoints: Safety endpoints will be analyzed in all participants. 1. Incidence, intensity and duration of each solicited (local and systemic) AE within 14 days post each dose in reactogenicity subgroup in the initial set of vaccination. (13,600 participants will be assigned into the reactogenicity subgroup (including 300 participants in “phase 2” portion, and 13,300 participants in “phase 3” portion of this study)) 2. Incidence, intensity, and causality of AEs occurring 0-28 days post each dose in all participants of each set of vaccinations (initial and crossover). 3. Incidence, intensity, and causality of SAEs, AESIs, and pregnancy events from the day of 1 st dose in the initial set of vaccination to 12 months after the 2 nd dose in crossover set of vaccination in all participants</p>\n<p>\n Secondary immunogenicity endpoints (for immunogenicity subgroup): The immunogenicity of LVRNA009 will be assessed in an immunogenicity subgroup of 3,400 participants in this study. The whole immunogenicity group includes 300 participants in “phase 2” portion, and 3,100 participants in “phase 3” portion of this study. Participants in the immunogenicity subgroup also belong to the reactogenicity subgroup. Cellular immune subgroup: 300 participants will be assigned to a cellular immune subgroup for specific cellular immune analysis. The cellular immune subgroup should be in the immunogenicity subgroup coming from the “phase 3” portion. Cross-neutralization subgroup: Serum from 160 participants in the immunogenicity subgroup who have received the study vaccine will be selected for cross-neutralization test. Cross-neutralization subgroup should be in the immunogenicity subgroup coming from the “phase 3” portion. 1. Geometric mean titer (GMT) and Geometric mean Increase (GMI) of SARS-CoV-2 virus neutralizing antibody responses and S-protein IgG antibody responses 14 days, 28 days, 3 months and 6 months after the 2 nd dose of the initial set of vaccination or the day of crossover vaccination (whichever comes earlier) , and 28 days, 3 months, 6 months and 12 months after the 2 nd dose in the crossover set of vaccination. 2. The seroconversion rate (SCR) of SARS-CoV-2 virus neutralizing antibody and S-protein IgG antibodies in seronegative participants at baseline, 14 days, 28 days, 3 months and 6 months after 2 nd dose of the initial set of vaccination or the day of crossover vaccination (whichever comes earlier) , and 28 days, 3 months, 6 months and 12 months after the 2 nd dose in the crossover set of vaccination. 3. The seroconversion rate (SCR) of SARS-CoV-2 virus neutralizing antibody and S-protein IgG antibodies in seropositive participants at baseline, 14 days, 28 days, 3 months and 6 months after the 2 nd dose of the initial set of vaccination or the day of crossover vaccination (whichever comes earlier) , and 28 days, 3 months, 6 months and 12 months after the 2 nd dose in the crossover set of vaccination. Seroconversion is defined as: GMT post vaccination ≥ 4-fold rise from baseline GMT value.</p>\n<p>\n Exploratory immunogenicity endpoints: 1. The specific cellular immune response (IL-2, IL-4, IL-13, IFN-γ) to SARS-CoV-2 (ELISpot) 7 days, 14 days, 28 days after the 2 nd dose of the initial set of vaccination in the cellular immune subgroup. 2. The cross-neutralizing ability of serum neutralizing antibodies collected 14 days and 28 days after the 2 nd dose of the initial set of vaccination in the cross-neutralization subgroup. 3. The immunological correlation of risk and protection against symptomatic COVID-19 and SARS-CoV-2 infection after initial set of vaccination. Note: Incidence density = number of cases during the observation period/number of person-year of observation, i.e., number of confirmed cases during this study period/1 year</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others1
      • scope_others_specifyImmunogenicity
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory1
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n The study sites have qualified staff to include medical doctors, study coordinators, nurses, clinical officers, laboratory tecchnologists,pharmacists and pharmaceutical technologists. They also have adequate facilities for emergency care and other research activities.</p>\n
      • other_details_explanation<p>\n No</p>\n
      • other_details_regulatory_notapproved<p>\n N/A</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_duration17-24 months
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorSaline
      • 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_states8
      • number_of_sites6
      • multi_country_listTanzania, Nigeria, Uganda, Ghana, Sierra Leone, Mali, Burkinafaso, Kenya
      • data_monitoring_committeeYes
      • total_enrolment_per_site500-1000
      • total_participants_worldwide34,000
      • 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_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenYes
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
      • subjects_specifyIlliterate participants. An impartial witness will be present during the consenting process
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameVidelis
      • investigator1_middle_name
      • investigator1_family_nameNduba
      • investigator1_qualificationMedical officer
      • investigator1_professional_address\"Siaya Clinical Trials Unit Siaya County Referral Hospital Hospital Road, Siaya Town Siaya County P.O. BOX 144-40600 Siaya, Kenya\"
      • investigator1_telephone(+254) 0724 522 474
      • investigator1_emailvnduba@gmail.com
      • organisations_transferred_Yes
      • number_participants5000
      • notification
      • approval_date22-11-2022
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted05-08-2022
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonThe reviewer queries have been addressed.
      • final_report<p>\n The executive summary is attached below.</p>\n
      • implication_results<p>\n Throughout the entire safety observation period, the safety and tolerability of the SARS-CoV-2 mRNA vaccine (LVRNA009) were deemed acceptable in the population aged 18 and above, following the administration of two doses. No clinically significant safety signals were detected. However, as the study was terminated early (not due to safety reasons) the study did not influence any policy changes.</p>\n
      • quantity_imported
      • quantity_dispensed
      • quantity_destroyed
      • quantity_exported
      • balance_site
      • final_date0000-00-00
      • modified2024-09-25 16:36:19
      • created2022-08-03 11:40:38
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id840
        • application_id1165
        • given_nameBernhards
        • middle_name
        • family_nameOgutu
        • qualificationMedical officer
        • professional_address\"Ahero Clinical Trials Unit Ahero County Referral Hospital Kisumu-Busia Road, Ahero Town Kisumu County P.O. BOX 169-40101, Ahero, Kenya\"
        • telephone+254 733 966 065
        • emailogutu6@gmail.com
        • created2022-08-03 13:28:05
        • modified2022-08-05 19:54:26
      • 1(array)
        • id841
        • application_id1165
        • given_nameLucas
        • middle_name
        • family_nameOtieno
        • qualificationMedical officer
        • professional_address\"Victoria Biomedical Research Institue Kisumu District Hospital Angawa Avenue, Milimani, Kisumu City Kisumu County P.O. BOX 1818-40100, Kisumu, Kenya \"
        • telephone(+254) 0720597654
        • emaillucas.tina0818@gmail.com
        • created2022-08-03 13:28:05
        • modified2022-08-05 19:54:26
      • 2(array)
        • id842
        • application_id1165
        • given_nameVidelis
        • middle_name
        • family_nameNduba
        • qualificationMedical officer
        • professional_address\"Siaya Clinical Trials Unit Siaya County Referral Hospital Hospital Road, Siaya Town Siaya County P.O. BOX 144-40600 Siaya, Kenya\"
        • telephone(+254) 0724 522 474
        • emailvnduba@gmail.com
        • created2022-08-03 13:28:05
        • modified2022-08-05 19:54:26
      • 3(array)
        • id843
        • application_id1165
        • given_nameBernhards
        • middle_name
        • family_nameOgutu
        • qualificationMedical officer
        • professional_address\"Homa Bay Clinical Trials Unit Homa Bay County Referral and Teaching Hospital Homa Bay Town Homa Bay County P.O. BOX 52-40300, Homa Bay, Kenya\"
        • telephone+254 733 966 065
        • emailogutu6@gmail.com
        • created2022-08-04 22:03:32
        • modified2022-08-05 19:54:26
      • 4(array)
        • id844
        • application_id1165
        • given_nameJacqueline
        • middle_name
        • family_nameMirera
        • qualificationMedical officer
        • professional_address\"CREA-N Machakos Machakos County Hospital Muvuti/Kiima-Kimwe Road, Machakos Town Machakos County P.O. BOX 19-90100, Machakos, Kenya\"
        • telephone+254 715 867 709
        • emailjacqueline.mirera@crean-health.com
        • created2022-08-04 22:03:32
        • modified2022-08-05 19:54:26
      • 5(array)
        • id845
        • application_id1165
        • given_nameJacqueline
        • middle_name
        • family_nameMirera
        • qualificationMedical officer
        • professional_address\"CREA-N Nakuru Nakuru County Hospital Nakuru-Sigor Road, Nakuru Town Nakuru County P.O. BOX 71-20100, Nakuru, Kenya\"
        • telephone+254 715 867 709
        • emailjacqueline.mirera@crean-health.com
        • created2022-08-04 22:03:32
        • modified2022-08-05 19:54:26
    • SiteDetail(array)
      • 0(array)
        • id1305
        • application_id1165
        • county_id41
        • site_nameSiaya Clinical Trials Unit
        • physical_addressSiaya County Referral Hospital Hospital Road, Siaya Town
        • contact_detailsP.O. BOX 144-40600 Siaya, Kenya
        • contact_personDr Videlis Nduba
        • site_capacity(null)
        • misc(null)
        • created2022-08-03 13:28:05
        • modified2022-08-05 19:54:26
        • County(array)
          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
      • 1(array)
        • id1306
        • application_id1165
        • county_id43
        • site_nameHoma Bay Clinical Trials Unit
        • physical_addressHoma Bay County Referral and Teaching Hospital Homa Bay Town
        • contact_detailsP.O. BOX 52-40300, Homa Bay, Kenya
        • contact_personDr Bernhards Ogutu
        • site_capacity(null)
        • misc(null)
        • created2022-08-04 22:40:18
        • modified2022-08-05 19:54:26
        • County(array)
          • id43
          • county_nameHoma Bay
          • created2012-06-15 10:27:10
          • modified2012-06-15 10:27:10
      • 2(array)
        • id1307
        • application_id1165
        • county_id42
        • site_nameAhero Clinical Trials Unit
        • physical_addressAhero County Referral Hospital Kisumu-Busia Road, Ahero Town
        • contact_detailsP.O. BOX 169-40101, Ahero, Kenya
        • contact_personDr Bernhards Ogutu
        • site_capacity(null)
        • misc(null)
        • created2022-08-04 22:40:18
        • modified2022-08-05 19:54:26
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 3(array)
        • id1308
        • application_id1165
        • county_id16
        • site_nameCREA-N Machakos
        • physical_addressMachakos County Hospital Muvuti/Kiima-Kimwe Road, Machakos Town
        • contact_detailsP.O. BOX 19-90100, Machakos, Kenya
        • contact_personDr Jacqueline Mirera
        • site_capacity(null)
        • misc(null)
        • created2022-08-04 22:40:18
        • modified2022-08-05 19:54:26
        • County(array)
          • id16
          • county_nameMachakos
          • created2012-06-15 10:23:55
          • modified2012-06-15 10:23:55
      • 4(array)
        • id1309
        • application_id1165
        • county_id32
        • site_nameCREA-N Nakuru
        • physical_addressNakuru County Hospital Nakuru-Sigor Road, Nakuru Town
        • contact_detailsP.O. BOX 71-20100, Nakuru, Kenya
        • contact_personDr Jacqueline Mirera
        • site_capacity(null)
        • misc(null)
        • created2022-08-04 22:40:18
        • modified2022-08-05 19:54:26
        • County(array)
          • id32
          • county_nameNakuru
          • created2012-06-15 10:25:52
          • modified2012-06-15 10:25:52
      • 5(array)
        • id1310
        • application_id1165
        • county_id42
        • site_nameVictoria Biomedical Research Institue
        • physical_addressKisumu District Hospital Angawa Avenue, Milimani, Kisumu City
        • contact_detailsP.O. BOX 1818-40100, Kisumu, Kenya
        • contact_personDr Lucas Tina
        • site_capacity(null)
        • misc(null)
        • created2022-08-04 22:40:18
        • modified2022-08-05 19:54:26
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
    • Sponsor(array)
      • 0(array)
        • id601
        • application_id1165
        • sponsorAIM Vaccine Co., Ltd AIM Innovation Biotechnology (Shanghai) Co.,
        • sponsor_typeIndustry
        • contact_personFan Zhang
        • addressBuilding 7, 1288 Zhongchun Road, Minhang District
        • telephone_number008613671828804
        • fax_number
        • cell_number13671828804
        • email_addressan.zhang@aimbio.com
        • created2022-08-03 13:28:05
        • modified2022-08-05 19:54:26
  • 4(array)
    • Application(array)
      • id1162
      • user_id693
      • trial_status_id2
      • abstract_of_study<p>\n <strong>Background:</strong></p>\n<p>\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>\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>\n <strong>Justification/Rationale:</strong></p>\n<p>\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>\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>\n <strong>Main Objectives:</strong></p>\n<p>\n <strong>Phase 2:</strong></p>\n<p>\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>\n • Anemia in subjects with sickle cell disease (SCD)</p>\n<p>\n • Safety</p>\n<p>\n Phase 3: 1. To determine the effect of mitapivat versus placebo on:</p>\n<p>\n • Anemia in subjects with sickle cell disease (SCD)</p>\n<p>\n • Sickle cell pain crises (SCPCs) in subjects with SCD</p>\n<p>\n Secondary objectives:</p>\n<p>\n <strong>Phase 2:</strong></p>\n<p>\n 1. To evaluate the effect of 2 doses of mitapivat versus placebo on:</p>\n<ul>\n <li>\n Anemia</li>\n <li>\n Markers of hemolysis and erythropoiesis</li>\n <li>\n Patient-reported fatigue</li>\n <li>\n Sickle cell pain crises (SCPCs)</li>\n</ul>\n<p>\n 2. To evaluate the pharmacokinetic and pharmacodynamic effects of mitapivat.</p>\n<p>\n <strong>Phase 3:</strong></p>\n<p>\n 1. To evaluate the effect of mitapivat versus placebo on:</p>\n<p>\n • Anemia in subjects with SCD</p>\n<p>\n • Markers of hemolysis</p>\n<p>\n • Markers of erythropoiesis</p>\n<p>\n • Patient-reported fatigue</p>\n<p>\n • Additional clinical efficacy measures related to SCPC</p>\n<p>\n <strong>Methods:</strong></p>\n<p>\n <strong>Overall Study design</strong></p>\n<p>\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) 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 Phase 2 portion of the study are not eligible to participate in the Phase 3 portion of the study.</p>\n<p>\n <strong>Study outcomes:</strong></p>\n<p>\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>\n <strong>Study duration:</strong></p>\n<p>\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 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</p>\n
      • laymans_summary<p>\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>\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>\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
      • short_titleAgios Study
      • protocol_noECCT/22/09/01
      • version_noAmendment 1 (V2.0)
      • date_of_protocol09-03-2022
      • study_drugMitapivat -Dr Ogutu and Dr Allan
      • 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
      • 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_applicantMillicent Aketch
      • declaration_date101-09-2022
      • declaration_principal_investigatorBernhards Ragama Ogutu
      • declaration_date201-09-2022
      • placebo_presentYes
      • study_objectives<p>\n <strong>Main objective:</strong></p>\n<p>\n <strong>Phase 2:</strong></p>\n<p>\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>\n • Anemia in subjects with sickle cell disease (SCD)</p>\n<p>\n • Safety</p>\n<p>\n <strong>Phase 3:</strong></p>\n<p>\n 1. To determine the effect of mitapivat versus placebo on:</p>\n<p>\n • Anemia in subjects with sickle cell disease (SCD)</p>\n<p>\n • Sickle cell pain crises (SCPCs) in subjects with SCD</p>\n<p>\n <strong>Secondary objectives:</strong></p>\n<p>\n <strong>Phase 2: </strong></p>\n<p>\n 1. To evaluate the effect of 2 doses of mitapivat versus placebo on:</p>\n<ul>\n <li>\n Anemia</li>\n <li>\n Markers of hemolysis and erythropoiesis</li>\n <li>\n Patient-reported fatigue</li>\n <li>\n Sickle cell pain crises (SCPCs)</li>\n</ul>\n<p>\n 2. To evaluate the pharmacokinetic and pharmacodynamic effects of mitapivat.</p>\n<p>\n <strong>Phase 3:</strong></p>\n<p>\n 1. To evaluate the effect of mitapivat versus placebo on:</p>\n<ul>\n <li>\n Anemia in subjects with SCD</li>\n <li>\n Markers of hemolysis Markers of erythropoiesis</li>\n <li>\n Patient-reported fatigue</li>\n <li>\n Additional clinical efficacy measures related to SCPC</li>\n</ul>\n
      • principal_inclusion_criteria<p>\n 1. Age ≥16 years; subjects age 16 or 17 years must physically have completed puberty.</p>\n<p>\n 2. Documented diagnosis of SCD (HbSS, HbSC, HbS/β0-thalassemia, HbS/β+ thalassemia, or other sickle cell syndrome variants).</p>\n<p>\n 3. At least 2 sickle cell pain crises (SCPCs) and no more than 10 SCPCs in the past 12 months.</p>\n<p>\n 4. Hemoglobin ≥5.5 and ≤10.5 g/dL.</p>\n<p>\n 5. If taking hydroxyurea, the hydroxyurea dose must be stable for at least 90 days before starting study drug.</p>\n<p>\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>\n 7. Other protocol-defined inclusion criteria may apply</p>\n
      • principal_exclusion_criteria<p>\n 1. Pregnant or breastfeeding.</p>\n<p>\n 2. Receiving regularly scheduled transfusions.</p>\n<p>\n 3. Hepatobiliary disorders including but not limited to significant liver disease or gallbladder disease.</p>\n<p>\n 4. Severe kidney disease.</p>\n<p>\n 5. Prior exposure to gene therapy or prior bone marrow or stem cell transplantation.</p>\n<p>\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>\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>\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>\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>\n 10. Other protocol defined exclusion criteria may apply.</p>\n
      • primary_end_points<p>\n <strong>Phase 2 Primary Endpoints:</strong></p>\n<p>\n 1. Percentage of participants with hemoglobin (Hb) response</p>\n<p>\n 2. Percentage of participants with treatment emergent adverse events (AEs) and treatment emergent serious adverse events (SAEs)</p>\n<p>\n <strong>Timepoint(s) of evaluation of this end point:</strong></p>\n<p>\n Phase 2 primary endpoint of percentage of participants with Hb response: Week 12</p>\n<p>\n Phase 2 primary endpoint of percentage of participants with treatment emergent AEs and treatment emergent SAEs: Up to Week 12</p>\n<p>\n <strong>Phase 3 Primary Endpoints:</strong></p>\n<p>\n 1. Percentage of participants with hemoglobin (Hb) response</p>\n<p>\n 2. Annualized rate of Sickle Cell Pain Crises (SCPCs)</p>\n<p>\n <strong>Timepoint(s) of evaluation of this end point:</strong></p>\n<ul>\n <li>\n Phase 3 primary endpoint of percentage of participants with Hb response: Week 52</li>\n <li>\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>Strathmore University Medical Centre (SUMC) Site  </strong></p>\n<p>\n The SUMC is designed for clinical trials and has a full clinical laboratory with bioanalytical capability.The Centre is managed by Strathmore University and the CREATES consortium.</p>\n<p>\n The Centre also has a dental unit. The medical centre is staffed by 2 pediatricians, 2 physicians, 1 medical officer, 1 clinical officer, 4 dental surgeons, 3 psychologists, 1 pharmacist, 1 visiting psychiatrist, 1 physician assistant, 4 nurses and 4 laboratory technologists.The facility supports healthcare to university students and staff and also general public.</p>\n<p>\n The centre currently runs a SCD clinic every Tuesday. Location The Sickle Cell study will be conducted at SUMC; recruitment will occur at the clinic. SUMC is located at Strathmore University in Madaraka Estate of Nairobi west, Nairobi County. SUMC will be staffed by qualified research personnel from KEMRI and SUMC.</p>\n<p>\n The site has a pharmacy, treatment area, clinical assessment area, data entry area, internal quality control and registration area and space where monitoring can be done. SUMC currently runs a SCD clinic with more than 200 patients on follow up comprising of both adults and children.</p>\n<p>\n Provision of medical care SUMC is an outpatient facility with a 2-bed holding unit and a separate emergency resuscitation area.</p>\n<p>\n The centre serves as a clinical trials facility for both paediatric and adult studies. The participants who will require inpatient care will be admitted to Coptic Hospital Ngong Road as SUMC already has an existing working arrangement. As for the Sickle cell disease, there is a database in place that has over 200 patients and we hope to base our recruitment on this list.The SUMC is also linked to other private, government, non-governmental and county health facilities, in Nairobi County that take care of patients with SCD. For the care of sickle cell patients, the SCD clinic will work closely with the study team.</p>\n<p>\n <strong>KEMRI Kondele Children's Hospital</strong></p>\n<p>\n The Kondele Children’s Hospital is designed for large clinical trials and has a full clinical laboratory including microbiology capability. The hospital is a KEMRI facility managed in collaboration with Jaramogi Oginga Odinga Teaching and Referral Hospital (JOOTRH). The KEMRI Kondele Children’s Hospital study site at JOOTRH will be staffed by KEMRI qualified research personnel. The site has a pharmacy, vaccination area, clinical assessment area, data entry area, internal quality control and registration area and space where monitoring can be done. The unit has conducted several clinical trials involving malaria drug, malaria vaccine and sickle cell drugs. Currently the unit is one of the site for a multi-Centre study for sickle cell disease.</p>\n<p>\n The KCH is part of the Jaramogi Oginga Odinga Teaching and Referral Hospital (JOOTRH). JOOTRH is the largest referral public health facility that is run by the County government of Kisumu. It is a 500-bed health facility with both pediatric and adult outpatient and inpatient care services. It has a fully-fledged clinical laboratory and radiological imaging services including CT-Scan and MRI services. The study team works very closely with both the pediatric and adult patient medical team in the care of patients with SCD. The hospital is surrounded by private, governmental and non-governmental health facilities, in Kisumu City. For the care of sickle cell patients, the study team works closely with other departments to ensure a multidisciplinary approach to the care of the study participants.</p>\n<p>\n At KCH, patients with SCD are managed according to the standard of care recommended by the Kenya Ministry of Health. The study participants will be offered the MOH standard of care including consultations, laboratory diagnosis and pharmacy care and the KCH site. Inpatient care will be offered at the JOOTRH hospital or any other hospital based on the needs of the participant.</p>\n
      • other_details_explanation<p>\n <strong>N/A</strong>, trial is being conducted in the USA</p>\n
      • other_details_regulatory_notapproved<table border=\"1\" cellpadding=\"1\" cellspacing=\"1\" style=\"width:500px;\">\n <tbody>\n <tr>\n <td>\n Regulatory Authority</td>\n <td>\n Dated Submitted</td>\n <td>\n Status</td>\n </tr>\n <tr>\n <td>\n Turkey</td>\n <td>\n 03 Dec 2021</td>\n <td>\n  </td>\n </tr>\n <tr>\n <td>\n Nigeria</td>\n <td>\n 11 Apr 2022</td>\n <td>\n  </td>\n </tr>\n <tr>\n <td>\n Kenya</td>\n <td>\n 10 Jun 2022</td>\n <td>\n  </td>\n </tr>\n <tr>\n <td>\n  </td>\n <td>\n  </td>\n <td>\n  </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • other_details_regulatory_approved<table border=\"1\" cellpadding=\"1\" cellspacing=\"1\" style=\"width:500px;\">\n <tbody>\n <tr>\n <td>\n Regualtory </td>\n <td>\n Approval Date </td>\n <td>\n Number of site per Country</td>\n </tr>\n <tr>\n <td>\n Canada</td>\n <td>\n 16 Nov 2021</td>\n <td>\n 4</td>\n </tr>\n <tr>\n <td>\n United Kingdom</td>\n <td>\n 13 Sep 2021</td>\n <td>\n 7</td>\n </tr>\n <tr>\n <td>\n Belgium</td>\n <td>\n 16 Feb 2022</td>\n <td>\n 8</td>\n </tr>\n <tr>\n <td>\n France</td>\n <td>\n 27 Jan 2022</td>\n <td>\n 6</td>\n </tr>\n <tr>\n <td>\n Germany</td>\n <td>\n 07 Apr 2022</td>\n <td>\n 4</td>\n </tr>\n <tr>\n <td>\n Italy</td>\n <td>\n 23 Feb 2022</td>\n <td>\n 8</td>\n </tr>\n </tbody>\n</table>\n<table border=\"1\" cellpadding=\"1\" cellspacing=\"1\" style=\"width:500px;\">\n <tbody>\n <tr>\n <td>\n Regulatory Authority</td>\n <td>\n Approved Date</td>\n <td>\n Number of site per country</td>\n </tr>\n <tr>\n <td>\n Netherlands</td>\n <td>\n 23 Dec 2021</td>\n <td>\n 1</td>\n </tr>\n <tr>\n <td>\n Brazil</td>\n <td>\n 21 Jan 2022</td>\n <td>\n 8</td>\n </tr>\n <tr>\n <td>\n Israel</td>\n <td>\n 09 Aug 2021</td>\n <td>\n 4</td>\n </tr>\n <tr>\n <td>\n United States of America</td>\n <td>\n 26 May 2022</td>\n <td>\n 23</td>\n </tr>\n <tr>\n <td>\n  </td>\n <td>\n  </td>\n <td>\n  </td>\n </tr>\n <tr>\n <td>\n  </td>\n <td>\n  </td>\n <td>\n  </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • other_details_regulatory_rejected<p>\n No Regulatory authority nor Ethics Committee has rejected this trial</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\n
      • notification<p>\n ePRO translation is expected by 31 Oct 2022. English speaking partiipants will be enrolled in the study untill the translations are submited to RA and EC and approved.</p>\n
      • approval_date20-12-2022
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted07-12-2022
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonAll the reviewer comments have been addressed
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2024-10-11 21:40:45
      • created2022-08-02 13:15:36
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id838
        • application_id1162
        • given_nameBernhards
        • middle_nameRagama
        • family_nameOgutu
        • qualificationMedical Doctor
        • professional_addressStrathmore University Medical Center_CREATES Madaraka Estate , Ole Sangale Road P.O Box 59857-00200 Nairobi
        • telephone+254 733812613
        • emailogutu6@gmail.com
        • created2022-08-02 13:16:15
        • modified2022-12-07 10:57:56
      • 1(array)
        • id847
        • application_id1162
        • given_nameGodfrey
        • middle_nameAllan
        • family_nameOtieno
        • qualificationMedical Doctor
        • professional_addressKondele Children\'s Hospital
        • telephone+254714481488
        • emailgaotieno@gmail.com
        • created2022-09-01 18:01:43
        • modified2022-12-07 10:57:56
    • SiteDetail(array)
      • 0(array)
        • id1297
        • application_id1162
        • county_id47
        • site_nameStrathmore University Medical Centre
        • physical_addressStrathmore University Medical Centre, Ole Sangale Rd
        • contact_details+254733813613
        • contact_personDr Bernhards Ogutu
        • site_capacity(null)
        • misc(null)
        • created2022-08-02 13:16:15
        • modified2022-12-07 10:57:56
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 1(array)
        • id1299
        • application_id1162
        • county_id42
        • site_nameVictoria Biomedical Research Institute
        • physical_addressButere County Hospital, Postal Code 40100, Kisumu, Kenya
        • contact_detailsTel: +254 720 597654 P.O. Box 7180
        • contact_personDr. Lucas Otieno Tina
        • site_capacity(null)
        • misc(null)
        • created2022-08-03 09:57:36
        • modified2022-12-07 10:57:56
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 2(array)
        • id1300
        • application_id1162
        • 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)
        • created2022-08-03 09:57:36
        • modified2022-12-07 10:57:56
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 3(array)
        • id1301
        • application_id1162
        • 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)
        • created2022-08-03 10:03:29
        • modified2022-12-07 10:57:56
        • County(array)
          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
      • 4(array)
        • id1302
        • application_id1162
        • county_id47
        • site_nameGertrude’s Children’s Hospital
        • physical_addressGertrude’s Children’s Hospital, 34 Muthaiga Road
        • contact_details+254 721245721
        • contact_personProf. Jessie Githanga
        • site_capacity(null)
        • misc(null)
        • created2022-08-03 10:03:29
        • modified2022-12-07 10:57:56
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 5(array)
        • id1303
        • application_id1162
        • county_id42
        • site_nameKEMRI Kondele Children\'s Hospital
        • physical_addressKondele Children\'s Hospital
        • contact_details+254714481488
        • contact_personDr Godfrey Allan Otieno
        • site_capacity(null)
        • misc(null)
        • created2022-08-03 10:03:29
        • modified2022-12-07 10:57:56
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 6(array)
        • id1304
        • application_id1162
        • county_id42
        • site_nameKombewa Clinical Research Centre
        • physical_addressKombewa, Opposite Kombewa Sub-County Hospital
        • contact_details+254721996988
        • contact_personDr Janet Oyieko
        • site_capacity(null)
        • misc(null)
        • created2022-08-03 10:03:29
        • modified2022-12-07 10:57:56
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
    • Sponsor(array)
      • 0(array)
        • id599
        • application_id1162
        • 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
        • created2022-08-02 13:16:15
        • modified2022-12-07 10:57:56
• page_options(array)
  • 55
  • 1010
• redir
• $request->data(array)
  • Application(array)
    • trial_therapeutic_exploratory1
• $this->validationErrors(array)
  • Permission(empty)
  • Aro(empty)
  • Aco(empty)
  • Application(empty)
  • User(empty)
  • TrialStatus(empty)
  • InvestigatorContact(empty)
  • Sponsor(empty)
  • SiteDetail(empty)
  • County(empty)
• Loaded Helpers(array)
  • 0Html
  • 1Form
  • 2Session
  • 3Text
  • 4Number
  • 5SimpleGraph
  • 6Paginator
  • 7DebugTimer
  • 8Toolbar
  • 9HtmlToolbar

App Constants

CakePHP Constants

PHP Environment

Included Files

Include Paths

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

Included Files

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