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• trial_statuses(array)
  • 1Recruiting
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• applications(array)
  • 0(array)
    • Application(array)
      • id1551
      • user_id1000
      • trial_status_id(null)
      • abstract_of_study<p>\n This study aims to advance the accuracy and reliability of the Binah.ai algorithm in the Kenyan population. Subjects will be recorded using the Binah.ai Recorder and their vital signs (pulse rate, oxygen saturation and blood pressure) and blood samples will be collected using reference devices and lab tests. A total of 20,000 participants will be recruited globally (Italy, India, Israel, Japan, USA), including 1,000 participants that will be enrolled in Zuri Health Medical Center, Kenya. The process includes training the algorithm with the newly collected data. Once the training is completed, new data collected will be used to validate the performance of the improved algorithm. We expect that this data collection study will improve the overall algorithm performance among the Kenyan population.</p>\n
      • study_title<p>\n Physiological and Biomarker Monitoring: Enhancing Vital Signs and Biomarkers Algorithm of Binah.AI in the Kenyan Population</p>\n
      • laymans_summary<p data-end=\"362\" data-start=\"0\">\n This study wants to make sure the Binah.ai health application works well for people in Kenya. The application checks your vital signs like heart rate, oxygen levels, and blood pressure just by using a smartphone. To do this, researchers will record volunteers using the Binah.ai Recorder and also check their vital signs and blood using standard medical equipment and lab tests.</p>\n<p data-end=\"694\" data-start=\"364\">\n In total, 20,000 people from around the world will take part, including 1,000 people in Kenya at Zuri Health Medical Center. The information collected will help train the application to better understand health signs in different people. After this training, researchers will test the updated application to see if it gives more accurate results.</p>\n<p data-end=\"795\" data-is-last-node=\"\" data-is-only-node=\"\" data-start=\"696\">\n The goal is to make sure the application works well and gives reliable health readings for people in Kenya.</p>\n<p>\n  </p>\n
      • short_titleZHR-001
      • protocol_noECCT/25/06/03
      • version_no3.0
      • date_of_protocol14-05-2025
      • study_drugBinah.ai recorder
      • disease_conditionVital signs
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device1
      • product_type_chemical_name
      • product_type_medical_device_nameBinah.ai recorder
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addresszurihealthresearch@gmail.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum0
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_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_applicantDr. Borna Nyaoke
      • declaration_date111-07-2025
      • declaration_principal_investigatorDr. Borna Nyaoke
      • declaration_date211-07-2025
      • placebo_presentNo
      • study_objectives<p style=\"margin-left:.75in;\">\n Collection of subjects recordings using the Binah.ai Recorder, and vital sign data and blood samples using reference devices and lab tests to enhance the Binah.ai algorithm performance on the population of Kenya.</p>\n<h2>\n  </h2>\n<p>\n  </p>\n
      • principal_inclusion_criteria<ol>\n <li>\n The subject must have the ability to understand and provide written informed consent.</li>\n <li>\n Male or Female subjects ≥18 and ≤65 of age.</li>\n <li>\n The subject must be willing and able to comply with study procedures.</li>\n <li>\n Subjects with the following co-morbid conditions.</li>\n</ol>\n<p style=\"margin-left:106.35pt;\">\n <em>Note: Healthy subjects without the following conditions are still eligible</em></p>\n<ol style=\"list-style-type:lower-roman;\">\n <li>\n Subject with Pre-diabetes or diabetes HbA1C 6.4-16%</li>\n <li>\n Subject with Hypertension with systolic measurements above 145 mmHg</li>\n <li>\n Subject with Total cholesterol with measurements of   >240 mg/dl or higher</li>\n <li>\n Subjects who are active smokers</li>\n</ol>\n<p>\n  </p>\n
      • principal_exclusion_criteria<ol>\n <li>\n The subject has compromised circulation, injury, or physical malformation of fingers, hands, ears or forehead/skull or other sensor Region of Interest (ROI) which would limit the ability to test ROI needed for the study.</li>\n</ol>\n<p style=\"margin-left:99.25pt;\">\n <em>Note: Certain malformations may still allow subjects to participate if the condition is noted and would not affect the particular areas utilized.</em></p>\n<ol>\n <li value=\"2\">\n The subject has a tattoo in the optical path which would limit the ability to conduct the tests needed for the study.</li>\n <li value=\"3\">\n Subjects with severe contact allergies to standard adhesives, latex or other materials found in pulse oximetry sensors, respiration monitor electrodes or other medical sensors used for measuring vital signs.</li>\n <li value=\"4\">\n Subject with a medical condition which in the opinion of the investigator, does not allow performing the study assessments.</li>\n <li value=\"5\">\n Subject unfit to participate in the study to the judgment of the investigator.</li>\n</ol>\n<p>\n  </p>\n
      • primary_end_points<p style=\"margin-left:49.65pt;\">\n Record 1000 subject’s vitals including: blood pressure, pulse rate and oxygen saturation using the Binah.ai recorder and reference devices. The data will be gathered by trained personnel and used to train and validate the Binah.ai algorithm to enhance the accuracy and reliability among the Kenyan population.</p>\n<p>\n  </p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety0
      • scope_efficacy0
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others1
      • scope_others_specifyAlgorithim testing
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other1
      • trial_other_specifyMedical device exploratory
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledNo
      • site_capacity(null)
      • staff_numbers<p>\n The study will be conducted at Zuri Health medical center, a Level III registered health facility in Nairobi which provides comprehensive primary healthcare services through a team of over 50 staff, including 30 clinical professionals (doctors, nurses, clinical officers, nutritionists, lab technicians, and pharmacists). Since launching in 2021, Zuri Health medical center has served over 200,000 patients, attending to approximately 100 patients weekly. Zuri Health medical center works with corporates and foundations to carry out wellness screenings and medical camps across the county with over 12,000 patients seen in Nairobi in 2024. Patients with non-communicable diseases diagnosed during the wellness screenings or medical camps are under follow-up at the medical center in the continuous care program</p>\n<p>\n Screening of all participants will be conducted at the Zuri Health Medical Center and consenting of study participants will take place in a private room at the medical centre by the Principal Investigator or designee.</p>\n<p>\n Principal Investigator- Dr. Borna Nyaoke MBChB,MPH- over 14 years of clinical trial experience</p>\n<p>\n Co-Investigator- Dr. Barbara Tarno MBChB</p>\n<p>\n  </p>\n
      • other_details_explanation<p>\n The study has also been conducted in the USA, Israel and India</p>\n
      • other_details_regulatory_notapproved<p>\n N/A</p>\n
      • other_details_regulatory_approved<p>\n Ethics Approval: </p>\n<p>\n Lokmanya Medical Research Center Ethical Committee, Pune, India- 1000 subjects- 1 site</p>\n<p>\n Salus IRB, Austin, Texas, USA- 1000 subjects- 1 site</p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration6 months
      • design_controlled_randomised
      • design_controlled_open
      • design_controlled_single_blind
      • design_controlled_double_blind
      • design_controlled_parallel_group
      • design_controlled_cross_over
      • design_controlled_other
      • design_controlled_specify
      • design_controlled_comparator
      • design_controlled_other_medicinal
      • design_controlled_placebo
      • design_controlled_medicinal_other
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaZuri Health Medical Centre
      • single_site_physical_address132 Manyani East Road, Nairobi, Kenya
      • single_site_contact_personDr. Borna Nyaoke
      • single_site_telephone0720734479
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states5
      • number_of_sites
      • multi_country_listItaly, India, Israel, Japan, USA
      • data_monitoring_committeeNo
      • total_enrolment_per_site1000
      • total_participants_worldwide20000
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyYes
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameBorna
      • investigator1_middle_nameAchieng
      • investigator1_family_nameNyaoke
      • investigator1_qualificationMBChB MPH
      • investigator1_professional_address132 Manyani East Road, Nairobi, Kenya
      • investigator1_telephone0756551551
      • investigator1_emailbornanyaoke12@gmail.com
      • organisations_transferred_No
      • number_participants1000
      • notification
      • approval_date21-11-2025
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted19-06-2025
      • is_child0
      • unsubmitted1
      • initial_date_submitted19-06-2025
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been addressed.
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-11-21 11:27:20
      • created2025-05-22 01:13:23
      • total_sites1
      • ecitizen_invoice375575
    • InvestigatorContact(array)
      • 0(array)
        • id1290
        • application_id1551
        • given_nameBorna
        • middle_nameAchieng
        • family_nameNyaoke
        • qualificationMBChB, MPH
        • professional_address132 Manyani East Road, Nairobi, Kenya
        • telephone0756551551
        • emailborna@zuri.health
        • created2025-05-22 01:29:28
        • modified2025-07-11 11:33:04
    • SiteDetail(array)
      • 0(array)
        • id1926
        • application_id1551
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2025-05-22 01:29:28
        • modified2025-07-11 11:33:04
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id840
        • application_id1551
        • sponsorBinah.ai Inc
        • sponsor_typeIndustry
        • contact_personKfir Oved
        • addressBinah.ai Inc. 265 Franklin St Suite 1702 Boston, MA 02110
        • telephone_number+972506577765
        • fax_number
        • cell_number+972506577765
        • email_addresskfir.oved@binah.ai
        • created2025-05-22 01:29:28
        • modified2025-07-11 11:33:04
  • 1(array)
    • Application(array)
      • id1548
      • user_id263
      • trial_status_id2
      • abstract_of_study<div>\n This is an interventional, multi-national, multi-centre, open-label, phase 3b study in adults (participants ≥ 18 years old), adolescents (participants ≥ 12 to < 18 years old) and</div>\n<div>\n children(participants ≥ 11 months to < 12 years old) with sickle cell disease (SCD), with SCD who have been on chronic transfusions to prevent primary stroke or recurrence of stroke (SCDTD), non-transfusion-dependent thalassaemia (NTDT) or transfusion-dependent thalassaemia (TDT).</div>\n<div>\n The purpose of this rollover study is to investigate the long-term safety of etavopivat in participants 11 months of age and older with SCD or thalassaemia who have completed a treatment period in previous etavopivat studies. Long-term clinical efficacy measures of etavopivat treatment will also be assessed.</div>\n<div>\n Etavopivat is an orally bioavailable, selective activator of erythrocyte pyruvate kinase (PKR), currently under development in clinical studies as a potential treatment for inherited haemoglobinopathies, including SCD and thalassemia.</div>\n<div>\n Approximately 325 participants are planned to be enrolled in the study in about 120 sites worldwide. All participants will receive etavopivat. Participants ≥ 12 years old will</div>\n<div>\n receive an oral dose of 400 mg QD administered as 2 × 200 mg tablets. Participants < 12 years old will receive an age- and weight-adjusted dose (400 mg QD equivalent</div>\n<div>\n dose) administered as granules</div>\n
      • study_title<div>\n An open-label, multi-centre, rollover study to characterise long-term safety and efficacy of etavopivat in adults, adolescents and children who have sickle cell disease or thalassaemia and have completed a treatment period in an etavopivat study.</div>\n
      • laymans_summary<div>\n A research study looking at long-term treatment with etavopivat in people with sickle cell disease or thalassaemia.</div>\n<div>\n The purpose of this rollover study is to investigate the long-term safety of etavopivat in participants 11 months of age and older with SCD or thalassaemia who have completed a treatment period in previous etavopivat studies.</div>\n<div>\n Long-term clinical efficacy measures of etavopivat treatment will also be assessed. This study will also ensure that participants who are benefiting from etavopivat treatment</div>\n<div>\n have prolonged access to the drug in the time before it is commercially available in their country.</div>\n<div>\n Etavopivat is an orally bioavailable, small-molecule activator of pyruvate kinase red blood cell (PKR) isozyme. The investigational medicinal product (IMP) is being developed for the treatment of inherited haemoglobinopathies, such as Sickle cell disease (SCD) and thalassemia</div>\n
      • short_titleFloral roll over study
      • protocol_noECCT/25/05/07
      • version_no1.0
      • date_of_protocol03-05-2024
      • study_drugEtavopivat
      • 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_nameetavopivat
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressamina.salim@iqvia.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_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_applicantSylvia Macharia
      • declaration_date120-05-2025
      • declaration_principal_investigatorDr Bernhards Ogutu
      • declaration_date220-05-2025
      • placebo_presentNo
      • study_objectives<ul>\n <li>\n To investigate long-term safety of etavopivat in adults, adolescents and children with SCD, SCDTD, TDT or NTDT transferring from other studies with etavopivat</li>\n <li>\n To investigate long-term clinical efficacy measures of etavopivat treatment in adults, adolescents and children with SCD transferring from other studies with etavopivat</li>\n <li>\n To evaluate the effects of etavopivat on hospitalisations in adults, adolescents and children with SCD transferring from other studies with etavopivat</li>\n <li>\n To investigate long-term clinical efficacy measures of etavopivat treatment in adults and adolescents with NTDT transferring from other studies with etavopivat</li>\n <li>\n To investigate long-term clinical efficacy measures of etavopivat treatment in adults and adolescents with TDT or SCDTD, transferring from other studies with etavopivat</li>\n</ul>\n
      • principal_inclusion_criteria<div>\n 1. Informed consent obtained before any study-related activities. Study-related activities are any procedures that are carried out as part of the study, including activities to determine suitability for the study. United Kingdom: Please see country specific requirements in Appendix 8 (Section10.8).</div>\n<div>\n 2. Participant must have ongoing participation in an etavopivat parent study (Table 4-1) for treatment of SCD or thalassaemia and have completed at least a treatment period of the parent study.</div>\n<div>\n 3. Participant must have derived clinical benefit from treatment with etavopivat, as determined by the investigator.</div>\n<div>\n 4. Any participant with dose reduction or temporary discontinuation will need to be rechallenged before transferring.</div>\n<div>\n 5. Participants on hydroxyurea (HU), crizanlizumab or l-glutamine oral powder (Endari®) treatment at the time of consent</div>\n<div>\n may be eligible if they:</div>\n<div>\n a. Have been on a stable dose during participation in the parent study (i.e., no changes to the dose except for changes to</div>\n<div>\n weight or age reasons).</div>\n<div>\n b. Have been compliant with the treatment regimen at the discretion of the investigator during participation of the parent</div>\n<div>\n study</div>\n
      • principal_exclusion_criteria<div>\n Participants are excluded from the study if any of the following criteria apply:</div>\n<div>\n 1. Previous participation in this study. Participation is defined as signed informed consent.</div>\n<div>\n 2. Female who is pregnant or intends to become pregnant or is of childbearing potential and not using adequate contraceptive method, as defined in Appendix 4 (Section 10.4).</div>\n<div>\n 3. Any disorder, except for conditions associated with SCD or thalassaemia, which in the investigator’s opinion might jeopardise participant’s safety or compliance with the protocol.</div>\n<div>\n 4. Participant withdrew or had permanent treatment discontinuation from an etavopivat clinical study.</div>\n<div>\n 5. Participants on permanent treatment dose reduction or temporary treatment discontinuation.</div>\n<div>\n 6. Use of any of the following within the timeframes prior to the transfer visit as stated:</div>\n<div>\n a. Use of voxelotor within participation of the parent study or anticipated need for this agent during this study</div>\n<div>\n b. Use of an experimental selectin antagonist (e.g., monoclonal antibody or small molecule) within the parent study or anticipated need for such agents during this study.</div>\n<div>\n c. Use of erythropoietin or other haematopoietic growth factor treatment within the parent study or anticipated need for such agents during this study.</div>\n<div>\n d. Receiving or use of concomitant medications that are strong inducers of cytochrome P450 (CYP) 3A4 within 2 weeks of the</div>\n<div>\n transfer visit or anticipated need for such agents during the study.</div>\n<div>\n 7. Current participation in a study that is not a designated parent study, or planned participation in any other clinical trial, for the duration of FLORAL</div>\n
      • primary_end_points<div>\n Number of TEAEs, reported for each indication and age group separately.</div>\n<div>\n Number of adverse reactions, reported for each indication and age group separately</div>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety0
      • scope_efficacy0
      • 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_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<div>\n Gertrude’s Children’s Hospital (GCH) is one of the largest hospitals in East and Central Africa dedicated exclusively to the care of children. For over 60 years, the hospital has provided high standards of paediatric care for children from birth to 21 years of age. The hospital is accredited by the Joint Commission International Accreditation and Safe Care, Netherlands following audits of the hospital facilities. GCH is a non- profit organization, chartered with the responsibility of provision of health services, fostering good health, carrying out research and teaching healthcare professionals. Based in Muthaiga, Nairobi, and spread out to various outpatient clinics all over Nairobi and in several other Counties, the hospital attends to over 300,000 children as outpatients and admits over 6,000 patients on average per year. The over 100-bed hospital offers comprehensive paediatric medical services and there are 21 specialist clinics that cover almost every aspect of paediatric healthcare from haematology, chest conditions, cardiology, dermatology, otorhinolaryngology, endocrinology, oncology and HIV/AIDS. Primary care services are also offered including a Well Baby and Immunization clinic. The laboratory is equipped with modern equipment and offers diagnostic laboratory testing in all areas of pathology and is headed by a pathologist supported by several other pathologists, laboratory manager and qualified medical laboratory technologists. The hospital laboratory and pharmacy cater for both children and adults. The laboratory is accredited by Kenya Accreditation Service as a medical testing laboratory (ISO15189:2012). Qualified pharmacists manage the hospital pharmacy. GCH has an up-to-date paediatric imaging facility that is managed by a team of radiologists and qualified radiographers. Most of the processes at the hospital are fully computerized and supported by a well-integrate Information Technology Department. The main hospital in Muthaiga is open 24/7 and offers 24-hour laboratory and pharmacy coverage.</div>\n<div>\n The Accident and Emergency Department is well equipped to deal with all forms of paediatric emergencies and has a crash cart and crash team on call, 24 hours a day. There are registered nurses, medical officers and specialists specifically trained in Emergency Triage Assessment and Treatment. The Team is fully trained to handle emergencies, including but not limited to airway obstruction and other breathing problems; circulatory impairment or shock; severely altered central nervous system function (coma or convulsive seizures); and severe dehydration which require urgent appropriate care to prevent death.</div>\n<div>\n The site has a multidisciplinary study team that comprises specialists and professionals in many fields of medicine including; medical officers, paediatricians, haematologists, oncologists, pathologists, nurses, pharmacists, medical laboratory technologists. The Team has members who have been trained on the job as study coordinators. The team members are experienced in clinical trials and have all been trained in Good Clinical Practice and most have successfully participated in several other clinical trials.</div>\n<div>\n Site Study staff details.</div>\n<div>\n <div>\n Principal Investigator</div>\n <div>\n Prof. Jessie Githanga Hematologist</div>\n <div>\n Prof Jessie Githanga Gertrude’s Children’s Hospital,</div>\n <div>\n P. O. Box 42325 -00100 GPO NAIROBI TEL: +254 721245721</div>\n <div>\n FAX: None</div>\n <div>\n Email: jgithanga3@gmail.com</div>\n <div>\n Co-Investigator</div>\n <div>\n Dr. Mercy Kamene Paediatrician</div>\n <div>\n Gertrude’s Children’s Hospital,</div>\n <div>\n P. O. Box 42325 -00100 GPO NAIROBI TEL: +254 +254 711 264 069/ +254 735</div>\n <div>\n 985 086</div>\n <div>\n FAX: None</div>\n <div>\n Email: mkamene@gerties.org</div>\n <div>\n  </div>\n <div>\n Co-Investigator</div>\n <div>\n Dr. Doreen Karimi Mutua Hematologist- Oncologist</div>\n <div>\n Dr. Doreen Karimi Mutua Gertrude’s Children’s Hospital,</div>\n <div>\n P. O. Box 42325 -00100 GPO NAIROBI TEL: +254722384218</div>\n <div>\n FAX: None</div>\n <div>\n Email: tessmutua@gmail.com</div>\n <div>\n  </div>\n <div>\n Study Doctor</div>\n <div>\n Dr Olivia Gathoni Medical Officer</div>\n <div>\n Gertrude’s Children’s Hospital,</div>\n <div>\n P. O. Box 42325 -00100 GPO NAIROBI TEL: +254 787643232</div>\n <div>\n FAX: None</div>\n <div>\n Email: oliviathoni@gmail.com</div>\n <div>\n  </div>\n <div>\n Study Pharmacist</div>\n <div>\n Dr. Winnie Owilla</div>\n <div>\n Gertrude’s Children’s Hospital,</div>\n <div>\n P. O. Box 42325 -00100 GPO NAIROBI TEL: +254 719483412</div>\n <div>\n FAX: None</div>\n <div>\n Email: wakoth@gerties.org</div>\n</div>\n<div>\n <div>\n Pharmaceutical technologist</div>\n <div>\n Cresencia Nekesa Makokha</div>\n <div>\n Cresencia Nekesa</div>\n <div>\n Gertrude’s Children’s Hospital,</div>\n <div>\n P. O. Box 42325 -00100 GPO NAIROBI TEL: +254 713005972</div>\n <div>\n FAX: None</div>\n <div>\n Email: cresencianekesa@gmail.com</div>\n <div>\n  </div>\n <div>\n Study nurses</div>\n <div>\n Hannah Wanjiku</div>\n <div>\n Gertrude’s Children’s Hospital,</div>\n <div>\n P. O. Box 42325 -00100 GPO NAIROBI TEL: +254 711747874</div>\n <div>\n FAX: None</div>\n <div>\n Email: hwanjiku@gerties.org</div>\n <div>\n  </div>\n <div>\n Jane Nduati</div>\n <div>\n Gertrude’s Children’s Hospital,</div>\n <div>\n P. O. Box 42325 -00100 GPO NAIROBI TEL: +254 728664511</div>\n <div>\n FAX: None</div>\n <div>\n Email: nduatijyne@gmail.com</div>\n</div>\n<div>\n  </div>\n<div>\n <div>\n Laboratory technician/technologist</div>\n <div>\n Charles Muia (technologist) Lead*</div>\n <div>\n Gertrude’s Children’s Hospital,</div>\n <div>\n P. O. Box 42325 -00100 GPO NAIROBI TEL: +254 721 882883</div>\n <div>\n FAX: None</div>\n <div>\n Email: cmuia@gerties.org</div>\n <div>\n  </div>\n <div>\n Herman Akumu (technologist)</div>\n <div>\n Gertrude’s Children’s Hospital,</div>\n <div>\n P. O. Box 42325 -00100 GPO NAIROBI TEL: +254 721 246232</div>\n <div>\n FAX: None</div>\n <div>\n Email: hakumu@gerties.org</div>\n</div>\n<div>\n  </div>\n<div>\n <div>\n Primary Study coordinator/Quality control officer</div>\n <div>\n Edwina Oboke</div>\n <div>\n Gertrude’s Children’s Hospital,</div>\n <div>\n P. O. Box 42325 -00100 GPO NAIROBI TEL: +254 726988256</div>\n <div>\n FAX: None</div>\n <div>\n Email: eoboke21@gmail.com</div>\n</div>\n<p>\n  </p>\n
      • other_details_explanation<p>\n The trial will not be conducted in the Sponsor country (Denmark) due to the very limited number of participants with Sickle Cell Disease</p>\n
      • other_details_regulatory_notapproved<div>\n Turkey JA Submitted 11 Jul 2024</div>\n<div>\n US FDA submitted 26 June 2024</div>\n<div>\n Nigeria National Foods and Drugs Authority submitted 15 October 2024</div>\n
      • other_details_regulatory_approved<ul>\n <li>\n Health Canada Submitted 16 Jul 2024 received an approval on 12 Aug 2024</li>\n <li>\n EMA Submitted 31 Jul 2024 received approval on 22 Nov 2024</li>\n</ul>\n<div>\n <div>\n  </div>\n</div>\n<p>\n  </p>\n
      • other_details_regulatory_rejected<p>\n Not applicable</p>\n
      • other_details_regulatory_halted<p>\n This trial has not been halted by any regulatory authorities.</p>\n
      • estimated_durationUp to 260 weeks
      • design_controlled_randomisedNo
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overYes
      • design_controlled_otherYes
      • design_controlled_specifyRollover
      • design_controlled_comparatorNon Randomized
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states17
      • number_of_sites7
      • multi_country_listCanada, Egypt, France, Germany, Ghana, Greece, India, Italy, Lebanon, Nigeria, Oman, Saudi Arabia, Spain, Turkey, USA,\nUnited Kingdom, Kenya
      • data_monitoring_committeeNo
      • total_enrolment_per_siteTotal enrolment in each Kenyan site: (if competitive enrolment, state minimum and maximum number per site.) As this is a rollover trial, we cannot predict the enrollment in each site as the parent trials have competitive enrollment
      • total_participants_worldwide325
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenYes
      • population_adolescentYes
      • population_above_18Yes
      • population_adultYes
      • population_elderlyYes
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
      • subjects_specifyConsent of pediatric participants (below 18 years of age) is obtained by means of parents or legally acceptable representatives
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameDr Bernhards
      • investigator1_middle_name
      • investigator1_family_nameOgutu
      • investigator1_qualificationMedical Doctor
      • investigator1_professional_addressStrathmore University- CREATES Ole Sangale Road, Madaraka Estate, P.O BOX 59857-00200, Nairobi, Kenya
      • investigator1_telephone254733812613/254733966065
      • investigator1_emailogutu6@gmail.com
      • organisations_transferred_Yes
      • number_participants25
      • notification
      • approval_date21-11-2025
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted09-10-2025
      • is_child0
      • unsubmitted1
      • initial_date_submitted19-08-2025
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments were addressed.
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-11-21 10:57:30
      • created2025-05-20 10:01:29
      • total_sites7
      • ecitizen_invoice372386
    • InvestigatorContact(array)
      • 0(array)
        • id1284
        • application_id1548
        • given_nameProf Jessie
        • middle_name
        • family_nameGithanga
        • qualificationMedical Doctor
        • professional_addressDepartment of Human Pathology University of Nairobi 19676-00200
        • telephone+254721245721
        • emailjgithanga3@gmail.com
        • created2025-05-20 10:32:05
        • modified2025-10-09 09:05:01
    • SiteDetail(array)
      • 0(array)
        • id1911
        • application_id1548
        • county_id47
        • site_nameGertrudes Childrens Hospital
        • physical_addressGertrude\'s Children\'s Hospital 34 Muthaiga road
        • contact_detailsjgithanga3@gmail.com
        • contact_personProf Jessie Githanga
        • site_capacity(null)
        • misc(null)
        • created2025-05-20 10:32:05
        • modified2025-10-09 09:05:01
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 1(array)
        • id1912
        • application_id1548
        • county_id42
        • site_nameKEMRI Kondele Children\'s Hospital
        • physical_addressCentre for Clinical Research Within Jaramogi Oginga Odinga Hospital
        • contact_detailsogutu6@gmail.com
        • contact_personDr Benhards Ogutu
        • site_capacity(null)
        • misc(null)
        • created2025-05-20 10:32:05
        • modified2025-10-09 09:05:01
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 2(array)
        • id1913
        • application_id1548
        • county_id41
        • site_nameKEMRI Siaya Clinical Research Annex
        • physical_addressSiaya County Referral hospital grounds
        • contact_detailsvduba@gmail.com
        • contact_personProf Videlis Nduba
        • site_capacity(null)
        • misc(null)
        • created2025-05-20 10:32:05
        • modified2025-10-09 09:05:01
        • County(array)
          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
      • 3(array)
        • id1914
        • application_id1548
        • county_id42
        • site_nameKEMRI/ WRAIR-Africa, Kombewa Clinical Research Center
        • physical_addressCentre for Clinical Research Within Jaramogi Oginga Odinga Hospital
        • contact_detailsjanet.oyieko@usamru-k.org or janet.oyieko@gmail.com
        • contact_personDr Janet Oyieko
        • site_capacity(null)
        • misc(null)
        • created2025-05-20 10:32:05
        • modified2025-10-09 09:05:01
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 4(array)
        • id1915
        • application_id1548
        • county_id35
        • site_nameKEMRI WALTER REED KERICHO
        • physical_addressKenya Medical Research Institute/ Walter Reed Project Off Hospital Road, Kericho, Kenya P.O. BOX 1357- 20200
        • contact_detailsisaac.tsikhutsu@usamru-k.org or itsikhutsu@yahoo.com
        • contact_personDr Isaac Tsikhutsu
        • site_capacity(null)
        • misc(null)
        • created2025-05-20 10:32:05
        • modified2025-10-09 09:05:01
        • County(array)
          • id35
          • county_nameKericho
          • created2012-06-15 10:26:16
          • modified2012-06-15 10:26:16
      • 5(array)
        • id1916
        • application_id1548
        • county_id42
        • site_nameKEMRI/ WRAIR-Africa, Kombewa Clinical Research Center
        • physical_addressCentre for Clinical Research Within Jaramogi Oginga Odinga Hospital
        • contact_detailswalter.otieno@usamru-k.org
        • contact_personDr Walter Otieno
        • site_capacity(null)
        • misc(null)
        • created2025-05-20 10:32:05
        • modified2025-10-09 09:05:01
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 6(array)
        • id1917
        • application_id1548
        • county_id42
        • site_nameCenter for Research in Therapeutic Sciences (CREATES)
        • physical_addressAhero County Hospital
        • contact_detailsogutu6@gmail.com
        • contact_personDr Benhards Ogutu
        • site_capacity(null)
        • misc(null)
        • created2025-05-20 10:32:05
        • modified2025-10-09 09:05:01
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
    • Sponsor(array)
      • 0(array)
        • id837
        • application_id1548
        • sponsorNovo Nordisk A/S
        • sponsor_typeOthers
        • contact_personIsabella Andreotti
        • addressNovo Allé, 2880 Bagsvaerd, Denmark
        • telephone_number+45-34481755
        • fax_number
        • cell_number+45-34481755
        • email_address7822-HQ-TM@novonordisk.com
        • created2025-05-20 10:32:05
        • modified2025-10-09 09:05:01
  • 2(array)
    • Application(array)
      • id1547
      • user_id993
      • trial_status_id2
      • abstract_of_study<p>\n The introduction of oral cholera vaccine (OCV) and its use in mass vaccination campaigns have proved a game-changer in the fight against cholera. A two dose OCV regimen works to prevent cholera for three to five years by effectively bridging emergency response and longer-term cholera control with a water, sanitation and hygiene (WASH) focus, demonstrating that cholera is not inevitable and that cholera control is not beyond reach. However, two dose OCV is poorly protective in young children who bear a large burden of cholera in endemic countries.</p>\n<p>\n We believe that a cholera conjugate vaccine will provide the desired characteristics of inducing an effective and lasting immune response across a wide age range including young children and provide a low cost and sustainable tool to end cholera. With a more effective response in young children, a conjugate vaccine can be incorporated into routine early childhood immunization programs providing early and direct protection to the age group with the highest burden of disease.</p>\n<p>\n We plan to conduct a phase II clinical trial to determine the immunogenicity and safety of single dose and two doses of <strong>OSP:rTTHc  cholera conjugate vaccine (CCV) with or without alum adjuvant</strong>. This will be a randomized, placebo-controlled, observer blind study in adults aged 18 to 45 years (cohort A) and children aged 5 to 17 years (cohort B) followed by a randomized, active-controlled, partial open label study in children aged 1 to 4 years (cohort C). KAVI-Institute of Clinical Research will recruit and enrol 390 participants from within Nairobi City County. </p>\n<p>\n The study will guide the future dosing schedule and formulation of CCV (with or without Aluminum phosphate adjuvant) expected to be needed in adults and children in cholera-endemic region. </p>\n<p>\n  </p>\n
      • study_title<p>\n A Phase II, randomized, controlled, age-descending study in adults and children to evaluate the safety and immunogenicity of the OSP:rTTHc Cholera Conjugate Vaccine in cholera-endemic region</p>\n
      • laymans_summary<div>\n The introduction of oral cholera vaccine (OCV) and its use in mass vaccination campaigns have proved a game-changer in the fight against cholera. A two dose OCV regimen works to prevent cholera for three to five years by effectively bridging emergency response and longer-term cholera control with a water, sanitation and hygiene (WASH) focus, demonstrating that cholera is not inevitable and that cholera control is not beyond reach. However, two dose OCV is poorly protective in young children who bear a large burden of cholera in endemic countries. We believe that a cholera conjugate vaccine will provide the desired characteristics of inducing an effective and lasting immune response across a wide age range including young children and provide a low cost and sustainable tool to end cholera. With a more effective response in young children, a conjugate vaccine can be incorporated into routine early childhood immunization programs providing early and direct protection to the age group with the highest burden of disease. This phase II study is intended to determine the immunogenicity and safety of single dose and two doses of OSP:rTTHc cholera conjugate vaccine (CCV) with or without alum adjuvant. The study will guide the future dosing schedule and formulation of CCV (with or without Aluminum phosphate adjuvant) expected to be needed in adults and children in a cholera-endemic region.</div>\n
      • short_titleIVI CCV 002
      • protocol_noECCT/25/05/13
      • version_no1.0
      • date_of_protocol09-04-2025
      • study_drugOSP:rTTHc cholera conjugate vaccine with or without Aluminum phosphate adjuvant
      • disease_conditionCholera
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines1
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorYes
      • comparator_nameEuvichol Plus
      • comparator_registeredPrequalified by WHO in 2017
      • comparator_countriesEuvichol-Plus® has been supplied to low and middle income countries which are cholera endemic or regularly experience cholera outbreaks through the WHO Stockpile funded by Global Alliance for Vaccines and Immunizations (GAVI) after receiving WHO PQ certification.
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressckamau@kaviuon.org
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter0
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum0
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_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_applicantProf Walter Jaoko
      • declaration_date129-07-2025
      • declaration_principal_investigatorProf Walter Jaoko
      • declaration_date229-07-2025
      • placebo_presentYes
      • study_objectives<p>\n <em>Primary Objective</em><em>s</em></p>\n<ol>\n <li>\n To evaluate the serum vibriocidal antibody titers against <em>V. cholerae</em> O1 Inaba and O1 Ogawa at 4 weeks after one dose of CCV (with or without alum) 25 μg / placebo in adults (aged 18 to 45 years) and in children (aged 5 to 17 years) compared to pre-vaccination.</li>\n <li>\n To evaluate the serum vibriocidal antibody titers against <em>V. cholerae </em>O1 Inaba and O1 Ogawa at 4 weeks after one dose of CCV (with or without alum) 25 μg / placebo or at 2 weeks after two doses of Euvichol®-Plus in children (aged 1 to 4 years) compared to pre-vaccination.</li>\n <li>\n To evaluate the OSP IgG antibody titers using ELISA, against <em>V. cholerae</em> O1 Inaba at 4 weeks after one dose of CCV (with or without alum) 25 μg / placebo in adults (aged 18 to 45 years) and in children (aged 5 to 17 years) compared to pre-vaccination.</li>\n <li>\n To evaluate the OSP IgG antibody titers using ELISA, against <em>V. cholerae</em> O1 Inaba at 4 weeks after one dose of CCV (with or without alum) 25 μg / placebo or at 2 weeks after two doses of Euvichol®-Plus in children (aged 1 to 4 years) compared to pre-vaccination.</li>\n</ol>\n<p style=\"margin-left:18.0pt;\">\n  </p>\n<p style=\"margin-left:18.0pt;\">\n <em>Secondary Objective</em></p>\n<ol>\n <li>\n To evaluate the serum vibriocidal antibody titers against <em>V. cholerae</em> O1 Inaba and O1 Ogawa at 4 weeks after two doses of CCV (with or without alum) 25 μg / placebo in adults (aged 18 to 45 years) and in children (aged 1 to 17 years) compared to pre-vaccination.</li>\n <li>\n To evaluate the serum vibriocidal antibody titers against <em>V. cholerae</em> O1 Inaba and O1 Ogawa at 4 weeks after each dose in heterologous boosting group of CCV with or without alum 25 μg (1st dose) and Euvichol®-Plus (2nd dose) or Euvichol®-Plus (1st dose) and CCV with or without alum 25 μg (2nd dose) in children (aged 1 to 4 years).</li>\n <li>\n To evaluate the OSP IgG antibody titers using ELISA, against <em>V. cholerae</em> O1 Inaba at 4 weeks after two doses of CCV (with or without alum) 25 μg / placebo in adults (aged 18 to 45 years) and in children (aged 1 to 17 years) compared to pre-vaccination.</li>\n <li>\n To evaluate the OSP IgG antibody titers using ELISA, against <em>V. cholerae</em> O1 Inaba at 4 weeks after heterologous booster dose of CCV 25 μg with or without alum (with Euvichol®-Plus as the 1st dose) or of Euvichol®-Plus (with CCV 25 μg with or without alum as the 1st dose) in children (aged 1 to 4 years) compared to pre-vaccination.</li>\n <li>\n To evaluate the safety of CCV (with or without alum) 25 μg after one and two doses of vaccination in adults (aged 18 to 45 years) and in children (aged 1 to 17 years; cohorts B and C combined as well as individually).</li>\n</ol>\n<p>\n  </p>\n<p>\n <em>Exploratory Objective</em><em>s</em></p>\n<ol>\n <li>\n To describe the anti-TT IgG at 4 weeks after each dose of CCV (with or without alum) 25 μg in adults (aged 18 to 45 years) and in subset of children (aged 1 to 17 years; subset of cohorts B and C combined as well as individually) compared to pre-vaccination.</li>\n <li>\n To describe the serum vibriocidal antibody titers against <em>V. cholerae</em> O1 Inaba and O1 Ogawa at 6 months after one dose of CCV 25 μg / placebo in adults (aged 18 to 45 years) and in children (aged 1 to 17 years; cohorts B and C combined as well as individually) compared to pre-vaccination.</li>\n <li>\n To describe the serum vibriocidal antibody titers against <em>V. cholerae</em> O1 Inaba and O1 Ogawa at 6 months after two doses of Euvichol®-Plus in children (aged 1 to 4 years) compared to pre-vaccination.</li>\n <li>\n To describe the OSP IgA and IgM antibody titers using ELISA, against <em>V. cholerae </em>O1 Inaba at 4 weeks after each dose of CCV (with or without alum) 25 μg in adults (aged 18 to 45 years) and in subset of children (aged 1 to 17 years; subset of cohorts B and C combined as well as individually) compared to pre-vaccination.</li>\n <li>\n To describe the OSP IgG, IgA and IgM using LUMINEX, antibody titers against <em>V. cholerae</em> O1 Inaba at 4 weeks after each dose of CCV (with or without alum) 25 μg in adults (aged 18 to 45 years) and in subset of children (aged 1 to 17 years; subset of cohorts B and C combined as well as individually) compared to pre-vaccination.</li>\n <li>\n To describe the OSP IgA and IgM using ELISA, antibody titers against <em>V. cholerae</em> O1 Inaba at 2 weeks after two doses of Euvichol®-Plus in subset of children (aged 1 to 4 years) compared to pre-vaccination.</li>\n <li>\n To describe the OSP IgG, IgA and IgM using LUMINEX, antibody titers against <em>V. cholerae</em> O1 Inaba at 2 weeks after two doses of Euvichol®-Plus in subset of children (aged 1 to 4 years) compared to pre-vaccination.</li>\n <li>\n To describe the OSP IgG antibody titers using ELISA, against <em>V. cholerae</em> O1 Inaba at 6 months after one dose of CCV (with or without alum) 25 μg in adults (aged 18 to 45 years) and in children (aged 1 to 17 years; cohorts B and C combined as well as individually) compared to pre-vaccination.</li>\n <li>\n To describe the OSP IgA and IgM antibody titers using ELISA, against <em>V. cholerae</em> O1 Inaba at 6 months after one dose of CCV (with or without alum) 25 μg in adults (aged 18 to 45 years) and in subset of children (aged 1 to 17 years; cohorts B and C combined as well as individually) compared to pre-vaccination.</li>\n <li>\n To describe the OSP IgG antibody titers using ELISA, against <em>V. cholerae</em> O1 Inaba at 6 months after two doses of Euvichol®-Plus in children (aged 1 to 4 years) compared to pre-vaccination.</li>\n <li>\n To describe the OSP IgA and IgM antibody titers using ELISA, against <em>V. cholerae</em> O1 Inaba at 6 months after two doses of Euvichol®-Plus in subset of children (aged 1 to 4 years) compared to pre-vaccination.</li>\n <li>\n To describe the OSP IgG, IgA and IgM using LUMINEX, antibody titers against <em>V. cholerae</em> O1 Inaba at 6 months after one dose of CCV (with or without alum) 25 μg in adults (aged 18 to 45 years) and in subset of children (aged 1 to 17 years; cohorts B and C combined as well as individually) compared to pre-vaccination.</li>\n <li>\n To describe the OSP IgG, IgA and IgM using LUMINEX, antibody titers against <em>V. cholerae</em> O1 Inaba at 6 months after two doses of Euvichol-Plus® in subset of children (aged 1 to 4 years) compared to pre-vaccination.</li>\n <li>\n To describe OSP-specific IgG and, IgA memory B cell responses at 4- and 24- weeks after one dose of CCV 25 μg in adults (aged 18 to 45 years) compared to pre-vaccination.</li>\n</ol>\n
      • principal_inclusion_criteria<p>\n <strong><em>Inclusion Criteria:</em></strong></p>\n<p>\n In order to be eligible to participate in this study, any individual must meet the following criteria:</p>\n<p style=\"margin-left:36.0pt;\">\n 1)     Individuals aged 1 to 45 years at consent</p>\n<p style=\"margin-left:36.0pt;\">\n 2)     Participants/ Participants’ legally authorized representative (LAR) willing to provide written informed consent to participate in the study voluntarily</p>\n<p style=\"margin-left:36.0pt;\">\n 3)     Participants who can comply with the study requirements</p>\n<p style=\"margin-left:36.0pt;\">\n 4)     Individuals in good health as determined by the outcome of medical history, physical examination, and the clinical judgment of the investigator</p>\n
      • principal_exclusion_criteria<p>\n <strong><em>Exclusion Criteria</em></strong></p>\n<p>\n An individual who meets any of the following criteria will be excluded from participation in this study:</p>\n<p style=\"margin-left:36.0pt;\">\n 1)     Known history or allergy to investigational vaccine components or other medications, or any other allergies deemed by the investigator to increase the risk of an adverse event if they were to participate in the trial</p>\n<p style=\"margin-left:36.0pt;\">\n 2)     Individuals with major congenital abnormalities which in the opinion of investigator may affect the participant’s participation in the study</p>\n<p style=\"margin-left:36.0pt;\">\n 3)     Known history of immune function disorders including immunodeficiency diseases (known HIV infection¥ or other immune function disorders) which in the opinion of investigator may affect the participant’s participation in the study or interfere with the assessment of the study objectives</p>\n<p style=\"margin-left:36.0pt;\">\n 4)     Use of systemic steroids within past 6 months (>10 mg/day prednisone equivalent for periods exceeding 2 consecutive weeks), or receive chemotherapy, radiation therapy or other immunosuppressive drugs within the past 6 months.</p>\n<p style=\"margin-left:36.0pt;\">\n 5)     Any abnormality or chronic disease which in the opinion of the investigator might be detrimental for the safety of the participant and interfere with the assessment of the study objectives</p>\n<p style=\"margin-left:36.0pt;\">\n 6)     Individuals with behavioral or cognitive impairment or psychiatric disease or neural disorders that, in the opinion of the investigator, could interfere with the participant’s ability to participate in the trial</p>\n<p style=\"margin-left:36.0pt;\">\n 7)     Individuals with splenectomy</p>\n<p style=\"margin-left:36.0pt;\">\n 8)     Individuals with a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time resulting in contraindication for IM injections/blood extractions</p>\n<p style=\"margin-left:36.0pt;\">\n 9)     Receipt of blood, blood-derived products, or immunoglobulin products in the past 3 months</p>\n<p style=\"margin-left:36.0pt;\">\n 10) Individuals who have received other vaccines from 4 weeks prior to the first dose of test vaccination or planned to receive any vaccine within 4 weeks of the last dose of the investigational product.  </p>\n<p style=\"margin-left:36.0pt;\">\n 11) Individuals with active or known previous Vibrio cholerae infection</p>\n<p style=\"margin-left:36.0pt;\">\n 12) Individuals with a history of severe diarrhea requiring hospitalization or emergency room visit within the last 5 years</p>\n<p style=\"margin-left:36.0pt;\">\n 13) Individuals with prior receipt of a cholera vaccine in the last 5 years</p>\n<p style=\"margin-left:36.0pt;\">\n 14) Any female participant who is lactating or pregnant</p>\n<p style=\"margin-left:36.0pt;\">\n 15) Females of childbearing potential who do not agree to use an effective birth control method* for at least 4 weeks before the screening and up to 12 weeks after the study vaccination.   </p>\n<p style=\"margin-left:36.0pt;\">\n 16) Individuals enrolled in another clinical trial within 6 months prior to enrollment, concomitantly enrolled or scheduled to be enrolled in another trial during study period</p>\n<p style=\"margin-left:36.0pt;\">\n 17) Individuals who are research staff involved with the clinical trial or family/household members of research staff</p>\n<p style=\"margin-left:36.0pt;\">\n 18) As per Investigator’s medical judgement, an individual could be excluded from the study despite meeting all inclusion/exclusion criteria mentioned above</p>\n
      • primary_end_points<p>\n <strong>Primary Objective 1 Endpoints</strong></p>\n<p>\n Serum vibriocidal antibody titers against V. cholerae O1 Inaba and O1 Ogawa at 28 days after one dose vaccination of CCV (with or without alum) 25 μg / placebo:</p>\n<p style=\"margin-left: 40px;\">\n ·       Proportion of participants achieving seroconversion (defined as at least 4-fold increase from baseline) of serum vibriocidal antibody titers at 28 days after vaccination</p>\n<p style=\"margin-left: 40px;\">\n ·       GMT of serum vibriocidal antibody titers at 28 days after vaccination compared to baseline</p>\n<p style=\"margin-left: 40px;\">\n ·       GMFR of serum vibriocidal antibody titers at 28 days after vaccination</p>\n<p>\n <strong>Primary Objective 2 Endpoints</strong></p>\n<p>\n Serum vibriocidal antibody titers against V. cholerae O1 Inaba and O1 Ogawa at 28 days after one dose vaccination of CCV (with or without alum) 25 μg or at 14 days after two doses of Euvichol®-Plus:</p>\n<p style=\"margin-left: 40px;\">\n ·       Proportion of participants achieving seroconversion of serum vibriocidal antibody titers at 28 days after one dose of CCV or at 14 days after two doses of Euvichol®-Plus</p>\n<p style=\"margin-left: 40px;\">\n ·       GMT of serum vibriocidal antibody titers at 28 days after one dose of CCV or at 14 days after two doses of Euvichol®-Plus compared to baseline</p>\n<p style=\"margin-left: 40px;\">\n ·       GMFR of serum vibriocidal antibody titers at 28 days after one dose of CCV or at 14 days after two doses of Euvichol®-Plus compared to baseline</p>\n<p>\n <strong>Primary Objective 3 Endpoints</strong></p>\n<p>\n IgG antibody responses to O-specific polysaccharide (OSP) using ELISA, against V. cholerae O1 Inaba at 28 days after one dose vaccination of CCV (with or without alum) 25 μg / placebo:</p>\n<p style=\"margin-left: 40px;\">\n ·       Proportion of participants achieving seroconversion (defined as at least 4-fold increase from baseline) of serum anti-OSP IgG antibody titer at 28 days after vaccination</p>\n<p style=\"margin-left: 40px;\">\n ·       Geometric Mean Titer (GMT) of serum anti-OSP IgG antibody at 28 days after vaccination compared to baseline</p>\n<p style=\"margin-left: 40px;\">\n ·       Geometric Mean Fold Rise (GMFR) of serum anti-OSP IgG antibody at 28 days after vaccination</p>\n<p>\n <strong>Primary Objective 4 Endpoints</strong></p>\n<p>\n IgG antibody responses to OSP using ELISA, against V. cholerae O1 Inaba at 28 days after one dose vaccination of CCV (with or without alum) 25 μg or at 14 days after two doses of Euvichol®-Plus:</p>\n<p style=\"margin-left: 40px;\">\n ·       Proportion of participants achieving seroconversion of serum anti-OSP IgG antibody titer at 28 days after one dose of CCV or at 14 days after two doses of Euvichol®-Plus</p>\n<p style=\"margin-left: 40px;\">\n ·       GMT of serum anti-OSP IgG antibody at 28 days after one dose of CCV or at 14 days after two doses of Euvichol®-Plus compared to baseline</p>\n<p style=\"margin-left: 40px;\">\n ·       GMFR of serum anti-OSP IgG antibody at 28 days after one dose of CCV or at 14 days after two doses of Euvichol®-Plus compared to baseline</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy0
      • 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_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n <strong>SITE INVESTIGATORS, INSTITUTIONAL AFFILIATIONS AND ROLES </strong></p>\n<p>\n <strong>Principal Investigator:      </strong>Prof. Walter Jaoko</p>\n<p style=\"margin-left:108.0pt;\">\n Director</p>\n<p style=\"margin-left:108.0pt;\">\n KAVI-Institute of Clinical Research</p>\n<p style=\"margin-left:108.0pt;\">\n University of Nairobi, P.O Box 19676 Nairobi-00202</p>\n<p style=\"margin-left:108.0pt;\">\n Tel: +254 727 555 254</p>\n<p style=\"margin-left:108.0pt;\">\n Email: <a href=\"mailto:wjaoko@kaviuon.org\">wjaoko@kaviuon.org</a></p>\n<p>\n  </p>\n<p>\n <strong>Key Personnel</strong></p>\n<p>\n Co-Investigator:                  Prof. Dalton Wamalwa</p>\n<p style=\"margin-left:108.4pt;\">\n Department of Paediatrics and Child Health</p>\n<p style=\"margin-left:108.4pt;\">\n University of Nairobi, P.O Box 19676 Nairobi-00202</p>\n<p style=\"margin-left:108.4pt;\">\n Tel: +254 721 239 493</p>\n<p style=\"margin-left:108.4pt;\">\n Email: <a href=\"mailto:dalton.wamalwa@uonbi.ac.ke\">dalton.wamalwa@uonbi.ac.ke</a></p>\n<p style=\"margin-left:108.4pt;\">\n Role: Consultant Pediatrician and will be responsible for review, treatment and care of pediatric study participants.</p>\n<p style=\"margin-left:108.4pt;\">\n  </p>\n<p>\n Co-Investigator:                  Prof. Omu Anzala</p>\n<p style=\"margin-left:108.0pt;\">\n Senior Scientist</p>\n<p style=\"margin-left:108.0pt;\">\n KAVI-Institute of Clinical Research</p>\n<p style=\"margin-left:108.0pt;\">\n University of Nairobi, P.O Box 19676 Nairobi-00202</p>\n<p style=\"margin-left:108.0pt;\">\n Tel: +254 727 555 279</p>\n<p style=\"margin-left:108.0pt;\">\n Email: <a href=\"mailto:oanzala@kaviuon.org\">oanzala@kaviuon.org</a>                                            </p>\n<p>\n                                            Role: Consultant Virologist and Immunologist, will provide oversight of immunology objectives in the study.           </p>\n<p>\n  </p>\n<p>\n Co-Investigator:                 Dr. Anne-Marie Macharia</p>\n<p style=\"margin-left:108.4pt;\">\n Department of Paediatrics and Child Health</p>\n<p style=\"margin-left:108.4pt;\">\n Kenyatta National Hospital</p>\n<p style=\"margin-left:108.4pt;\">\n P.O Box 20723 Nairobi-00202</p>\n<p style=\"margin-left:108.4pt;\">\n Tel: +254 722 726 884</p>\n<p style=\"margin-left:108.4pt;\">\n Email: <a href=\"mailto:Annemarie.macharia@gmail.com\">Annemarie.macharia@gmail.com</a></p>\n<p style=\"margin-left:108.4pt;\">\n Role: Consultant Paediatrician, will be responsible for day-to-day care of paediatric study participants.</p>\n<p>\n Co-Investigator:                  Dr. Michael Mutua</p>\n<p style=\"margin-left:108.4pt;\">\n Clinic Manager</p>\n<p style=\"margin-left:108.4pt;\">\n KAVI-Institute of Clinical Research</p>\n<p style=\"margin-left:108.4pt;\">\n University of Nairobi, P.O Box 19676 Nairobi-00202</p>\n<p style=\"margin-left:108.4pt;\">\n Tel: +254 724 653 138</p>\n<p style=\"margin-left:108.4pt;\">\n Email: <a href=\"mailto:mmutua@kaviuon.org\">mmutua@kaviuon.org</a></p>\n<p style=\"margin-left:108.4pt;\">\n Role: Medical Manager and will be responsible for recruitment, and clinic aspects of the clinical trial including medical care and oversight, eligibility determination, site staff training and safety reporting.</p>\n<p>\n  </p>\n<p>\n Co-Investigator:                  Dr. Muna Aden</p>\n<p style=\"margin-left:108.4pt;\">\n Head of Research Division,</p>\n<p style=\"margin-left:108.4pt;\">\n Nairobi Health Directorate,</p>\n<p style=\"margin-left:108.4pt;\">\n Nairobi City County Government</p>\n<p style=\"margin-left:108.4pt;\">\n Tel: +254 713440560</p>\n<p style=\"margin-left:108.4pt;\">\n Email: <a href=\"mailto:munaaaden.1@gmail.com\">munaaaden.1@gmail.com</a></p>\n<p style=\"margin-left:108.4pt;\">\n Role: Epidemiologist, will guide recruitment activities in Nairobi County and provide cholera surveillance updates from the Ministry of Health, Kenya.</p>\n<p>\n  </p>\n<p>\n Pharmacist:                        Dr. Kefa Bosire</p>\n<p style=\"margin-left:108.4pt;\">\n KAVI-Institute of Clinical Research</p>\n<p style=\"margin-left:108.4pt;\">\n University of Nairobi, P.O Box 19676 Nairobi-00202</p>\n<p style=\"margin-left:108.4pt;\">\n Tel: +254 713 542 111</p>\n<p style=\"margin-left:108.4pt;\">\n Email: <a href=\"mailto:kbosire@kaviuon.org\">kbosire@kaviuon.org</a></p>\n<p style=\"margin-left:108.4pt;\">\n Role: Pharmacist of Record, will provide oversight for the investigational product management and the unblinded part of the clinical trial.</p>\n<p>\n  </p>\n<p>\n Laboratory Manager:          Mr. John Gachie</p>\n<p style=\"margin-left:108.4pt;\">\n KAVI-Institute of Clinical Research</p>\n<p style=\"margin-left:108.4pt;\">\n University of Nairobi, P.O Box 19676 Nairobi-00202</p>\n<p style=\"margin-left:108.4pt;\">\n Tel: +254 714 569 073</p>\n<p style=\"margin-left:108.4pt;\">\n Email: <a href=\"mailto:jgachie@kaviuon.org\">jgachie@kaviuon.org</a></p>\n<p style=\"margin-left:108.4pt;\">\n Role: Laboratory Manager, will provide oversight on day-to-day laboratory component of the clinical trial including sample collection, processing and shipment.</p>\n<p>\n Data/ICT Manager:             Mr. Moses Mundia Muriuki</p>\n<p style=\"margin-left:108.4pt;\">\n KAVI-Institute of Clinical Research</p>\n<p style=\"margin-left:108.4pt;\">\n University of Nairobi, P.O Box 19676 Nairobi-00202</p>\n<p style=\"margin-left:108.4pt;\">\n Tel: +254 720 462 793</p>\n<p style=\"margin-left:108.4pt;\">\n Email: <a href=\"mailto:mmuriuki@kaviuon.org\">mmuriuki@kaviuon.org</a></p>\n<p style=\"margin-left:108.4pt;\">\n Role: Data Manager, will provide oversight on data management including data capture, data entry and transmission, and query resolution.</p>\n<p>\n  </p>\n<p>\n Regulatory Affairs Officer:    Ms. Catherine Kamau</p>\n<p>\n /Internal Monitor:                  KAVI-Institute of Clinical Research</p>\n<p>\n                                              University of Nairobi, P.O Box 19676 Nairobi-00202</p>\n<p style=\"margin-left:108.4pt;\">\n Tel: +254 786 982 777</p>\n<p style=\"margin-left:108.4pt;\">\n Email: <a href=\"mailto:ckamau@kaviuon.org\">ckamau@kaviuon.org</a></p>\n<p style=\"margin-left:108.4pt;\">\n Role: Regulatory Affairs Officer, will provide oversight on regulatory compliance and be the liaison person with the research ethics committee and the Pharmacy and Poisons Board</p>\n<p>\n  </p>\n<p>\n Study Coordinator:             Ms. Valerie Awuondo</p>\n<p style=\"margin-left:108.4pt;\">\n KAVI-Institute of Clinical Research</p>\n<p style=\"margin-left:108.4pt;\">\n University of Nairobi, P.O Box 19676 Nairobi-00202</p>\n<p style=\"margin-left:108.4pt;\">\n Tel: +254 731 422 602</p>\n<p style=\"margin-left:108.4pt;\">\n Email: <a href=\"mailto:vawuondo@kaviuon.org\">vawuondo@kaviuon.org</a></p>\n<p style=\"margin-left:108.4pt;\">\n Role: Nurse and Study Coordinator, will coordinate the day-to-day affairs of the study including recruitment, scheduling study visits and coordinate vaccination, sample collection and follow-up of study participants. </p>\n<p>\n <strong>SITE CAPACITY</strong></p>\n<p>\n <strong> Research Clinic</strong></p>\n<p>\n This study will be conducted at the KAVI-ICR Kenyatta National Hospital (KNH) Research Clinic which is located within the premises of the College of Health Sciences, University of Nairobi. The Institute is made up of 3 wings. One wing exclusively hosts the KAVI-ICR Research Laboratory which comprises of 5 laboratories (Safety, PBMC, Tissue Culture, Molecular and Pathogen Sequencing Labs). The floor also hosts our biorepositories that we use to freeze our samples, lab staff offices as well as the institution’s main back up UPS. The second wing hosts administrative, finance, Information Technology (IT), research offices as well as the mucosal lab. This same wing also hosts the investigational product pharmacy. The third wing primarily host the research clinic comprising of a reception/waiting area, 3 counseling rooms, 3 clinic rooms, 1 procedure room, a fully equipped emergency room, research offices, a data room and secure filing room. The second and the third wing also have conference rooms capable of sitting between 20 – 40 people as well as facilitating teleconference meetings. The pharmacy, laboratory and data rooms and offices have secure restricted access doors. All scheduled routine study visits and associated procedures will be conducted at the KAVI-ICR KNH Clinic.</p>\n<p>\n  </p>\n<p>\n Routine medical care for trial participants is provided on-site at the clinic, including general medical care, medication dispensing, HIV counselling and testing, family planning counselling, and provision of HIV post-exposure prophylaxis. The emergency room has resuscitation equipment including a cardiac defibrillator, oxygen cylinders, and emergency drugs in the event of anaphylaxis. Our procedure room is equipped for protocol specific requirements such administration of investigational product and venous blood sample collection.</p>\n<p>\n  </p>\n<p>\n The nearby Kenyatta National Hospital is the main referral facility for non-study related health care and has capacity to provide:</p>\n<ol>\n <li>\n Outpatient and inpatient care for most medical conditions including specialized adult and paediatric care.</li>\n <li>\n Inpatient care for most surgical conditions.</li>\n</ol>\n<p>\n  </p>\n<p>\n In case of medical emergencies at the research clinic, participants will be evacuated by ambulance service to Coptic Hospital for inpatient care including Intensive Care Unit admission if necessary.</p>\n<p>\n KAVI-ICR has also identified community-based organizations that offer support for drug and alcohol addictions as well as victims of gender-based violence.</p>\n<p>\n  </p>\n<p>\n <strong>Personnel</strong></p>\n<p>\n The site has adequate staff with vast experience in conducting clinical trials. In addition to the list of investigators provided on this document, the site has the following staff who will be involved directly in conducting the trial:</p>\n<ol>\n <li>\n Clinical Officers – 4</li>\n <li>\n Nurse Counselors – 4</li>\n <li>\n Community Liaison Officers – 3</li>\n <li>\n Pharmaceutical Technologists – 2</li>\n <li>\n Laboratory Staff - 5</li>\n <li>\n IT Manager – 1</li>\n <li>\n Data Clerks – 4</li>\n <li>\n Quality Assurance Officers - 2</li>\n</ol>\n<p>\n  </p>\n<p>\n All research staff are trained in Good Clinical Practice (GCP) and Protection of Human Subjects Research (HSP) at minimum. All staff undergo periodic Standard Operating Procedures (SOP) training as well as Study Specific Procedures (SSP) training prior to the beginning of the trial and as frequently as is required thereafter.</p>\n<p>\n  </p>\n<p>\n <strong>Pharmacy</strong></p>\n<p>\n The pharmacy is located on the 3rd floor at the University of Nairobi, College of Health Sciences in Kenyatta National and Referral Hospital in Nairobi along Ngong Road. This pharmacy space measures approximately 24 square meters and is divided into pharmacy office and the vaccine (IP) pharmacy. The IP pharmacy has a Sanyo MDF -80°C freezer, a Panasonic -80°C freezer, a Sanyo 2-8 refrigerator, a class II biosafety cabinet, open shelves and a lockable cabinet which act as room temperature storage unit. The room has an air conditioner unit for ambient temperature regulation. All these units are powered by the mains electricity but there exists a UPS and two generators on site which work as back-up facilities. </p>\n<p>\n  </p>\n<p>\n Transmitters connected to the freezer, fridge and the lockable cabinet send data to the pharmacy computer, which is programmed to call relevant staff in the event of temperature excursions or power failure, and which downloads the temperature data stored in the Eltek Temperature Monitoring system. Room temperature can also be controlled in a similar manner. Access to the pharmacy is restricted and is limited to the pharmacy staff by the use of magnetic access cards. All visitors to the pharmacy must sign a visitor’s log and must be accompanied by at least one of the pharmacy staff. Security of the entire site including the pharmacy, is maintained by the University of Nairobi security staff. A back-up pharmacy is available at the KAVI-Kangemi site for emergency transfer of the Investigational Products in case of catastrophic power failure. Monitoring of the pharmacy activities is usually conducted by a single monitor facilitated by the study sponsor. Pharmacy staff who are un-blinded do not participate in the safety assessment of volunteers. </p>\n<p>\n  </p>\n<p>\n <strong>Laboratory</strong></p>\n<p>\n The main lab occupies the 2^nd floor of the KAVI-ICR building at the College of Health sciences (University of Nairobi) and it is accredited to Good Clinical Laboratory Practice standards (GCLP). The laboratory is also registered with KMLTTB (Kenya Medical Technicians and Technologists Board) which is the regulatory body under Ministry of Health, Kenya governing all diagnostic and clinical research laboratories in the country. The lab has capacity to perform HLA molecular tissue typing, serological assays for HIV, HBV, and HCV (using ELISA) and RPR (syphilis), hematology (CBC and differential), biochemistry (liver and renal function tests), urinalysis, and pregnancy tests, PCR tests (CT/NG, HIV Viral Load), PBMC separation, intracellular cytokine staining, mucosal sample processing, ELISpot, FlowCytometry, HIV Viral mobility assays and a variety of basic immunological assays e.g. B cell sorting and antibody response determination. There is ongoing capacity building to improve the ability to conduct COVID-19 related trials. Turn-around time for results is approximately 3 days but more critical results can be provided within 24hours.</p>\n<p>\n  </p>\n<p>\n KAVI-ICR has engaged the services of the Pathologists LANCET Kenya Laboratories and Pathcare Kenya Labs as back-ups and referral to the main KAVI-ICR Lab.</p>\n<p>\n  </p>\n<p>\n <strong>Data Management</strong></p>\n<p>\n Data management is mainly through online and offline data capture system and datafax. In addition to the electronic swipe cards that limit access to the data office, access to the database is password controlled and staff have limited access levels to the database. Study documents that contain volunteer identifiers are stored separately in fireproof cabinets located in a different office within the site facilities. There are 2 computers dedicated to data entry. During power outages, all critical operations are supported by a diesel-powered generator and a UPS system. The site has data management SOPs including data backup and disaster management. Off-site long-term archiving of study documents is outsourced to a company called The Filing Room.</p>\n<p>\n  </p>\n<p>\n The study will be conducted in compliance to the Kenya Data Protection Act of 2019.</p>\n<p>\n  </p>\n<p>\n During the informed consent process prior to joining the study, site staff will take adequate time to explain to the study participants about confidentiality, privacy, and data protection. We will explain to them about the measures the site will take to ensure their privacy and confidentiality is maintained such as using unique identifiers on their records and specimen, and safe restricted storage of any records bearing their names. Participants will be informed about their rights as study participants in terms of accessing, correcting, and restricting the use of their child’s data in the research study as stipulated in the ICF. Participants will also be informed that research study is highly regulated with oversight from the Sponsor, ethics committee and regulatory authorities who ensure the site complies with all requirements of data protection and confidentiality.      </p>\n<p style=\"margin-left:108.4pt;\">\n  </p>\n
      • other_details_explanation
      • other_details_regulatory_notapproved<p>\n Not applicable</p>\n
      • other_details_regulatory_approved<p>\n Not applicable</p>\n
      • other_details_regulatory_rejected
      • other_details_regulatory_halted
      • estimated_duration20 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_otherYes
      • design_controlled_specifyObserver Blind, Partially Open
      • design_controlled_comparatorEuvichol-Plus and NSaline
      • design_controlled_other_medicinalYes
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKAVI - Institute of Clinical Research, University of Nairobi
      • single_site_physical_address3rd Floor, Faculty of Health Sciences Building, University of Nairobi, KNH Grounds, Off Ngong Road P.O Box 19676-00202 Nairobi KENYA
      • single_site_contact_personProf Walter Jaoko
      • single_site_telephone+254727555254
      • multiple_sites_member_stateNo
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites
      • multi_country_list
      • data_monitoring_committeeYes
      • total_enrolment_per_siteKAVI-Institute of Clinical Research will enroll all 390 participants
      • total_participants_worldwide390
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerYes
      • population_childrenYes
      • population_adolescentYes
      • population_above_18Yes
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
      • subjects_specifyChildren aged 1 year to less than 18 years, requiring parental consent.
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameWalter
      • investigator1_middle_name
      • investigator1_family_nameJaoko
      • investigator1_qualificationMBCHB, MTropMed, PhD, PGD (Health Research Ethics)
      • investigator1_professional_addressKAVI-Institute of Clinical Research, University of Nairobi, P.O Box 19676 Nairobi-00202
      • investigator1_telephone+254727555254
      • investigator1_emailwjaoko07@gmail.com
      • organisations_transferred_Yes
      • number_participants390
      • notification
      • approval_date07-10-2025
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted29-07-2025
      • is_child0
      • unsubmitted1
      • initial_date_submitted30-05-2025
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been addressed.
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-11-10 13:30:04
      • created2025-05-19 15:46:26
      • total_sites1
      • ecitizen_invoice372275
    • InvestigatorContact(array)
      • 0(array)
        • id1300
        • application_id1547
        • given_nameWalter
        • middle_name
        • family_nameJaoko
        • qualificationMBCHB, MTropMed, PhD, PGD (Health Research Ethics)
        • professional_addressKAVI-Institute of Clinical Research, University of Nairobi, P.O Box 19676 Nairobi-00202
        • telephone+254727555254
        • emailwjaoko07@gmail.com
        • created2025-05-29 08:38:53
        • modified2025-07-29 13:27:47
    • SiteDetail(array)
      • 0(array)
        • id1936
        • application_id1547
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2025-05-29 08:38:53
        • modified2025-07-29 13:27:47
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id845
        • application_id1547
        • sponsorInternational Vaccine Institute (IVI)
        • sponsor_typeResearch Institution
        • contact_personDr Naveena Aloysia DÇor, MBBS, MD
        • addressSNU Research Park, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea
        • telephone_number+82 2 881 1539
        • fax_number
        • cell_number+82 10 6802 2865
        • email_addressNaveena.Dcor@ivi.int
        • created2025-05-29 08:38:53
        • modified2025-07-29 13:27:47
  • 3(array)
    • Application(array)
      • id1542
      • user_id263
      • trial_status_id2
      • abstract_of_study<div>\n SCD is caused by a specific point mutation (E6V) in the gene encoding hemoglobin (Hb) subunit beta that leads to the production of abnormal Hb (“sickle hemoglobin” or HbS). Sickled haemoglobin leads to several patho-physiological changes that culminates in the vascular obstruction and ischemia responsible for much of the observed morbidity in SCD. Prior to July 2017, the only drug specifically approved for the treatment of SCD was hydroxyurea (HU). HU reduces painful crises and the need for blood transfusions at least in part by increasing levels of fetal hemoglobin (HbF), which reduces RBC sickling and improves blood flow. Unfortunately, HU is often poorly tolerated, and its widespread use is limited by concerns about its potential impact on fertility and reproduction, challenges achieving and maintaining an efficacious dose due to its hematologic toxicities, and requirements for monthly monitoring.</div>\n<div>\n  </div>\n<div>\n In the US, recently approved treatment options include L-glutamine, voxelotor, and crizanlizumab-tmca. L-glutamine is indicated to reduce the acute complications of SCD, though its adoption remains somewhat limited by lingering questions regarding limitations of the clinical studies, cost concerns, potential for reduced adherence due to twice-daily administration. Voxelotor leads to increased Hb O2 affinity along with a reduction in clinical markers of hemolysis and an increase in Hb levels. Crizanlizumab-tmca administered via intravenous (IV) infusion, has been shown to reduce the incidence of VOCs in patients with SCD. While these new therapies provide promise, additional therapies with the potential to target the underlying pathophysiology of SCD are still needed to manage patients with this devastating disease.</div>\n<div>\n  </div>\n<div>\n Etavopivat is a potent and effective activator of pyruvate kinase red blood cell PKR in both human and mouse red blood cells (RBC). The potential clinical consequence of PKR activation was demonstrated in cellular assays with RBC from patients with SCD in which etavopivat increased haemoglobin-oxygen (Hb-O2) affinity and reduced sickling under severe hypoxic conditions. The study is made up of two parts:</div>\n<div>\n •<strong> Double-blind treatment period</strong>: Research patients will take the study drug (etavopivat or placebo, depending on which treatment group they are in) for 52 weeks. This part of the study is “double-blind,” meaning neither the patient nor study doctor will know which specific treatment (etavopivat or placebo) the patient is receiving. For every 1 participant receiving a placebo, two will receive etavopivat.</div>\n<div>\n <strong>• Open-label extension: </strong>Patients who complete the double-blind treatment period will be eligible to receive etavopivat in the 52-week open-label extension. In this part of the study, the participant will receive etavopivat even if he/she was assigned to receive placebo in the double-blind treatment period.</div>\n<div>\n  </div>\n<div>\n This is an interventional, multi-national, multi-centre, randomised (2:1), double-blind, placebo controlled, Phase 3 study in participants aged 12 and older with sickle cell disease (SCD), who had 2−15 vaso-occlusive crises (VOCs) in the year prior to screening and who have moderate to severe anaemia. This study will enroll up to approximately 408 adult and adolescent patients with SCD, including a maximum of 100 in the age group 12 to 17 years. Kenya is expected to contribute a total of 67 participants to the study population. </div>\n<div>\n  </div>\n<div>\n Participants will be seen at the study sites at week 2 and week 6 then approximately every 6 weeks until week 52 which is the End of Blinded Treatment in the study. Participants in the open-label extension will have visits at weeks 52,56,60,68,76,84,92 and 104. Week 104 is the end of study treatment and will be followed by an end of study visit after 4 weeks. Safety will be monitored throughout the study, and PD, QoL, and clinical outcome measures will be performed at specified visits.</div>\n
      • study_title<p>\n A global phase 3, randomised, double-blind and placebo-controlled study evaluating the efficacy and safety of etavopivat in adolescents and adults with sickle cell disease.</p>\n
      • laymans_summary<div>\n <strong>What is the problem/background?</strong></div>\n<div>\n Sickle cell disease (SCD) is a disease that can be passed on from both parents to a child. It affects the red blood cells that carry oxygen to the body. Normal red blood cells have a circular shape and are very flexible. For patients with SCD, their red blood cells can look like a sickle or crescent moon and become very stiff. These sickle-shaped red blood cells can get stuck in the blood vessels leading to early destruction of these abnormal red blood cells.</div>\n<div>\n <div>\n These blocked blood vessels and loss of red blood cells makes it hard for the blood to transport oxygen. The lack of oxygen can cause severe body pains, which is a key symptom of SCD. </div>\n <div>\n These results in the manifestation of SCD including; recurrent pain referred to as a painful vaso-occlusive crisis (VOC), low blood level and organ damage. </div>\n <div>\n Before 2017, the only known medication approved for preventing the painful episodes and other SCD problems was hydroxyurea. Hydroxyurea works by reducing the number of the sickle red blood cells.</div>\n <div>\n <p>\n Sickle cell disease is associated with significant burden in quality of life. The cure is not readily and locally available. The available medications include drugs for; pain relief, boosting low blood level, prevention of infection and vaccination to prevent infection that is common in Sickle Cell Disease. They are also provided with mental and social support. However, despite these treatments, people with Sickle Cell Disease continue to suffer due to problems of SCD resulting in early death because, none of them results in both significant improvement of blood level and a reduction in the rate of pain episodes and other SCD problems. More research and development of SCD treatments are necessary to improve the effects of the disease and quality of life of the Sickle cell patients.</p>\n </div>\n <div>\n  </div>\n <div>\n <strong>What questions is the study trying to answer?</strong></div>\n <div>\n Etavopivat is a small molecule that can activate a specific protein found in the red blood cells. This protein helps the red blood cells to make energy and to bind oxygen, ultimately improving the health of the red blood cells. These effects may help in treating blood disorders such as sickle cell disease.</div>\n <div>\n The objective of the present study is to confirm how well and how safe etavopivat is compared to placebo on annualised vaso-occlusive crises (VOC) rates, measures of end organ damage,functional exercise capacity, as measured by the 6-minute walk test, and quality of life measures (including fatigue) in adolescents and adults with sickle cell disease enrolled in the study.</div>\n <div>\n A placebo is a medication with similar physical characteristics (shape, color, taste, packing) as the etavopivat but does not contain any active chemical ingredients that affect the body.</div>\n <div>\n  </div>\n <div>\n <strong>Where is the study taking place, how many people does it involve and how are they selected?</strong></div>\n <div>\n The study will be conducted in many centres across the world including at 4 sites in Kenya, in children aged 12 years and above and adult patients aged 18 years and older with 2-15 VOC. Globally, about 408 patients will be enrolled into the study. Kenya is expected to contribute a total of 67 participants to the study population.  Of 408 participants, up to 100 participants will be children and teenagers between 12 and 17 years old, with approximately 25 expected to be enrolled across the 4 sites in Kenya.</div>\n <div>\n  </div>\n <div>\n <strong>What does the study involve for those who are in it?</strong></div>\n <div>\n The participants will be asked to come to 20 visits at the clinic. The participants will have physical examinations as well as other tests, including a walking exercise, heart checks and blood and urine tests. During specific clinic visits, participants will be asked to answer short questionnaires about their health and quality of life. In some countries, participants may also have additional blood samples collected for future research if they accept to do so. Every day during the study, participants will use the Study App to register when they took the study medicine and register if they had any sickle cell pain.</div>\n <div>\n Participants will have a two times chance to receive the etavopivat or the placebo in the first 52 weeks of the study after which they will all receive etavopivat for another 52 weeks. Etavopivat or placebo will be taken once a day for the entire duration of the study.</div>\n <div>\n  </div>\n <div>\n <strong>What are the benefits and risks/costs of the study for those involved?</strong></div>\n <div>\n Necessary precautions have been put in the design and planned conduct of this study in order to minimise risks and inconveniences of participation. The etavopivat safety data, deriving from the nonclinical safety studies and data from Phase 1 studies and the Phase 2 part of study 4202-HEM-301, have not identified major safety issues. Together with the benefit data that has been gathered and presented, this supports further clinical development of etavopivat and suggests that participants with SCD enrolled in this study have the potential to benefit from treatment with etavopivat and that such benefits could be clinically meaningful. The research study will be done at no cost to the participants and they will be reimbursed for “out-of-pocket” expenses, such as travel costs as well as for time spent, meals and inconvenience.</div>\n <div>\n  </div>\n <div>\n <strong>How will the study benefit society?</strong></div>\n <div>\n By participating in the study, the participants will help contribute to the new information on the dosage and usefulness of etavopivat in the management of SCD. Upon public availability of the study results, the results will be disseminated to various community stakeholders.</div>\n <div>\n  </div>\n <div>\n <strong>When does the study start and finish?</strong></div>\n <div>\n The study will start as soon as ethical approval is received. Duration of study participation for an individual patient may last up to 112 weeks and includes the screening period (up to 4 weeks before study treatment), the double-blind treatment period of the study for up to 52 weeks, participation in the open-label extension treatment period for up to 52 weeks and an End of Study (EOS) visit at 4 weeks after the last dose of study drug.</div>\n</div>\n<p>\n  </p>\n
      • short_titleHibiscus 2 - Site 252
      • protocol_noECCT/25/05/05
      • version_no3
      • date_of_protocol30-09-2024
      • study_drugEtavopivat
      • 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_nameetavopivat
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressamina.salim@iqvia.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_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_applicantNatasha Boshoff
      • declaration_date128-05-2025
      • declaration_principal_investigatorDr Videlis Nduba - PI
      • declaration_date228-05-2025
      • placebo_presentYes
      • study_objectives<div>\n The objective of the present study is to confirm efficacy and safety of etavopivat (compared to</div>\n<div>\n placebo) on annualised vaso-occlusive crises (VOC) rates, measures of end organ damage,</div>\n<div>\n functional exercise capacity, as measured by the 6-minute walk test (6MWT), and quality of life</div>\n<div>\n (QOL) measures (including fatigue) in adolescents and adults with sickle cell disease (SCD)</div>\n<div>\n enrolled in the study. Additional Patient Reported Outcome (PRO) QOL measures, including pain,</div>\n<div>\n emotional and functional impact, will also be used to confirm efficacy of etavopivat in adult and</div>\n<div>\n adolescents with SCD. These results are intended to support additional clinical studies within the</div>\n<div>\n etavopivat SCD program.</div>\n
      • principal_inclusion_criteria<div>\n  </div>\n<div>\n <ol>\n <li>\n Informed consent obtained before any study-related activities. Study-related activities are any procedures that are carried out as part of the study, including activities to determine suitability for the study.</li>\n <li>\n Male or female.</li>\n <li>\n Age 12 years or above at the time of signing the informed consent.</li>\n <li>\n Confirmed diagnosis of sickle cell disease.\n <ul>\n <li>\n Documentation of sickle cell disease (SCD) genotype (sickle cell haemoglobin (HbSS), HbSβ0-thalassemia or other sickle cell syndrome variants) based on prior history of laboratory testing or screening test results from central laboratory. Molecular genotyping is not required. SCD genotype may be determined from the results of haemoglobin (Hb) electrophoresis, high-performance liquid chromatography (HPLC) or similar testing. Note that Hb electrophoresis is performed by the central laboratory at screening.</li>\n </ul>\n </li>\n <li>\n Have 2−15 episodes of documented VOC (defined in protocol section 8.2.2) within the 12 months prior to screening. Documentation must exist in the participant’s medical record prior to randomisation. Events based solely on participant recall without supporting documentation should not be counted towards eligibility.</li>\n <li>\n Hb ≥5.0 and ≤10.0 g/dL (≥50 and ≤100 g/L) at screening.</li>\n <li>\n Participants on hydroxyurea (HU) treatment at the time of consent may be eligible if they:\n <ul>\n <li>\n Have been on a stable dose (no more than a 20% change in dosing) for at least 90 days prior to start of study treatment with no anticipated need for dose adjustments during the study (except for weight-based changes)</li>\n <li>\n and have been ≥80% compliant with planned regimen prior to the time of consent, at the discretion of the investigator.</li>\n </ul>\n </li>\n <li>\n Participants on l-glutamine oral powder (Endari®) treatment at the time of consent may be eligible if they:\n <ul>\n <li>\n Have been on a stable dose for ≥12 months at the time of consent (i.e., no changes to the dose except for changes to weight or for safety reasons) and</li>\n <li>\n Have been ≥80% compliant with the planned regimen during the 12 months prior to the time of consent, at the discretion of the investigator.</li>\n </ul>\n </li>\n </ol>\n</div>\n<ol>\n <li>\n Informed consent obtained before any study-related activities. Study-related activities are any procedures that are carried out as part of the study, including activities to determine suitability for the study.</li>\n <li>\n Male or female.</li>\n <li>\n Age 12 years or above at the time of signing the informed consent.</li>\n <li>\n Confirmed diagnosis of sickle cell disease.\n <ul>\n <li>\n Documentation of sickle cell disease (SCD) genotype (sickle cell haemoglobin (HbSS), HbSβ0-thalassemia or other sickle cell syndrome variants) based on prior history of laboratory testing or screening test results from central laboratory. Molecular genotyping is not required. SCD genotype may be determined from the results of haemoglobin (Hb) electrophoresis, high-performance liquid chromatography (HPLC) or similar testing. Note that Hb electrophoresis is performed by the central laboratory at screening.</li>\n </ul>\n </li>\n <li>\n Have 2−15 episodes of documented VOC (defined in protocol section 8.2.2) within the 12 months prior to screening. Documentation must exist in the participant’s medical record prior to randomisation. Events based solely on participant recall without supporting documentation should not be counted towards eligibility.</li>\n <li>\n Hb ≥5.0 and ≤10.0 g/dL (≥50 and ≤100 g/L) at screening.</li>\n <li>\n Participants on hydroxyurea (HU) treatment at the time of consent may be eligible if they:\n <ul>\n <li>\n Have been on a stable dose (no more than a 20% change in dosing) for at least 90 days prior to start of study treatment with no anticipated need for dose adjustments during the study (except for weight-based changes)</li>\n <li>\n and have been ≥80% compliant with planned regimen prior to the time of consent, at the discretion of the investigator.</li>\n </ul>\n </li>\n <li>\n Participants on l-glutamine oral powder (Endari®) treatment at the time of consent may be eligible if they:\n <ul>\n <li>\n Have been on a stable dose for ≥12 months at the time of consent (i.e., no changes to the dose except for changes to weight or for safety reasons) and</li>\n <li>\n Have been ≥80% compliant with the planned regimen during the 12 months prior to the time of consent, at the discretion of the investigator.</li>\n </ul>\n </li>\n</ol>\n
      • principal_exclusion_criteria<p style=\"margin-left: 6.8pt;\">\n 1. Known or suspected hypersensitivity to study intervention or related products.</p>\n<p style=\"margin-left: 6.8pt;\">\n 2. Previous dosing in this study or participated in other etavopivat trials.</p>\n<p style=\"margin-left: 6.8pt;\">\n 3. More than one rescreening for this study as specified in 5.4 of study protocol.</p>\n<p style=\"margin-left: 6.8pt;\">\n 4. Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using adequate contraceptive method, as defined in Appendix 4 (Section 10.4) of study protocol. Pregnancy test must be negative at screening and day of randomisation.</p>\n<p style=\"margin-left: 6.8pt;\">\n 5. Participation (i.e., signed informed consent) in any other interventional clinical study within 28 days or 5 half-lives of trial product, whichever is longer, before dosing.</p>\n<p style=\"margin-left: 6.8pt;\">\n 6. Use of voxelotor or similar agent within 28 days prior to starting study treatment or anticipated need for this agent during the study.</p>\n<p style=\"margin-left: 6.8pt;\">\n 7. Use of a selectin antagonist (e.g., crizanlizumab, monoclonal antibody or small molecule) within 28 days or 5 half-lives (whichever is longer) prior to starting study treatment or anticipated need for such agents during the study.</p>\n<p style=\"margin-left: 6.8pt;\">\n 8. Receiving regularly scheduled blood (red blood cells - RBC) transfusion therapy (also termed chronic, prophylactic or preventive transfusion) or ≥ 6 transfusion events in the previous 12 months (i.e., an average of 1 transfusion event every 60 days).</p>\n<p style=\"margin-left: 6.8pt;\">\n 9. Participants who have received an RBC transfusion for any reason within 90 days prior to the screening visit are only eligible if HbA (adult Hb) <10% by Hb electrophoresis is documented prior to starting study treatment.</p>\n<p style=\"margin-left: 6.8pt;\">\n 10. Receiving or use of concomitant medications that are strong inducers of CYP3A4 (see Section 6.8) within 2 weeks of starting study treatment or anticipated need for such agents during the study.</p>\n<p style=\"margin-left: 6.8pt;\">\n 11. Use of erythropoietin or other haematopoietic growth factor treatment within 28 days of starting study treatment or anticipated need for such agents during the study.</p>\n<p style=\"margin-left: 6.8pt;\">\n 12. Receipt of prior cellular-based therapy (e.g., haematopoietic cell transplant, gene modification therapy).</p>\n<p style=\"margin-left: 6.8pt;\">\n 13. Hepatic dysfunction characterized by:</p>\n<ul>\n <li>\n Alanine aminotransferase (ALT) >4.0 × upper limit of normal (ULN) or</li>\n <li>\n Direct bilirubin >3.0 × ULN.</li>\n</ul>\n<p style=\"margin-left: 6.8pt;\">\n 14. Participants with active and clinically significant bacterial, fungal, parasitic or viral infection requiring systemic therapy at time of screening or randomisation. If infection is acute, participants should delay screening until active therapy has been completed.</p>\n<p style=\"margin-left: 6.8pt;\">\n Note: Infection prophylaxis is allowed and may be required in some regions of the world where malaria is endemic</p>\n<p style=\"margin-left: 6.8pt;\">\n 15. Participants who are not taking or are unable to take antimalarial prophylaxis at the time of consent and during the study if they live in areas of endemic malaria where prophylaxis is recommended.</p>\n<p style=\"margin-left: 6.8pt;\">\n 16. Diagnostic test results positive for human immunodeficiency virus (HIV) type 1 (HIV-1) or HIV-2 infection.</p>\n<p style=\"margin-left: 6.8pt;\">\n 17. Active infection with hepatitis B virus (hepatitis B surface antigen [HepBsAg] and hepatitis B core antibody [HepBcAb] positive).</p>\n<p style=\"margin-left: 6.8pt;\">\n 18. Active hepatitis C (HepC) infection (HepC Ab positive with positive HepC PCR).</p>\n<p style=\"margin-left: 6.8pt;\">\n 19. Severe renal dysfunction (estimated glomerular filtration rate [eGFR] at screening, calculated by the central laboratory <30 mL/min/1.73 m2) or on chronic dialysis.</p>\n<p style=\"margin-left: 6.8pt;\">\n 20. Presence or history of malignant neoplasm (other than basal or squamous cell skin cancer, in situ carcinomas of the cervix or in situ prostate cancer) within 5 years prior to screening.</p>\n<p style=\"margin-left: 6.8pt;\">\n 21. History of unstable or deteriorating cardiac or pulmonary disease within 6 months prior to consent including but not limited to the following:</p>\n<ul>\n <li>\n Unstable angina pectoris or myocardial infarction or elective coronary intervention.</li>\n <li>\n Congestive heart failure requiring hospitalization.</li>\n <li>\n Uncontrolled clinically significant arrhythmias.</li>\n <li>\n Any history of overt clinical stroke.</li>\n</ul>\n<p style=\"margin-left: 6.8pt;\">\n 22. Presence of clinically significant gastrointestinal disorders potentially affecting absorption of trial product and/or nutrients, as judged by the investigator. This includes major surgery involving the stomach or small intestine (prior cholecystectomy is acceptable).</p>\n<p style=\"margin-left: 6.8pt;\">\n 23. Participants with iron deficiency (e.g., serum iron less than the lower limit of normal</p>\n<p style=\"margin-left: 6.8pt;\">\n [LLN] or ferritin <10 µg/L) who are not taking or are unable to take iron supplements at the time of consent and during the study or if there is a concern for gastrointestinal bleed as the cause. Participants with low serum iron levels due to chronic inflammation or other causes in which supplemental iron therapy is not indicated are not excluded.</p>\n<p style=\"margin-left: 6.8pt;\">\n 24. Participants with folate (or folic acid or Vitamin B9) or Vitamin B12 deficiency</p>\n<p style=\"margin-left: 6.8pt;\">\n (e.g., folate or Vitamin B12 levels less than the LLN) who are not taking or are unable to take supplements before the first dose of trial product and during the study.</p>\n<p style=\"margin-left: 6.8pt;\">\n 25. History of deep venous thrombosis requiring systemic anti-coagulation therapy for</p>\n<p style=\"margin-left: 6.8pt;\">\n ≥6 weeks, occurring within 6 months prior to randomisation.</p>\n<p style=\"margin-left: 6.8pt;\">\n Note: participants on ≥6 months of chronic or prophylactic anti-coagulation therapy are allowed in the study. </p>\n<p style=\"margin-left: 6.8pt;\">\n 26. Any disorder, unwillingness, or inability which in the investigator’s opinion, might jeopardise the participant’s safety or compliance with the protocol.</p>\n<p style=\"margin-left: 6.8pt;\">\n 27. Mental incapacity, language barriers or unwillingness to comply with the requirements of the protocol, which may preclude adequate understanding or co-operation during the study as judged by the investigator.</p>\n<p style=\"margin-left: 6.8pt;\">\n 28. Inadequate venous access as determined by the investigator or site staff.</p>\n<p style=\"margin-left: 6.8pt;\">\n 29. Anticipated change in lifestyle (e.g., eating, exercise or sleeping pattern) during the study.</p>\n<p style=\"margin-left: 6.8pt;\">\n 30. Six-minute walking distance on standardized 6MWT below 100 m at screening.</p>\n<p style=\"margin-left: 6.8pt;\">\n 31. Any surgery scheduled for the duration of the study, or other indications, that would impact walking ability at the discretion of the investigator.</p>\n
      • primary_end_points<p style=\"margin-left: 6.8pt;\">\n <strong>Primary</strong></p>\n<p style=\"margin-left: 6.8pt;\">\n Number of adjudicated vaso-occlusive crises (VOC) events with a medical contact^a</p>\n<p style=\"margin-left: 6.8pt;\">\n  </p>\n<p style=\"margin-left: 6.8pt;\">\n <strong>Secondary</strong></p>\n<p style=\"margin-left: 6.8pt;\">\n Confirmatory</p>\n<ul>\n <li>\n Change in haemoglobin (Hb) >1 g/dL (yes/no)</li>\n <li>\n Time to onset of first adjudicated VOC^a</li>\n <li>\n Change in distance travelled during the 6-minute walking test (6MWT)</li>\n <li>\n Change in standardised T-score on the PROMIS Fatigue 7a Scale</li>\n</ul>\n<p style=\"margin-left: 6.8pt;\">\n  </p>\n<p style=\"margin-left: 6.8pt;\">\n a. See protocol section 8.2.2 for description.</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_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n <u><strong>Site 252 – KEMRI-CRDR Siaya Site</strong></u></p>\n<p style=\"margin-left: 6.2pt;\">\n KEMRI/CRDR Siaya Clinical Research Annex is located in Siaya County within Siaya County Referral Hospital Grounds. Siaya County is located about 70 km West of Kisumu. The administrative offices of the PI, Procurement and Human Resource functions are housed at the KEMRI Kisian Campus. KEMRI has a modern research annex at with capacity to conduct Phase I to Phase IV studies through training and experience.</p>\n<p style=\"margin-left: 6.2pt;\">\n After community mobilization, recruitment, screening and enrollment, Investigational Product storage and dispensation and follow-up study activities will occur at the study clinic.</p>\n<p style=\"margin-left: 6.2pt;\">\n Site investigators responsible for day to day running of the project includes: the Principal Investigator-Study oversight, 2 Medical Officers- Medical Officers do eligibility, randomization, supervise the study clinicians who do safety assessments, and safety assessment and reporting during follow up, 2 Pharmacists and 2 Pharmaceutical technologists-IP management, 6 Nurses- vital signs and anthropometric assessments, 6 Quality Assurance/Quality Control Officers- quality check of site processes and documentations and ethics/ regulatory authority submissions, 4 Clinical Officers-eligibility assessments and safety assessments during screening and follow up, 7 Community Interviewers- Community engagement team does community mobilization, participant recruitment and retention activities, 4 Data personnel- Data team does local system maintenance, data transcription and support all other departments with internet services, 3 administrative officers- do administrative activities and 5 Laboratory Personnel- Laboratory team does biological sample management.</p>\n<p style=\"margin-left: 6.2pt;\">\n <strong>Prof. </strong><strong>Videlis Nduba</strong><strong>, Principal Investigator</strong></p>\n<p style=\"margin-left: 6.2pt;\">\n Will be responsible for the overall conduct of the trial at this study site, administrative actions between site, Institutional Review Boards, and the sponsor, oversight of site activities and clinical care provision to study participants. He will contribute to the writing of the scientific report.</p>\n<p style=\"margin-left: 6.2pt;\">\n <strong>Dr.  </strong><strong>Mercy Mwale</strong><strong>, Dr. Mike Odoyo, Sub- Investigator</strong></p>\n<p style=\"margin-left: 6.2pt;\">\n Will be responsible for the clinical conduct of the trial, the care provided to patients, oversight of study activities at the site. Reviewing potential Study participants for eligibility, supervising Clinical Officers, review of laboratory results, adverse events and serious adverse events surveillance, documentation and reporting, providing first hand clinical care to participants. Data entry.</p>\n<p style=\"margin-left: 6.2pt;\">\n <strong>Dr. Emily Naiserian Nyakeriga Pharmacist</strong></p>\n<p style=\"margin-left: 6.2pt;\">\n Application of import license for Investigational Products, IMP accountability from receipt to storage, cold chain maintenance, preparation and dispensing and accountability logs, and IMP destruction. Supervision of the Pharmaceutical Technologists at each of the study sites.</p>\n<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\">\n <tbody>\n <tr>\n <td style=\"width: 162px; height: 34px;\">\n <p align=\"center\">\n <strong>Site Staff Name</strong></p>\n </td>\n <td style=\"width: 153px; height: 34px;\">\n <p align=\"center\">\n <strong>Designation</strong></p>\n </td>\n <td style=\"width: 172px; height: 34px;\">\n <p align=\"center\">\n <strong>Qualification</strong></p>\n </td>\n <td style=\"width: 162px; height: 34px;\">\n <p align=\"center\">\n <strong>Experience</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 162px; height: 18px;\">\n <p>\n Prof Videlis Nduba</p>\n </td>\n <td style=\"width: 153px; height: 18px;\">\n <p>\n PI</p>\n </td>\n <td style=\"width: 172px; height: 18px;\">\n <p>\n MBChB, PhD</p>\n </td>\n <td style=\"width: 162px; height: 18px;\">\n <p>\n 16 years</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 162px; height: 18px;\">\n <p>\n Dr. Mercy Muderi Mwale</p>\n </td>\n <td style=\"width: 153px; height: 18px;\">\n <p>\n Sub-Investigator</p>\n </td>\n <td style=\"width: 172px; height: 18px;\">\n <p>\n MBChB</p>\n </td>\n <td style=\"width: 162px; height: 18px;\">\n <p>\n 4 years</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 162px; height: 18px;\">\n <p>\n Dr. Mike Onyango Odoyo</p>\n </td>\n <td style=\"width: 153px; height: 18px;\">\n <p>\n Sub-Investigator</p>\n </td>\n <td style=\"width: 172px; height: 18px;\">\n <p>\n MBChB</p>\n </td>\n <td style=\"width: 162px; height: 18px;\">\n <p>\n 2 years</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 162px; height: 18px;\">\n <p>\n Emily Nyakeriga</p>\n </td>\n <td style=\"width: 153px; height: 18px;\">\n <p>\n Study Pharmacist</p>\n </td>\n <td style=\"width: 172px; height: 18px;\">\n <p>\n BPharm</p>\n </td>\n <td style=\"width: 162px; height: 18px;\">\n <p>\n 4 years</p>\n <div>\n  </div>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • other_details_explanation<p>\n The trial will not be conducted in the Sponsor country (Denmark) due to the very limited number of participants with Sickle Cell Disease.</p>\n
      • other_details_regulatory_notapproved<ul>\n <li style=\"margin-left: 7.1pt;\">\n Saudi Food & Drug Authority (SFDA) - Saudi Arabia: 04 Nov 2024</li>\n <li style=\"margin-left: 7.1pt;\">\n National Agency for Food and Drug Administration and Control (NAFDAC) - Nigeria: 14 Nov 2024</li>\n <li style=\"margin-left: 7.1pt;\">\n Food and Drugs Authority (FDA) - Ghana: 18 Nov 2024</li>\n <li style=\"margin-left: 7.1pt;\">\n European Medicines Agency (EU Clinical Trial Regulation) - European Union: 11 Nov 2024</li>\n <li style=\"margin-left: 7.1pt;\">\n Uganda National Drug Authority - Uganda: 25 Mar 2025</li>\n</ul>\n
      • other_details_regulatory_approved<p style=\"margin-left: 8.65pt;\">\n Initial Health Authority approvals have been received in the following countries for the current study (NN7535-7807):</p>\n<ul>\n <li style=\"margin-left: 7.1pt;\">\n USA - 15 June 2024* (47 sites)</li>\n <li style=\"margin-left: 7.1pt;\">\n Canada – 12 August 2024  (8 sites)</li>\n <li style=\"margin-left: 7.1pt;\">\n Australia – 26 August 2024 (6 sites)</li>\n <li style=\"margin-left: 7.1pt;\">\n UK – 13 September 2024 (6 sites)</li>\n <li style=\"margin-left: 7.1pt;\">\n Brazil – 10 October 2024 (6 sites)</li>\n <li style=\"margin-left: 7.1pt;\">\n India - 20 November 2024 (14 sites)</li>\n <li style=\"margin-left: 7.1pt;\">\n Turkey - 19 December 2024 (5 sites)</li>\n</ul>\n<p style=\"margin-left: 7.1pt;\">\n *The US FDA does not issue approval letters for protocols. According to the Code of Federal Regulations, an IND applicant may proceed with a clinical investigation once the applicant has been notified by the FDA that the investigation may proceed, or after 30 days if the IND is not placed on Clinical Hold. As of 31 January 2024, there has not been communication of a clinical hold from the FDA.</p>\n
      • other_details_regulatory_rejected<p>\n Not applicable</p>\n
      • other_details_regulatory_halted<p>\n Not applicable</p>\n
      • estimated_duration52 weeks
      • 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_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_states21
      • number_of_sites4
      • multi_country_listAustralia, Belgium, Brazil, Canada, Columbia, France,\nGhana, Greece, India, Italy, Lebanon, Kenya, Netherlands, Nigeria, Oman, Saudi Arabia,\nSpain, Turkey, Uganda, United Kingdom, USA
      • data_monitoring_committeeYes
      • total_enrolment_per_siteCompetitive enrolment with a maximum of 16 patients per site:\n1. Dr Ogutu – 16\n2. Dr Nduba - 16\n3. Dr Chite Asirwa - 16\n4. Dr Mutua – 16
      • total_participants_worldwide408
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenYes
      • population_adolescentYes
      • population_above_18Yes
      • population_adultYes
      • population_elderlyYes
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
      • subjects_specifyConsent of pediatric participants (below 18 years of age) is obtained by means of parents or legally acceptable representatives
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameBernhards
      • investigator1_middle_name
      • investigator1_family_nameOgutu
      • investigator1_qualificationMBCHB, PHD
      • investigator1_professional_addressAhero Clinical Trails Unit, CREATES Strathmore University, PO.Box 54-40100, Kisumu, Kenya
      • investigator1_telephone+254 733812613 / +254733966065
      • investigator1_emailogutu6@gmail.com
      • organisations_transferred_Yes
      • number_participantsApproximately 67 from 4 sites
      • notification
      • approval_date15-10-2025
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted19-05-2025
      • is_child0
      • unsubmitted1
      • initial_date_submitted19-05-2025
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been addressed. Prof Kokwaro (Email approval) and Kimotho approved.
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-10-15 18:08:31
      • created2025-05-14 10:39:18
      • total_sites1
      • ecitizen_invoice371383
    • InvestigatorContact(array)
      • 0(array)
        • id1272
        • application_id1542
        • given_nameVidelis
        • middle_name
        • family_nameNduba
        • qualificationMBCHB, PhD
        • professional_addressKEMRI CRDR Siaya Clinical Research Annex, P.O. Box 144-40600, Siaya, Kenya
        • telephone+254 724 522 474
        • emailvnduba@gmail.com
        • created2025-05-14 10:42:17
        • modified2025-05-28 15:01:56
    • SiteDetail(array)
      • 0(array)
        • id1900
        • application_id1542
        • county_id41
        • site_nameKEMRI CRDR Siaya Clinical Research Annex
        • physical_addressKEMRI CRDR Siaya Clinical Research Annex, P.O. Box 144-40600, Siaya, Kenya
        • contact_details+254 724522474 / +254 700 111 395 / vnduba@gmail.com
        • contact_personDr Videlis Nduba
        • site_capacity(null)
        • misc(null)
        • created2025-05-14 10:42:17
        • modified2025-05-28 15:01:56
        • County(array)
          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
    • Sponsor(array)
      • 0(array)
        • id832
        • application_id1542
        • sponsorNovo Nordisk A/S
        • sponsor_typeOthers
        • contact_personNadine Jabbour
        • addressNovo Allé, 2880 Bagsvaerd, Denmark
        • telephone_number+45-34486032
        • fax_numberN/A
        • cell_number+45-34486032
        • email_addressNDJO@novonordisk.com
        • created2025-05-14 10:42:17
        • modified2025-05-28 15:01:56
  • 4(array)
    • Application(array)
      • id1540
      • user_id32
      • trial_status_id(null)
      • abstract_of_study<div>\n Background: Malaria in pregnancy remains a substantial public health concern in endemic regions, with first-trimester infections being particularly harmful. The World Health Organization (WHO) now recommends artemether-lumefantrine (AL), an artemisinin-based combination therapy (ACT), as the first-line treatment for uncomplicated malaria in the first trimester of pregnancy, replacing quinine. This recommendation followed a comprehensive review of observational data on inadvertent first-trimester exposures from pregnancy exposure registries, which showed that initial concerns about the teratogenicity of artemisinin derivatives raised by preclinical studies and animal models did not apply to human pregnancies.</div>\n<div>\n Several other highly effective ACTs are used in sub-Saharan Africa, a trend likely to increase rapidly as part of WHO's multiple first-line strategies. Moreover, novel treatments that show promise against resistant strains and may potentially impede their emergence or spread could become available. SAFIRE aims to efficiently generate evidence on the safety and efficacy of antimalarials for treating uncomplicated malaria in the first trimester. Each of the antimalarials to be evaluated in this SAFIRE trial should meet the following criteria:</div>\n<div>\n •<span style=\"white-space:pre\"> </span>Registered antimalarial product for the treatment of uncomplicated malaria or at minimum, confirmation of a favourable benefit/risk ratio for the treatment of uncomplicated malaria in a confirmatory Phase III program in children or adults with P. falciparum infection</div>\n<div>\n •<span style=\"white-space:pre\"> </span>No teratogenic concerns in preclinical studies</div>\n<div>\n In the case of antimalarials with a teratogenic signal in preclinical studies:</div>\n<div>\n •<span style=\"white-space:pre\"> </span>No significant safety concerns in women inadvertently treated with these drugs in the first trimester (from observational studies and/or pregnancy exposure registries), </div>\n<div>\n •<span style=\"white-space:pre\"> </span>Ideally, no significant safety, tolerability and efficacy concerns in clinical trials during the second and third trimesters of pregnancy would be preferred.</div>\n<div>\n Justification: It took over two decades to accumulate sufficient evidence for WHO to recommend AL for use in the first trimester. There is an urgent need to expedite this process and provide informed guidance to health care providers and mothers on other potentially effective and safe antimalarials, especially in the context of the increased threat of resistance against AL. Furthermore, stringent regulatory authorities now encourage more research involving pregnant women.</div>\n<div>\n Objectives: The primary efficacy objective in the initial phase of this adaptive platform trial is to confirm the efficacy of alternative antimalarials in pregnant women in the first trimester with uncomplicated malaria by demonstrating non-inferiority to the current standard of care with AL. The key safety objective is to assess their non-inferiority compared with AL in terms of safety regarding pregnancy outcomes. </div>\n<div>\n Study design: SAFIRE is a multicentre, open-label, randomised, non-inferiority, adaptive platform trial (APT). The rationale for a non-inferiority approach is that if these newer drugs prove to be non-inferior to AL in terms of efficacy and safety, they offer secondary advantages such as longer post-treatment prophylaxis or simpler dosing regimens (once instead of twice daily for 3 days). These benefits could improve treatment adherence and effectiveness in real-world settings.</div>\n<div>\n The study employs a Bayesian adaptive design, allowing for interim analyses and potential early stopping for safety. The rule for making decisions during interim analysis is to stop enrolment to a new intervention arm if there is more than an 85% chance that the hazard ratio for the safety endpoint exceeds 1.1 (the non-inferiority margin) relative to the standard of care. These frequent interim analyses for safety will allow for the early stopping of the trial arm if safety concerns arise and enable more efficient use of resources and timely decision-making based on accumulating evidence.</div>\n<div>\n The adaptive platform trial design evaluates multiple interventions and uses a shared control group, reducing administrative burden and allowing efficient participant allocation. It provides a flexible framework for introducing new treatment arms, which is ideal for assessing multiple promising antimalarials for first-trimester use.</div>\n<div>\n SAFIRE is an open-ended trial that continuously evaluates new antimalarials without a set end date, adapting to emerging treatments and research priorities in malaria during pregnancy.</div>\n<div>\n The protocol uses a modular design with a master protocol outlining the overall framework and intervention-specific appendices (ISAs) for each antimalarial. This approach enables efficient addition or removal of treatment arms without full master protocol revision, enhancing flexibility and responsiveness.</div>\n<div>\n Methods: Pregnant women in their first trimester (≤13 weeks' gestation) with confirmed uncomplicated Plasmodium falciparum malaria will be randomly assigned to receive either the standard of care with artemether-lumefantrine (AL) or a newer antimalarial. The details of the newer antimalarials, corresponding sample sizes, and allocation ratio are described in ISAs. The primary efficacy endpoint is PCR-adjusted adequate clinical and parasitological response (ACPR) by day 42. The key safety endpoint is a composite of fetal loss or major congenital anomalies. Secondary efficacy endpoints include PCR-unadjusted cure rates (i.e, the cumulative rate  of women without recurrent malaria infection due to treatment failure or reinfection), serving as a proxy for the duration of post-treatment prophylaxis.</div>\n<div>\n Collaboration and funding: The initial phase of the study is co-sponsored by the Liverpool School of Tropical Medicine (LSTM) and the Medicines for Malaria Venture (MMV) and is funded by Global Health EDCTP3, the EU, UKRI, and SERI of the Swiss Confederation. As this is an open-ended platform trial, additional sponsors and funders may be added in the future as new treatment arms are incorporated. </div>\n<div>\n Ethical considerations and governance: The trial adheres to stringent ethical standards, including obtaining informed consent from all participants and providing close monitoring for adverse events. An independent Data Safety Monitoring Board will monitor the safety data as they accumulate with predefined stopping rules.</div>\n<div>\n Significance: SAFIRE is designed to inform WHO policy. By expanding the range of safe and effective treatment options, SAFIRE has the potential to improve the management of malaria in early pregnancy, an important period for the developing placenta and fetus, and contribute to better maternal and child health outcomes in endemic areas.</div>\n<div>\n  </div>\n
      • study_title<p>\n A multicentre open-label, non-inferiority adaptive platform randomised controlled trial to evaluate the efficacy, safety, and tolerability of antimalarials for the treatment of uncomplicated malaria in the first trimester of pregnancy</p>\n
      • laymans_summary<div>\n The SAFIRE study aims to find effective treatments with acceptable safety for malaria in early pregnancy, a particularly sensitive time for the adverse consequences of malaria in pregnancy for both mother and baby. Currently, WHO recommends the antimalarial drug artemether-lumefantrine (AL) for the treatment of uncomplicated malaria in the first trimester of pregnancy. Other promising treatments are being rolled out in malaria-endemic countries for use in adults and children and data on current exposures in the first trimester are limited and insufficient to support a recommendation.  This is due to the fact that pregnant women are often excluded from clinical trials to protect fetuses, unintentionally depriving them of newer, potentially better treatments. Instead, they often received older, less effective drugs. The International Council for Harmonisation (ICH E21) and stringent regulatory authorities (e.g. EMA, FDA and MHRA) now encourage pregnant women to be included in well-designed studies to ensure they can safely benefit from medical advances. </div>\n<div>\n This study will compare AL with the newer antimalarial drugs that have shown no significant safety concerns in laboratory studies, accidental use during early pregnancy, or trials in later pregnancy stages. The main goal is to see if these new drugs work as well as AL in treating malaria and are safe for the mother, her pregnancy and the developing baby. The newer antimalarials being tested also offer additional benefits to pregnant women, such as preventing new malaria infections for longer after treatment than the current standard treatment (AL). Also, they can be taken just once a day instead of twice daily, like AL. A simpler dosing schedule could improve adherence to the study medication, meaning women are more likely to take the full course of treatment as prescribed. This, in turn, enhances its effectiveness in real-world settings. Future antimalarials to be tested will include those with improved resistance profiles, offering more effective options for combating drug-resistant strains.</div>\n<div>\n SAFIRE uses a special “Bayesian Adaptive Platform Trial” (APT) design. This open-ended approach allows researchers to add new interventions under the same protocol, leveraging the existing trial network with infrastructure. The use of a common protocol with innovative adaptive statistical design allows the trial to stop early if it becomes clear that the new drugs are unsafe. APTs were commonly used in COVID-19 trials because they help researchers respond quickly to new information. This APT protocol uses a typical multi-part structure, including a “master protocol” that serves as the overall blueprint for the study, outlining the general design, core methods, and shared elements across all treatments being tested, followed by “Intervention-Specific Appendices (ISAs)”, providing detailed information about each specific antimalarial treatment being evaluated. ISAs can be easily added or removed as new treatments become available or as existing ones are found to be ineffective or unsafe. This flexible approach allows researchers to efficiently adapt the study as new information emerges without completely redesigning the entire trial each time a change is needed.</div>\n<div>\n This multi-centre trial will be conducted in several countries in Africa where malaria is very common. Women will be randomly assigned to receive either AL or one of the new treatments. Participants will be seen daily for 4 days, then weekly for 6 weeks to assess the response to treatment, and then monthly until delivery. Their health and outcomes will be closely monitored during and after pregnancy. Newborns will be followed for 6 months. An independent data safety and monitoring board (DSMB) will regularly monitor safety data as it accumulates. By finding more treatment options, this study could improve care for pregnant women with malaria and lead to better health for mothers and babies in areas where malaria is widespread. The results will help inform global health policies and potentially change how we treat malaria in early pregnancy.</div>\n<div>\n  </div>\n
      • short_titleSAFIRE
      • protocol_noECCT/25/05/12
      • version_no2.0
      • date_of_protocol20-03-2025
      • study_drugDihydroartemisinin-piperaquine, Pyronaridine-artesunate
      • disease_conditionMalaria
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_nameDihydroartemisinin-piperaquine, Pyronaridine-artesunate
      • product_type_medical_device_name
      • comparatorYes
      • comparator_nameArtemether-Lumefantrine (Lumiter)
      • comparator_registeredYes
      • comparator_countriesKanya
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressruth.njoroge@ke.lstmed.ac.uk
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter0
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum0
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_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_applicantDr. Ruth Njoroge
      • declaration_date130-05-2025
      • declaration_principal_investigatorDr. Hellen Barsosio
      • declaration_date230-05-2025
      • placebo_presentNo
      • study_objectives<p>\n The primary efficacy objective in the initial phase of this adaptive platform trial is to confirm the efficacy of alternative antimalarials in pregnant women in the first trimester with uncomplicated malaria by demonstrating non-inferiority to the current standard of care with AL.</p>\n<p>\n The key safety objective is to assess their non-inferiority compared with AL in terms of safety regarding pregnancy outcomes. </p>\n
      • principal_inclusion_criteria<div>\n •<span style=\"white-space:pre\"> </span>≥2 weeks and <14 weeks (13-6/7 weeks inclusive) gestation from the last menstrual period (LMP) as assessed by echography </div>\n<div>\n •<span style=\"white-space:pre\"> </span>Microscopy confirmed P. falciparum mono or mixed infections, regardless of symptoms. </div>\n<div>\n •<span style=\"white-space:pre\"> </span>Emancipated minor and aged ≥16 years</div>\n<div>\n •<span style=\"white-space:pre\"> </span>Haemoglobin ≥ 7 g/dL </div>\n<div>\n •<span style=\"white-space:pre\"> </span>Residence within the health facility catchment area </div>\n<div>\n •<span style=\"white-space:pre\"> </span>Willingness to adhere to study requirements and to deliver the baby at the local health facility </div>\n<div>\n •<span style=\"white-space:pre\"> </span>Ability to provide written informed consent</div>\n
      • principal_exclusion_criteria<div>\n •<span style=\"white-space:pre\"> </span>Known allergy to any of the study drugs</div>\n<div>\n •<span style=\"white-space:pre\"> </span>History of known pregnancy complications or poor obstetric history, such as repeated miscarriages, stillbirths, or eclampsia</div>\n<div>\n •<span style=\"white-space:pre\"> </span>History or presence of major illnesses likely to influence pregnancy outcome; </div>\n<div>\n •<span style=\"white-space:pre\"> </span>Known HIV positive</div>\n<div>\n •<span style=\"white-space:pre\"> </span>Any significant illness at the time of screening requiring hospitalisation, including severe malaria</div>\n<div>\n •<span style=\"white-space:pre\"> </span>Intent to move out of the study catchment area before delivery or planned delivery out of the catchment area</div>\n<div>\n •<span style=\"white-space:pre\"> </span>Recent (2 weeks) treatment with antimalarials or antimicrobials with antimalarial activity (chloroquine, AL, DP, PA, SPAQ, ASAQ, MQAS, azithromycin, clindamycin, tetracycline, quinolones, cotrimoxazole and SP)</div>\n<div>\n •<span style=\"white-space:pre\"> </span>Twin/multiple pregnancy detected</div>\n<div>\n •<span style=\"white-space:pre\"> </span>Non-viable pregnancy confirmed by ultrasound or doppler</div>\n<div>\n •<span style=\"white-space:pre\"> </span>Known history or evidence of clinically significant cardiovascular disorders or family history of sudden death or congenital long QT syndrome or current co-administration of other drugs that might contribute to a prolonged QTc interval or cause “Torsades de Point” </div>\n<div>\n •<span style=\"white-space:pre\"> </span>Chronic medical condition requiring frequent medications (e.g., TB, suspected hepatic lesions, liver disease, sickle cell disease, diabetes, epilepsy, asthma and hypertension)</div>\n<div>\n •<span style=\"white-space:pre\"> </span>Prior randomisation in this study during the current pregnancy</div>\n
      • primary_end_points<div>\n PCR-adjusted adequate clinical and parasitological response (ACPR) by Day 42</div>\n<div>\n A composite endpoint of miscarriage, stillbirth, or major congenital anomalies. </div>\n<div>\n  </div>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety0
      • scope_efficacy0
      • 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_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<div>\n <u><strong>Chief Investigator</strong></u></div>\n<div>\n Prof Feiko ter Kuile, MD, PhD, Professor of Tropical Epidemiology, Department of Clinical Sciences, Liverpool School of Tropical Medicine (LSTM), Pembroke Place, L3 5QA Liverpool, United Kingdom Tel +44 151 705 3287; and KEMRI-CGHR, P.O. Box 1578, Kisumu 40100, Phone: +254 708 739 228, Email:  feiko.terkuile@lstmed.ac.uk</div>\n<div>\n <u><strong>Principal Investigator</strong></u></div>\n<div>\n Dr Hellen Barsosio, MD, Clinical Epidemiologist, KEMRI Centre for Global Health Research (CGHR), P.O. Box 1578, Kisumu 40100, Kenya, Phone: +254 719 436 833, Email: hellen.barsosio@lstmed.ac.uk  </div>\n<div>\n <u><strong>Co-Investigator</strong></u></div>\n<div>\n •<span style=\"white-space:pre\"> </span>Sally Wambui Ndungu, MD, trial manager, Sally.Wambui@ke.lstmed.ac.uk</div>\n<div>\n •<span style=\"white-space:pre\"> </span>Simon Kariuki, PhD, Head Malaria Division, skariuki1578@gmail.com,  skkariuki@kemri.go.ke </div>\n<div>\n •<span style=\"white-space:pre\"> </span>Evelyn Delylah Ondieki, MPH, study coordinator, evelyne.delylah@lstmed.ac.uk </div>\n<div>\n •<span style=\"white-space:pre\"> </span>Kephas Otieno, MSc, head malaria laboratory, kotieno@kemri.org, koti72@gmail.com </div>\n<div>\n •<span style=\"white-space:pre\"> </span>Miriam Chombe, MSc, laboratory scientist, mchomba@kemri.go.ke </div>\n<div>\n •<span style=\"white-space:pre\"> </span>Benard Omondi, PharmD, Pharmaco-epidemiologist, benard.omondi@ke.lstmed.ac.uk</div>\n<div>\n •<span style=\"white-space:pre\"> </span>Patricia Odera-Ojwang , MD, Consultant paediatrician, pattojey@gmail.com</div>\n<div>\n •<span style=\"white-space:pre\"> </span>Jonathan Schultz, MD, Infectious Disease specialist, rix1@cdc.gov</div>\n<div>\n •<span style=\"white-space:pre\"> </span>Bixa Ogola, PhD, laboratory scientist, bixa.ogola@gmail.com</div>\n<div>\n  </div>\n
      • other_details_explanation<p>\n N/A</p>\n
      • other_details_regulatory_notapproved<p>\n N/A</p>\n
      • other_details_regulatory_approved<p>\n N/A</p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration28 months
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorArtemether-Lumefantrine
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaThe Kenya Medical Research Institute (KEMRI), Centre for Global Health Research (CGHR)
      • single_site_physical_addressP.O. Box 1578-40100, Kisumu, Kenya.
      • single_site_contact_personDr. Hellen Barsosio
      • single_site_telephone+254719436833
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_statesThree
      • number_of_sites
      • multi_country_listKenya\nMali\nBurkina Faso
      • data_monitoring_committeeYes
      • total_enrolment_per_site504
      • total_participants_worldwide504
      • 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_elderlyNo
      • gender_female1
      • gender_male0
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenYes
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameFeiko
      • investigator1_middle_name
      • investigator1_family_nameter Kuile
      • investigator1_qualificationMD, PhD
      • investigator1_professional_addressKEMRI CGHR 1578-40100 Kisumu, Kenya
      • investigator1_telephone+254708739228
      • investigator1_emailfeiko.terkuile@lstmed.ac.uk
      • organisations_transferred_No
      • number_participants504
      • notification
      • approval_date15-10-2025
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted30-05-2025
      • is_child0
      • unsubmitted1
      • initial_date_submitted30-05-2025
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been addressed
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-10-15 18:43:00
      • created2025-05-09 07:50:31
      • total_sites1
      • ecitizen_invoice370504
    • InvestigatorContact(array)
      • 0(array)
        • id1291
        • application_id1540
        • given_nameHellen
        • middle_name
        • family_nameBarsosio
        • qualificationMD, PhD
        • professional_addressKEMRI CGHR 1578-40100 Kisumu, Kenya
        • telephone+254719436833
        • emailhellen.barsosio@lstmed.ac.uk
        • created2025-05-26 11:39:54
        • modified2025-06-10 11:17:45
    • SiteDetail(array)
      • 0(array)
        • id1927
        • application_id1540
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2025-05-26 11:39:54
        • modified2025-06-10 11:17:45
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id841
        • application_id1540
        • sponsorLiverpool School of Tropical Medicine (LSTM)
        • sponsor_typeResearch Institution
        • contact_personProf Feiko ter Kuile, MD, PhD
        • addressPembroke Place, Liverpool L3 5QA, UK.
        • telephone_number+44 0151 7053794
        • fax_number+44 0151 7053794
        • cell_number+44 0151 7053794
        • email_addresslstmgov@lstmed.ac.uk
        • created2025-05-26 11:39:54
        • modified2025-06-10 11:17:45
• page_options(array)
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• redir
• $request->data(array)
  • Application(empty)
• $this->validationErrors(array)
  • Permission(empty)
  • Aro(empty)
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  • User(empty)
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  • InvestigatorContact(empty)
  • Sponsor(empty)
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  • 1Form
  • 2Session
  • 3Text
  • 4Number
  • 5SimpleGraph
  • 6Paginator
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App Constants

CakePHP Constants

PHP Environment

Included Files

Include Paths

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

Included Files

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    • 1CORE/Model/Behavior/ContainableBehavior.php
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