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  • 1Recruiting
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• applications(array)
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    • Application(array)
      • id282
      • user_id81
      • trial_status_id6
      • abstract_of_study<p>\n The inherited disease sickle cell anaemia is common in Kenya where more than 4000 children are born with the condition each year. On the basis of positive data from clinical trials, an increasing number of patients with sickle cell anaemia in the North are now being treated with hydroxyurea.  No trials of hydroxyurea have been conducted in Africa where the safety and effectiveness of the drug are therefore unknown. We aim to conduct a multi-center phase I/II clinical trial to investigate the safety of hydroxyurea as a supportive treatment in children with sickle cell disease in Kenya, Angola and the DRC. In total, 450 children aged 12 months - 10 years (150 in each site) will be enrolled into the study. All will be placed on hydroxyurea and monitored closely to investigate both safety and efficacy of the drug over a 48 month period. If successful, we hope that this study will lead to a larger trial that will shape national management policies for all children born with sickle cell anaemia in Africa.</p>\n
      • study_title<p>\n REALIZING EFFECTIVENESS ACROSS CONTINENTS WITH HYDROXYUREA (REACH):  A PHASE I/II PILOT STUDY OF HYDROXYUREA FOR CHILDREN WITH SICKLE CELL ANAEMIA.</p>\n
      • laymans_summary<p>\n The inherited disease sickle cell anaemia is common in Kenya where more than 4000 children are born with the condition each year. On the basis of positive data from clinical trials, an increasing number of patients with sickle cell anaemia in the North are now being treated with hydroxyurea.  No trials of hydroxyurea have been conducted in Africa where the safety and effectiveness of the drug are therefore unknown. We aim to conduct a multi-center phase I/II clinical trial to investigate the safety of hydroxyurea as a supportive treatment in children with sickle cell disease in Kenya, Angola and the DRC. In total, 450 children aged 12 months - 10 years (150 in each site) will be enrolled into the study. All will be placed on hydroxyurea and monitored closely to investigate both safety and efficacy of the drug over a 48 month period. If successful, we hope that this study will lead to a larger trial that will shape national management policies for all children born with sickle cell anaemia in Africa.</p>\n
      • short_titleREACH Trial
      • protocol_noECCT/14/04/01
      • version_noversion 1.1
      • date_of_protocol11-03-2014
      • study_drugHydroxyurea
      • 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_nameHydroxyurea
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressctfuser@kemri-wellcome.org
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
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      • applicant_approval_letter1
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      • applicant_participating_countries0
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      • applicant_detailed_budget1
      • applicant_indemnity_pi1
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      • applicant_hard_copies(null)
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      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantProf Thomas Williams
      • declaration_date108-04-2014
      • declaration_principal_investigatorProf Thomas Williams
      • declaration_date208-04-2014
      • placebo_presentNo
      • study_objectives<p>\n a) General objectives<br />\n To conduct an early phase clinical trial to establish whether or not hydroxyurea could potentially provide both a safe and effective option for the management of children living with SCA in the African context. If no major safety concerns are revealed in this early phase trial it is anticipated that this trial will be followed with a larger, definitive, late-phase trial investigating safety and efficacy in a broad range of hospital settings in Africa.<br />\n b) Specific objectives<br />\n i) To monitor the safety of hydroxyurea therapy, specifically documenting significant haematological toxicities (cytopaenias) and infections.<br />\n ii) To evaluate the benefits of hydroxyurea therapy, using both laboratory (i.e. fetal haemoglobin and haemoglobin concentrations and white blood cell counts) and clinical parameters (such as pain, hospitalization and growth parameters).<br />\n iii) To investigate the feasibility of hydroxyurea dose-escalation on laboratory and clinical parameters.<br />\n iv) To explore the pharmacokinetic and genetic basis for any observed inter-patient variability in the clinical or laboratory response to hydroxyurea<br />\n vi) To evaluate the economic cost of providing hydroxyurea therapy in the REACH study sites.</p>\n
      • principal_inclusion_criteria<ol>\n <li>\n Children 2-10 years of age who attend the children's Sickle Cell Disease Clinics (with a diagnosis confirmed by haemoglobin electrophoresis) at trial sites and who volunteer to participate in the trial</li>\n <li>\n Weight at least 10kg at the time of enrolment</li>\n <li>\n A stated willingness to comply with all study-related treatments, evaluations and follow-up</li>\n</ol>\n
      • principal_exclusion_criteria<ol>\n <li>\n Parent, guardian, or child unable or unwilling to provide written informed consent or verbal assent</li>\n <li>\n The presence of one or more of the known medical conditions:\n <ul>\n <li>\n acute or chronic infectious disease,</li>\n <li>\n HIV, or</li>\n <li>\n malignancy</li>\n </ul>\n </li>\n <li>\n Acute or chronic severe malnutrition based on WHO standards</li>\n <li>\n Haematological criteria at screening:\n <ul>\n <li>\n Hb<4.0g/dl</li>\n <li>\n Hb<6.0g/dl plus absolute reticulocyte count (ARC)<100x10^⁹/l</li>\n <li>\n reticulocytopaenia (ARC<80+Hb<7.0g/dl)</li>\n <li>\n thrombocytopaenia (platelets<80x10^⁹/l</li>\n <li>\n neutropaenia (<1.0x10^⁹/l)</li>\n </ul>\n </li>\n <li>\n Hydroxyurea treatment within the previous 6 months</li>\n</ol>\n
      • primary_end_points<p>\n This is primarily a safety study and the primary end points will therefore be the development of a range of toxicities measured both clinically and haematologically.</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic1
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic1
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic1
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology1
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other1
      • trial_other_specifytherapeutic exploratory
      • trial_therapeutic_exploratory1
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledNo
      • site_capacity(null)
      • staff_numbers<p>\n Total staff: 6</p>\n<ol>\n <li>\n Professor Thomas Neil Williams MBBS PHD- Site PI</li>\n <li>\n Mr George Mochamah Clinical Officer- Patient Recruitment</li>\n <li>\n Esther KIvaya--Trial Monitor</li>\n <li>\n Dr Jimmy Shangala BPharm- Trial Pharmacist</li>\n <li>\n Mr Emmanuel Mabibo Diploma in Community Development- Clinical Assistant</li>\n <li>\n Ms Maurine Maoni Clinical Officer- Patient Recruitment & followup</li>\n</ol>\n
      • other_details_explanation<p>\n Hydroxyurea is already used as an established treatment for Sickle Cell Disease in the Unites States of America. The aim of this study is to see whether it can also be used safely and effectively in the context of Africa.</p>\n<p>\n  </p>\n
      • other_details_regulatory_notapproved<p>\n N/A</p>\n
      • other_details_regulatory_approved<p>\n Cincinnati Children's Hospital Institutional Review Board, final approval 23rd December 2013. One site per country in four countries including Kenya. (Mbale Uganda-RECRC IN-COM 133/2014, Monkole, Congo-Nref: 001/CEFA-MOnkole/CEL/2019)</p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration18 years
      • design_controlled_randomised
      • design_controlled_open
      • design_controlled_single_blind
      • design_controlled_double_blind
      • design_controlled_parallel_group
      • design_controlled_cross_over
      • design_controlled_other
      • design_controlled_specify
      • design_controlled_comparator
      • design_controlled_other_medicinal
      • design_controlled_placebo
      • design_controlled_medicinal_other
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKilifi County Hospital
      • single_site_physical_addressHospital Grounds, Off Bofa Road, Kilifi, Kenya
      • single_site_contact_personProfessor Thomas Neil Williams
      • single_site_telephone+254733411021
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states4
      • number_of_sites
      • multi_country_listAngola\nDemocratic Republic of Congo\nKenya\nUganda
      • data_monitoring_committeeYes
      • total_enrolment_per_site150
      • total_participants_worldwide600
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerYes
      • population_childrenYes
      • population_adolescentYes
      • population_above_18No
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
      • subjects_specifyChildren <18 years of age
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameRussell
      • investigator1_middle_name
      • investigator1_family_nameWare
      • investigator1_qualificationMD, PhD Paediatric Haematology/Oncology
      • investigator1_professional_addressDivision of Haematology, Cincinnati Children\'s Hospital, Cincinnati, Ohio, USA
      • investigator1_telephone513-636-4266
      • investigator1_emailrussell.ware@cchmc.org
      • organisations_transferred_No
      • number_participants150
      • notification<p>\n REACH uses commercially available hydroxyurea manufactured by Bristol Myers Squib.</p>\n<p>\n The study has been going on for the last 4 and a half years in all the 4 sites. </p>\n
      • approval_date07-07-2014
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted27-03-2020
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2023-09-25 14:20:58
      • created2014-03-10 10:01:25
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id196
        • application_id282
        • given_nameThomas
        • middle_nameNeil
        • family_nameWilliams
        • qualificationMBBS DCH DTM&H MRCP PhD Professor of Heamoglobinopathy Research, Imperial College London Honorary Consultant Paediatrician
        • professional_addressKEMRI/Wellcome Trust Research Programme PO Box 230-80108 Kilifi Kenya
        • telephone+254 41 7522063
        • emailtom.n.williams@gmail.com
        • created2014-03-10 12:36:53
        • modified2020-03-27 12:32:22
    • SiteDetail(array)
      • 0(array)
        • id242
        • application_id282
        • county_id(null)
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        • misc(null)
        • created2014-03-10 12:36:53
        • modified2020-03-27 12:32:22
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id155
        • application_id282
        • sponsorCincinnati Children\'s Hospital
        • sponsor_typeResearch Institution
        • contact_personProf Russell Ware
        • addressDivision of Haematology, Cincinnati Children\'s Hospital, Cincinnati, Ohio, USA
        • telephone_number513-636-4266
        • fax_number
        • cell_numberNone
        • email_addressrussell.ware@cchmc.org
        • created2014-03-10 12:36:53
        • modified2020-03-27 12:32:22
  • 1(array)
    • Application(array)
      • id153
      • user_id21
      • trial_status_id5
      • abstract_of_study<p>\n <strong>Design</strong>: A 2x2x2 open-label factorial multi-centre trial, conducted in 9 centres in 4 countries (Kenya, Malawi, Uganda, Zimbawe)</p>\n<p>\n <strong>Participants:</strong> 1800 HIV-infected patients including adults, adolescents and children aged 5 years or older with low CD4 counts about to initiate combination antiretroviral therapy (ART). At the Eldoret site, 250 participants will be enrolled.</p>\n<p>\n <strong>Intervention</strong>: Three methods to reduce early mortality following ART initiation</p>\n<p style=\"margin-left: 40px;\">\n (i) increasing the potency of ART with a 12 week induction period using 4 antiretroviral drugs from 3 classes<br />\n (ii) augmented prophylaxis against opportunistic/bacterial infections and helminths for 12 weeks<br />\n (iii) macronutrient intervention using ready-to-use supplementary food for 12 weeks.</p>\n<p>\n Each intervention will be compared with standard of care, which in previously untreated patients presenting late with very low CD4 counts is to initiate ART with 3 drugs from 2 classes, together with cotrimoxazole prophylaxis and macronutrient intervention only for those with low BMI (or low weight-for-height/mid-upper arm<br />\n circumference in children).</p>\n<p>\n <strong>Duration</strong>:
        </p>\n<ul>\n <li>\n Participants will be randomised over 1.5-2 years.</li>\n <li>\n
        Each intervention will be administered in addition to standard of care for 12 weeks.</li>\n <li>\n
        Each participant will be followed for 48 weeks in the trial.</li>\n <li>\n
        The overall trial duration is 3 years.</li>\n</ul>\n
      • study_title<p>\n Reduction of EArly mortaLITY in HIVinfected adults and children starting antiretroviral therapy (REALITY)</p>\n
      • laymans_summary(null)
      • short_titleReduction of EArly mortaLITY in adults and children
      • protocol_noECCT/12/09/02
      • version_no1.01
      • date_of_protocol04-04-2012
      • study_drugRaltegravir
      • disease_conditionHIV
      • 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_nameIsentress
      • product_type_medical_device_name
      • comparator(null)
      • comparator_name(null)
      • comparator_registered(null)
      • comparator_countries(null)
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressaksudoi@hotmail.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter0
      • applicant_statement1
      • applicant_participating_countries0
      • applicant_addendum0
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd(null)
      • applicant_prev_data(null)
      • applicant_stability_data(null)
      • applicant_analysis_cert(null)
      • applicant_pictorial_sample(null)
      • applicant_gcp_training(null)
      • applicant_dsmb_charter(null)
      • applicant_detailed_budget(null)
      • applicant_indemnity_pi(null)
      • applicant_practice_license(null)
      • applicant_registration_ctr(null)
      • applicant_pan_african(null)
      • applicant_hard_copies(null)
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      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantAllan K Sudoi
      • declaration_date112-06-2013
      • declaration_principal_investigatorAbraham M Siika, MBChB, MMed, Msc - Site Principal Investigator
      • declaration_date212-06-2013
      • placebo_presentNo
      • study_objectives(null)
      • principal_inclusion_criteria<p>\n 1. Aged 5 years or older<br />\n 2. Documented HIV infection by HIV ELISA or HIV rapid test<br />\n 3. Naive to ART<br />\n 4. CD4 T-cell count <100 cells/mm3 on blood test taken at screening for REALITY<br />\n 5. Results of screening haematology and biochemistry tests available and no contraindications to planned ART according to national guidelines<br />\n 6. Patient/carer provide informed consent (and children <18 years assent, as appropriate according to their age and knowledge of HIV status)</p>\n<p>\n The lower age limit is because CD4 counts are less reliable predictors of immunodeficiency under 5 years: CD4 counts are recommended by guidelines in older children.<br />\n No patient with a CD4 count above 100 cells/mm3 should have ART delayed in order to subsequently meet eligibility criteria. Rather, patients eligible for REALITY will be those testing HIV positive for the first time with a low CD4 count (i.e. those delaying presentation to care), or those who have defaulted before initiating ART and only return to care at an advanced stage of immuno-deficiency.</p>\n
      • principal_exclusion_criteria<p>\n 1. Contraindications to any proposed antiretroviral drugs (including integrase inhibitors), isoniazid, fluconazole, albendazole or azithromycin<br />\n 2. Pregnant or breastfeeding or intending to become pregnant during the first 12 weeks of the study<br />\n 3.. Ever known to have previously received single-dose nevirapine for prevention of mother-to-child transmission (mother or child).</p>\n
      • primary_end_points<p>\n All-cause mortality over the first 24 weeks after starting ART</p>\n
      • scope_diagnosis0
      • scope_prophylaxis1
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic1
      • 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_use1
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n Abraham M. Siika MBChB, MMed, MS- Site Leader/ Principal Investigator</p>\n<p>\n Kara Wools-Kaloustian MD- Co-investigator</p>\n<p>\n Winston M Nyandiko, MBChB,MMed- Co-investigator</p>\n<p>\n Priscilla Cheruiyot, BScN, MPH- Site Coordinator</p>\n<p>\n Charles Kwobah, MBChB- Medical Officer</p>\n<p>\n Mercy Karoney  MBChB- Medical Officer</p>\n<p>\n Simon Wachira Njuguna, B Pharm, MPSK - Pharmacist of Record</p>\n<p>\n Kipruto Kirwa, BSc, MPH, PhD- Quality Manager</p>\n<p>\n Martha Mokaya, BSc, MBA- Data Manager</p>\n<p>\n Wilson Lokitala Ekiru, BSc IT- Assistant Data Manager</p>\n<p>\n Agnes M. Nzioka, Dip Clin Med- Research Clinical Officer</p>\n<p>\n Betty Meli, Dip Clin Med- Research Clinical Officer</p>\n<p>\n Michael Tanui, Dip Clin Med- Research Clinical Officer</p>\n<p>\n Julie Choge -  Recruitment Officer</p>\n<p>\n Amina Msuo Shali - Recruitment Officer</p>\n<p>\n Dorothy Mwimali -  Recruitment Officer</p>\n<p>\n Cecilia Chebet, Dip Counselling - Recruitment Officer</p>\n<p>\n Beatrice Jakait, B Pharm- Back-up Pharmacist</p>\n<p>\n Chris Sande, KHRCN- Study Nurse</p>\n
      • other_details_explanation<p>\n Whilst WHO guidelines now advocate earlier initiation of ART in HIV-infected adults and children 5 years or older at <350 rather than <200 cells/mm3, in clinical practice, substantial numbers continue to present for care late in HIV infection - in both resource-rich and resource-limited settings. Given experience in resource-rich countries, this will continue to be a feature of ART rollout programmes for the forseeable future. However, the consequences of such late presentation, in terms of early morbidity/mortality on ART, are far more severe in resource-limited settings. To maximise benefits of ART, it is essential to identify which interventions, if any, in addition to ART could reduce high early death rates. Data from both adults and older children demonstrate the highest early mortality in those initiating ART with CD4 cell counts <50 cells/mm3 (see Section 1.1 of the protocol): early mortality rates approximately halve in those with CD4 cell counts 50-99 cells/mm3 and halve again with pre-ART CD4 cell counts >100 cells/mm3. Thus those with CD4 <100 cells/mm3 have substantial risks, and present in sufficient numbers, that interventions of proven benefit in this group could rapidly improve ART outcomes.</p>\n
      • other_details_regulatory_notapproved<p>\n N/A</p>\n
      • other_details_regulatory_approved<p>\n Moi Teaching and Referral Hospital/Moi University Institutional Research and Ethics Committee (IREC). Approval granted on 20 June 2012.</p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_durationPArticipants will be randomized over 1.5 to 2 years. The overall study will take three years
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorStandard 2 NRTI+NNRTI plu
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherYes
      • design_controlled_medicinal_specifyIsoniazid, Fluconazole, Azithromycin,Albendazole
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states4
      • number_of_sites2
      • multi_country_listZimbabwe, Uganda, Malawi, Kenya
      • data_monitoring_committeeYes
      • total_enrolment_per_site250 at Eldoret Site
      • total_participants_worldwide1800
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenYes
      • population_adolescentYes
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameAnthony
      • investigator1_middle_name
      • investigator1_family_nameEtyang
      • investigator1_qualificationMBChB
      • investigator1_professional_addressKEMRI Wellcome Trust Research Programme PO BOX 230 Kilifi, 80108 Kenya.
      • investigator1_telephone+ 254 41 752 2063
      • investigator1_emailAetyang@kilifi.kemri-wellcome.org
      • organisations_transferred_No
      • number_participants250 at Eldoret Site (200 adults and 50 Children)
      • notification
      • approval_date04-04-2012
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted12-06-2013
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2018-03-26 12:24:16
      • created2013-06-11 12:27:30
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id97
        • application_id153
        • given_nameAbraham
        • middle_nameMosigisi
        • family_nameSiika
        • qualificationMBChB, MMed, MSc
        • professional_addressP O Box, 4606-30100, Eldoret
        • telephone0721280785
        • emailamsiika@africaonline.co.ke
        • created2013-06-11 12:37:44
        • modified2013-06-12 16:38:34
    • SiteDetail(array)
      • 0(array)
        • id123
        • application_id153
        • county_id27
        • site_nameMoi University Clinical Research Centre
        • physical_addressAMPATH at MTRH, Nandi Road, Eldoret
        • contact_detailsP O Box 4606-30100, Eldoret
        • contact_personAllan Sudoi
        • site_capacity(null)
        • misc(null)
        • created2013-06-11 12:37:44
        • modified2013-06-12 16:38:34
        • County(array)
          • id27
          • county_nameUasin Gishu
          • created2012-06-15 10:25:15
          • modified2012-06-15 10:25:15
      • 1(array)
        • id124
        • application_id153
        • county_id3
        • site_nameKEMRI Wellcome Trust Research Programme
        • physical_addressKilifi
        • contact_detailsPO BOX 230 Kilifi, 80108 Kenya
        • contact_personDr Anthony Etyang
        • site_capacity(null)
        • misc(null)
        • created2013-06-11 13:02:53
        • modified2013-06-12 16:38:34
        • County(array)
          • id3
          • county_nameKilifi
          • created2012-05-31 16:15:49
          • modified2012-05-31 16:15:49
    • Sponsor(array)
      • 0(array)
        • id78
        • application_id153
        • sponsorMedical Research Council, UK
        • sponsor_type(null)
        • contact_personDirector, Regional Centre London
        • addressAviation House, 125 Kingsway, London
        • telephone_number+44 (0) 20 7670 4700
        • fax_number+44 (0) 20 7670 4816
        • cell_number+44 (0) 20 7670 4700
        • email_addressREALITY@ctu.mrc.ac.uk
        • created2013-06-11 12:37:44
        • modified2013-06-12 16:38:34
  • 2(array)
    • Application(array)
      • id577
      • user_id613
      • trial_status_id8
      • abstract_of_study<p>\n Tuberculosis (TB) is one of the most important global health problems. According to recent estimates from the World Health Organization (WHO), 8.6 million new cases and 1.3 million deaths from TB occurred in 2012. The vast majority of TB cases and TB deaths are in developing countries. The spread of HIV has fuelled the TB epidemic, and TB is the leading cause of death among patients infected with HIV. The national case notification rate is 217/100 000, whilst in Kericho County, the rate is 246 /100 000. TB treatment takes 6 months in Kenya and this relatively long treatment is associated with relatively poor compliance and high relapse rates than if the regimen were shorter. This contributes to increase in patient morbidity and mortality, Mycobacterium tuberculosis transmission and drug resistant TB. Treatment adherence is critical in TB treatment success and a shorter regimen may improve adherence. This highlights the need to shorten further the duration of TB treatment. This study aims to evaluate the efficacy, safety and tolerability of 2 treatment regimens versus the standard drug susceptible TB treatment regimen currently used in Kenya. Male or female participants who are 12 years or older with smear positive pulmonary TB will be enrolled and randomized into either 8 weeks of Rifampicin, Isoniazid, Pyrazinamide, Ethambutol followed by 18 weeks of Rifampicin and Isoniazid or 8 weeks of Rifapentine, Isoniazid, Pyrazinamide, Ethambutol followed by 9 weeks of Rifapentine and Isoniazid or 8 weeks of Rifapentine, Isoniazid, Pyrazinamide, Moxifloxacin followed by 9 weeks of Rifapentine, Isoniazid and Moxifloxacin. The Kericho site will recruit 80-100 participants and follow them up for 18 months. If shorter TB treatment regimen is efficacious compared to current 6 month TB treatment duration, this will potentially have important public health implications by increasing TB cure rates, potentially reducing TB transmission and preventing emergency of MDR TB.</p>\n
      • study_title<p>\n Rifapentine-containing treatment shortening regimens for pulmonary tuberculosis: A randomized, open-label, controlled phase 3 clinical trial.</p>\n
      • laymans_summary<p>\n Tuberculosis (TB) is one of the most important global health problems. According to recent estimates from the World Health Organization (WHO), 8.6 million new cases and 1.3 million deaths from TB occurred in 2012. The vast majority of TB cases and TB deaths are in developing countries. The spread of HIV has fuelled the TB epidemic, and TB is the leading cause of death among patients infected with HIV. The national case notification rate is 217/100 000, whilst in Kericho County, the rate is 246 /100 000. TB treatment takes 6 months in Kenya and this relatively long treatment is associated with relatively poor compliance and high relapse rates than if the regimen were shorter. This contributes to increase in patient morbidity and mortality, Mycobacterium tuberculosis transmission and drug resistant TB. Treatment adherence is critical in TB treatment success and a shorter regimen may improve adherence. This highlights the need to shorten further the duration of TB treatment. This study aims to evaluate the efficacy, safety and tolerability of 2 treatment regimens versus the standard drug susceptible TB treatment regimen currently used in Kenya. Male or female participants who are 12 years or older with smear positive pulmonary TB will be enrolled and randomized into either 8 weeks of Rifampicin, Isoniazid, Pyrazinamide, Ethambutol followed by 18 weeks of Rifampicin and Isoniazid or 8 weeks of Rifapentine, Isoniazid, Pyrazinamide, Ethambutol followed by 9 weeks of Rifapentine and Isoniazid or 8 weeks of Rifapentine, Isoniazid, Pyrazinamide, Moxifloxacin followed by 9 weeks of Rifapentine, Isoniazid and Moxifloxacin. The Kericho site will recruit 80-100 participants and follow them up for 18 months. If shorter TB treatment regimen is efficacious compared to current 6 month TB treatment duration, this will potentially have important public health implications by increasing TB cure rates, potentially reducing TB transmission and preventing emergency of MDR TB.</p>\n
      • short_titleRifapentine-containing treatment shortening regimens for pulmonary tuberculosis:
      • protocol_noECCT/16/12/02
      • version_no2.0
      • date_of_protocol14-05-2015
      • study_drugRifapentine, Moxifloxacin, Isoniazid, Rifampicin, Pyrazinamide, Ethambutol
      • disease_conditionPulmonary Tuberculosis
      • 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_nameRifapentine, Moxifloxacin, Isoniazid, Rifampicin, Pyrazinamide, Ethambutol
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressisaac.tsikhutsu@usamru-k.org
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries1
      • 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_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantISAAC TSIKHUTSU, P.O. BOX 1357 KERICHO
      • declaration_date114-12-2016
      • declaration_principal_investigatorBEATRICE KORIR , P.O. BOX 1357 KERICHO
      • declaration_date214-12-2016
      • placebo_presentNo
      • study_objectives<h1>\n <strong>1.</strong><strong>OBJECTIVES</strong></h1>\n<h2>\n 1.1PRIMARY OBJECTIVE</h2>\n<p style=\"margin-left:63.35pt;\">\n 9.1.1 To evaluate the efficacy of a rifapentine-containing regimen to determine whether the single substitution of rifapentine for rifampin makes it possible to reduce to seventeen weeks the duration of treatment for drug-susceptible pulmonary tuberculosis.</p>\n<p style=\"margin-left:63.35pt;\">\n 9.1.2 To evaluate the efficacy of a rifapentine-containing regimen that in addition substitutes moxifloxacin for ethambutol and continues moxifloxacin during the continuation phase to determine whether it is possible to reduce to seventeen weeks the duration of treatment for drug-susceptible pulmonary tuberculosis.</p>\n<p style=\"margin-left:63.0pt;\">\n  </p>\n<h2>\n 1.2SECONDARY OBJECTIVES</h2>\n<p style=\"margin-left:63.35pt;\">\n 9.2.1 To evaluate the safety of the investigational regimens.</p>\n<p style=\"margin-left:63.35pt;\">\n 9.2.2 To evaluate the tolerability of the investigational regimens.</p>\n<p style=\"margin-left:63.35pt;\">\n 9.2.3 To collect and assess biospecimens from consenting participants for the purpose of research on discovery and validation of TB biomarkers.</p>\n<p style=\"margin-left:63.35pt;\">\n 9.2.4 To determine the correlation of mycobacterial and clinical markers with time to culture conversion, culture status at completion of eight weeks of treatment, treatment failure, and relapse.</p>\n<p style=\"margin-left:63.35pt;\">\n 9.2.5 To conduct a pharmacokinetic/pharmacodynamic (PK/PD) study of the test drugs.  The main objectives of the PK/PD study are to characterize study drug PK parameters and to determine relationships between treatment outcomes and PK parameters.</p>\n<p style=\"margin-left:63.35pt;\">\n 9.2.6 To evaluate the pharmacokinetics of efavirenz-based antiretroviral treatment among patients with TB/HIV co-Infection taking efavirenz-based combination antiretroviral therapy and TB treatment with rifapentine.</p>\n<p>\n  </p>\n
      • principal_inclusion_criteria<p>\n Suspected pulmonary tuberculosis plus one or both of the following: a) at least one sputum specimen positive for acid-fast bacilli on smear microscopy OR b) at least one sputum specimen positive for M. tuberculosis by Xpert MTB/RIF testing, with semiquantitative result of ‘medium’ or ‘high’ and rifamycin resistance not detected</p>\n
      • principal_exclusion_criteria<p>\n Individuals will be excluded from enrollment if, at the time of enrollment, their M. tuberculosis isolate is already known to be resistant to any one or more of the following: rifampin, isoniazid, pyrazinamide, ethambutol, or fluoroquinolones. Screening, baseline, and Week 2 study visit sputum cultures all fail to grow M. tuberculosis. M. tuberculosis cultured or detected through molecular assays (Cepheid Xpert MTB/RIF or Hain MTBDRplus assays) from sputum obtained around the time of study entry is determined subsequently to be resistant to one or more of isoniazid, rifampin, or fluoroquinolones.</p>\n
      • primary_end_points<p>\n Primary Efficacy End Point: TB disease-free survival at twelve months after study treatment assignment. Primary Safety End Point: Proportion of participants with grade 3 or higher adverse events during study treatment.</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic1
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic1
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n The Kericho CRC, established in 1998, is located 260 km Northwest of Nairobi in Kericho town on the grounds of the Ministry of Health, Kericho County Referral Hospital. USAMRU-K has been in Kenya for 45 years and has partnered with KEMRI since 1980. KEMRI is a Government of Kenya para-state corporation responsible for health research. The CRC has three integrated main components: HIV care, HIV and microbiology research. Since 2003 the CRS has been conducting diverse studies including randomized, double-blind, placebo controlled and IND/FDA-regulated studies The CRS has 181 local and one U.S. staff with appropriate trainings to support the clinical trials and HIV care and treatment programs. The staff includes; 10 doctors, 3 pharmacists, 12 clinical officers, 25 nurses, 36 laboratory technologists and six 6 accountants among others. The CRS has a Community Advisory Board, strong community engagement programs, efficient participant recruitment, retention and follow-up processes. The CRS protocols are reviewed by the KEMRI and WRAIR IRBs. The CRS’s, secure physical infrastructure includes: 1) 13,400 square feet (sq. ft.) clinical research building for reception, waiting areas, clinical procedures, consultation, sample collection, pharmacy, quality assurance, IT servers, data entry, participants’ chart archives, and sample storage, 2) 26,115 sq. ft. Laboratory space, 3) two liquid nitrogen plants, 4) four back-up generators 5) 13,500 sq. ft. administration and 6) 6,000 sq. ft. store. Both the CRC pharmacy and laboratory are approved by the National Institute of Allergy and Infectious Diseases/Division of AIDS (NIAID/DAIDS) to participate in DAIDS sponsored vaccine (Site # 1502) and therapeutics (Site #12501) and International Maternal, Pediatric, and Adolescent AIDS Clinical Trials (IMPAACT) Group (Site # 5121) studies, the only research site with such approval in Kenya. The lab is also College of American Pathologists (CAP) accredited and consists of three main sections: HIV, Microbiology and Mycobacterium Tuberculosis (TB). The KEMRI/WRP CRC research activities are integrated with a large comprehensive public health HIV care, treatment and prevention program managed by KEMRI/WRP and supported by PEPFAR which covers a population of about 2.7 million people in the SRV which is also the CRS research catchment area. Elements supported by the program includes: antiretroviral therapy (ART), non-ART, TB/HIV co-infections, PMTCT, HIV Testing and Counseling (HTC), primary HIV infection prevention in both low and high-risk populations, Orphans and Vulnerable Children (OVC), and Voluntary Medical Male Circumcision (VMMC). Kenya had an estimated population in 2012 of 43 million people, 22% of whom are urban and with an annual population growth rate of 2.4%. The adult (15-64 years) HIV/AIDS prevalence rate is 5.6% (6.9% in women, and 4.4% in men). HIV prevalence among children aged 18 months to 14 years was 0.9%. In 2013, the country notified a total of 89,760 TB cases (all forms of tuberculosis) of whom 37% were also HIV infected and the South Rift Valley had a total of 4,302 TB cases in 2013.</p>\n
      • other_details_explanation<p>\n The trial will be conducted also in the host country of the sponsor</p>\n
      • other_details_regulatory_notapproved<p>\n WALTER REED ARMY INSTITUTE OF RESERACH(WRAIR IRB)- 26-07-2016</p>\n
      • other_details_regulatory_approved<p>\n CDC IRB- 15-10-2016</p>\n
      • other_details_regulatory_rejected
      • other_details_regulatory_halted
      • estimated_duration2 years
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorComparator is the standar
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKEMRI/WRP, KERICHO
      • single_site_physical_addressP.O. BOX 1357, KERICHO
      • single_site_contact_personISAAC TSIKHUTSU
      • single_site_telephone0729 110 124
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states14
      • number_of_sites
      • multi_country_listKenya, Botswana, Malawi, South Africa, Uganda, USA, Spain, China, Vietnam, Peru, Zimbabwe, India, Thailand, Haiti
      • data_monitoring_committeeYes
      • total_enrolment_per_siteminimum 80, maximum 100
      • total_participants_worldwide2500
      • 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_specifyWe will enroll children between 12 to 17 years
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameBEATRICE
      • investigator1_middle_name
      • investigator1_family_nameKORIR
      • investigator1_qualificationKRN,BSN
      • investigator1_professional_addressP.O.BOX 1357 KERICHO
      • investigator1_telephone0702119191
      • investigator1_emailBeatrice.Korir@usamru-k.org
      • organisations_transferred_No
      • number_participants100
      • notification<p>\n N/A</p>\n
      • approval_date10-01-2017
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted18-05-2020
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2024-10-28 15:36:37
      • created2016-12-13 10:02:09
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id373
        • application_id577
        • given_nameISAAC
        • middle_name
        • family_nameTSIKHUTSU
        • qualificationMBCHB,MMED,FPCCM
        • professional_addressP.O. BOX 1357 KERICHO
        • telephone0729 110 124
        • emailIsaac.Tsikhutsu@usamru-k.org
        • created2016-12-13 10:26:19
        • modified2020-05-18 11:12:00
    • SiteDetail(array)
      • 0(array)
        • id470
        • application_id577
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2016-12-13 10:26:19
        • modified2020-05-18 11:12:00
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id299
        • application_id577
        • sponsorU.S. Centers for Disease Control and Prevention
        • sponsor_typeResearch Institution
        • contact_personKimberley Chapman
        • address1600 Clifton Road, Atlanta, Georgia USA 30329-4027
        • telephone_number(404) 639-7570/800-232-4636
        • fax_number
        • cell_number(404) 639-7570/800-232-4636
        • email_addresstbtcstudy31@cdc.gov
        • created2016-12-13 10:26:19
        • modified2020-05-18 11:12:00
  • 3(array)
    • Application(array)
      • id1111
      • user_id32
      • trial_status_id7
      • abstract_of_study<div>\n Title:<span style=\"white-space:pre\"> </span>Safety and Efficacy of L9LS, a Human Monoclonal Antibody Against Plasmodium falciparum, in an Age De-Escalation, Dose-Escalation Trial and a Randomized, Placebo-Controlled, Double-Blind Trial of Children in Western Kenya</div>\n<div>\n Study Description:<span style=\"white-space:pre\"> </span>A two-part, phase 2 trial evaluating the safety and tolerability of one-time subcutaneous (SC) administration of monoclonal antibody (MAb) L9LS in healthy Kenyan children aged 5 months to 10 years, as well as the protective efficacy of one or two doses of L9LS against naturally occurring Plasmodium falciparum (Pf) infection among Kenyan children aged 5 to 59 months at enrollment, in a setting of perennial high transmission. The primary study hypotheses are that L9LS will be safe and will produce protection against malaria infection. Before study agent administration, all subjects will be given dihydro-artemisinin-piperaquine (DP) to clear any preexisting Pf blood-stage infection.</div>\n<div>\n  </div>\n<div>\n Part 1: Age de-escalation and dose-escalation study</div>\n<div>\n In a stepwise fashion, children aged 5-10 years will receive 5 mg/kg of L9LS or placebo and be followed for 3 months to assess tolerability and safety. If acceptable tolerability and safety profiles are met at 1-week post-injection, we will administer the 5-mg/kg dose of L9LS or placebo to children aged 5-59 months while enrolling another cohort of children aged 5-10 years at a dose of 10 mg/kg of L9LS or placebo. If after 1 week, the 10-mg/kg dose is found to be safe in children aged 5-10 years and the 5-mg/kg dose is found to be safe in children aged 5-59 months, we will then administer a 20 mg/kg dose of L9LS or placebo to children aged 5-10 years and a 10-mg/kg dose of L9LS or placebo to children aged 5-59 months. Finally, if these doses are found safe after 1 week, we will administer a 20-mg/kg dose of L9LS or placebo to children aged 5-59 months. Should tolerability and safety of all doses be acceptable in children aged 5-59 months, we will move to part 2 of the trial. Dosing in part 1 of the study will be weight-based and all doses will be administered SC in a double-blinded fashion. We will enroll 12 participants in each age-dose group in a 3:1 ratio of L9LS to placebo, and all participants will be followed for a total of 3 months.</div>\n<div>\n  </div>\n<div>\n Part 2: Efficacy study</div>\n<div>\n Children 5-59 months of age will be randomized to receive a 10-19 mg/kg dose of L9LS or placebo by SC administration. There will be two L9LS cohorts, one 5-17 months of age and another 18-59 months of age, which will constitute one L9LS arm. A placebo arm will be composed of children 5–59 months of age. They will be followed over 12 months with monthly blood smear microscopy and polymerase chain reaction (PCR) and twice-monthly symptomatology and care-seeking behavior questionnaires. Dosing will be based on three weight bands; all doses will be administered SC with fixed doses of 75 mg L9LS or 150 mg L9LS or a combination of the two (225 mg L9LS), resulting in a range of 10-19 mg/kg in a double-blinded fashion. Blood will be drawn to assess antibody titers at baseline, and at three additional time points over 12 months to establish pharmacokinetics (PK). Participants in the L9LS arm will be randomized 1:1 at baseline to receive either a second L9LS injection or a placebo injection to evaluate the additional efficacy of a second dose administered 6 months after the first dose. (Those in the placebo arm will receive a second injection of placebo.) Participants will be followed for an additional 6 months after the second injection with monthly blood smear microscopy and PCR, and a blood draw at month 11 to assess L9LS PK.</div>\n<div>\n Objectives:</div>\n<div>\n Primary Objectives:</div>\n<div>\n Part 1:</div>\n<div>\n 1.<span style=\"white-space:pre\"> </span>Safety: To evaluate the safety and tolerability of L9LS administered at doses of 5 mg/kg, 10 mg/kg, and 20 mg/kg by SC administration to healthy Kenyan children.</div>\n<div>\n Part 2:</div>\n<div>\n 2.<span style=\"white-space:pre\"> </span>Safety: To evaluate the safety and tolerability of L9LS administered at doses of 10-19 mg/kg by SC administration to healthy Kenyan children.</div>\n<div>\n 3.<span style=\"white-space:pre\"> </span>Efficacy: To assess the efficacy of two doses of L9LS at a concentration of 10-19 mg/kg, administered SC to participants aged 5-59 months of age against first/only Pf malaria infection diagnosed by blood smear microscopy (irrespective of fever) over 12 months compared to placebo.</div>\n<div>\n  </div>\n<div>\n Secondary Objectives:</div>\n<div>\n 1.<span style=\"white-space:pre\"> </span>To assess the efficacy of one dose of L9LS at 10-19 mg/kg against first/only Pf malaria infection diagnosed by blood smear microscopy over 3 and 6 months compared to placebo.</div>\n<div>\n 2.<span style=\"white-space:pre\"> </span>To assess the efficacy of one dose of L9LS at 10-19 mg/kg against first/only Pf malaria infection diagnosed by blood smear microscopy over 12 months compared to placebo.</div>\n<div>\n 3.<span style=\"white-space:pre\"> </span>To evaluate the efficacy of L9LS at 10-19 mg/kg against first/only Pf malaria infection as detected by PCR over 6 and 12 months compared to placebo.</div>\n<div>\n 4.<span style=\"white-space:pre\"> </span>To assess protection of L9LS at 10-19 mg/kg against clinical malaria (first/only and all episodes) at 6 and 12 months compared to a placebo.</div>\n<div>\n 5.<span style=\"white-space:pre\"> </span>To assess the primary objective and secondary objectives 1-4 among children 5-17 months of age.</div>\n<div>\n 6.<span style=\"white-space:pre\"> </span>To assess the primary objective and secondary objectives 1-4 among children 18-59 months of age.</div>\n<div>\n 7.<span style=\"white-space:pre\"> </span>To evaluate the PK of L9LS throughout the study at weight-based dose levels of 5 mg/kg, 10 mg/kg, and 20 mg/kg (part 1) and fixed doses of 10-19 mg/kg (part 2) in healthy Kenyan children, and</div>\n<div>\n a.<span style=\"white-space:pre\"> </span>To correlate L9LS serum concentration with Pf infection risk.</div>\n<div>\n b.<span style=\"white-space:pre\"> </span>To correlate L9LS serum concentration with clinical malaria risk.</div>\n<div>\n Endpoints:<span style=\"white-space:pre\"> </span>Primary Endpoints:</div>\n<div>\n 1.<span style=\"white-space:pre\"> </span>Part 1 and Part 2: Incidence and severity of local and systemic adverse events (AEs) occurring within 7 days after the administration of L9LS, and incidence of serious adverse events (SAEs) throughout the study period.</div>\n<div>\n 2.<span style=\"white-space:pre\"> </span>Part 2: Pf blood-stage infection as detected by microscopic examination of thick blood smear for 52 weeks after administration of L9LS or placebo.</div>\n<div>\n  </div>\n<div>\n Secondary Endpoints:</div>\n<div>\n Data from one or both parts of this study will be used to assess the following endpoints:</div>\n<div>\n 1.<span style=\"white-space:pre\"> </span>Pf blood-stage infection as detected by microscopic examination of thick blood smear for 24 weeks after administration of L9LS or placebo.</div>\n<div>\n 2.<span style=\"white-space:pre\"> </span>Pf blood-stage infection as detected by RT-PCR for 24 and 52 weeks after administration of L9LS or placebo.</div>\n<div>\n 3.<span style=\"white-space:pre\"> </span>Incidence of clinical malaria (definition 1, see section 2.2.2.3) for 24 and 52 weeks after administration of L9LS or placebo.</div>\n<div>\n 4.<span style=\"white-space:pre\"> </span>Incidence of clinical malaria (definition 2, see section 2.2.2.3) for 24 and 52 weeks after administration of L9LS or placebo.</div>\n<div>\n 5.<span style=\"white-space:pre\"> </span>Measurement of L9LS in sera of recipients (parts 1 and 2).</div>\n<div>\n 6.<span style=\"white-space:pre\"> </span>PK analysis of L9LS and the association of L9LS concentration with Pf infection risk.</div>\n<div>\n 7.<span style=\"white-space:pre\"> </span>PK analysis of L9LS and the association of L9LS concentration with clinical malaria risk.</div>\n<div>\n  </div>\n<div>\n Study Population:<span style=\"white-space:pre\"> </span>We will enroll a total of 396 healthy Kenyan children, including 72 ages 5 months to 10 years residing in western Kenya for part 1 and 324 ages 5-59 months for part 2.</div>\n<div>\n  </div>\n
      • study_title<p>\n Safety and Efficacy of L9LS, a Human Monoclonal Antibody Against <em>Plasmodium falciparum</em>, in an Age De-Escalation, Dose-Escalation Trial and a Randomized, Placebo-Controlled, Double-Blind Trial of Children in Western Kenya</p>\n
      • laymans_summary<div>\n Malaria is a disease that affects many people in the world, more so in sub-Saharan Africa. It is caused by parasites carried by mosquitoes. When the mosquitoes bite people, the parasites can pass into their blood and cause illness, which if not treated in a timely manner or sufficiently, can cause severe illness or even death. In effect, despite there being medicines to cure malaria, it is still responsible for a huge number of admissions and deaths, especially in Africa. This informs the need to come up with new ways to reduce the impact of malaria, for example, through preventing people from getting malaria in the first place. </div>\n<div>\n  </div>\n<div>\n This is a research study to test an experimental drug, called L9LS, for malaria. L9LS is a type of drug called a monoclonal antibody. Antibodies are natural products made by the human body to fight infection by blocking germs such as bacteria and parasites. Monoclonal means that all the antibodies in the drug are exactly the same. The study drug stays in the blood for several months and blocks the parasite that causes malaria. We hope that, if enough of the drug is in the blood, it will prevent people from getting malaria.</div>\n<div>\n  </div>\n<div>\n The study aims to find out how safe the drug is and whether it prevents malaria and if so, to what extent. This study will be conducted in two parts. In the first part, involving 72 participants, the study will investigate how safe and well tolerated three different increasing doses of the study drug are by administering each dose to older children first (5-10 years of age) then to younger children (5-59 months of age) 1 week after each different dose, if it is well tolerated and safe in the older age group. The study will proceed to part 2 if the doses are safe and well tolerated in the younger age group, as determined by a data safety and monitoring board. The second part of the study will investigate whether the drug prevents malaria, and if so, to what extent. It will enroll an equal number of children aged between 5-17 months and those aged 18-59 months, totalling to about 324 participants. Each age category will further have 3 groups of children assigned by chance to each group. The first group will receive two doses of the study drug 6 months apart, the 2nd group will receive the study drug then placebo (saltwater/an inactive substance similar to study drug) 6 months after, and the 3rd group will receive two doses of the placebo 6 months part. </div>\n<div>\n Other objectives which will be explored by the study include comparing the study drug level with the possibility of getting a malaria infection or detecting malaria parasites in the blood.</div>\n<div>\n  </div>\n<div>\n The study will take place at Siaya County Referral Hospital and Kogelo Dispensary, both in Siaya County, western Kenya. The study duration will be approximately 24 months, with a participant in Part 1 of the study taking 4-5 months and a participant in Part 2 of the study taking 13-14 months.</div>\n<div>\n  </div>\n<div>\n The study procedures in Part 1 will entail assessing participant eligibility, getting consent and enrollment into the study. On enrollment, participants will receive a standard dose of antimalarial  followed by the study drug or placebo after 2 weeks. They will then have another 10 study visits within a 3 months period to monitor various safety measures. The study procedures in Part 2 will entail assessing participant eligibility, getting consent and enrollment into the study. On enrollment, participants will receive a standard dose of antimalarial followed by the study drug or placebo after 2 weeks. They will then have a study visit every month up to end of month 6 when they will receive the 2nd dose of either the study drug or placebo. Other follow up visits will be conducted monthly until end of 12 months from the date of initial study drug or placebo dose. These follow-up visits will assess both safety and efficacy measures.</div>\n<div>\n  </div>\n<div>\n The study will provide information on the safety and usefulness of L9LS as a therapy used in </div>\n<div>\n the prevention of malaria.</div>\n<div>\n  </div>\n
      • short_titleAnti-malaria MAb in Kenyan chi
      • protocol_noECCT/22/05/03
      • version_no2.0
      • date_of_protocol28-03-2022
      • study_drugL9LS
      • disease_conditionMalaria
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals1
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_nameL9LS
      • product_type_medical_device_name
      • comparatorNo
      • comparator_nameInactive Normal Saline
      • comparator_registeredYes
      • comparator_countriesGlobal
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addresstonysangke@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_applicantTony Sang
      • declaration_date126-05-2022
      • declaration_principal_investigatorTitus Kwambaai
      • declaration_date226-05-2022
      • placebo_presentYes
      • study_objectives<p>\n <u>Primary Objectives</u>:</p>\n<p>\n Part 1:</p>\n<ol>\n <li>\n Safety: To evaluate the safety and tolerability of L9LS administered at doses of 5 mg/kg, 10 mg/kg, and 20 mg/kg by SC administration to healthy Kenyan children.</li>\n</ol>\n<p>\n Part 2:</p>\n<ol>\n <li value=\"2\">\n Safety: To evaluate the safety and tolerability of L9LS administered at doses of 10-19 mg/kg by SC administration to healthy Kenyan children.</li>\n <li value=\"3\">\n Efficacy: To assess the efficacy of two doses of L9LS at a concentration of 10-19 mg/kg, administered SC to participants aged 5-59 months of age against first/only Pf malaria infection diagnosed by blood smear microscopy (irrespective of fever) over 12 months compared to placebo.</li>\n</ol>\n<p style=\"margin-left:18.0pt;\">\n 1.      To assess the efficacy of one dose of L9LS at 10-19 mg/kg against first/only Pf malaria infection diagnosed by blood smear microscopy over 3 and 6 months compared to placebo.</p>\n<p style=\"margin-left:18.0pt;\">\n 2.      To assess the efficacy of one dose of L9LS at 10-19 mg/kg against first/only Pf malaria infection diagnosed by blood smear microscopy over 12 months compared to placebo.</p>\n<p style=\"margin-left:18.0pt;\">\n 3.      To evaluate the efficacy of L9LS at 10-19 mg/kg against first/only Pf malaria infection as detected by PCR over 6 and 12 months compared to placebo.</p>\n<p style=\"margin-left:18.0pt;\">\n 4.      To assess protection of L9LS at 10-19 mg/kg against clinical malaria (first/only and all episodes) at 6 and 12 months compared to a placebo.</p>\n<p style=\"margin-left:18.0pt;\">\n 5.      To assess the primary objective and secondary objectives 1-4 among children 5-17 months of age.</p>\n<p style=\"margin-left:18.0pt;\">\n 6.      To assess the primary objective and secondary objectives 1-4 among children 18-59 months of age.</p>\n<p>\n To evaluate the PK of L9LS throughout the study at weight-based dose levels of 5 mg/kg, 10 mg/kg, and 20 mg/kg (part 1) and fixed doses of 10-19 mg/kg (part 2) </p>\n<p style=\"margin-left:18.0pt;\">\n       in healthy Kenyan children, and</p>\n<p style=\"margin-left:54.0pt;\">\n a.       To correlate L9LS serum concentration with Pf infection risk.</p>\n<p>\n To correlate L9LS serum concentration with clinical malaria risk.</p>\n
      • principal_inclusion_criteria<p style=\"margin-left:36.0pt;\">\n 1.      Healthy children aged 5 months to 10 years (Part 1) or 5-59 months (Part 2).</p>\n<p style=\"margin-left:36.0pt;\">\n 2.      Weight ≥5 kg and weight ≤30 kg (Part 1) or weight ≥5 kg and ≤22.5 kg (Part 2)</p>\n<p style=\"margin-left:36.0pt;\">\n 3.      Hemoglobin level ≥8 g/dL.</p>\n<p style=\"margin-left:36.0pt;\">\n 4.      Height and weight Z-scores >-2.</p>\n<p style=\"margin-left:36.0pt;\">\n 5.      Living within Alego-Usonga sub-county.</p>\n<p style=\"margin-left:36.0pt;\">\n 6.      Able to participate for the duration of the trial.</p>\n<p>\n Parent and/or guardian of participant able to provide informed consent</p>\n
      • principal_exclusion_criteria<ol>\n <li>\n Known sickle cell disease.</li>\n <li>\n Taking long-term cotrimoxazole.</li>\n <li>\n Enrolled in another clinical trial.</li>\n <li>\n Received any doses of any malaria vaccine.</li>\n <li>\n Participation in part 1 of this study (for individuals being screened for enrollment into part 2)</li>\n <li>\n Age < 12 months at the time the RTS,S/AS01 vaccine is anticipated to become available in the whole of Siaya County</li>\n <li>\n Current significant medical condition (cardiac, hepatic, renal, or hematological) or evidence of any other serious underlying medical condition identified by medical history, physical examination, or laboratory examination.</li>\n <li>\n History of any other illness or condition which, in the investigator's judgment, may substantially increase the risk associated with the subject’s participation in the protocol or compromise the scientific objectives.</li>\n <li>\n Any history of menses.</li>\n <li>\n Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the subject to understand and comply with the study protocol.</li>\n <li>\n Parental/guardian study comprehension examination score of <80% correct or per investigator discretion.</li>\n <li>\n Hemoglobin, white blood cell, absolute neutrophil, or platelet count outside the local laboratory-defined limits of normal. (Subjects may be included at the investigator’s discretion for “not clinically significant” values.)</li>\n <li>\n Alanine transaminase (ALT) or creatinine (Cr) level above the local laboratory-defined upper limit of normal. (Subjects may be included at the investigator’s discretion for “not clinically significant” values.)</li>\n <li>\n Infected with HIV.</li>\n <li>\n Known or documented sickle cell disease by history. (Note: Known sickle cell trait is NOT exclusionary.)</li>\n <li>\n Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, endocrine, rheumatologic, autoimmune, hematological, oncologic, or renal disease by history, physical examination, and/or laboratory studies.</li>\n <li>\n Receipt of any investigational product within the past 30 days.</li>\n <li>\n Participation or planned participation in an interventional trial with an investigational product until the last required protocol visit. (Note: Past, current, or planned participation in observational studies is NOT exclusionary.)</li>\n <li>\n History of a severe allergic reaction or anaphylaxis.</li>\n <li>\n Severe asthma (defined as asthma that is unstable or required emergency care, urgent care, hospitalization, or intubation during the past 2 years, or that has required the use of oral or parenteral corticosteroids at any time during the past 2 years).</li>\n <li>\n Pre-existing autoimmune or antibody-mediated diseases including but not limited to: systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren’s syndrome, or autoimmune thrombocytopenia.</li>\n <li>\n Known immunodeficiency syndrome.</li>\n <li>\n Known asplenia or functional asplenia.</li>\n <li>\n Use of chronic (≥14 days) oral or IV corticosteroids (excluding topical or nasal) at immunosuppressive doses (i.e., prednisone >10 mg/day) or immunosuppressive drugs within 30 days of day 0.</li>\n <li>\n Receipt of a live vaccine within the past 4 weeks or a killed vaccine within the past 2 weeks prior to study agent administration.</li>\n <li>\n Receipt of immunoglobulins and/or blood products within the past 6 months.</li>\n <li>\n Known allergies or contraindication to dihydroartemisinin-piperaquine.</li>\n <li>\n Clinical signs of malnutrition.</li>\n <li>\n Other condition(s) that, in the opinion of the investigator, would jeopardize the safety or rights of a subject participating in the trial, interfere with the evaluation of the study objectives, or render the subject unable to comply with the protocol.</li>\n <li>\n Use or known need at the time of enrolment (DP administration) for concomitant prohibited medication.  Patients taking any of the following drugs:\n <ol style=\"list-style-type:lower-alpha;\">\n <li>\n Antimicrobial agents of the following classes (systemic use only):\n <ol style=\"list-style-type:lower-roman;\">\n <li>\n Macrolides (e.g. erythromycin, clarithromycin, azithromycin, roxithromycin)</li>\n <li>\n Fluoroquinolones (e.g., levofloxacin, moxifloxacin, sparfloxacin)</li>\n <li>\n Pentamidine</li>\n </ol>\n </li>\n <li>\n Antiarrhythmic agents (e.g. amiodarone, sotalol)</li>\n <li>\n Antihistamines (e.g. promethazine)</li>\n <li>\n Antifungals (systemic): ketoconazole, fluconazole, itraconazole</li>\n <li>\n Antiretrovirals: Saquinavir</li>\n <li>\n Diuretics (e.g. hydrochlorothiazide, furosemide)</li>\n <li>\n Antipsychotics (neuroleptics): haloperidol, thioridazine</li>\n <li>\n Antidepressants: imipramin, citalopram, escitalopram</li>\n <li>\n Antiemetics: domperidone, chlorpromazine, ondansetron </li>\n </ol>\n </li>\n <li>\n Increased risk of salivary gland hypofunction (dryness of the mouth, swelling under the tongue and/or below the ear, halitosis)</li>\n</ol>\n<p>\n  </p>\n
      • primary_end_points<ol>\n <li>\n Parts 1 & 2: Incidence and severity of local and systemic AEs occurring within 7 days after the administration of L9LS, and incidence of SAEs throughout the study period.</li>\n <li>\n Part 2: Pf blood-stage infection as detected by microscopic examination of thick blood smear for 52 weeks after administration of L9LS or placebo.</li>\n</ol>\n<p>\n  </p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory1
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n <strong>Co-Principal Investigators:</strong></p>\n<p>\n Titus Kwambai, MD, PhD, Epidemiologist Centers for Disease Control and Prevention Kenya Malaria Program Phone: +254 722207281 Email: qbb5<a href=\"mailto:LSteinhardt@cdc.gov\">@cdc.gov</a></p>\n<p>\n Laura Steinhardt, PhD, MPH Malaria Branch, US CDC 1600 Clifton Rd., Atlanta, GA 30329 Phone: +1-404-718-4794 Email: <a href=\"mailto:LSteinhardt@cdc.gov\">LSteinhardt@cdc.gov</a></p>\n<p>\n Peter D. Crompton, MD, MPH, Chief, Malaria Infection Biology and Immunity Section Laboratory of Immunogenetics (LIG), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Phone: 240-383-7640 Email: <a href=\"mailto:pcrompton@niaid.nih.gov\">pcrompton@niaid.nih.gov</a></p>\n<p>\n <strong>Co-Investigators</strong></p>\n<p>\n Kevin K’Orimba, MD, MPH,KEMRI Center for Global Health Research (CGHR) P.O. Box: 1578 - 40100, Kisumu, Kenya , Phone: +254722324496, E-mail: <a href=\"mailto:korimbakevin@gmail.com\">korimbakevin@gmail.com</a>, Role(s): A, B, C, D, E, F, G</p>\n<p>\n Martina Oneko, MD ,KEMRI CGHR,P.O. Box: 1578 - 40100, Kisumu, Kenya,Phone: +254-717-747-279, Email: <a href=\"mailto:tinaoneko@gmail.com\">tinaoneko@gmail.com</a>,Role(s): A, B, C, D, E, F, G</p>\n<p>\n Simon Kariuki, PhD,KEMRI CGHR,Phone: +254 725 389 246, Email: <a href=\"mailto:skariuki1578@gmail.com\">skariuki1578@gmail.com</a>,Role(s): A, B, E, F, G</p>\n<p>\n Tony Sang, BPharm,KEMRI CGHR,P.O. Box: 1578 - 40100, Kisumu, Kenya<br />\n Phone: +254 721 246 875,Email: <a href=\"mailto:tonysangke@gmail.com\">tonysangke@gmail.com</a></p>\n<p>\n Kephas Otieno, MSc,KEMRI CGHR, P.O. Box: 1578 - 40100, Kisumu, Kenya<br />\n Phone: +254 721 405 643,Email: kotieno72@yahoo.com,Role(s):</p>\n<p>\n <strong>Trial Pharmacist</strong></p>\n<p>\n Tony Sang, BPharm,KEMRI CGHR,P.O. Box: 1578 - 40100, Kisumu, Kenya</p>\n<p>\n Phone: +254 721 246 875,Email: <a href=\"mailto:tonysangke@gmail.com\">tonysangke@gmail.com</a></p>\n<p>\n Lilian Otieno, DipPharm, BA,KEMRI Center for Global Health Research (CGHR) P.O. Box: 1578 - 40100, Kisumu, Kenya , Phone: +254723934572, Email: <a href=\"mailto:lotieno@kemricdc.org\">lotieno@kemricdc.org</a>, <a href=\"mailto:otililly@yahoo.com\" style=\"font-size: 9pt; font-family: Arial, sans-serif;\">otililly@yahoo.com</a></p>\n<p>\n <strong>Regulatory Officer</strong></p>\n<p>\n Lilian Otieno, DipPharm, BA,KEMRI Center for Global Health Research (CGHR) P.O. Box: 1578 - 40100, Kisumu, Kenya , Phone: +254723934572, Email: <a href=\"mailto:lotieno@kemricdc.org\">lotieno@kemricdc.org</a>, <a href=\"mailto:otililly@yahoo.com\" style=\"font-family: Arial, sans-serif; font-size: 9pt;\">otililly@yahoo.com</a></p>\n<p>\n <strong>Study Coordinator</strong></p>\n<p>\n Reuben Yego, BSPH,KEMRI Center for Global Health Research (CGHR) P.O. Box: 1578 - 40100, Kisumu, Kenya , Phone: +254723934572, E-mail: <a href=\"mailto:lotieno@kemricdc.org\">lotieno@kemricdc.org</a>, <a href=\"mailto:otililly@yahoo.com\" style=\"font-size: 9pt; font-family: Arial, sans-serif;\">otililly@yahoo.com</a></p>\n<p>\n  </p>\n
      • other_details_explanation<p>\n N/A</p>\n
      • other_details_regulatory_notapproved<p>\n FDA-Submission done, awaiting Approval</p>\n
      • other_details_regulatory_approved<p align=\"left\" style=\"margin-left:144pt;\">\n Bill and Melinda Gates Foundation-DAC BMGF-DAC</p>\n<p align=\"left\" style=\"margin-left:144pt;\">\n National Institute of Allergy and Infectious Diseases (NIAID)</p>\n<p align=\"left\" style=\"margin-left:144pt;\">\n LSTM-Research Ethics Committee (LSTM-REC)</p>\n
      • other_details_regulatory_rejected<p>\n NONE</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration2 years
      • 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_comparatorsterile isotonic (0.9%) n
      • 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_countriesNo
      • multiple_member_states
      • number_of_sites2
      • multi_country_list
      • data_monitoring_committeeYes
      • total_enrolment_per_site72 for part 1 and 324 for part 2.
      • total_participants_worldwide396
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerYes
      • population_childrenYes
      • population_adolescentNo
      • population_above_18No
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
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      • investigator1_given_nameTitus
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      • investigator1_qualificationMD, PhD
      • investigator1_professional_addressCenters for Disease Control and Prevention Kenya Malaria Program
      • investigator1_telephone+254 722207281
      • investigator1_emailqbb5@cdc.gov
      • organisations_transferred_Yes
      • number_participants396
      • notification
      • approval_date08-08-2022
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        • given_nameTitus
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        • professional_addressCenters for Disease Control and Prevention Kenya Malaria Program
        • telephone+254 722207281
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        • given_nameLaura
        • middle_name
        • family_nameSteinhardt
        • qualificationPhD, MPH, Epidemiologist
        • professional_addressMalaria Branch Center for Global Health Centers for Disease Control and Prevention
        • telephone+14047184794
        • emailLSteinhardt@cdc.gov
        • created2022-01-26 15:53:08
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        • given_nameRobert
        • middle_nameA
        • family_nameSeder
        • qualificationMD
        • professional_addressVaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases (NIAID), NIH
        • telephone301-594-8483
        • emailrseder@mail.nih.gov
        • created2022-01-26 15:54:33
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        • physical_addressOff Hospital Road, Siaya Township
        • contact_details0722207281
        • contact_personDr. Titus Kwambai
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        • site_nameKogelo Health Center
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        • sponsorOffice of Clinical Research Policy and Regulatory Operations (OCRPRO), Division of Clinical Research (DCR), NIAID
        • sponsor_typeResearch Institution
        • contact_personRobert A. Seder, MD
        • addressVaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases (NIAID), NIH
        • telephone_number+1-301-594-8483
        • fax_number
        • cell_number+1-301-594-8483
        • email_addressrseder@mail.nih.gov
        • created2022-01-26 15:26:17
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      • abstract_of_study<address>\n Diarrhoea caused by <em>Shigella </em>(shigellosis) is of major public health importance. <em>Shigella</em> causes a high burden of disease in low- and middle-income countries (LMICs), where 70% of all cases occur in children under 5 years of age who form the target population for disease prevention through vaccination. However, there are no licensed <em>Shigella</em> vaccines in routine use, with several candidates still in various stages of clinical development. <em>Shigella</em> human infection studies (HIS) have played a key role in vaccine development. These models also allow for the evaluation of immunity and other non-immunological parameters that are important to understand resistance and/or susceptibility to disease. This is particularly useful in individuals from endemic areas with varying levels of prior exposure and immunity to <em>Shigella</em>. Thus, establishing a <em>Shigella</em> HIS would enable the testing of interventions such as vaccines in a population that would most benefit from a subsequent vaccine and has potential to accelerate vaccine development. Here, the goal is to successfully establish a <em>Shigella sonnei </em>human infection model in Kenyan adults. This will be achieved by conducting dose-finding and dose verification <em>Shigella</em> studies that safely and reproducibly induce ≥60% attack rates. In this study, we aim to use <em>Shigella</em> HIS in healthy adults to develop a model as a platform to test vaccines, to study immune responses identifying potential correlates of infection, and non-immunological factors mediating and influencing susceptibility to disease. To achieve this, the study will be carried out in two phases over a period of 12-14 months. Phase A will enroll (N=up to 40 volunteers) and Phase B will enroll an additional (N=30 volunteers). To be eligible to receive a dose of 53G, volunteers must pass the screening visit. We will vary the dose of bacteria in individuals enrolled for challenge to identify the dose needed to cause ≥60% shigellosis (attack rate) (Phase A) followed by testing and demonstrate the reproducibility of the model (Phase B). Thus, the main outcomes of the study will be: (1) optimisation of bacterial dose for infection success (≥60% attack rate); and (2) safety. To achieve this, we will screen healthy adults (18-45 years of age) who will be recruited from known areas of Kilifi County and screened for their exposure to <em>S. sonnei</em> (by measuring antibodies) to enroll up to 70 individuals to conduct <em>S. sonnei</em> infection studies with clinical monitoring, including monitoring for safety, detection of bacterial shedding in stool, and sampling for measures of immunity and non-immunological parameters. In addition, we will comprehensively characterize immunity and identify potential immunological targets in various laboratory assays. Once established, the model will accelerate <em>Shigella</em> vaccine development by facilitating the early selection of the most promising vaccines for more extensive testing in LMICs.</address>\n<p>\n  </p>\n
      • study_title<p>\n Safety and feasibility of a <em>Shigella sonnei</em> 53G controlled human infection model in Kenyan adults: a dose finding and dose verification study</p>\n
      • laymans_summary<p>\n <strong>What is the problem/background?</strong></p>\n<p>\n Diarrhoea caused by the bacteria <em>Shigella</em> is a major public health problem. <em>Shigella</em> is the leading cause of moderate to severe diarrhoea in infants and children in low- and middle-income countries (LMICs) with approximately seventy-five million episodes of diarrhoea occurring annually mainly over the child’s first three years of life. There are 4 main different types of <em>Shigella</em> and one of these, <em>Shigella sonnei</em>, has been found to be a common cause of diarrhoea in Kenya. There are no vaccines available against the disease; however, a number are currently in development and being tested in clinical trials including in trials being conducted in Kenya. There is an urgent need to accelerate the development of these vaccines especially in the advent of resistance to drugs used to treat the disease. Thus, human infection studies (HISs) are needed to test the usefulness of candidate vaccines so that vaccines showing evidence of efficacy can then be prioritised for testing in Phase 2/3 clinical trials in the target age population. Furthermore, there is need to study how the humans respond against to infection and the association between these immune responses with protection may help better understand resistance and/or susceptibility, including characterizing and identifying potential targets for second- or third-generation vaccines. Human infection studies for <em>Shigella</em> have been an important tool in the advancing of the understanding of the disease, how immunity develops, and efficacy of interventions such as vaccines. These, however, have largely been undertaken in individuals not exposed to infection. Human infection studies have been undertaken using <em>Shigella sonnei</em> 53G strain in the USA and Thailand. The expansion of the <em>Shigella</em> HISs to areas where infection commonly occurs, like Kenya, will help address the need to facilitate greater use of the model as a tool to accelerate <em>Shigella</em> vaccine development. </p>\n<p>\n <strong>What questions are we trying to answer?</strong></p>\n<p>\n We wish to understand:</p>\n<ul>\n <li>\n Human and bacterial factors that determine how vulnerability to and recovery from disease develops.</li>\n <li>\n What dose of bacteria is required to reliably cause disease in ≥60% of the volunteers.</li>\n <li>\n How immunity develops in individuals who have past exposure to <em>Shigella sonnei</em>.</li>\n</ul>\n<p>\n <strong>Where is the study taking place, how many people does it involve, and how are they selected? </strong></p>\n<p>\n The study will take place in Kilifi, Kenya. Kilifi County (Kilifi North, Kilifi Town, Kilifi South, and Mtwapa) will be where volunteers will be recruited and undergo the infection phase of the study. The study will involve the recruitment and screening of adults (18-45 years of age, up to 70 volunteers are required) from Kilifi County to determine eligibility for participation and past exposure to the strain of <em>Shigella</em> used for infection. This will be done after a programme of sensitisation and information giving about the study to local community leaders, as well local regulatory and ethical boards. The study will be conducted in two phases (A and B) where volunteers will be enrolled as follows:</p>\n<p style=\"margin-left:.5in;\">\n 1. Phase A (N = up to 40 volunteers) dose-finding: to determine the dose of <em>Shigella</em> <em>sonnei</em> 53G bacteria that will cause infection and result in diarrhoea in at least 60% of the volunteers. Volunteers in Phase A will be enrolled in successive cohorts each with N = 10 volunteers receiving a varying dose of <em>Shigella</em> <em>sonnei</em> 53G bacteria.</p>\n<p style=\"margin-left:.5in;\">\n 2. Phase B (N = 30 volunteers dose verification: further validation of the disease rate assessing infectivity of the dose in Phase A found to give rise to diarrhoea in ≥60% of the volunteers. Volunteers in Phase B will be enrolled into two successive cohorts with N = 15 volunteers in each cohort receiving the dose of bacteria found to reliably cause diarrhoea in ≥60% of volunteers.</p>\n<p>\n For each of these phases, eligibility for enrolment will be based on the health status and level of past exposure to<em> Shigella sonnei </em>(determined by history or serology). To determine these, a clinical assessment and laboratory tests will be performed with blood, saliva, stool, and urine samples taken at the point of screening for each individual volunteer.</p>\n<p>\n <strong>What does the study involve for those who are in it?</strong></p>\n<p>\n All volunteers will attend a screening visit to determine if they are eligible based on review of medical history, a clinical assessment including to check the functioning of the heart, and laboratory tests. For screening, a blood sample of 76 mL will be collected in addition to urine, saliva, and stool samples. For enrolment, volunteers with no exclusionary clinical disease and medical history will be considered and will be screened for past exposure to <em>Shigella</em>. Those that meet the eligibility criteria after screening (there will be screening events for each cohort of volunteers enrolled) will be asked to be part of the challenge phase of the study. In the infection phase, volunteers will be enrolled into Phase A or into Phase B of the study for <em>Shigella</em> infection and will stay at the in-patient challenge facility located within close proximity to KEMRI CGMRC in Kilifi County where they will remain for about 14 days as in-patients. Phase A will happen before Phase B.</p>\n<p>\n Volunteers will be asked to stay at the facility starting five days before infection (to undertake health checks to be sure they are well). During the first 5 days, a COVID-19 test will be performed. In addition, a blood sample will be taken to test for presence of antibiotics that might have impact on establishment of infection. If a volunteer is found to be infected with COVID-19 and/or have antibiotics in their blood, the volunteer will be discharged from the facility before receiving the <em>Shigella</em> germ. On the sixth day, all volunteers will be given a dose of the <em>Shigella</em> germ. After infection, volunteers will be checked regularly by the study doctors and nurses. Five days after the challenge (study day 6), all volunteers will be given a 3-day course of antibiotics to clear the <em>Shigella</em> from their body. After completion of the antibiotics and having 2 stool cultures showing the <em>Shigella</em> is out of their body, volunteers will be able to return home. If the study doctor thinks it is necessary, antibiotics may be started before day 6. The inpatient period will last approximately 14 days. To set up the human infection model we must first reliably induce an infection which will result in disease in ≥60% of the volunteers. We will:</p>\n<p>\n 1. For Phase A: Healthy volunteers, 18–45 years old, will be enrolled into at least one of three cohorts to be given different doses of <em>Shigella</em> <em>sonnei</em> 53G bacteria in suspension to drink. During this part of the study, we want to find out the dose of 53G needed to cause an infection in about 6 of every 10 people. As mentioned before, the study will occur at the challenge in-patient facility within proximity of KEMRI CGMRC in Kilifi County where volunteers will remain for about 14 days. All volunteers will be treated with an antibiotic if they meet criteria (early treatment) or on day 6 after drinking the bacterial suspension. If the study doctor thinks it is important for the health of the volunteer, antibiotics may be started before day 6. Volunteers will be monitored until they have cleared the infection (i.e., no <em>Shigella</em> bacteria being detected in two consecutive negative stool samples with resolution of symptoms). It is likely that some volunteers might require treatment before day 6 based on their clinical presentation (see section 6.1.6.5).</p>\n<p>\n 2. For Phase B: Based on results from Phase A, volunteers will be given the dose of 53G found to cause infection in about 6 of 10 recipients. The rest of Phase B will be the same as described above for Phase A. All volunteers will be treated with an antibiotic on day 6 after infection and will be monitored until they have cleared the infection (i.e., no <em>Shigella</em> bacteria being detected in stool based on two stools with consecutive negative results and resolved symptoms). It is likely that some volunteers might require treatment before day 6 based on their clinical presentation.</p>\n<p>\n During the first 5 days at the in-patient facility, volunteers will be checked to be sure they are well. During this time, COVID-19 and antibiotic testing will be performed. If a volunteer is found to be infected with COVID-19, i.e., found to have detectable virus, the volunteer will be referred for management according to the guidelines at time of testing and discharged from the in-patient facility before receiving the <em>Shigella</em> germ. Five days before infection, all volunteers eligible for enrolment (both Phases A and B) will be invited to the inpatient facility for COVID-19 testing and enrolled for infection after a confirmed negative test result. Any volunteers who are found to be positive will be referred for management based on the prevailing guidelines and their participation in the study will be discontinued.</p>\n<p>\n Multiple samples (blood, saliva, stool, and urine) will be taken for those enrolled for admission (both Phase A and B). For both phases, blood samples will be drawn as follows: five days before challenge (up to 9 mL); a day before challenge (71 mL); days one, two, and three (9 mL each day); day four (49 mL); day five (5 mL); day six (59 mL); day seven (5 mL); day eight (59 mL); day nine (5 mL); day fifteen (29 mL); day twenty-nine (49 mL); day fifty-seven (44 mL); and then at 6 months (day 181) and 12 months (day 366) (40 mL and 10 mL each time point, respectively). In addition, stool and saliva samples will be collected at various time points during the study. For the entire duration of the study (12-14 months), up to a total of 544 mL of blood per volunteer will be drawn for both Phase A and Phase B. The total volume of blood collected in the study is within the limits of the volume taken about the same as during a single unit of blood donation. In addition to blood sampling, clinical assessments will be repeated a day before infection, including collection of a urine sample. Observed antibiotic treatment for shigellosis will be given on day 6, or earlier if the participant meets early treatment criteria.</p>\n<p>\n During the in-patient period, if a volunteer develops signs and symptoms of COVID-19, samples will be taken for testing and if found to be positive (by PCR testing), they will be isolated and symptomatic management for coronavirus disease administered. At the same time, the volunteer will be treated with antibiotics against shigellosis as outlined in this protocol, after which he/she will exit the inpatient phase of the study (only after two stools with consecutive negative stool results and resolved symptoms) and be referred for management or managed based on the COVID-19 guidelines prevailing at the time of diagnosis. For infection control, volunteers will be released only after clearance of the <em>S.</em> <em>sonnei</em> 53G in their stool as evidenced by two negative stool culture results.</p>\n<p>\n <strong>What are the benefits and risks/costs of the study for those involved?  </strong></p>\n<p>\n Human infection studies with <em>Shigella</em> have been conducted in healthy adults in the United States and Thailand and have been proven safe in these individuals. The risks relate to the development of shigellosis which is the primary objective of the study. Illness caused by <em>Shigella </em>ranges from mild (watery diarrhoea being the main symptom) to severe (fever and abdominal pain with frequent bloody stools containing mucus). Volunteers may complain of nausea, vomiting, headache, muscle and/or joint aches, and other symptoms associated with the disease. Symptoms typically are self-resolving in 5-7 days. However, administration of an effective antibiotic will significantly reduce, or eliminate, symptoms within 24 hours of initiation. There is potential risk of developing redness and swelling in various joints in the body, typically 1 to 3 weeks after the onset of diarrhoea. This risk is higher in persons with a particular genetic marker and therefore for this study, potential volunteers who are positive for this genetic marker will be excluded from participation. There is the possibility of increased risk of developing an intestinal disorder causing pain in the stomach, wind, diarrhoea, and constipation. There is the risk of pain, bruising, or infection at the site of venipuncture. There might be risks relating to the possibility of developing an allergic reaction or other side effects due to administration of the antibiotic treatment. There is also a risk of the study staff acquiring the infection from volunteers who will be administered the <em>S. sonnei</em> 53G strain. Therefore, proper personal protective equipment will be worn by staff, and good personal hygiene such as frequent hand washing will be followed by staff and volunteers.</p>\n<p>\n Volunteers are required to be residents in the inpatient unit for safety monitoring and to reduce the risk of spreading the infection. This is a considerable cost to the volunteers on their time but is a requirement for the study to be successful. There are no direct benefits to individuals participating in this study other than gaining information about their health. There might be a perception of benefit from clinical assessment and laboratory screening. However, a successful outcome of the study could lead to the development of a model that will allow easier and more reproducible evaluation of preventive and therapeutic measures against disease due to <em>S. sonnei</em>. Despite there being no direct benefits to the study volunteers, all volunteers will have their transport costs reimbursed (a range between Ksh200 and Ksh1,000) and will be compensated for all out-of-pocket expenses for each study visit during the entire duration of the study (at a rate of Ksh500 for each clinic visit and at a rate of Ksh2,000 per overnight stay).</p>\n<p>\n <strong>How will the study benefit society?  </strong></p>\n<p>\n This work is necessary for enhancing our understanding of how <em>Shigella</em> infection develops, the type of immunity involved, and the establishment of a model to test interventions such as vaccines in a population that has a high burden of infection with this bacterium and the resulting morbidity and mortality associated with both the acute and more long-term aspects of this disease, which would most benefit from a subsequent vaccine. The successful application of such interventions will benefit society by reducing diarrhoea attributed to <em>S. sonnei</em>, a major cause of illness, death, and impediment to national development. The establishment of this human infection model in Kenya provides a way of studying the disease in a very detailed way that is not possible in natural infections. In addition, the establishment of this model in Kenya will ultimately provide a pathway to support efforts to accelerate the efficacy testing of the most promising <em>Shigella </em>vaccine candidates, particularly providing an option for testing these vaccines against important types that lack the field incidence to be assessed in Phase 3 trials. </p>\n<p>\n <strong>When does the study start and finish?</strong></p>\n<p>\n The study will start upon receipt of ethical and regulatory clearance and activation by the study Sponsor. The duration of volunteer participation is 12-14 months from screening to final follow-up. Data collection, analysis, and write-up will take place over three years.</p>\n<p>\n  </p>\n<p>\n  </p>\n
      • short_titleShigella 53G study in Kenya
      • protocol_noECCT/23/04/02
      • version_no1.5
      • date_of_protocol28-03-2024
      • study_drugShigella sonnei 53G Challenge
      • disease_conditionShigellosis
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals1
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressCGMRCCSC@kemri-wellcome.org
      • applicant_covering_letter1
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      • applicant_indemnity_cover1
      • applicant_opinion_letter1
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      • declaration_applicantStellamaris Akinyi
      • declaration_date120-08-2024
      • declaration_principal_investigatorMelissa Kapulu Principal Investigator
      • declaration_date220-08-2024
      • placebo_presentNo
      • study_objectives<p>\n <strong>Primary Objectives</strong></p>\n<p>\n (a) To determine the safety of increasing doses of lyophilised <em>S. sonnei</em> 53G in Kenyan adults.</p>\n<p>\n (b) To identify a safe dose of lyophilised <em>S. sonnei</em> 53G that consistently yields a shigellosis attack rate of ≥60% in Kenyan adults</p>\n<p>\n <strong>Secondary Objectives</strong></p>\n<p>\n (a) To determine effects of lyophilized <em>S. sonnei</em> 53G on stool output and clinical symptoms.</p>\n<p>\n (b) To estimate qualitative and quantitative faecal shedding patterns of the <em>S. sonnei</em> 53G challenge strain following experimental infection.</p>\n<p>\n (c) To measure mucosal and systemic immune responses to O antigen (O-Ag) on the lipopolysaccharide (LPS) “O” LPS, and invasion protein antigens IpaB and IpaC (both IgA and IgG) following challenge with 53G.</p>\n<p>\n <strong>Exploratory objectives </strong></p>\n<p>\n (a) To undertake exploratory systems biology, microbiome, and other omics-based analyses (including proteomics using antigen arrays and transcriptomics) and their association with clinical outcomes and/or levels of pre-existing immunity to identify potentially protective antigens and immune response profiles in individuals protected from shigellosis.</p>\n<p>\n (b) To identify inflammatory markers and other markers of innate immunity (i.e., anti-microbial peptides and defensins) associated with pre-existing immune responses and outcomes following challenge.</p>\n<p>\n (c) To evaluate serum bactericidal antibody (SBA) titers against <em>S. sonnei</em> 53G at baseline and following challenge and determine the association between baseline titers and outcomes following challenge.</p>\n<p>\n (d) To determine the proportion of seroconversions (≥4-fold rise over baseline) to key <em>Shigella</em> “O” LPS and Ipa antigens by comparing titers at baseline compared to those at post-infection days 8, 15 or 366.</p>\n<p>\n  </p>\n<p>\n  </p>\n
      • principal_inclusion_criteria<p>\n To be eligible to participate, each volunteer must fulfill all of the following criteria:</p>\n<p>\n 1. Healthy adults between 18 and 45 years of age (inclusive) Kilifi County residents.</p>\n<p>\n 2. Able and willing (in the Investigator’s opinion) to comply with all study requirements.</p>\n<p>\n 3. Provide informed consent.</p>\n<p>\n 4. Demonstrate comprehension of the protocol procedures and knowledge of study by passing a test of understanding (pass grade 100%).</p>\n<p>\n 5. Use of effective method of contraception for the entire duration of study (prior to study start and up to study completion) (women only). Female volunteers will be asked to provide evidence of their method of contraception for the study team to verify. Effective contraception is defined as a contraceptive method with failure rate of less than 1% per year when used consistently and correctly, in accordance with the product label. Examples of these include: combined oral contraceptives; injectable progestogen; implants of etenogestrel or levonorgestrel; intrauterine device or intrauterine system; male partner sterilisation at least 6 months prior to the female volunteer’s entry into the study, and the relationship is monogamous; male condom combined with a vaginal spermicide (foam, gel, film, cream or suppository); and male condom combined with a female diaphragm, either with or without a vaginal spermicide (foam, gel, film, cream, or suppository).</p>\n<p>\n 6. Willingness to participate for an inpatient stay lasting approximately 14 days or longer and an outpatient follow-up lasting about 12 months from challenge.</p>\n<p>\n 7. Available for all planned follow-up visits.</p>\n<p>\n  </p>\n
      • principal_exclusion_criteria<p>\n Any of the following constitutes exclusion criterion:</p>\n<p>\n 1. Presence of a significant medical condition (e.g., psychiatric conditions, alcohol or illicit drug abuse/dependency, or gastrointestinal disease, such as peptic ulcer, symptoms or evidence of active gastritis or gastroesophageal reflux disease, inflammatory bowel disease), or other laboratory abnormalities which in the opinion of the investigator precludes participation in the study.</p>\n<p>\n 2. Known immunosuppressive illness for example those with cancer, on immunosuppressive therapy, HIV etc.</p>\n<p>\n 3. Positive serology results for HIV, HBsAg, or HCV antibodies.</p>\n<p>\n 4. Evidence of inflammatory arthritis on exam and/or HLA-B27 positive.</p>\n<p>\n 5. Family history of inflammatory arthritis.</p>\n<p>\n 6. Clinically significant abnormalities in screening lab haematology or serum chemistry, as determined by PI or PI in consultation with the research monitor and Sponsor.</p>\n<p>\n 7. Known allergies to fluoroquinolones, β-lactams or trimethoprim-sulfamethoxazole (any of the three are exclusionary).</p>\n<p>\n 8. Fewer than 3 stools per week or more than 3 stools per day as the usual frequency.</p>\n<p>\n 9. History of diarrhoea in the 2 weeks prior to planned inpatient phase.</p>\n<p>\n 10. Use of antibiotics during the 7 days before receiving the challenge inoculum dosing.</p>\n<p>\n 11. Use of prescription and/or OTC medications that contain imodium, acetaminophen, aspirin, ibuprofen, and/or other non-steroidal anti-inflammatory drugs, during the 48 hours prior to investigational product administration.</p>\n<p>\n 12. Confirmed PCR positive for SARS-COV-2 before challenge i.e., Day -5 or -3.</p>\n<p>\n 13. Use of any medication known to affect the immune function [e.g., oral steroids, parenteral steroids, or high-dose inhaled steroids (>800μg/day of beclomethasone dipropionate or equivalent and others); nasal and topical steroids are allowed] within 30 days preceding receipt of the challenge inoculum or planned use during the active study period.</p>\n<p>\n 14. Serologic evidence of prior <em>S. sonnei</em> infection as determined by ELISA.</p>\n<p>\n 15. A chronic disease (such as hypertension, diabetes, hyperlipidemia, or anxiety/depression) for which doses of prescription medications are not stable for at least the past 3 months.</p>\n<p>\n 16. Have known immunocompromised household contacts for example those with cancer, on immunosuppressive therapy, HIV etc.</p>\n<p>\n 17. A clinically significant abnormality on physical examination, including a systolic blood pressure >140 mm Hg or diastolic blood pressure >90 mm Hg, or a resting pulse >100 beats/min or <55 beats/min (<50 beats/min for conditioned athletes).</p>\n<p>\n 18. Pregnant, nursing, or planning to become pregnant within 29 days of receipt of the study product.</p>\n<p>\n 19. In the 4 weeks following challenge, volunteer will be living with or having daily contact with elderly persons aged 70 years or more, diapered individuals, persons with disabilities, children <2 years old, a woman known to be pregnant or nursing, or anyone with diminished immunity. This includes contact at work, home, school, day-care, nursing homes, or similar places.</p>\n<p>\n 20. Work in a health care setting, day care center, or as a food handler in the 4 weeks following the challenge with <em>S. sonnei</em>.</p>\n<p>\n 21. Use of any investigational drug or any investigational vaccine within 60 days preceding challenge, or planned use during the 6 months after receipt of the study agent.</p>\n<p>\n 22. Have received a licensed, live vaccine within 28 days or a licensed inactivated vaccine within 14 days of receiving the challenge inoculum.</p>\n<p>\n 23. Inability to comply with inpatient rules and regulations.</p>\n<p>\n 24. Has any other condition that, in the opinion of the Investigator, would jeopardize the safety or rights of a volunteer (e.g., infection with another detected pathogen) or would render the volunteer unable to comply with the protocol.</p>\n<p>\n 25. Received blood or blood products within the past six months.</p>\n<p>\n In addition to the exclusion criteria above, efforts will be made to prioritize volunteers with low levels of antibodies to the challenge organism. Because the level of antibodies to the challenge strain are currently unknown in this population, ongoing testing prior to volunteer enrollment will be utilized to define an algorithm for volunteer selection. This process will be defined in the SOP prior to volunteer enrolment.</p>\n<p>\n  </p>\n
      • primary_end_points<p>\n 1. The primary endpoint is safety of volunteers at each evaluated dose level.</p>\n<ul>\n <li>\n Occurrence and severity of solicited adverse events (AEs) through 11 days post-challenge.</li>\n <li>\n Occurrence, severity, and relatedness of unsolicited AEs through 11 days post-challenge.</li>\n <li>\n Occurrence, severity, and relatedness of serious adverse events (SAEs) throughout the entire study.</li>\n <li>\n Occurrence of abnormal clinical laboratory values within 11 days post-challenge.</li>\n <li>\n Percent of volunteers with nausea, vomiting, anorexia, abdominal pain/cramps rated as moderate to severe.</li>\n</ul>\n<p>\n The severity of these will be graded based on the definitions outlined in the protocol.</p>\n<p>\n 2. Confirmation of the dose with an acceptable safety profile as determined by the PSRT and DSMB that gives an attack rate of ≥60% of shigellosis in Kenyan adults.</p>\n<p>\n  </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_specifyDose finding and verification
      • trial_human_pharmacology1
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other1
      • trial_other_specifyHuman challenge study with deliberate infection of healthy volunteers
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledNo
      • site_capacity(null)
      • staff_numbers<p>\n Medical officer - 3<br />\n Clinical officer - 3<br />\n Nurses - 3<br />\n Fieldworkers - 5<br />\n Research and Assistant Research Officers and Lab technicians - 5<br />\n Study Coordinator - 1<br />\n Pharmacisit - 1<br />\n Data Manager - 1<br />\n Data Clerk - 3<br />\n The inpatient facility is already staffed with 4 clincians and locum 20 nurses.<br />\n All staff are trained in basic life support and resuscitation facilitaties are available.</p>\n
      • other_details_explanation<p>\n Not applicable.</p>\n
      • other_details_regulatory_notapproved<p>\n Submission is only to PPB.</p>\n
      • other_details_regulatory_approved<p>\n Not applicable.</p>\n
      • other_details_regulatory_rejected<p>\n Not applicable</p>\n
      • other_details_regulatory_halted<p>\n Not applicable.</p>\n
      • estimated_duration3 years
      • design_controlled_randomised
      • design_controlled_open
      • design_controlled_single_blind
      • design_controlled_double_blind
      • design_controlled_parallel_group
      • design_controlled_cross_over
      • design_controlled_other
      • design_controlled_specify
      • design_controlled_comparator
      • design_controlled_other_medicinal
      • design_controlled_placebo
      • design_controlled_medicinal_other
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKEMRI-Wellcome Trust Research Programme (KWTRP) Centre for Geographic Medical Research - Coast (CGMRC), Kilifi, Kenya.
      • single_site_physical_addressKEMRI-Wellcome Trust Research Programme, Off Bofa Road, Kilifi County Hospital, Kilifi, Keny
      • single_site_contact_personMelissa Kapulu
      • single_site_telephone+254 709 983463
      • multiple_sites_member_stateNo
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites
      • multi_country_list
      • data_monitoring_committeeYes
      • total_enrolment_per_site70
      • total_participants_worldwide70
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsNo
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameMelissa
      • investigator1_middle_name
      • investigator1_family_nameKapulu
      • investigator1_qualificationBSc MSc PhD
      • investigator1_professional_addressKEMRI-Wellcome Trust Research Programme, P. O. Box 230, Kilifi, Kenya 80108
      • investigator1_telephone+254 709 983463
      • investigator1_emailmkapulu@kemri-wellcome.org
      • organisations_transferred_No
      • number_participants70
      • notification
      • approval_date21-08-2024
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted14-04-2023
      • is_child0
      • unsubmitted1
      • initial_date_submitted14-04-2023
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been addressed. The Re-inspection has recommended the site (Kilifi county referral Hospital) for use in the study
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
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      • quantity_destroyed(null)
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      • balance_site(null)
      • final_date(null)
      • modified2025-02-28 13:21:28
      • created2023-03-30 08:56:23
      • total_sites(null)
      • ecitizen_invoice(null)
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        • application_id1245
        • given_nameMelissa
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        • qualificationBSc MSc PhD
        • professional_addressKEMRI-Wellcome Trust Research Programme, P. O. Box 230, Kilifi, Kenya 80108
        • telephone+254 709 983463
        • emailmkapulu@kemri-wellcome.org
        • created2023-03-30 11:29:40
        • modified2024-08-20 14:34:06
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        • application_id1245
        • given_nameFredrick
        • middle_name
        • family_nameSawe
        • qualificationMBChB M.Med
        • professional_addressP.O. BOX 1357 20200 KERICHO
        • telephone+254 703 247902
        • emailFredrick.Sawe@usamru-k.org
        • created2023-03-30 11:51:29
        • modified2024-08-20 14:34:06
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      • 0(array)
        • id1467
        • application_id1245
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2023-03-30 11:29:40
        • modified2024-08-20 14:34:06
        • County(empty)
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      • 0(array)
        • id654
        • application_id1245
        • sponsorUniversity of Oxford
        • sponsor_typeResearch Institution
        • contact_personProf Philip Bejon
        • addressUniversity Offices, Wellington Square, Oxford, OX1 2JD, UK
        • telephone_number+44 1865 270000
        • fax_number
        • cell_number+44 1865 270000
        • email_addresskwtrpsponsor@kemri-wellcome.org
        • created2023-03-30 11:29:40
        • modified2024-08-20 14:34:06
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