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  • 1Recruiting
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• applications(array)
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    • Application(array)
      • id466
      • user_id306
      • trial_status_id7
      • abstract_of_study<p>\n Important life decisions are often taken under stress. More generally, it has been shown that living in the context of poverty may lead to stress (see Haushofer, Johannes and Ernst Fehr, “On the Psychology of Poverty.”  <em>Science </em>344 (2014), 862–867.) Therefore, it is highly important to understand the impact of stress on economic decision-making, because if stress biases decision making (or influences individuals in other negative ways), it may actually worsen poverty, creating a negative feedback loop.</p>\n<p>\n Because the study is motivated by understanding the impact of poverty, we have chosen the context of informal settlement in Nairobi, where research has shown stress levels are high. By allowing us to understand the link between poverty, stress, and economic decision-making, we hope that in the long run this study will inform the design of poverty interventions in Kenya and beyond. For example, if the study finds that stress levels affect social cooperation, this will give us reason to believe that interventions that reduce stress would have an impact on conflict.     </p>\n<p>\n The objective of this study is to explore the effect of hormones on economic behavior. More specifically, it will explore how stress affects in-group/out-group behavior. This study will answer questions on whether stress increases in-group biases and tendency to protect the in-group, or whether stress increases the need for cooperation, increasing positive interaction with the out-group.</p>\n<p>\n         The proposed study will administer hydrocortisone to healthy male participants, and then tests its effects on in-group/out-group behavior. A wide variety of economic games (including dictator, trust, and public goods) will be played. Participants will also play multiple other games requiring social interaction between in-group and out-group participants. The main hypothesis is that higher levels of cortisol will increase prosocial behavior towards the in-group and antisocial behavior towards the out-group.</p>\n
      • study_title<p>\n Hormones and Economic Choice: Evaluating the Effects of Hydrocortisone Administration on Economic Decision Making, Psychology and Social Behavior among Adult Males in Nairobi, Kenya</p>\n
      • laymans_summary(null)
      • short_titleHormones and Economic Choice
      • protocol_noECCT/15/12/04
      • version_no1
      • date_of_protocol20-11-2015
      • study_drugHyrdocortisone
      • disease_conditionNone. This study is on healthy adults
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones1
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device1
      • product_type_chemical_nameHydrocortisone
      • product_type_medical_device_nameCapsule
      • comparator(null)
      • comparator_name(null)
      • comparator_registered(null)
      • comparator_countries(null)
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addresskelvin.kinyua@busaracenter.org
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
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      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries0
      • applicant_addendum0
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      • applicant_complete_form(null)
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      • applicant_contractual_agreement(null)
      • declaration_applicantColin West
      • declaration_date120-11-2015
      • declaration_principal_investigatorJohannes Haushofer
      • declaration_date220-11-2015
      • placebo_presentYes
      • study_objectives(null)
      • principal_inclusion_criteria<p class=\"p1\">\n Healthy adult volunteers between the ages 18-40</p>\n
      • principal_exclusion_criteria<p class=\"p1\">\n Weighs more than 190 lbs (86.2 kg); substantial consumption of alcohol, tobacco, or other drugs; candidate has any of the following infections or medical conditions (liver disease, kidney disease, thyroid disease or hypothyroidism, diabetes, current malaria, TB, osteoporosis, muscle disorder, glaucoma, eye infection, stomach ulcer, ulcerative colitis, diverticulitis, recent abdominal surgery, any heart problem, high or low blood pressure, strongyloides infection, herpes or any genital ulcer disease, immunodeficiency, any other infection or condition); uses or recently used any of the following medications (drugs that induce hepatic enzymes, troleandomycin, chronic high dose aspirin, oral anticoagulants, heart or BP medication, recent vaccination); or has a mental health concern (severe stress, history of depression, anxiety or other psychiatric disorder, is under psychiatric treatment).</p>\n<p class=\"p1\">\n For full details see submitted Checklist for Subject Inclusion</p>\n
      • primary_end_points<p class=\"p1\">\n The primary endpoints of this study  are: salivary cortisol concentration (nanomol/l), a self-report measure of participant's subjective emotional state (PANAS: positive and negative affect schedule), and a series of economic games and behavioral tasks (all of which are standard paradigms in economic and psychological research). </p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety0
      • scope_efficacy0
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response1
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others1
      • scope_others_specifyExploring the effect of low-doses of hormones on economic and social behaviors
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other1
      • trial_other_specifyBehavioral economics research trial on hormones and economic decision making.
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p class=\"p1\">\n The Busara Center for Behavioral Economics lab team has extensive training in conducting scientifically controlled lab experiments, and years of experience in designing, leading, and managing experimental protocols. The lab is under the direction of Busara's senior leadership team: Johannes Haushofer (Prof. at Princeton University), Jeremy Shapiro (PhD in Economics at MIT), Chaning Jang (PhD in Economics, University of Hawaii), and James Vancel (Managing Director of Busara). For more detailed qualifications, see CVs included in this package. </p>\n<p class=\"p1\">\n Study Coordinators: the on-site research staff at Busara will coordinate the study. Busara's staff are managed by Joseph Muiruri (Mr. Mururi is a graduate of the University of Nairobi, and has extensive experience supporting scientific experiments and managing lab project). </p>\n<p class=\"p1\">\n Site facilities: Busara is located in a compound with 24-hr security. The lab facility includes a networked computer cluster (touchscreen computers that can be used by illiterate participants), a waiting room; lab space for saliva sampling, a -20 deg C freezer for specimen storage, continuous and uninterrupted power through a backup system. </p>\n<p class=\"p1\">\n Emergency facilities: Busara has a fully equipped first aid kit, and a licensed nurse will be on-site at all times during this study. </p>\n
      • other_details_explanation<p class=\"p1\">\n The study is designed to understand the impact of poverty. Research has shown that stress levels are high in informal settlements in Nairobi. We hope that our study will inform poverty interventions in Kenya and beyond. </p>\n
      • other_details_regulatory_notapproved<p class=\"p1\">\n None. This study has already been approved by all other applicable regulatory authorities.</p>\n
      • other_details_regulatory_approved<p class=\"p1\">\n 1) Princeton University Institutional Review Board for Human Subjects: approved June 15, 2015 for single site in Kenya;</p>\n<p class=\"p1\">\n 2) Kenya Medical Research Institute (KEMRI): approved October 5, 2015 for single site in Kenya </p>\n
      • other_details_regulatory_rejected<p>\n None. </p>\n
      • other_details_regulatory_halted<p>\n None.</p>\n
      • estimated_duration1 year
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorPlacebo controlled
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaBusara Center for Behavioral Economics
      • single_site_physical_addressJonathan Court, Ngong Road, Nairobi 0200
      • single_site_contact_personJames Vancel
      • single_site_telephone+(254) 725 066 428
      • multiple_sites_member_stateNo
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites
      • multi_country_list
      • data_monitoring_committeeYes
      • total_enrolment_per_site11,500 (Single-site in Kenya)
      • total_participants_worldwide11,500
      • 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_nameJohannes
      • investigator1_middle_name
      • investigator1_family_nameHaushofer
      • investigator1_qualificationProfessor, Princeton University
      • investigator1_professional_address427 Peretsman Scully Hall, Princeton, NJ 08540
      • investigator1_telephone001-609-258-7167
      • investigator1_emailhaushofer@princeton.edu
      • organisations_transferred_No
      • number_participants11,500
      • notification<p>\n Note: hard copies of this application were submitted to the PPB offices on November 20, 2015</p>\n
      • approval_date11-03-2016
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted17-12-2015
      • 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)
      • modified2019-09-30 09:42:57
      • created2015-12-17 16:18:45
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id304
        • application_id466
        • given_nameJohannes
        • middle_name
        • family_nameHaushofer
        • qualificationProfessor, Princeton University
        • professional_address427 Peretsman Scully Hall, Princeton, NJ 08540
        • telephone001-609-258-7167
        • emailhaushofer@princeton.edu
        • created2015-12-17 16:25:59
        • modified2015-12-17 18:11:06
    • SiteDetail(array)
      • 0(array)
        • id363
        • application_id466
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2015-12-17 16:25:59
        • modified2015-12-17 18:11:06
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id237
        • application_id466
        • sponsorPrinceton University, Department of Psychology
        • sponsor_type(null)
        • contact_person
        • addressPeretsman Scully Hall, Princeton, NJ 08540
        • telephone_number001-609-258-4793
        • fax_number
        • cell_number001-609-258-4793
        • email_addresslscalice@princeton.edu
        • created2015-12-17 16:25:59
        • modified2015-12-17 18:11:06
  • 1(array)
    • Application(array)
      • id441
      • user_id56
      • trial_status_id7
      • abstract_of_study<p>\n  Abstract (300 words):<br />\n Introduction: Hormonal forms of contraception, are used by >150 million women worldwide. Some epidemiologic studies conducted in a variety of contexts have suggested that women using some types of hormonal contraceptives may be at increased risk of HIV acquisition; however, the results across multiple studies have been mixed, with some studies demonstrating increased HIV risk but others not showing increased HIV risk. The best way to address this uncertainty and provide clear policy guidance is with evidence from a large, well designed, randomised clinical trial.<br />\n Objectives: The main objective of this study is to compare the risks of HIV acquisition between women randomised to depot medroxyprogesterone acetate (DMPA), levonorgestrel (LNG) implant, and copper intrauterine device (IUD).<br />\n Methods: We aim to conduct an open-label, 3 armed randomised clinical trial in 12 sites across east and southern Africa comparing DMPA, LNG implant, and copper IUDs. This research design will greatly reduce many of the important limitations to the current body of observational evidence, including selection bias and many confounding factors whether known or unknown. In East Africa, the only site will be the  KEMRI-RCTP study centre at Lumumba health centre in Kisumu County. The Lumumba study site will enrol approximately 1000 sexually active, HIV-negative women, 16-35 years old, seeking effective contraception, willing to be randomised to any of the study arms, and not desiring pregnancy for the duration of study participation. Participants will be randomly allocated to one of three study arms in a 1:1:1 ratio: DMPA, LNG implant, copper IUD. Participants will be followed for upto 18 months per woman or until closure of the study or study site<br />\n Anticipated results: This study has the potential to address the hormonal contraceptive uncertainty among senior policy makers in countries that are highly dependent on injectable progestins and have high HIV prevalence. Results from this study will permit clear guidance for policymakers and programs, clearly formulated counselling messages, and ultimately allow women to make informed choices. Failure to undertake this research will leave a critical public health question unanswered.</p>\n
      • study_title<p>\n <strong>A Multi Centre, Open label, Randomized Clinical Trial, Comparing HIV incidence and Contraceptive Benefits in Women using Depot Medroxyprogesterone Acetate, Levernogestrel (LNG) implant and Copper Intrauterine Devices (IUD).</strong></p>\n<p>\n <strong>Short Title :<em> The Evidence for Contraceptive options and HIV Outcomes (ECHO) Trial</em></strong></p>\n
      • laymans_summary<p>\n N/A</p>\n
      • short_titleThe Evidence for Contraceptive options and HIV Outcomes (ECHO) Trial
      • protocol_noECCT/15/12/02
      • version_no2.0
      • date_of_protocol30-01-2015
      • study_drug Depot Medroxyprogesterone Acetate, Levernogestrel (LNG) implant and Copper Intrauterine Devices (IUD)
      • disease_conditionHIV incidences
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones1
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_nameCopper IUD
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressaachoka@kemri-ucsf.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_countries0
      • 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_applicantImeldah Wakhungu, P.O BOX 614-40100 KISUMU , Mobile No. +254-726605720 email address: iwakhungu@kemri-ucsf.org
      • declaration_date126-10-2015
      • declaration_principal_investigatorProf Elizabeth Anne Bukusi, Principal Investigator P.O BOX 614 -40100, KISUMU
      • declaration_date226-10-2015
      • placebo_presentNo
      • study_objectives<h2>\n Primary Objective</h2>\n<p>\n To compare the risks of HIV acquisition between women randomised to DMPA, LNG implant, and copper IUDs</p>\n<h2>\n Secondary Objectives</h2>\n<ul>\n <li>\n To compare pregnancy rates among women randomised to DMPA, LNG implant, and copper IUDs</li>\n <li>\n To compare rates of serious adverse events among women randomised to DMPA, LNG implant,  and copper IUDs</li>\n <li>\n To compare rates ofadverse events that lead tomethod discontinuation among women randomised to  DMPA, LNG implant,  and copper IUDs</li>\n <li>\n To compare contraceptive method continuation rates among women randomisedto DMPA, LNG implant, and copper IUDs</li>\n</ul>\n<h2>\n Tertiary Objectives</h2>\n<ul>\n <li>\n To evaluate whether age modifies the hormonal contraception and HIV acquisition relationship</li>\n <li>\n To evaluate whether HSV-2 status modifies the hormonal contraception and HIV acquisition relationship</li>\n <li>\n To evaluate early HIV disease progression among seroconvertersrandomisedto DMPA, LNG implant, and copper IUDs</li>\n</ul>\n
      • principal_inclusion_criteria<p>\n <strong> Inclusion Criteria</strong><br />\n To be eligible for the study a woman must meet all of the following criteria:<br />\n • 16-35 years of age<br />\n o Previously pregnant16 and 17 year olds, where permissible by national regulations and local IRB approval<br />\n • HIV-seronegative<br />\n • Wants to use effective contraception<br />\n • Is able and willing to provide written informed consent<br />\n • Agrees to be randomised to either DMPA, LNG implant, or copper IUD<br />\n • Agrees to use assigned method for 18 months<br />\n • Agrees to follow all study requirements<br />\n • Intends to stay in the study area for the next 18 months, and willing and able to provide adequate locator information<br />\n • If has had a recent third trimester birth, is at least 6 weeks postpartum<br />\n • Is sexually active (has had vaginal sex within the last 3 months) or was pregnant within the last 3 months<br />\n • Agrees not to participate in studies of drugs or vaccines or any other clinical research study while participating in this study.<br />\n  </p>\n
      • principal_exclusion_criteria<p>\n <strong>Exclusion Criteria</strong><br />\n A woman who reports or is found to have during the screening exam any of the following criteria will be excluded from the study:<br />\n • Reported medical contraindications (WHO MEC Category 3 or 4) to DMPA, LNG implant, or copper IUDs, including:<br />\n o recent septic abortion<br />\n o suspicious unexplained vaginal bleeding<br />\n o breast, cervical, uterine, or ovarian cancer<br />\n o high BP or heart disease, venous thromboembolism, stroke, or diabetes<br />\n o liver disease or liver tumours<br />\n o use of liver enzyme inducing medications (see Appendix 9)<br />\n • Is found to have pelvic tuberculosis or uterine fibroids with distortion of the uterine cavity on pelvic exam<br />\n • Has untreated mucopurulent cervicitis on exam, untreated pelvic inflammatory disease (PID), or untreated known gonorrhea or chlamydia<br />\n • Has  received a DMPA or NET-En injection in the last 6 months<br />\n • Has used an implant or an IUD in the last 6 months<br />\n • Is pregnant or intending to become pregnant in the next 18 months<br />\n • Has had a hysterectomy or sterilization<br />\n • Has previously participated in the study<br />\n • Has any condition (social or medical) which in the opinion of the investigator would make study participation unsafe or complicate data interpretation.</p>\n
      • primary_end_points<p>\n <strong> Primary Endpoint</strong></p>\n<p>\n <br />\n • HIV infection as measured by documented HIV seroconversion occurring post-enrolment.</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety0
      • scope_efficacy0
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others1
      • scope_others_specifyComparing HIV Incidence and Contraceptive Benefits in Women using Depot Medroxyprogesterone Acetate (DMPA), Levonorgestrel (LNG) Implant, and Copper Intrauterine Devices (IUDs)
      • 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 Number of staff: </p>\n<p>\n  </p>\n
      • other_details_explanation<p>\n Not Applicable</p>\n
      • other_details_regulatory_notapproved<p>\n None</p>\n
      • other_details_regulatory_approved<p>\n <strong>FHI 360</strong>: Approved February 25th 2015</p>\n<p>\n <strong>WHO : </strong>Approved January 7th 2015</p>\n<p>\n <strong>KEMRI ERC: </strong>Approved 15th Sept 2015</p>\n<p>\n <strong>A total of 12 sites </strong></p>\n<p>\n <strong>Number of sites per country:</strong></p>\n<p>\n <strong>Kenya :- 1 site</strong></p>\n<p>\n <strong>Zambia : -1 site</strong></p>\n<p>\n <strong>Swaziland :- 1 site</strong></p>\n<p>\n <strong>South Africa :- 9 sites</strong></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 in total, 18months follow up per participant
      • 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_comparatorCompare the risks of HIV
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKEMRI-RCTP Study center , Lumumba
      • single_site_physical_addressLUMUMBA HEALTH CENTRE , AGOI STREET, KISUMU
      • single_site_contact_personProf. Bukusi
      • single_site_telephone+254-726605720
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states4 states
      • number_of_sites
      • multi_country_listSouth Africa, Swaziland, Zambia, Kenya
      • data_monitoring_committeeYes
      • total_enrolment_per_site1,000
      • total_participants_worldwide7,800
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentYes
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male0
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenYes
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameNot Applicable. KEMRI RCTP-Lumumba Study Center is the only Kenyan site.
      • investigator1_middle_nameNot Applicable
      • investigator1_family_nameNot Applicable
      • investigator1_qualificationNot Applicable
      • investigator1_professional_addressNot Applicable
      • investigator1_telephoneNot Applicable
      • investigator1_emailiwakhungu@kemri-ucsf.org
      • organisations_transferred_Yes
      • number_participants1,000
      • notification<p>\n NONE</p>\n
      • approval_date11-04-2016
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted28-05-2020
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonYour study is now approved
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2020-05-28 11:08:15
      • created2015-10-24 11:00:26
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id294
        • application_id441
        • given_nameProf Elizabeth
        • middle_nameAnne
        • family_nameBukusi
        • qualificationMBChB, M.Med (ObGyn), MPH, PhD , PGD(Research Ethics)
        • professional_addressP.O BOX 614 -40100 KISUMU
        • telephoneLand line 254 20 6751748(Nairobi) 254 57 2021036
        • emailebukusi@kemri.org
        • created2015-10-24 11:10:53
        • modified2020-05-28 11:08:15
    • SiteDetail(array)
      • 0(array)
        • id351
        • application_id441
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2015-10-24 11:10:53
        • modified2020-05-28 11:08:15
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id229
        • application_id441
        • sponsorFHI 360
        • sponsor_typeResearch Institution
        • contact_personNikki Messenger
        • address359 Blackwell St. Durham, NC, 27707 USA
        • telephone_number1.919.544.7040 Ext. 11723
        • fax_numberNot applicable
        • cell_numberNot applicable
        • email_addressnmessenger@fhi360.org
        • created2015-10-24 11:10:53
        • modified2020-05-28 11:08:15
  • 2(array)
    • Application(array)
      • id437
      • user_id301
      • trial_status_id6
      • abstract_of_study<p>\n  </p>\n<p align=\"center\">\n <strong>Aspirin Supplementation for Pregnancy Indicated Risk Reduction In Nulliparas (ASPIRIN): </strong><strong>A</strong> <strong>Prospective randomized, placebo-controlled, double-blinded clinical trial in western Kenya.</strong></p>\n<p align=\"center\">\n  </p>\n<p>\n <strong><u>Background:</u></strong>Preterm birth (PTB) remains the leading cause of neonatal mortality and long term disability throughout the world.  Though complex in its origins, a growing body of evidence suggests that first trimester administration of low dose aspirin (LDA) holds promise to reduce the rate of PTB substantially.</p>\n<p>\n <strong><u>Hypothesis:</u></strong>First trimester administration of aspirin will reduce the risk of preterm birth.</p>\n<p>\n <strong><u>Study Design Type:</u></strong>Prospective randomized, placebo-controlled, double-blinded multicenter clinical trial. Trial will be individually randomized with one-to-one ratio (intervention/control)</p>\n<p>\n <strong><u>Population:</u></strong>Nulliparous women between the ages of 18and 40,with a singleton pregnancy between 6 0/7 weeks and 13 6/7 weeks gestational age (GA) confirmed by ultrasound prior to enrollment, no more than two previous first trimester pregnancy losses, and no contraindications to aspirin. Minors who are ≥ 14 years of age may be enrolled if permitted by the country’s ethical guidelines. </p>\n<p>\n <strong><u>Intervention:</u></strong>Daily administration of low dose (81 mg) aspirin[also known as acetylsalicylic acid (ASA], initiated between 6 0/7 weeks and 13 6/7 weeks GA and continued to 36 0/7 weeks GA, compared to an identical appearing placebo.Compliance and outcomes will be assessed biweekly.</p>\n<p>\n <strong><u>Outcomes:</u></strong></p>\n<p>\n <strong><em>Primary outcome</em>:</strong> To determine whether daily LDA initiated between 6 0/7 -13 6/7 weeksGA and continued to 36 0/7 weeks GA reduces the risk of PTB (birth prior to 37 0/7 weeksGA).</p>\n<p>\n  </p>\n<p>\n <strong><em>Secondary outcomes</em></strong> of interest are the rate of preeclampsia/eclampsia, small for gestational age (SGA), and perinatal mortality.</p>\n<p>\n  </p>\n
      • study_title<p>\n  </p>\n<p align=\"center\">\n <strong>Aspirin Supplementation for Pregnancy Indicated Risk Reduction In Nulliparas (ASPIRIN): </strong><strong>A</strong> <strong>Prospective randomized, placebo-controlled, double-blinded clinical trial in western Kenya.</strong></p>\n
      • laymans_summary(null)
      • short_title A Randomized Controlled Trial of ASPIRIN in Nulliparous Pregnant Women(ASPIRIN STUDY)
      • protocol_noECCT/15/12/01
      • version_noAspirin Protocol V1.0
      • date_of_protocol10-03-2015
      • study_drugLow Dose (81mg) Aspirin(Acetylsalicylic acid)(ASA)
      • disease_conditionPreterm Births
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device1
      • product_type_chemical_nameAcetylsalicylic Acid (ASA)
      • product_type_medical_device_nameAcetylsalicylic Acid (ASA)
      • comparator(null)
      • comparator_name(null)
      • comparator_registered(null)
      • comparator_countries(null)
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressdrpaulnyongesa@yahoo.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries1
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd(null)
      • applicant_prev_data(null)
      • applicant_stability_data(null)
      • applicant_analysis_cert(null)
      • applicant_pictorial_sample(null)
      • applicant_gcp_training(null)
      • applicant_dsmb_charter(null)
      • applicant_detailed_budget(null)
      • applicant_indemnity_pi(null)
      • applicant_practice_license(null)
      • applicant_registration_ctr(null)
      • applicant_pan_african(null)
      • applicant_hard_copies(null)
      • applicant_signed_checklist(null)
      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantDr Paul Nyongesa
      • declaration_date123-10-2015
      • declaration_principal_investigatorProf Fabian Esamai
      • declaration_date223-10-2015
      • placebo_presentYes
      • study_objectives(null)
      • principal_inclusion_criteria<h3>\n 1.1.1          Inclusion Criteria</h3>\n<p style=\"margin-left:.25in;\">\n §  Nulliparous women between 18 – 40 years of age. Minors who are ≥ 14 years of age may be enrolled if permitted by the country’s ethical guidelines. </p>\n<p style=\"margin-left:.25in;\">\n §  No more than two previous first trimester pregnancy losses</p>\n<p style=\"margin-left:.25in;\">\n §  No medical contraindications to aspirin;</p>\n<p style=\"margin-left:.25in;\">\n §  Single live intrauterine pregnancy (IUP) between 6 0/7 and 13 6/7 weeks GA corroborated by an earlydating ultrasound and with heart rate greater than >110 bpm.</p>\n
      • principal_exclusion_criteria<h3>\n 1.1.1          Exclusion Criteria</h3>\n<p style=\"margin-left:.25in;\">\n §  Women prescribed dailyaspirin for more than 7 days;</p>\n<p style=\"margin-left:.25in;\">\n §  Multiple gestations;</p>\n<p style=\"margin-left:.25in;\">\n §  Fetal anomaly by ultrasound (Note most fetal anomalies are not detectable by ultrasounds done at this early gestation. Subsequent discovery of a fetal anomaly is not viewed as an exclusion.);</p>\n<p style=\"margin-left:.25in;\">\n §  Hemoglobin  <7.0 gm/dl at screening;</p>\n<p style=\"margin-left:.25in;\">\n §  Any other medical conditions that may be considered a contraindication per the judgment of the site investigator (e.g., Lupus, Type 1 Diabetes, hypertension, or any other known significant disease)</p>\n
      • primary_end_points<p>\n <strong><em>Primary end point: </em></strong>Delivery at < 37 0/7 weeks gestation</p>\n<p>\n Secondary endpoints:  Preeclampsia and eclampsia,,</p>\n<p>\n                                  Small for gestational age(less than 10th percentile) and</p>\n<p>\n                                  Perinatal mortality(stillbirths and first week neonatal deaths)</p>\n
      • scope_diagnosis1
      • scope_prophylaxis1
      • scope_therapy0
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use1
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n Capacity of The Global Network Kenya Site 12:</p>\n<p>\n TheGlobal Network  Kenya site12 is a research unit of the Global Network for Women's and Children's Health Research and part of the Academic Model Providing Access to Health Care(AMPATH) program in Western Kenya. AMPATH supports the Ministry of Health in 8 counties of Western Kenya Region with a catchment population of 21 million people .</p>\n<p>\n Kenya site 12 has 12 clusters for the Aspirin study located at: Amukura/421,Lukolis/411,Nasewa/425,Matayos/415,Madende/Khayo/414,Khunyangu/422,Bumala B/418, Bokoli/413,Chwele /417,Sirisia/426,Makunga/419,Mumias/423</p>\n<p>\n Number of Study Staff: 60-100 including Investigators, sonograghers,study,clinical and field coordinators, registry and data personnel, community health workers and support stall.</p>\n<p>\n Investigators and study coordinators: Principal Investigator: Prof Fabian Esamai, Consultant Paediatrician  and Professor of Child Health, Moi University, Senior Foreign Investigator with The Global Network for Women's and Children's Health with many years research experience (see CV). Dr. Paul Nyongesa, Consultant Obstetrician/Gynaecologist, Senior Lecturer, Moi University (see CV) and M/s Emma Achieng, Senior Tutor in Midewifery and Study Coordinator with Global Network for 5years.</p>\n<p>\n Site Facilities:</p>\n<p>\n Moi University, College of Health Sciences, Medical School, Moi Teaching and Referral Hospital and Western Kenya Region of Community Health Units,Dispensaries,Health Centres, sub-County and County Referral Hospitals. </p>\n
      • other_details_explanation<p>\n Not applicable</p>\n
      • other_details_regulatory_notapproved<p>\n Not applicable</p>\n
      • other_details_regulatory_approved<p>\n   1. Christiana Care Institutional Review Board, New Jersey, USA  approved on 27th April 2015</p>\n<p>\n   2. JNMC Insttutional Ethics Committee on Human Subjects, Belgaum, India.approved 28th March 2015 for one site  </p>\n
      • other_details_regulatory_rejected<p>\n Not applicable</p>\n
      • other_details_regulatory_halted<p>\n Not applicable</p>\n
      • estimated_duration18months
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorPlacebo
      • design_controlled_other_medicinalYes
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states6
      • number_of_sites12
      • multi_country_listDemocratic Republic of Congo, Zambia, Kenya,Nagpur India,Belgaum India, Pakistan and Guatemala
      • data_monitoring_committeeYes
      • total_enrolment_per_site150
      • total_participants_worldwide 11,920
      • population_less_than_18_yearsYes
      • population_uteroYes
      • population_preterm_newbornYes
      • population_newbornYes
      • population_infant_and_toddlerNo
      • population_childrenNo
      • 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_contraceptionNo
      • subjects_pregnant_womenYes
      • subjects_nursing_womenYes
      • subjects_emergency_situationYes
      • subjects_incapable_consentYes
      • subjects_specifyParticipants incapable of giving consent personally,such as pregnant adolescent minors will assent and have informed consent given by husbands, if married, or guardians.
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameDr Paul Nyongesa
      • investigator1_middle_nameJohn
      • investigator1_family_nameObanda
      • investigator1_qualificationMbChB(U.O.N.), MMed(OB Gyn)(U.O.N.)
      • investigator1_professional_addressCollege of Health Sciences,Moi University,Dept of Reproductive Health Box 4606 30100 Eldoret ,Kenya
      • investigator1_telephone0733 788 063
      • investigator1_emaildrpaulnyongesa@yahoo.com
      • organisations_transferred_No
      • number_participants 1800
      • notification<p>\n Not applicable</p>\n
      • approval_date16-02-2016
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted07-12-2015
      • 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)
      • modified2017-01-06 13:10:11
      • created2015-10-22 12:04:18
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id293
        • application_id437
        • given_nameProf Fabian Esamai
        • middle_nameOmoding
        • family_nameEsamai
        • qualificationMbChB, MMed(Paed),MPH,PhD
        • professional_addressCollege of Health Sciences,Moi University,Dept of Child Health and Paediatrics Box 4606 30100 Eldoret ,Kenya
        • telephone0733 836 410
        • emailfesamai2007@gmail.com
        • created2015-10-22 12:23:49
        • modified2015-12-07 13:28:38
    • SiteDetail(array)
      • 0(array)
        • id350
        • application_id437
        • county_id40
        • site_nameAmukura, Lukolis,Nasewa,Matayos,Khunyangu, Bumala B
        • physical_addressWestern Kenya
        • contact_details Box 4606 30100 Eldoret, Kenya.0733 788 063 and 0733 836 410
        • contact_personDr. Paul Nyongesa and Prof Fabian Esamai
        • site_capacity(null)
        • misc(null)
        • created2015-10-22 12:23:49
        • modified2015-12-07 13:28:38
        • County(array)
          • id40
          • county_nameBusia
          • created2012-06-15 10:26:51
          • modified2012-06-15 10:26:51
      • 1(array)
        • id354
        • application_id437
        • county_id39
        • site_nameSirisia, Chwele, Bokoli
        • physical_addressWestern Kenya
        • contact_details Box 4606 30100 Eldoret, Kenya.0733 788 063 and 0733 836 410
        • contact_personDr. Paul Nyongesa and Prof Fabian Esamai
        • site_capacity(null)
        • misc(null)
        • created2015-10-29 10:38:39
        • modified2015-12-07 13:28:38
        • County(array)
          • id39
          • county_nameBung\'oma
          • created2012-06-15 10:26:45
          • modified2012-06-15 10:26:45
      • 2(array)
        • id355
        • application_id437
        • county_id37
        • site_nameMakunga, Mumias
        • physical_addressWestern Kenya
        • contact_details Box 4606 30100 Eldoret, Kenya.0733 788 063 and 0733 836 410
        • contact_personDr. Paul Nyongesa and Prof Fabian Esamai
        • site_capacity(null)
        • misc(null)
        • created2015-10-29 10:38:39
        • modified2015-12-07 13:28:38
        • County(array)
          • id37
          • county_nameKakamega
          • created2012-06-15 10:26:29
          • modified2012-06-15 10:26:29
    • Sponsor(array)
      • 0(array)
        • id228
        • application_id437
        • sponsorEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
        • sponsor_type(null)
        • contact_personMenachem Miodovnik, MD
        • addressNational Institutes of Health 6100 Executive Blvd, Rm 4B03A Bethesda, MD 20892-7510
        • telephone_number): 301-451-5031
        • fax_number: 301-496-3790
        • cell_number): 301-451-5031
        • email_addressMenachem.Miodovnik@nih.gov
        • created2015-10-22 12:23:49
        • modified2015-12-07 13:28:38
  • 3(array)
    • Application(array)
      • id419
      • user_id85
      • trial_status_id1
      • abstract_of_study<div>\n Plasmodium falciparum (P. falciparum) malaria is a major cause of morbidity and mortality in Africa. Siaya County in Western Kenya is holoendemic for malaria(1). At the Siaya Hospital outpatient department alone, data abstraction shows 2000-4000 cases of uncomplicated malaria seen at the facility annually.</div>\n<div>\n Concurrent with preventive measures, World Health Organization (WHO) guidelines recommend artemisinin-based combination therapies (ACT) are used to treat uncomplicated P. falciparum malaria to prevent development of resistance and to improve treatment outcome.</div>\n<div>\n  </div>\n<div>\n Artemisinin produces rapid clearance of parasitemia and resolution of symptoms by reducing parasite number by 100- to 1000-fold per asexual cycle of the parasite. Artemisinin and its derivatives are rapidly eliminated. It is therefore given in combination with 4-aminoquinoline drugs which have a longer half-life. This requires a three day course of treatment. Evidence suggests that compliance to this 3-day regimen is low, thereby reducing treatment effectiveness. In addition, emergence of resistance to artemisinin may become a considerable problem in the coming years(2). New drug combinations are required. Particularly, effective single dose combination treatments will likely improve effectiveness.</div>\n<div>\n  </div>\n<div>\n A fixed dose combination of two therapeutic agents Ferroquine (FQ) and Artefenomel (OZ439) will be evaluated as single day-single dose treatment of uncomplicated malaria. This will be a Phase IIb safety, tolerability, pharmacokinetic and efficacy trial. The target population will be adults <70 years old and children >6months with uncomplicated malaria.</div>\n<div>\n Patients will be randomized to up to four treatment arms containing both FQ and OZ439. The dose of OZ439 will be fixed at 800mg in each arm. However the dose of FQ will vary with each arm receiving a higher dose than the previous cohort. The primary outcome will be PCR-adjusted Adequate Clinical and Parasitological Response (ACPR) at day 28. Total follow up time per patient will be at least 67 days from study entry to close out. Safety endpoints will be based on clinical and laboratory identified adverse events.</div>\n<div>\n If this combination proves to be effective and safe in areas where artemisinin-resistant P. falciparum is absent or rare complementary trials may be performed to determine whether a similar clinical benefit exists in locations where resistance to artemisinin and chloroquine have developed.</div>\n
      • study_title<div>\n A Randomized, Double-blind, Phase IIb Study to Investigate the Efficacy, Safety, Tolerability and Pharmacokinetics of a Single Dose Regimen of Ferroquine (FQ) with Artefenomel (OZ439) in Adults and Children with Uncomplicated Plasmodium falciparum Malaria.</div>\n
      • laymans_summary<p style=\"margin-left:36.0pt;\">\n Malaria is responsible for considerable morbidity and mortality, particularly in Western Kenya. Malaria is best treated with a combination of drugs as this prevents development of drug resistance. Currently, uncomplicated malaria is treated with a three day course of treatment which is associated with considerable defaulting-many patients do not complete the three day dose.</p>\n<p style=\"margin-left:36.0pt;\">\n This is a proposed phase IIb trial of a single dose treatment of ferroquine and artefenomel in the treatment of uncomplicated malaria. Patients will be entered into the trial based on their age groups, beginning with older patients. All patients will receive the same dose (or a weight adjusted dose) of Artefenomel 800mg, but will be randomly assigned to varying doses of Ferroquine. The objective is to determine safety, tolerability and efficacy of the combination of treatment.   </p>\n
      • short_titleFALCI Study
      • protocol_noECCT/15/11/05
      • version_no1.0
      • date_of_protocol20-11-2014
      • study_drugFerroquine & Artefenomel
      • disease_conditionMalaria
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_nameFerroquine & Artefenomel
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addresstsang@kemricdc.org
      • applicant_covering_letter1
      • applicant_protocol1
      • 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_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data0
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi0
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantDr Tony Sang
      • declaration_date116-11-2015
      • declaration_principal_investigatorDr Grace Kaguthi
      • declaration_date216-11-2015
      • placebo_presentNo
      • study_objectives<p style=\"margin-left:36.0pt;\">\n <em>Primary Objective</em></p>\n<p style=\"margin-left:18.0pt;\">\n To determine whether a single dose combination of OZ439/FQ is an efficacious treatment for uncomplicated Plasmodium falciparum (P. falciparum) malaria in adults and children</p>\n<p style=\"margin-left:36.0pt;\">\n  </p>\n<p style=\"margin-left:54.0pt;\">\n <em>Secondary Objectives</em></p>\n<ol style=\"list-style-type:lower-alpha;\">\n <li>\n To evaluate the efficacy of OZ439/FQ:</li>\n <li>\n To determine the incidence of recrudescence and re-infection</li>\n <li>\n To determine the time to relief of fever and parasite clearance</li>\n <li>\n To evaluate the safety and tolerability of OZ439/FQ</li>\n <li>\n To evaluate the pharmacokinetics of OZ439/FQ:</li>\n <li>\n To characterize the pharmacokinetics of OZ439 in plasma, FQ and its active metabolite SSR97213 in blood</li>\n <li>\n To determine the blood/plasma ratio for FQ and SSR97213 in some patients at limited time points in selected sites.</li>\n <li>\n To further explore efficacy of OZ439/FQ:</li>\n <li>\n To evaluate the proportion of patients with gametocytes at each parasitological assessment</li>\n <li>\n To characterize gametocyte carriage</li>\n <li>\n To evaluate the relationship between Adequate Clinical &</li>\n <li>\n Parasitological Response (ACPR) and exposure to OZ439/FQ</li>\n</ol>\n<p style=\"margin-left:54.0pt;\">\n  </p>\n<p style=\"margin-left:36.0pt;\">\n m. To explore the relationship between Kelch-13 genotype and parasite clearance kinetics</p>\n
      • principal_inclusion_criteria<ul>\n <li>\n <span style=\"font-size:12px;\"> Male or female patient aged > 6 months old and < 70 years old</span>\n <ul>\n <li>\n <span style=\"font-size:12px;\">- Cohort 1 = 14 years<age<70 35=\"\" and=\"\" body=\"\" span=\"\" weight=\"\" years=\"\"></age<70></span></li>\n <li>\n <span style=\"font-size:12px;\">- Cohort 2 = 5 years < age ≤ 14 years</span></li>\n <li>\n <span style=\"font-size:12px;\">- Cohort 3 = 2 years < age ≤ 5 years</span></li>\n <li>\n <span style=\"font-size:12px;\">- Cohort 4 = 6 months < age ≤ 2 years</span></li>\n </ul>\n </li>\n <li>\n <span style=\"font-size:12px;\">Body weight ≥ 5 kg and ≤ 90 kg.</span></li>\n <li>\n <span style=\"font-size:12px;\">Presence of mono-infection by P. falciparum with: Fever, as defined by axillary temperature ≥ 37.5°C or oral/rectal/tympanic temperature ≥ 38°C, or history of fever in the previous 24 hours (history of fever must be documented) and, microscopically (blood smear) confirmed parasite infection, ranging from 1000 to 100 000 asexual parasites/μL of blood.</span></li>\n <li>\n <span style=\"font-size:12px;\">Informed Consent Form signed by the patient or parent</span></li>\n</ul>\n
      • principal_exclusion_criteria<ul>\n <li>\n Presence of severe malaria (according to WHO definition)</li>\n <li>\n Anti-malarial treatment:\n <ul>\n <li>\n With piperaquine -based compound, mefloquine, naphthoquine or sulphadoxine/pyrimethamine (SP) within the previous 6 weeks (after their inhibition of new infections has fallen below 50%).</li>\n <li>\n With amodiaquine or chloroquine within the previous 4 weeks. </li>\n <li>\n With quinine, halofantrine, lumefantrine-based compounds and any other anti-malarial treatment or antibiotics with antimalarial activity (including cotrimoxazole, tetracyclines, quinolones and fluoroquinolones, and azithromycin) within the past 14 days.</li>\n <li>\n With any herbal products or traditional medicines, within the past 7 days.</li>\n </ul>\n </li>\n <li>\n Known history or evidence of clinically significant disorders</li>\n <li>\n Previous treatment within 5 times the half-life or within the last 14 days, whichever the longest which are: P-gp substrates, CYP2D6 main substrates and/or strong CYP2C or CYP3A inhibitors and/or moderate inhibitors but inhibiting both CYP2C and CYP3A and/or CYP inducers</li>\n <li>\n Mixed Plasmodium infection</li>\n <li>\n Severe vomiting</li>\n <li>\n Severe malnutrition</li>\n <li>\n Laboratory parameters with clinical significant abnormalities and/or reaching critical values. For Liver Function Test: aspartate transferase [AST >2 upper limit of normal (ULN)], or alanine transferase [ALT >2 ULN] or total bilirubin [>1.5 ULN]. </li>\n <li>\n Presence of Hepatitis A IgM (HAV-IgM), Hepatitis B surface antigen (HBs Ag) or Hepatitis C antibody (HCV Ab)</li>\n</ul>\n<div>\n <ul>\n <li>\n Previous participation in any malaria vaccine study or received malaria vaccine in any other circumstance</li>\n <li>\n Female patient of child bearing potential or male patient having a partner of child bearing potential not willing to use an effective contraceptive(s) method(s) for the duration of the study</li>\n <li>\n Positive pregnancy test at study screening for female participants of childbearing potential.</li>\n <li>\n Family history of sudden death or of congenital prolongation of the QTc interval or known congenital prolongation of the QTc-interval or any clinical condition known to prolong the QTc interval e.g., patients with a history of symptomatic cardiac arrhythmias or with clinically relevant bradycardia.</li>\n <li>\n QTcF > 450 ms at screening or pre-dose.</li>\n <li>\n Hypokalemia (<3.5 mmol/L), hypocalcemia (< 2.0 mmol/L) or hypomagnesemia (< 0.5 mmol/L) at screening or pre-dose.</li>\n <li>\n Any treatment known to induce a lengthening of QT interval</li>\n </ul>\n</div>\n<p>\n  </p>\n
      • primary_end_points<p>\n PCR-adjusted Adequate Clinical and Parasitological Response (ACPR) at Day 28</p>\n<div>\n <u>Secondary Endpoints</u></div>\n<div>\n Efficacy Endpoints</div>\n<div>\n • PCR - adjusted ACPR at Day 42 and 63.</div>\n<div>\n • PCR - crude ACPR at Day 28, 42 and 63.</div>\n<div>\n • Kaplan Meier analysis for:</div>\n<div style=\"margin-left: 40px;\">\n - Time to re-emergence</div>\n<div style=\"margin-left: 40px;\">\n - Time to recrudescence</div>\n<div style=\"margin-left: 40px;\">\n - Time to re-infection</div>\n<div>\n • Parasite clearance time (PCT).</div>\n<div>\n • Fever clearance time (FCT).</div>\n<div>\n • Parasite reduction rate (PRR).</div>\n<div>\n  </div>\n<div>\n <u>Safety Endpoints</u></div>\n<div>\n • Adverse events, including Serious Adverse Events (SAE), Adverse</div>\n<div>\n Event of Special Interest (AESI) and Treatment Emergent Adverse</div>\n<div>\n Event (TEAE).</div>\n<div>\n • Clinical laboratory tests, vital signs and ECG, including:</div>\n<div style=\"margin-left: 40px;\">\n - Liver Function test (LFT)</div>\n<div style=\"margin-left: 40px;\">\n - QTc assessment</div>\n<div>\n • Physical examination and clinical signs and symptoms related to uncomplicated P. falciparum malaria (fever, dizziness, headache,</div>\n<div>\n nausea, anorexia, vomiting, diarrhea, itching, urticaria, skin rash, abdominal pain, joint pain, muscle pain, palpitations, sleep problems,</div>\n<div>\n confusion, hearing problems, vision problems, and fatigue).</div>\n<div>\n  </div>\n<div>\n <u>Pharmacokinetic (PK) Endpoints</u></div>\n<div>\n • Pharmacokinetic parameters (mainly CL/F, Vss/F, Cmax, AUC as relevant) of OZ439 in plasma, FQ and SSR97213 in blood and plasma</div>\n<div>\n • Blood/plasma ratio for FQ and SSR97213 (some patients in selected sites).</div>\n<div>\n  </div>\n<div>\n <u>Exploratory Endpoints</u></div>\n<div>\n • Time to clearance of gametocytemia on blood smear for patients with gametocytes at baseline,</div>\n<div>\n • Time to appearance of gametocytemia on blood smear for patients with no gametocytes at baseline and time to clearance</div>\n<div>\n • RT-PCR to measure gametocyte maturation stage (expression of Pfs25 mRNA)</div>\n<div>\n • Correlation between Kelch-13 genotype status and parasite clearance kinetics</div>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response1
      • scope_pharmacogenetic1
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory1
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledNo
      • site_capacity(null)
      • staff_numbers<p>\n The Siaya Hospital outpatient department sees between 300 and 500 confirmed malaria cases every month aged 6 months to up to 70 years. There are no anticipated challenges to accruing the required sample size. There is also capacity to meet protocol safety monitoring by availability of ECG machine, reliable and reproducible laboratories and availability of trained and experienced microscopists to review slides. There is a pool of clinical research staff experienced in quality and regulatory requirements, informed consent and data entry. The site's clinical research staff include the following:</p>\n<ul>\n <li>\n Principal Investigator - Dr Grace Kaguthi, MBChB,MSc</li>\n <li>\n Co-Investigator - Dr Videlis Nduba, MBChB, MPH</li>\n <li>\n Study Medical Officer - Dr Michael Mutua, MBChB</li>\n <li>\n Pharmacist - Dr Tony Sang, BPharm</li>\n <li>\n Clinical Officers x 3</li>\n <li>\n Pharmaceutical Tecnologist x 2</li>\n <li>\n Nurses x 8</li>\n <li>\n Lab Technicians x 2</li>\n <li>\n Phlebotomist x 1</li>\n <li>\n Data Officers x 3</li>\n <li>\n QA/QC officers x 3</li>\n</ul>\n
      • other_details_explanation<p>\n N/A</p>\n
      • other_details_regulatory_notapproved<p>\n None</p>\n
      • other_details_regulatory_approved<p>\n KEMRI Scientific and Ethics Review Unit approved the protocol on 02-sep-2015</p>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration1-2 years
      • design_controlled_randomised
      • design_controlled_open
      • design_controlled_single_blind
      • design_controlled_double_blind
      • design_controlled_parallel_group
      • design_controlled_cross_over
      • design_controlled_other
      • design_controlled_specify
      • design_controlled_comparator
      • design_controlled_other_medicinal
      • design_controlled_placebo
      • design_controlled_medicinal_other
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_statesEighteen sites
      • number_of_sitesFour sites
      • multi_country_listAfrican Countries: Gabon, Uganda, Kenya, Burkina Faso, Benin & Mozambique\nAsia-Pacific Region: Indonesia & Vietnam
      • data_monitoring_committeeYes
      • total_enrolment_per_site0 to 120 participants
      • total_participants_worldwide662
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerYes
      • 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_specifyMinor participants i.e. below 18 years of age for whom Informed Consent Form will be signed by their legally acceptable representative. In addition, in accordance with local regulation, minors aged ≥ 13 years with capacity for writing will sign an Assent Form.
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameGrace
      • investigator1_middle_nameKiringa
      • investigator1_family_nameKaguthi
      • investigator1_qualificationMBChB, MSc
      • investigator1_professional_addressKEMRI/Centre for Respiratory Diseases Research (CRDR)
      • investigator1_telephone+254 729 489743
      • investigator1_emailskiringa@gmail.com
      • organisations_transferred_Yes
      • number_participants120
      • notification
      • approval_date01-02-2016
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted28-02-2020
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report<p>\n As attached</p>\n
      • implication_results<p>\n No impact on current practice due to futility.</p>\n
      • quantity_imported279
      • quantity_dispensed36
      • quantity_destroyed279
      • quantity_exported0
      • balance_site 0
      • final_date0000-00-00
      • modified2021-01-06 14:13:54
      • created2015-09-15 15:12:37
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id285
        • application_id419
        • given_nameGrace
        • middle_nameKiringa
        • family_nameKaguthi
        • qualificationMBChB, MSc
        • professional_addressKEMRI/Centre for Respiratory Diseases Research (CRDR)
        • telephone+254 729 489743
        • emailskiringa@gmail.com
        • created2015-09-15 15:34:53
        • modified2020-02-28 14:56:33
    • SiteDetail(array)
      • 0(array)
        • id338
        • application_id419
        • county_id41
        • site_nameKEMRI Center for Respiratory Diseases Research
        • physical_addressSiaya County Referral Hospital, Siaya
        • contact_details+254 729489743
        • contact_personDr Grace Kaguthi
        • site_capacity(null)
        • misc(null)
        • created2015-09-15 15:34:53
        • modified2020-02-28 14:56:33
        • County(array)
          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
      • 1(array)
        • id343
        • application_id419
        • county_id42
        • site_nameKEMRI Walter Reed Kombewa
        • physical_addressKombewa District Hospital
        • contact_detailsjanet.oyieko@usamru-k.org, Tel:+254 721 996988
        • contact_personDr Janet Oyieko
        • site_capacity(null)
        • misc(null)
        • created2015-10-09 13:03:57
        • modified2020-02-28 14:56:33
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 2(array)
        • id344
        • application_id419
        • county_id42
        • site_nameKEMRI Kisumu
        • physical_addressJaramogi Oginga Odinga Teaching & Referral Hospital
        • contact_detailsPhone: +254 733 812613 Email: ogutu6@gmail.com
        • contact_personDr Bernhards Ogutu
        • site_capacity(null)
        • misc(null)
        • created2015-10-09 13:03:57
        • modified2020-02-28 14:56:33
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
    • Sponsor(array)
      • 0(array)
        • id222
        • application_id419
        • sponsorSanofi Aventis
        • sponsor_typeIndustry
        • contact_personValerie Nicol
        • address1 Avenue Pierre Brossolette 91385 CHILLY-MAZARIN CEDEX France
        • telephone_number+33 (0)1 53 77 40 00
        • fax_number
        • cell_number+33 (0)1 53 77 40 00
        • email_addressvalerie.Nicol@sanofi.com
        • created2015-09-15 15:34:53
        • modified2020-02-28 14:56:33
  • 4(array)
    • Application(array)
      • id416
      • user_id137
      • trial_status_id5
      • abstract_of_study<p>\n This study (VAC-040) is required to assess the safety and tolerability of the single-vial formulation of PATH-wSP manufactured by BioFarma, prior to use of this new formulation in such an infant population in a Phase 2 dose-ranging, proof-of-concept study. This randomized, placebo-controlled, double-blind trial is designed to sequentially evaluate PATH‑wSP at two escalating doses (0.6 mg and 1 mg) in both adults and toddlers.  The following cohorts will be tested:</p>\n<p>\n <strong>Adult (18-40 years old) Cohorts: </strong></p>\n<p style=\"margin-left:.25in;\">\n ·       Two 0.6 mg doses of PATH-wSP (18 subjects) <strong>or</strong> saline (6 subjects) with a 28-day interval between doses.</p>\n<p style=\"margin-left:.25in;\">\n ·       Two 1 mg doses of PATH-wSP (18 subjects) <strong>or</strong> saline (6 subjects) with a 28-day interval between doses.</p>\n<p>\n <strong>Toddler (12-19 months old) Cohorts</strong>:</p>\n<p style=\"margin-left:.25in;\">\n ·       Two 0.6 mg doses of PATH-wSP (18 subjects) <strong>or</strong> saline (6 subjects) with a 28-day interval between doses, and pentavalent vaccine co-administered with the second dose.</p>\n<p>\n Two 1 mg doses of PATH-wSP (50 subjects) <strong>or</strong> saline (25 subjects) with a 28-day interval between doses, and pentavalent vaccine co-administered with the second dose.</p>\n<p>\n Each participant (adults and toddlers) will undergo a total of 6 scheduled visits, including at least one screening visit, two vaccination visits (scheduled 28 days apart), two safety visits at 7 days post each vaccination and a final visit at 28 days post the final vaccination.  In addition, daily reactogenicity assessments for 7 days post vaccination will be completed by fieldworkers using a standard home visit diary.  Participants will be followed beyond 28 days post final visit if they have ongoing adverse events or have laboratory abnormalities that require continued monitoring.  </p>\n<p>\n Primary objectives of this study are:</p>\n<ol>\n <li>\n To evaluate the safety and tolerability of 2 dose levels (0.6 mg and 1 mg) of PATH-wSP vaccine, administered in a 2-series schedule, through 4 weeks post vaccination in healthy adults.</li>\n <li>\n To evaluate the safety and tolerability of 2 dose levels (0.6 mg and 1 mg) of PATH-wSP vaccine, administered in a 2-series schedule, through 4 weeks post vaccination in healthy toddlers when co-administered with a booster dose of licensed pentavalent vaccine (diphtheria, tetanus, whole-cell pertussis, <em>Haemophilus influenzae</em> type b, and hepatitis B combined vaccine) at the second vaccination.</li>\n</ol>\n
      • study_title<p>\n A Phase 1/2, Randomized, Placebo-controlled, Double-blind Study to Assess the Safety, Tolerability, and Immunogenicity of <em>Stretococcus pneumoniae </em>Whole Cell Vaccine, Inactivated and Adsorbed to Aluminum Hydroxide (PATH-wSP) in Healthy Kenya Young Adults (18 - 40years) and Toddlers (12 - 19months)</p>\n
      • laymans_summary(null)
      • short_titleVAC040
      • protocol_noECCT/15/11/04
      • version_no2.0
      • date_of_protocol18-09-2015
      • study_drugPATH-wSP is an adsorbed suspension of Streptococcus pneumoniae Whole Cell Vaccine [SPWCV] and Alum
      • disease_conditionActive Immunization for the prevention of Pneumococcal disease
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines1
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparator(null)
      • comparator_name(null)
      • comparator_registered(null)
      • comparator_countries(null)
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addresskenya-vac010@fhi360.org
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter0
      • applicant_statement1
      • applicant_participating_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)
      • applicant_signed_checklist(null)
      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantGeorge Belai
      • declaration_date113-11-2015
      • declaration_principal_investigatorAnthony Scott
      • declaration_date213-11-2015
      • placebo_presentYes
      • study_objectives(null)
      • principal_inclusion_criteria<ul>\n <li>\n Healthy adults who are 18 to 40 years old, or toddlers who are 12 to 19 months old on the day of randomization (Day 0), inclusive of the age ranges.</li>\n <li>\n Participants (or parent in the case of toddlers) must provide voluntary written/thumb-printed informed consent for the subject to participate in the study.</li>\n <li>\n Participants (or parent in the case of toddlers) must be able to comprehend and comply with study requirements and procedures and must be willing and able to return for all scheduled follow-up visits.</li>\n <li>\n Participants (or parent in the case of toddlers) must have a readily identifiable place of residence to ensure home visits can be undertaken reliably and must also have a consistent means of telephone contact for the duration of trial participation.</li>\n <li>\n Participants must be resident in the study area with no plans to travel outside the study area during the period of study participation.</li>\n <li>\n Participants must be willing to not consume (ingest) herbal or other local traditional medications within 28 days of randomization and during the course of the study.  Subject’s parent(s) must be willing to not administer such medications to their toddler, and subject’s mother must be willing to not consume herbal medication that may transmit to her toddler through breast milk.</li>\n</ul>\n<p>\n <strong>Adults only</strong></p>\n<ul>\n <li>\n Adult female participants must have a negative serum pregnancy test at screening and urine pregnancy test prior to each vaccination.  They will be advised through the informed consent process to avoid becoming pregnant for the duration of the study, and must agree to employ an effective form of birth control for the duration of the study.  Adult female subjects with documented sterilization via tubal ligation or hysterectomy may be eligible for the study without required use of birth control.</li>\n</ul>\n<p>\n Note: Effective forms of birth control are the following: credible history of continuous abstinence from heterosexual activity, hormonal contraceptives (oral, injectable, implant, patch, and ring), double-barrier contraceptives (condom or diaphragm, either with spermicide) and intrauterine device.  When using contraceptives, subjects must have been using their current contraceptive for the past two months to be eligible.</p>\n<p>\n <strong>Toddlers only:</strong></p>\n<ul>\n <li>\n Toddlers must have been born full-term, and have a mid-upper arm circumference > 11.5 cm at the time of enrollment.</li>\n <li>\n Toddlers must have completed their Kenyan infant EPI schedule (Table 5) through 9 months, with the following <u>minimum</u> requirements: 1 birth dose of BCG, 3 doses of DTwPHibHep, 3 doses of OPV (birth dose is not required), 3 doses of PCV, and 1 dose of measles vaccine.  If additional vaccines are introduced into the routine EPI schedule in Kenya or are given in campaigns during the period of the study, receipt of these vaccines would not be required for a toddler to be eligible for randomization</li>\n</ul>\n
      • principal_exclusion_criteria<p style=\"margin-left:.25in;\">\n A participant who meets any of the following criteria at screening will not be eligible for randomization but may be reconsidered based on resolution of exclusion criteria at a later date if reevaluation falls within the screening period:Use of any investigational or nonregistered drug within 90 days of randomization or planned during the course of study participation.</p>\n<ul>\n <li style=\"margin-left: 0.25in;\">\n Use of any of the potentially hepatotoxic drugs listed in Appendix 9 within 28 days of randomization or during the course of study participation.  This list will be provided to all participants/participant's parents at screening, who will be instructed to notify study staff immediately in the event that use of any listed drug becomes necessary.</li>\n <li style=\"margin-left: 0.25in;\">\n History of administration of any licensed vaccine within 14 days of administration of study vaccine.  Administration of any licensed, non-study vaccine during enrollment is prohibited through at least 14 days after final study vaccination.  If additional vaccines are introduced into the routine EPI schedule in Kenya or are given in campaigns during the period of the study, receipt of these vaccines would not exclude a toddler unless administration of the vaccine was considered to alter the safety of the study participant or to influence the assessment of the primary or secondary endpoints in some significant way.</li>\n <li style=\"margin-left: 0.25in;\">\n Chronic, clinically significant pulmonary, cardiovascular, hepatobiliary, gastrointestinal, renal, neurological, or hematological functional abnormality or major congenital defects or illness that requires medical therapy, based on medical history or clinical assessment.</li>\n <li style=\"margin-left: 0.25in;\">\n History of anaphylactic shock.</li>\n <li style=\"margin-left: 0.25in;\">\n History of a serious reaction to any prior vaccination or known hypersensitivity to any component of the study vaccines.</li>\n <li style=\"margin-left: 0.25in;\">\n History of immunosuppression or immunodeficiency, inclusive of human immunodeficiency virus (HIV) infection by medical history (including that of an enrolled toddler’s mother) or by HIV testing at screening.  Toddler participants will be excluded if their mother is known to be HIV positive from testing during the perinatal or post-delivery period.</li>\n <li style=\"margin-left: 0.25in;\">\n Evidence of active hepatitis infection (B or C) by serologic testing at screening.</li>\n <li style=\"margin-left: 0.25in;\">\n Any screening laboratory test (chemistry or hematology) or vital sign measurement with toxicity grade ≥ 1.  A participant may repeat each abnormal laboratory assessment or vital sign once during the screening period for a subject to remain eligible for randomization.</li>\n <li style=\"margin-left: 0.25in;\">\n Acute illness (moderate or severe) and/or fever (axillary temperature ≥ 37.5°C).</li>\n</ul>\n<p style=\"margin-left:.25in;\">\n Note: Participants with an acute illness/fever may return once for a repeat screening visit within the 28-day screening period and still qualify for randomization if the acute illness has resolved.  A minimum of 72 hours following a <u>documented</u> fever must pass before the subject can be re-screened and vaccinated.</p>\n<ul>\n <li style=\"margin-left: 0.25in;\">\n Positive test for malaria (blood film) at screening that remains positive post treatment when retested prior to vaccination.</li>\n</ul>\n<p>\n Note: Participants may be treated for malaria and retested during the screening period.  A rapid antigen test for malaria will be undertaken on the day of each vaccination to ensure a subject with a concurrent malaria infection is not vaccinated.</p>\n<ul>\n <li>\n Disorders that require chronic administration (defined as more than 14 consecutive days) of immunosuppressants or other immune-modifying drugs within the past 6 months prior to the administration of the study vaccine.  An immunosuppressant dose of glucocorticoid will be defined as a systemic dose >10 mg of prednisone per day for adults or equivalent in toddlers.  The use of topical glucocorticoids will be permitted.</li>\n <li>\n Administration of immunoglobulins and/or any blood products within the 6 months preceding enrollment in the study, or anticipation of such administration during the study period.</li>\n <li>\n Known disturbance of coagulation or other blood disorder (e.g., thalassemia, sickle cell disease, thrombocytopenia, disorders of the lymphocytes, severe anemia at birth) in adult participant or in self/first-degree relative of toddler participant; or receipt of anticoagulants in the past three weeks (aspirin as needed and nonsteroidal anti-inflammatory drugs are acceptable).</li>\n <li>\n History of meningitis, seizures or any neurological disorder (all participants) or major psychiatric disorder (adults).</li>\n <li>\n Any medical or social condition that in the opinion of the investigator will interfere with the study objectives or pose a risk to the study participant or may prevent the participant from completing the study follow-up.</li>\n <li>\n An employee (or first-degree relative of employee) of the Sponsor, the CRO, or any investigator or site personnel.</li>\n</ul>\n<p>\n <strong>Adults only</strong></p>\n<ul>\n <li>\n Female participants who are pregnant or breast-feeding.</li>\n <li>\n Suspicion or recent history (within the past year) of alcohol or substance abuse.</li>\n</ul>\n<p>\n <strong>Toddlers only</strong></p>\n<ul>\n <li>\n Prior vaccination with a pentavalent booster (following the primary series).</li>\n <li>\n Family history of suspected primary immunodeficiency in first-degree relative.</li>\n <li>\n Had a sibling die of likely sudden infant death syndrome (SIDS) or die suddenly and <u>without</u> apparent other cause or preceding illness in the first year of life.</li>\n <li>\n Has evidence of a clinically significant congenital abnormality as judged by the PI.</li>\n <li>\n Evidence of fetal alcohol syndrome or maternal history of alcohol abuse during pregnancy.</li>\n</ul>\n
      • primary_end_points<p>\n <strong>Safety</strong>:</p>\n<p>\n Safety and tolerability of PATH-wSP vaccine including co-administration of PATH-wSP and licensed pentavalent vaccine at the second vaccination to toddlers will be evaluated based on the following analyses:</p>\n<ul>\n <li>\n Occurrence and severity of solicited local and systemic adverse events (AEs) and clinical laboratory abnormalities through 1 week post vaccination.</li>\n <li>\n Occurrence, severity, and relatedness to vaccination of all AEs and serious adverse events (SAEs) through 4 weeks post vaccination.</li>\n</ul>\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_specifyTolerability
      • trial_human_pharmacology1
      • 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 A. Site staff The research site is well equipped with various clinical research expertise: 4 Physician Principal Investigators; 3 Non-Physician Principal Investigators; 1 Clinical Research Coordinator; 2 Clinical officers; 3 Research Nurses; 1 Laboratory technologists 1 Pharmacist; 1 Pharmaceutical Technologist; 5 Fieldworkers 1 Data manager and 3 Data clerks.</p>\n<p>\n B. Operation Hours The clinic operates for 8 hours (8am – 4pm) 5 days a week. After-hours, weekends and public holidays, participants who need to be reviewed will be seen at Kilifi County hospital by the research staff. All departments are sufficiently covered and operate fully from Monday to Friday 0800 to 1600 hours. The principal Investigator, study clinicians and field staff, are always on call throughout and can be reached as necessary.</p>\n<p>\n C. Clinical and research Services The site has a HDSS, the Kilifi Health Demographic Surveillance System which they use to locate potential research subjects. The site staff has been trained on Good Clinical Practice (GCP), Good Clinical Laboratory Practice (GCLP) and human Subject Protection in addition to their professional competencies. Clinical facilities providing healthcare to research participants include: Outpatient Clinics and in-patient Adult and Pediatric Wards with a high dependence unit in the Kilifi County Hospital, Research Laboratories, Radiology Facilities, Pharmacy, Clinical Trials Facility, Administrative Offices and IT department. The site has capacity for and has previously been involved in Phase 1, 2, and 3 trials.</p>\n<p>\n D. Laboratory services Clinical laboratory is equipped to handle various tests including: Hematology, Biochemistry, Microbiology, and Microscopy. The Research Laboratory has capability of Immunoglobulin isotyping analysis, Conventional and real time Quantitative Polymerase Chain Reaction (qRT-PCR, 8color (FACS Canto) flow cytometry capabilities for phenotyping cellular surface molecules and intra-cellular staining, HPLC analysis for hemoglobin genotype screening, Serological assay capabilities (ELISA), specimen storage-15 minus-80 degrees freezers.</p>\n<p>\n E. Sample Collection and processing Samples collection is done at the phlebotomy room, which is furnished with phlebotomy chairs and worktops. At the phlebotomy room participants are appropriately identified and logged in the study phlebotomy log book capturing all the relevant details. After sample collection the sample is transported to the processing area under optimal conditions where they are logged in, processed and analyzed as appropriate and the ones to be stored are transferred to storage area/freezer room where they are stored until when they are due for further analysis at the site or shipment to next destination as specified in the protocol. The results are reviewed and verified before they are dispatched to the clinician for patient management and transcription onto the paper CRF.</p>\n<p>\n F. Data Entry and Query Handling Data collection is done on source documents then transcribed into paper CRF before being entered into eCRF. All data collected is identified using each participant’s unique study number. All areas where paper and electronic data are stored have controlled access, the cabinets are lockable and the computers are password protected. Queries are raised during internal quality check and are flagged to be resolved by the staff who made the error. Queries on eCRF are raised electronically during data cleaning and responded to by the IT and clinical team.</p>\n
      • other_details_explanation<p>\n The <em>Streptococcus pneumoniae</em> vaccine (PATH-wSP) is a whole cell pneumococcal vaccine in development for use in countries where conjugate pneumococcal vaccines are cost prohibitive.  It is anticipated that PATH-wSP would be administered in conjunction with other vaccines currently endorsed by WHO for an infant Expanded Program on Immunization (EPI).  This would include combination vaccines that specifically have other whole cell components.  Therefore the clinical development plan is designed to test the safety of PATH-wSP co-administered with a pentavalent combination vaccine which contains a whole cell pertussis component.  Such a trial could not be conducted in the USA, where only acellular pertussis is being used.  The EPI program in Kenya includes administration of whole cell pertussis.  Given that pneumonia remains an important cause of infant mortality in Kenya, the Kenyan people would benefit greatly from introduction of an effective and less costly vaccine against pneumococcus.</p>\n
      • other_details_regulatory_notapproved<p>\n None</p>\n
      • other_details_regulatory_approved<p>\n None</p>\n
      • other_details_regulatory_rejected<p>\n Not Applicable</p>\n
      • other_details_regulatory_halted<p>\n Not Applicable</p>\n
      • estimated_duration12 months in the field
      • 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_comparatornormal saline control
      • design_controlled_other_medicinalYes
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKEMRI-Wellcome Trust Research Program
      • single_site_physical_addressCenter for Geographic Medicine, PO Box 230, Kilifi 80108, Kenya
      • single_site_contact_personDr. Anthony Scott
      • single_site_telephone+254 705 412719
      • multiple_sites_member_stateNo
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites
      • multi_country_list
      • data_monitoring_committeeYes
      • total_enrolment_per_site147 participants
      • total_participants_worldwide147 participants
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerYes
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameJohn Anthony
      • investigator1_middle_name
      • investigator1_family_nameScott
      • investigator1_qualificationBM BCh, MSc
      • investigator1_professional_addressKEMRI-Wellcome Trust Research Programme, PO Box 230, Kilifi 80108, Kenya
      • investigator1_telephone+254 705 412719
      • investigator1_emailascott@ikilifi.org
      • organisations_transferred_Yes
      • number_participants48 adults (18-40 years) and 99 toddlers (12-19 months)
      • notification<p>\n None</p>\n
      • approval_date09-02-2016
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted13-11-2015
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report<div>\n SYNOPSIS</div>\n<div>\n Sponsor: PATH Vaccine Solutions</div>\n<div>\n  </div>\n<div>\n Name of Test Article: PATH-wSP</div>\n<div>\n  </div>\n<div>\n Study Title: A Phase 1/2, Randomized, Placebo-Controlled, Observer-Blind Study to Assess the Safety, Tolerability, and Immunogenicity of Streptococcus pneumoniae Whole Cell Vaccine, Inactivated and Adsorbed to Aluminum Hydroxide (PATH-wSP) in Healthy Kenyan Young Adults (18 to 40 years) and Toddlers (12 to 21 months)</div>\n<div>\n  </div>\n<div>\n Investigator and Study Center: This study was conducted at a single center in Kenya. The Principal Investigator was Anthony Scott, MBChB, DTM & H, MSc.</div>\n<div>\n  </div>\n<div>\n Publications: None</div>\n<div>\n  </div>\n<div>\n Phase: 1/2</div>\n<div>\n Initiation Date (first subject enrolled): 10 August 2016</div>\n<div>\n  Objectives:</div>\n<div>\n <strong>Primary Objectives</strong></div>\n<div>\n  </div>\n<div>\n •   To evaluate the safety and tolerability of 2 dose levels (0.6 mg and 1.0 mg) of Streptococcus pneumoniae whole cell antigen with aluminum hydroxide adjuvant PATH-wSP vaccine, administered in a 2-series schedule, 4 weeks apart, in healthy adults.</div>\n<div>\n  </div>\n<div>\n •   To evaluate the safety and tolerability of 2 dose levels (0.6 mg and 1.0 mg) of PATH-wSP vaccine, administered in a 2-series schedule, 8 weeks apart, in healthy toddlers when co-administered with a booster dose of licensed pentavalent vaccine (diphtheria, tetanus, whole cell pertussis, Haemophilus influenzae type b [Hib], and hepatitis B combined vaccine) at the second vaccination.</div>\n<div>\n <div>\n <strong>Secondary Objective</strong></div>\n <div>\n •   To assess immunogenicity of PATH-wSP vaccine when given as a 2-vaccination series to adults and toddlers.</div>\n <div>\n  </div>\n <div>\n <strong>Exploratory Objectives</strong></div>\n <div>\n  </div>\n <div>\n •   To evaluate the potential for sera from PATH-wSP-immunized subjects to afford passive protection in an animal challenge model (subset of subjects).</div>\n <div>\n  </div>\n <div>\n •   To identify novel antibody targets for future vaccine candidates using peripheral blood mononuclear cells (PBMCs; i.e., lasmablasts) stimulated in vitro (adults only).</div>\n <div>\n  </div>\n <div>\n <div>\n METHODS</div>\n <div>\n Design: This single-center, observer-blind, Phase 1/2 study was for the sequential testing of 2 escalating doses of PATH-wSP (0.6 mg and 1.0 mg) in healthy adults followed by toddlers.</div>\n <div>\n  </div>\n <div>\n This study was a dose escalation study, and sequential cohorts of subjects were identified to allow safety evaluations of dosing to occur progressively during the study. The following PATH-wSP cohorts were defined for adult and toddler subjects:</div>\n <div>\n  </div>\n <div>\n •   Adult Cohort 1: Two 0.6 mg doses of PATH-wSP (12 subjects) or saline (12 subjects) with a 28-day interval between doses.</div>\n <div>\n <div>\n Adult Cohort 2: Two 1.0 mg doses of PATH-wSP (12 subjects) or saline (12 subjects) with a 28-day interval between doses.</div>\n <div>\n  </div>\n <div>\n •   Toddler Cohort 1: Two 0.6 mg doses of PATH-wSP (50 subjects) or saline (50 subjects) with a 56-day interval between doses, and pentavalent vaccine co-administered with the second dose.</div>\n <div>\n  </div>\n <div>\n •   Toddler Cohort 2: Two 1.0 mg doses of PATH-wSP (50 subjects) or saline (50 subjects) with a 56-day interval between doses, and pentavalent vaccine co-administered with the second dose.</div>\n <div>\n  </div>\n <div>\n Because of a safety signal observed among toddlers in a previous study, safety monitoring focused on cases of suspected pneumonia.</div>\n <div>\n  </div>\n <div>\n Number of Subjects (planned and analyzed): A total of 48 adults (24 subjects per cohort) and 200 toddlers (100 subjects per cohort) were planned and enrolled in the study.</div>\n <div>\n  </div>\n <div>\n Diagnosis and Main Criteria for Inclusion: Healthy adults who were 18 to 40 years old, inclusive, or toddlers who were 12 to 21 months old, inclusive, on the day of randomization (Day 0) were eligible for inclusion. Toddlers must have completed their primary Expanded Programme on Immunization vaccines with, at minimum, 1 Bacille Calmette-Guérin, 3 diphtheria and tetanus toxoid </div>\n <div>\n with whole cell pertussis, Hib, and hepatitis B, 1 measles, 3 oral polio (with the exception of the birth dose), 3 pneumococcal conjugate, and 2 rotavirus vaccinations.</div>\n <div>\n  </div>\n <div>\n Investigational Products, Dose and Mode of Administration, Batch Number: </div>\n <div>\n PATH-wSP vaccine or saline was administered as a 2-vaccination series intramuscularly at Weeks 0 and 4 in adults at 0.6 or 1.0 mg or Weeks 0 and 8 in toddlers at 0.6 or 1.0 mg, with a pentavalent vaccine co-administered with the second dose. For both cohorts, Batch 8020115 was the 0.6-mg dose and Batch 8030115 was the 1.0-mg dose.</div>\n <div>\n <strong> Endpoints:</strong></div>\n <div>\n <strong>Primary Endpoints</strong></div>\n <div>\n  </div>\n <div>\n Safety and tolerability of PATH-wSP vaccine including co-administration of PATH-wSP and licensed pentavalent vaccine at the second vaccination to toddlers will be evaluated based on the following analyses:</div>\n <div>\n  </div>\n <div>\n •   Occurrence and severity of solicited local and systemic adverse events (AEs) and clinical laboratory abnormalities through 1 week post-vaccination.</div>\n <div>\n  </div>\n <div>\n •   Occurrence, severity, and relatedness to vaccination of unsolicited AEs and serious adverse events (SAEs) from Day 0 through the last study contact.</div>\n <div>\n  </div>\n <div>\n Secondary Endpoints</div>\n <div>\n  </div>\n <div>\n The immunoglobulin G (IgG) response to pneumococcal-specific proteins (pneumolysoid and pneumococcal surface protein A family 1 [PspA-Fam1]) measured by enzyme-linked immunosorbent assay, and the IgG response to 9 pre-selected pneumococcal proteins measured on the Meso Scale Discovery platform, will be evaluated based on the following analyses:</div>\n <div>\n  </div>\n <div>\n •   IgG geometric mean concentration and geometric mean fold rise (GMFR) (from baseline) 4 weeks after the second vaccination.</div>\n <div>\n  </div>\n <div>\n •   Percentage of subjects with IgG concentration of a predefined threshold level (responders), measured 4 weeks after the second vaccination.</div>\n <div>\n <div>\n <strong>Endpoints:</strong></div>\n <div>\n <strong>Primary Endpoints</strong></div>\n <div>\n  </div>\n <div>\n Safety and tolerability of PATH-wSP vaccine including co-administration of PATH-wSP and licensed pentavalent vaccine at the second vaccination to toddlers will be evaluated based on the following analyses:</div>\n <div>\n  </div>\n <div>\n •   Occurrence and severity of solicited local and systemic adverse events (AEs) and clinical laboratory abnormalities through 1 week post-vaccination.</div>\n <div>\n  </div>\n <div>\n •   Occurrence, severity, and relatedness to vaccination of unsolicited AEs and serious adverse events (SAEs) from Day 0 through the last study contact.</div>\n <div>\n  </div>\n <div>\n <strong>Secondary Endpoints</strong></div>\n <div>\n  </div>\n <div>\n The immunoglobulin G (IgG) response to pneumococcal-specific proteins (pneumolysoid and pneumococcal surface protein A family 1 [PspA-Fam1]) measured by enzyme-linked immunosorbent assay, and the IgG response to 9 pre-selected pneumococcal proteins measured on the Meso Scale Discovery platform, will be evaluated based on the following analyses:</div>\n <div>\n  </div>\n <div>\n •   IgG geometric mean concentration and geometric mean fold rise (GMFR) (from baseline) 4 weeks after the second vaccination.</div>\n <div>\n  </div>\n <div>\n •   Percentage of subjects with IgG concentration of a predefined threshold level (responders), measured 4 weeks after the second vaccination.</div>\n <div>\n  </div>\n </div>\n </div>\n </div>\n</div>\n<p>\n <strong><u> RESULTS</u></strong></p>\n<div>\n <u>Subject Disposition</u>: A total of 85 adult subjects were screened in the adult cohort, and 48 subjects were randomized: 12 subjects in each of the 0.6 mg PATH-wSP, 1.0 mg PATH-wSP, Cohort 1 Saline, and Cohort 2 Saline groups. All subjects completed the Day 56 safety visit. All but 1 subject missed no home visits. Two subjects discontinued after randomization.</div>\n<div>\n  </div>\n<div>\n A total of 388 toddler subjects were screened in the toddler cohort, and 200 subjects were randomized:50 subjects in each of the 0.6 mg PATH-wSP, 1.0 mg PATH-wSP, Cohort 1 Saline, and Cohort 2 Saline groups. Overall, 99.5% of subjects completed all clinic visits. Only 3 toddlers missed at least 1 home visits; no toddlers missed all home visits. Three (1.5%) toddlers discontinued after randomization. One toddler’s parent withdrew consent for further blood draws after the first vaccination, and 1 toddler was discontinued after safety unblinding, but both toddlers continued safety assessments. The third toddler’s parent withdrew consent from the study after receiving both vaccines and exited the study.</div>\n<div>\n  </div>\n<div>\n Baseline Demographics: Overall, there were 30 men (62.5%) and 18 women (37.5%) in the adult cohort; which were consistent across treatment groups. The mean (SD) age of all adult subjects was  28.4 (6.63) years. The mean (SD) height of all adult subjects was 162.1 (7.64) cm, and the mean (SD) weight was 57.9 (8.99) kg, with no major variations in height and weight between groups.</div>\n<div>\n  </div>\n<div>\n The proportion of male (46.5%) and female (53.5%) toddlers was well balanced. The mean (SD) age of all toddler subjects was 16.4 (2.58) months. The mean (SD) height of all toddler subjects was 76.0 (5.33) cm, and the mean (SD) weight was 9.1 (1.25) kg, with no major variations in height and weight between groups.</div>\n<div>\n  </div>\n<div>\n No noteworthy differences were observed between treatment groups in any demographic characteristic.  Immunogenicity Results: Tested dose levels of PATH-wSP induced a modest immune response against multiple pneumococcal proteins at approximately 1 month after each of a 2-dose vaccination series. </div>\n<div>\n In both adults and toddlers, immune responses based on GMFR ratio comparisons between the 0.6 mg and 1.0 mg dose level of PATH-wSP were mostly similar after Vaccination 2; however, there was a slight increase in immune response with 1.0 mg in toddlers. In the adult cohort, there were greater proportions of higher fold rises in the 0.6 mg PATH-wSP group compared with the 1.0 mg PATH-wSP group post- Vaccination 2. When comparing the PATH-wSP doses in toddler subjects, the proportion of</div>\n<div>\n seroresponders showed variable results based on the specific pneumococcal proteins. Taken together, the results do not suggest a dose-dependent immune response to pneumococcal antigens.</div>\n<div>\n Safety Results: Overall, PATH-wSP was well-tolerated in both age cohorts, and there were no notable changes in safety laboratory parameters, including all liver function-related assays. Most reactogenicity events (REs) were mild or moderate and resolved within 24 to 48 hours. Differences in reactogenicity between PATH-wSP and Saline groups were primarily minor and limited to REs of mild or moderate severity. The incidence of Grade 1 and 2 pain and swelling/hardness at the injection site was higher in adults receiving PATH-wSP than in those that received saline. Similarly, the incidence of local reactions (including Grade 1 and 2 tenderness and swelling/hardness at the injection site) was higher in toddlers receiving PATH-wSP than in the saline cohorts. Post-vaccination loss of appetite and irritability were frequent in the toddler cohort, although there was no difference in incidence between treatment groups. In general, REs did not differ between Vaccination 1 and 2 in the adult cohort and were only</div>\n<div>\n slightly more frequent and severe after Vaccination 2 in the toddler cohort.</div>\n<div>\n <div>\n While treatment-emergent adverse events (TEAEs) were common in both adult and toddler cohorts, most were considered not treatment related. Reported vaccine-related TEAEs were all in the toddler cohort and resolved during the study. Mild vaccination site induration (in 2 subjects in the 1.0 mg PATH-wSP group) was the only vaccine-related TEAE reported in PATH-wSP groups and hence the only observed adverse drug reaction.</div>\n <div>\n  </div>\n <div>\n Pneumonia was not observed in the adult cohort and was infrequent in the toddler cohort, with no notable trends across treatment groups.</div>\n <div>\n  </div>\n <div>\n In toddlers, there was a trend toward increased relative risk of non-severe lower respiratory tract infections (LRTIs) in the 0.6 mg PATH-wSP group associated with increased rates of upper respiratory tract infections (URTIs) during Cohort 1. It is noteworthy that Cohort 1 was conducted during what is historically the peak respiratory syncytial virus (RSV) season in Kilifi, Kenya.</div>\n <div>\n  </div>\n <div>\n There were no treatment-emergent SAEs in the adult cohort. Fourteen treatment-emergent SAEs were reported in the toddler cohort, but with no notable trends across treatment groups. The only SAEs that were considered vaccine-related at the time of their occurrence were 3 events reported in the toddler Saline group. All SAEs resolved during the study.</div>\n <div>\n  </div>\n <div>\n There were no deaths during the study.</div>\n <div>\n No subjects had a TEAE leading to study discontinuation.</div>\n <div>\n  There were no notable trends from baseline to post-vaccination in clinical laboratory parameters or vital signs in either the adult or toddler cohorts. Overall, few subjects in either cohort had abnormal physical examination findings post-vaccination, and these were related to reported AEs when detected.</div>\n <div>\n  </div>\n <div>\n CONCLUSIONS: The PATH-wSP vaccine was well-tolerated in all age cohorts with no meaningful difference in rates of local and systemic solicited AEs (reactogenicity) following vaccination with PATH-wSP. When observed, reactogenicity was primarily mild or moderate and of limited duration.</div>\n <div>\n  </div>\n <div>\n Most TEAEs were unrelated to the study vaccine and all related TEAEs resolved during the study. No vaccine-related treatment-emergent SAEs were observed in any subject that received PATH-wSP. There There were no notable trends from baseline to post-vaccination in clinical laboratory parameters or vital signs in either the adult or toddler cohorts. Overall, few subjects in either cohort had abnormal  physical examination findings post-vaccination, and these were related to reported AEs when detected.</div>\n <div>\n <div>\n  </div>\n <div>\n CONCLUSIONS: The PATH-wSP vaccine was well-tolerated in all age cohorts with no meaningful difference in rates of local and systemic solicited AEs (reactogenicity) following vaccination with PATH-wSP. When observed, reactogenicity was primarily mild or moderate and of limited duration.</div>\n <div>\n  </div>\n <div>\n Most TEAEs were unrelated to the study vaccine and all related TEAEs resolved during the study. No vaccine-related treatment-emergent SAEs were observed in any subject that received PATH-wSP. There were no meaningful trends in either SAEs or vaccine-related TEAEs. No deaths were reported during the study and no subject had a TEAE leading to discontinuation of the vaccination schedule.</div>\n <div>\n  </div>\n <div>\n Pneumonia cases were not observed in the adult cohort and were infrequent in the toddler cohort, with no notable trends across treatment groups. A higher incidence of LRTIs was observed in the PATH-wSP 0.6 mg toddler group than in the corresponding saline group. This imbalance in LRTIs between the active and control groups in Cohort 1 was within random fluctuation in relative risk of LRTI (95%  confidence interval [CI]: 0.63, 26.2), and was limited to cases of mild-to-moderate severity. It is, however, notable when considered in the context of the increased relative risk of (primarily mild) LRTIs observed in the</div>\n <div>\n 0.6 mg PATH-wSP group of the VAC-010 study (2.21 at lower limit of 95% CI). The trend toward an increased relative risk of non-severe LRTIs in the 0.6 mg PATH-wSP toddler group of the current study was associated with a significant seasonal imbalance in the incidence of URTIs between Cohort 1 (38.0% to 54.0%) and Cohort 2 (6% to 8%). Similarly, the onset of LRTI events in the combined 0.6 mg PATH- wSP group of the VAC-010 study also occurred during peak RSV season in Western Kenya where </div>\n <div>\n the study was conducted. This suggests that PATH-wSP vaccination may, in the context of viral URTI, potentiate LRTIs of primarily mild to-moderate severity in toddlers.</div>\n <div>\n  </div>\n <div>\n Tested doses of PATH-wSP injections induced an immune response against multiple pneumococcal proteins. In both adults and toddlers, immune response based on GMFR ratio comparisons between the 0.6 mg and 1.0 mg dose of PATH-wSP was mostly similar after Vaccination 2; however, there was a slight increase in immune response with 1.0 mg in toddlers.</div>\n <div>\n  In addition to the GMFR analysis, the proportion of adult and toddler subjects presenting a 2-fold, 3-fold or 4-fold response to the pre-selected pneumococcal proteins was evaluated. Overall, less than approximately 20% of the subjects tested developed a 3-fold or higher response rate, while less than 50% developed a 2-fold or higher response rate.</div>\n <div>\n  </div>\n <div>\n In the adult cohort, there were greater proportions of higher fold rises in the 0.6 mg PATH-wSP group compared with the 1.0 mg PATH-wSP group post-Vaccination 2. When comparing the PATH-wSP doses in toddler subjects, the proportion of seroresponders showed variable results based on the specific pneumococcal proteins. Taken together, the results do not suggest a dose-dependent immune response to pneumococcal antigens. It is noteworthy, however, that most subjects had measurable levels of </div>\n <div>\n antibodies against all the proteins tested, likely due to prior priming with S. pneumococcus. The expected high rates of pneumococcal colonization in this adult and toddler population may have blunted the immune response to PATH-wSP, as has been observed with pneumococcal conjugate vaccine. </div>\n <div>\n Any hypo-responsiveness effect of colonization would likely be reduced in the target infant population, given the lower prevalence of pneumococcal carriage.</div>\n <div>\n  </div>\n <div>\n PATH-wSP was well tolerated by both adults and toddlers and induced an appropriate immune response as assessed during this study. However, given the possible role of PATH-wSP in contributing to an increased relative risk of LRTI in toddlers during the peak RSV season and the uncertainty that vaccination was affording benefit, the Sponsor concluded that additional evidence of benefit exceeding risk must be generated in another (larger) clinical trial enrolling toddlers age 12 months and greater before conducting studies in the target population of infants age 6-8 weeks of age. Given this change to the development plan, the institution financing the vaccine’s development decided to end their support.</div>\n <div>\n  </div>\n <div>\n Date of Report: 14 December 2018</div>\n <div>\n  </div>\n <div>\n  </div>\n </div>\n <div>\n  </div>\n</div>\n<div>\n  </div>\n
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        • given_nameJohn Anthony
        • middle_nameGerard
        • family_nameScott
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        • telephone+254 705 412719
        • emailascott@ikilifi.org
        • created2015-08-31 14:09:50
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        • email_addressslamola@path.org
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