Request History

• Restore to current request
• applications/index/page:58/sort:protocol_no/direction:desc/approved:1
• applications/index/page:67/sort:study_title/direction:desc/approved:2
• applications/index/page:63/sort:study_title/direction:asc/approved:1
• applications/index/page:60/sort:study_title/direction:desc/approved:1

Session

• Config(array)
  • userAgent9c3d2c89526db53b7b69e8c9faa06145
  • time1746043444
  • countdown10

Request

Cake Params

• plugin(null)
• controllerapplications
• actionindex
• named(array)
  • sortstudy_title
  • directiondesc
  • approved2
  • page5
• pass(empty)
• isAjax(false)
• paging(array)
  • Application(array)
    • page5
    • current5
    • count501
    • prevPage(true)
    • nextPage(true)
    • pageCount101
    • order(array)
      • Application.study_titledesc
    • limit5
    • options(array)
      • page5
      • order(array)
        • Application.study_titledesc
      • sortstudy_title
      • directiondesc
    • paramTypenamed

Post data

• Application(array)
  • approved2

Query string

No querystring data.

Cookie

To view Cookies, add CookieComponent to Controller

Current Route

• keys(array)
  • 0controller
  • 1action
• options(empty)
• defaults(array)
  • plugin(null)
• template/:controller/:action/*

Sql Logs

Logs

View Variables

• trial_statuses(array)
  • 1Recruiting
  • 2Not yet recruiting
  • 3Suspended
  • 4Stopped
  • 5Completed
  • 6In follow-up
  • 7Analysing
  • 8Writing-up
  • 9Application withdrawn
• applications(array)
  • 0(array)
    • Application(array)
      • id436
      • user_id32
      • trial_status_id5
      • abstract_of_study<div>\n Malaria morbidity and mortality have been reduced substantially as malaria control interventions have been scaled up across Africa, including in Kenya. Nonetheless, malaria continues to cause considerable morbidity and mortality, especially in children under 5 years of age living in sub Saharan Africa.  As we aim for a reduction in malaria burden, and towards malaria elimination, it has become clear that new tools to fight malaria are urgently needed. A highly efficacious vaccine would be an important addition to complement current malaria control measures and to contribute to elimination efforts. Among the different vaccine approaches used to prevent malaria infection, whole Plasmodium falciparum sporozoite (PfSPZ) vaccines have shown consistent, high-level protection in a number of phase I clinical trials. </div>\n<div>\n  </div>\n<div>\n The candidate malaria vaccine, PfSPZ Vaccine, consists of aseptic purified, cryopreserved, radiation-attenuated Plasmodium falciparum (Pf) sporozoites, which when given by direct venous inoculation (DVI) to malaria naïve volunteers in the United States was safe, well tolerated and showed dose-dependent, high protection against controlled human malaria infection.  The Kenya Medical Research Institute and the U.S. Centers for Disease Control and Prevention, in collaboration with NIH and Sanaria, propose to conduct a study to measure safety, immunogenicity and efficacy of this novel candidate malaria vaccine when given to infants from 5 to 12 months inclusive.  The study will be conducted in Siaya County in western Kenya. Initially, in Part 1 of the trial, 120 children will be recruited into an age de-escalation and dose escalation study to document safety of the vaccine in three age groups (children aged 5–12 years, children aged 13 – 59 months, and infants aged 5–12 months) and at the following dosages of sporozoites versus placebo: 1.35 x 105, 2.7 x 105, 4.5 x 105, 9.0 x 105 PfSPZ vaccine (only the higher two doses in children aged 5–12 years), given as a single injection by direct venous inoculation (DVI). Part 1, age de-escalation and dose escalation, will begin with administration of 4.5 x 105 PfSPZ in 12 children aged 5–12 years (8 vaccine, 4 placebo), provided to a limited number of participants each day (for example, approximately 3 participants each day on days 1–4).  The PfSPZ Vaccine dose will only be increased to the next level when safety has been assessed in participants of the first group, and earliest at 14 days after the first injection. At this time, the lowest dose (1.35 x 105) will be administered to children age 13-59 months, with doses doubling every two weeks, after assessment of safety signals, until the final dose of 9.0 x 105 PfSPZ is reached. The lowest dose will be administered to infants 5–12 months after this dosage has shown to be safe in 13-59 months-olds, and doses will be doubled every two weeks, after assessment of safety signals, until the dose of 9.0 x 105 PfSPZ is reached. Overall vaccine doses will only be increased if they are assessed as well tolerated and the safety data are acceptable for further evaluation of the vaccine at a higher dose, applicable to all the age groups. All of these proposed doses have been shown to be well tolerated with no serious safety signals in studies in US adults and, in African adults at the two lowest doses.  Therefore, based on the critical importance of dose in mediating protection with this vaccine, the 2 highest dosages found to be well tolerated will be used for the Part 2 of the trial, which will measure safety and efficacy of the PfSPZ vaccine. The highest well tolerated dosage (likely to be 9.0 x 105 PfSPZ) will be administered by DVI 3 times to 104 infants (group 1), and 4 times to 104 infants (group 2); the second highest dosage (likely to be 4.5 x 105 PfSPZ) will be given 3 times to another study arm of 104 infants (group 3) to document a dose response and to understand whether the lower dose is highly efficacious in this age-category.  The rationale for the amount of PfSPZ Vaccine (4.5 x 105  or  9.0 x 105 PfSPZ), number of doses ( 3 or 4) and intervals between doses ( 4 and 8 weeks) is based on data from ongoing studies in US and African adults for conferring durable immunity and protection, and will be further informed by the dose escalation trial. Another group of 104 infants will receive 3 (n=52; group 4) or 4 (n=52; group 5) doses of normal saline (NS) by direct venous injection as placebo. The dosing interval in all 3 dose groups will be 8 weekly (0, 8,16 weeks), while the doses in the 4 dose groups will be given at 0, 4, 8 and 16 weeks. The main objectives of this study are to measure the safety, tolerability and immunogenicity of PfSPZ Vaccine in infants (measured in Part 1 and Part 2 of this trial) and to determine whether PfSPZ Vaccine administered by DVI to infants provides high-level protection (point estimate >60%) against Pf infection during 6 months following the last vaccine dose when compared to a placebo group (Part 2 of the trial).  A secondary objective will be to measure safety tolerability, immunogenicity and efficacy during 12 months follow-up.</div>\n<div>\n  </div>\n
      • study_title<p>\n Safety, Tolerability and Efficacy of PfSPZ Vaccine Administered by Direct Venous Inoculation (DVI) to Healthy Children and Infants 5 Months through 12 Years of Age Living in an Area of High Malaria Transmission in Western Kenya: Age de-escalation and Dose Escalation and a Double Blind, Randomized Placebo-Controlled Trial for Safety and Efficacy</p>\n
      • laymans_summary<div>\n Malaria morbidity and mortality have been reduced substantially as malaria control interventions have been scaled up across Africa, including in Kenya. Nonetheless, malaria continues to cause considerable morbidity and mortality, especially in children under 5 years of age living in sub Saharan Africa.  As we aim for a reduction in malaria burden, and towards malaria elimination, it has become clear that new tools to fight malaria are urgently needed. A highly efficacious vaccine would be an important addition to complement current malaria control measures and to contribute to elimination efforts. Among the different vaccine approaches used to prevent malaria infection, whole Plasmodium falciparum sporozoite (PfSPZ) vaccines have shown consistent, high-level protection in a number of phase I clinical trials. </div>\n<div>\n  </div>\n<div>\n The candidate malaria vaccine, PfSPZ Vaccine, consists of aseptic purified, cryopreserved, radiation-attenuated Plasmodium falciparum (Pf) sporozoites, which when given by direct venous inoculation (DVI) to malaria naïve volunteers in the United States was safe, well tolerated and showed dose-dependent, high protection against controlled human malaria infection.  The Kenya Medical Research Institute and the U.S. Centers for Disease Control and Prevention, in collaboration with NIH and Sanaria, propose to conduct a study to measure safety, immunogenicity and efficacy of this novel candidate malaria vaccine when given to infants from 5 to 12 months inclusive.  The study will be conducted in Siaya County in western Kenya. Initially, in Part 1 of the trial, 120 children will be recruited into an age de-escalation and dose escalation study to document safety of the vaccine in three age groups (children aged 5–12 years, children aged 13 – 59 months, and infants aged 5–12 months) and at the following dosages of sporozoites versus placebo: 1.35 x 105, 2.7 x 105, 4.5 x 105, 9.0 x 105 PfSPZ vaccine (only the higher two doses in children aged 5–12 years), given as a single injection by direct venous inoculation (DVI). Part 1, age de-escalation and dose escalation, will begin with administration of 4.5 x 105 PfSPZ in 12 children aged 5–12 years (8 vaccine, 4 placebo), provided to a limited number of participants each day (for example, approximately 3 participants each day on days 1–4).  The PfSPZ Vaccine dose will only be increased to the next level when safety has been assessed in participants of the first group, and earliest at 14 days after the first injection. At this time, the lowest dose (1.35 x 105) will be administered to children age 13-59 months, with doses doubling every two weeks, after assessment of safety signals, until the final dose of 9.0 x 105 PfSPZ is reached. The lowest dose will be administered to infants 5–12 months after this dosage has shown to be safe in 13-59 months-olds, and doses will be doubled every two weeks, after assessment of safety signals, until the dose of 9.0 x 105 PfSPZ is reached. Overall vaccine doses will only be increased if they are assessed as well tolerated and the safety data are acceptable for further evaluation of the vaccine at a higher dose, applicable to all the age groups. All of these proposed doses have been shown to be well tolerated with no serious safety signals in studies in US adults and, in African adults at the two lowest doses.  Therefore, based on the critical importance of dose in mediating protection with this vaccine, the 2 highest dosages found to be well tolerated will be used for the Part 2 of the trial, which will measure safety and efficacy of the PfSPZ vaccine. The highest well tolerated dosage (likely to be 9.0 x 105 PfSPZ) will be administered by DVI 3 times to 104 infants (group 1), and 4 times to 104 infants (group 2); the second highest dosage (likely to be 4.5 x 105 PfSPZ) will be given 3 times to another study arm of 104 infants (group 3) to document a dose response and to understand whether the lower dose is highly efficacious in this age-category.  The rationale for the amount of PfSPZ Vaccine (4.5 x 105  or  9.0 x 105 PfSPZ), number of doses ( 3 or 4) and intervals between doses ( 4 and 8 weeks) is based on data from ongoing studies in US and African adults for conferring durable immunity and protection, and will be further informed by the dose escalation trial. Another group of 104 infants will receive 3 (n=52; group 4) or 4 (n=52; group 5) doses of normal saline (NS) by direct venous injection as placebo. The dosing interval in all 3 dose groups will be 8 weekly (0, 8,16 weeks), while the doses in the 4 dose groups will be given at 0, 4, 8 and 16 weeks. The main objectives of this study are to measure the safety, tolerability and immunogenicity of PfSPZ Vaccine in infants (measured in Part 1 and Part 2 of this trial) and to determine whether PfSPZ Vaccine administered by DVI to infants provides high-level protection (point estimate >60%) against Pf infection during 6 months following the last vaccine dose when compared to a placebo group (Part 2 of the trial).  A secondary objective will be to measure safety tolerability, immunogenicity and efficacy during 12 months follow-up.</div>\n<div>\n  </div>\n
      • short_titlePfSPZ Malaria Vaccine
      • protocol_noECCT/16/02/05
      • version_no1.0
      • date_of_protocol10-10-2015
      • study_drugPfSPZ Malaria Vaccine
      • disease_conditionMalaria
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines1
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_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_letter1
      • applicant_statement1
      • applicant_participating_countries0
      • applicant_addendum0
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data0
      • 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_african0
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan0
      • applicant_contractual_agreement0
      • declaration_applicantDr Tony Sang
      • declaration_date112-02-2016
      • declaration_principal_investigatorDr Martina Oneko
      • declaration_date212-02-2016
      • placebo_presentYes
      • study_objectives<div>\n <strong>Primary objectives:</strong></div>\n<div>\n Part 1: Age de-esclation and dose escalation trial in children and infants (5 months -12 years)</div>\n<div>\n Measure the safety, tolerability and immunogenicity of PfSPZ Vaccine administered at escalating dosages by DVI in older children aged 5–12 years (highest two doses only), younger children aged 13-59 months, and infants 5-12M (at vaccination) at doses of 1.35x105, 2.7x105, 4.5x105, 9.0x105 PfSPZ Vaccine given as a single dose.</div>\n<div>\n  </div>\n<div>\n <div>\n Part 2: Safety and efficacy trial in infants (5-12M inclusive) living in an area of high malaria transmission</div>\n <ul>\n <li>\n Primary Objective 1: Safety, Tolerability and Immunogenicity in infants (5-12M inclusive)\n <ul>\n <li>\n Measure the safety, tolerability and immunogenicity of the highest safe and well tolerated dose 666 of PfSPZ Vaccine administered by DVI in 3 or 4 doses to infants 5-12M inclusive of age. Dosage will be determined during the age de-escalation and dose escalation trial (Part 1) based on safety and tolerability.</li>\n </ul>\n </li>\n <li>\n Primary Objective 2: Efficacy in infants (5-12M inclusive)\n <ul>\n <li>\n Determine whether PfSPZ Vaccine administered by DVI to infants 5-12M inclusive of age at the highest safe and well tolerated dose of PfSPZ vaccine provides high-level (point estimate > 60%) protection against naturally acquired Pf infection, measured by blood smear microscopy, during 6 months following the last vaccine dose when compared to a control (placebo) group.</li>\n </ul>\n </li>\n </ul>\n <div>\n <strong>Secondary Objectives:</strong></div>\n <ul>\n <li>\n Secondary Objective 1: Determine safety and efficacy of alternative dosages of PfSPZ Vaccine at 6676 months after last vaccination</li>\n <li>\n Secondary Objective 2: Determine safety and efficacy of each dosage of PfSPZ Vaccine at 12 678 months after last vaccination</li>\n <li>\n Secondary Objective 3: Determine whether PfSPZ Vaccine administered by DVI to infants 5-12M 680 inclusive of age at any of the given doses of PfSPZ Vaccine provides high-level (point estimate > 60%) protection against naturally acquired Pf infection, measured by PCR, during 6 and 12 months following the last vaccine dose when compared to a control (placebo) group.</li>\n <li>\n Secondary Objective 4: Assess the cellular immunity and antibody responses induced by PfSPZ Vaccine</li>\n <li>\n Secondary Objective 5: Determine whether measured immune responses correlate with protection against Pf infection</li>\n <li>\n Secondary Objective 6: Determine the safety, tolerability, efficacy and immunological response provided by the addition of a booster dose 12 months after the primary vaccination series in infants 5M-12M of age on enrolment (dependent on achieving a statistically significant point estimate of at least 60% VE during 6 months follow-up)</li>\n </ul>\n <p>\n <strong>Exploratory Objectives</strong></p>\n <ul>\n <li>\n Objective 1: Determine the efficacy of PfSPZ Vaccine against Pf infection at specific parasite density thresholds (Pf parasite density >400 or >5000 parasites per microliter)</li>\n <li>\n Exploratory Objective 2: Determine the efficacy of PfSPZ Vaccine against malaria hospitalization (defined as hospitalization and Pf parasite density >5000 parasites per microliter or hemoglobin <5g/dl determined to be caused by malaria).</li>\n <li>\n Exploratory Objective 3: Determine whether any of the PfSPZ vaccination schedules has an effect on the prevalence of anemia as measured during the month 6 and month 12 visits</li>\n <li>\n Exploratory Objective 4: Measure allele-specific efficacy and selection of vaccine-resistant Pf genotypes through a genome-wide sieve analysis.</li>\n </ul>\n</div>\n<p>\n  </p>\n
      • principal_inclusion_criteria<ul>\n <li>\n Healthy children 5 months – 12 years (Part 1) and healthy infants 5 -12M inclusive (Part 2) </li>\n <li>\n HIV negative </li>\n <li>\n Able to participate for the duration of the study. </li>\n <li>\n Parents/guardians over the age of 18 years able and willing to provide informed consent/permission. The consent/permission will be in writing.  For adult parents or guardians who are illiterate, an impartial witness can sign the consent/permission form on behalf of the parent and the parent/guardian will provide a thumbprint</li>\n</ul>\n<div>\n  </div>\n
      • principal_exclusion_criteria<ul>\n <li>\n Positive HIV test or breastfeeding infants or children of a known HIV positive mother (per Kenyan guidelines, these HIV exposed breastfeeding children should be on cotrimoxazole)</li>\n <li>\n Refusal of HIV testing</li>\n <li>\n Elevated ALT (liver function test) ≥2x ULN ( ALT >84 U/L)  </li>\n <li>\n Abnormal hematological parameters defined as: hemoglobin < 8 g/dl, WBC <1500 / mm3, neutrophils <750/ mm3, platelet count <75.000/ mm3</li>\n <li>\n Abnormal renal function test with creatinine >0.9 mg/dL</li>\n <li>\n Known sickle cell disease</li>\n <li>\n Current use of systemic immunosuppressant pharmacotherapy</li>\n <li>\n Current significant medical condition (cardiac, hepatic, renal, or hematological) or evidence of any other serious underlying medical condition identified by medical history, physical examination, or laboratory examination</li>\n <li>\n History of a splenectomy</li>\n <li>\n History of neurologic disorder (including seizures, other than uncomplicated febrile seizures)</li>\n <li>\n Known allergy to any component of the vaccine formulation, history of anaphylactic response to mosquito-bites, or known allergy to first or second line anti-malarials used to treat malaria</li>\n <li>\n Plan to participate in another investigational vaccine/drug research during or within 1 month of this study end</li>\n <li>\n Prior participation in a malaria vaccine trial</li>\n <li>\n Participation in the PfSPZ Vaccine Trial Part 1 (for Part 2 only)</li>\n <li>\n History of any other illness or condition which, in the investigator's judgment, may substantially increase the risk associated with the subject’s participation in the protocol or compromise the scientific objectives</li>\n <li>\n Child/orphan in institutional care</li>\n</ul>\n<div>\n  </div>\n
      • primary_end_points<p>\n Incidence of Pf parasitemia with parasite density >0 by thick blood smear</p>\n
      • scope_diagnosis0
      • scope_prophylaxis1
      • scope_therapy0
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response1
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory1
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n The study will be conducted at Siaya County Referral Hospital and Wagai Dispensary. </p>\n<p>\n Staff will include a study pediatrician and PI, a study site coordinator, a regulatory officer, administrative officer, data manager and data clerk, part time statistical support, sufficient clinical staff, including medical officers, clinical officers, nurses, quality assurance officers, community workers, laboratory personnel, including part time laboratory supervisor, and laboratory technicians and technologists, a pharmacist and pharmacist technician.  </p>\n<p>\n PI - Dr Martina Oneko, MD,Pediatrician</p>\n<p>\n PI - Dr Mary Hamel, MD</p>\n<p>\n Study Site Coordinator - Reuben Yego</p>\n<p>\n Pharmacist - Dr Tony Sang, BPharm</p>\n<p>\n Laboratory supervisor - Kephas Otieno, MSc</p>\n<p>\n Administrative officer - Diana Okello, MBA</p>\n<p>\n Data Manager - Wycliffe Odongo</p>\n<p>\n Data clerks</p>\n<p>\n Medical officer - To be hired</p>\n<p>\n Clinical officers</p>\n<p>\n Nurses</p>\n<p>\n Quality Assurance officers</p>\n<p>\n Community workers</p>\n<p>\n Laboratory personnel</p>\n<p>\n Laboratory technicians and technologists</p>\n<p>\n pharmacist technologist</p>\n<p>\n The trial budget also includes sufficient clinical supplies to test for malaria and provide treatment for common childhood diseases in the outpatient setting, ITNs for enrolled children, laboratory supplies for laboratory procedures, including immunological and molecular studies, transport costs, transport reimbursement for enrolled children.  </p>\n<p>\n  </p>\n
      • other_details_explanation<p>\n The proposed PfSPZ Vaccine has shown to be very safe and well tolerated in subjects in the US and Africa. High -level protective efficacy has been demonstrated in malaria naïve adult individuals, and therefore should be evaluated in African infants in an area of intense malaria transmission who continue to experience the highest morbidity and mortality from malaria and have not been exposed to frequent malaria infections.</p>\n
      • other_details_regulatory_notapproved<p>\n None</p>\n
      • other_details_regulatory_approved<p>\n KEMRI Scientific Ethics Review Unit approved the trial on 27-Oct-2015</p>\n<p>\n CDC IRB approved the trial on 10-Nov-2015</p>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n Not applicable</p>\n
      • estimated_duration3 years
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorNormal saline placebo
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites2 sites anticipated in Kenya.
      • multi_country_list
      • data_monitoring_committeeYes
      • total_enrolment_per_siteWe will have only one site in Kenya
      • total_participants_worldwide536 participants
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerYes
      • population_childrenYes
      • population_adolescentNo
      • population_above_18No
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
      • subjects_specifywe will enroll children below 12 years. Parental consent will be sought
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameMartina
      • investigator1_middle_name
      • investigator1_family_nameOneko
      • investigator1_qualificationMD, Pediatrician
      • investigator1_professional_addressKEMRI Center for Global Health Research, P.O.Box 1578-40100, Kisumu, Kenya
      • investigator1_telephone+254 717 747279
      • investigator1_emailmoneko@kemricdc.org
      • organisations_transferred_No
      • number_participants120 participants for the age de-escalation component of the study\n416 participants for the main study
      • notification
      • approval_date18-05-2016
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted15-12-2020
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report<div style=\"margin-left: 28.35pt;\">\n <p style=\"margin-left: 0.3in;\">\n <strong>Safety, Tolerability and Efficacy of PfSPZ Vaccine Administered by Direct Venous Inoculation (DVI) to Healthy Children and Infants 5 Months through 9 Years of Age Living in an Area of High Malaria Transmission in Western Kenya</strong></p>\n <p>\n <strong>Leadership/Partnership:</strong></p>\n</div>\n<ul>\n <li>\n <strong>Kenya: </strong>Dr. Martina Oneko (site Principal Investigator)</li>\n <li>\n <strong>LSTM: </strong>Prof. Feiko ter Kuile (co-Investigator)</li>\n <li>\n <strong>CDC contact person:</strong> Dr. Laura Steinhardt (Co Principal Investigator), Dr Aaron Samuels (CDC-Kenya)</li>\n</ul>\n<p style=\"margin-left: 0.35in;\">\n <strong>Brief background</strong></p>\n<p>\n Double blind, randomized placebo controlled trial of PfSPZ Vaccine, consisting of cryopreserved, radiation-attenuated Plasmodium falciparum (Pf) sporozoites, which when given by direct venous inoculation showed dose-dependent, high level protection against controlled human malaria infection. The trial is divided into Part 1 – age de-escalation and dose escalation involving children between 5 months and 9 years inclusive, and Part 2, a 4-arm placebo controlled safety and efficacy trial in infants 5 to 12 months of age.</p>\n<p style=\"margin-left: 0.35in;\">\n <strong>Progress report</strong></p>\n<p>\n <strong>Overall Primary objective: </strong>Evaluate the safety, tolerability, immunogenicity and efficacy of PfSPZ Vaccine in infants in a high-transmission malaria setting in western Kenya by: 1) conducting and completing placebo controlled age de-escalation and dose escalation phase 2 trial in children and infants of 5 months through 9 years of age inclusive to evaluate safety and tolerability of increasing vaccine doses and to determine the safe doses to be used in the Part 2 safety and efficacy trial in infants; and 2) conducting and completing a placebo-controlled phase 2 trial to evaluate the safety, tolerability, immunogenicity, and efficacy against <em>Plasmodium falciparum </em>(Pf) infection of the three highest doses found to be safe in Part 1</p>\n<p>\n <strong>Primary Objective Part 1: </strong><em>Age de-escalation and dose escalation trial in children and infants (5 months – 9 years): </em>Measure the safety, tolerability and immunogenicity of PfSPZ Vaccine administered at escalating dosages by DVI in older children aged 5–9 years (highest three doses only), younger children aged 13–59 months, and infants 5–12M (at vaccination) at doses of 1.35x10⁵, 2.7x10⁵, 4.5x10⁵, 9.0x10⁵ and 1.8 x 10⁶ PfSPZ Vaccine given as a single dose or, for the two highest doses in two doses at 8 week intervals.</p>\n<ol style=\"list-style-type: lower-alpha;\">\n <li>\n <strong>Status</strong>: Data collection and analysis have been concluded. The CSR report is being finalized by the sponsor Sanaria.</li>\n <li>\n <strong>Major findings/accomplishments</strong>:</li>\n</ol>\n<p style=\"margin-left: 17.85pt;\">\n Find below the findings of Part 1 unblinded.</p>\n<p style=\"margin-left: 17.85pt;\">\n <u>Recruitment: </u>Study start was on 4 July, 2016, recruitment ended in November 2016.</p>\n<p style=\"margin-left: 17.85pt;\">\n Total number of consented participants: 282</p>\n<p style=\"margin-left: 17.85pt;\">\n Total number of enrolled participants:  165</p>\n<p style=\"margin-left: 17.85pt;\">\n Total number of screening failures: 117 participants</p>\n<p style=\"margin-left: 17.85pt;\">\n <u>Vaccinations: </u>156 participants, the target sample size, were successfully vaccinated with either 1 or 2 doses of the PfSPZ Vaccine, according to the dosing schedule. An additional 9 participants received an incomplete intravenous vaccination and were subsequently replaced, but followed up for safety. The last vaccination took place on 13 January 2017.</p>\n<p style=\"margin-left: 17.85pt;\">\n <u>Safety: </u>There were no Grade 3 related adverse events (AEs), laboratory abnormalities, or significant electrocardiogram changes post vaccination. Among participants of all ages, 26.8% of vaccine recipients and 35.8% of placebo recipients experienced a solicited AE that was considered related within seven days of immunization. Related systemic AEs were less common in vaccine recipients (10 of 112, or 8.9%) compared to placebo recipients (8 of 53, or 15.1%), solicited local symptoms at the injection site, primarily mild pain and swelling, occurred in 20.5% of vaccine recipients and 22.6% of placebo recipients. There was no obvious dose or age relationship.  Unsolicited AEs in the 28-day period following each vaccination deemed to be possibly or probably related occurred in nine of 112 (8.0%) vaccine recipients and 1 placebo recipient (1.9%); all were mild, resolved, and occurred within 7 days of vaccine/placebo injection. Three serious AEs were related to incident malaria infection. One severe malarial anemia occurred in a child 44 days after receiving her first dose of 9.0x10⁵ PfSPZ and two children in the 13–59-month-old group, both of whom had received one dose of 1.8x10⁶ PfSPZ Vaccine, experienced simple febrile seizures associated with malaria, one 26 days and the other 4 days after vaccination. One 8-year-old boy who received one injection of normal saline placebo developed an abscess on his finger after a capillary blood draw on vaccination day that was therefore considered related to a study procedure but not the study product. All grade 3 events resolved.</p>\n<p style=\"margin-left: 17.85pt;\">\n We had 4 DSMB (Data Safety and Monitoring Board) meetings, the last two on 05 December 2016 and  on 06 March 2017. On 05 December 2016 it was concluded that there were no safety concerns regarding the use of 4.5x10⁵, 9.0x10⁵ and 1.8 x 10⁶ doses of PfSPZ Vaccine in infants and that Part 2 of the study could start with these doses. On 06 March 2017 the results of second vaccinations at the 2 highest doses in infants were reviewed. As there were no safety concerns, we were allowed to continue Part 2 vaccinations, proceeding to vaccination 2 and later to vaccination 3, in the infants.</p>\n<ol style=\"list-style-type: lower-alpha;\">\n <li value=\"3\">\n <strong>Significance of those findings/accomplishments</strong>:</li>\n</ol>\n<p style=\"margin-left: 0.25in;\">\n Conclusion of Part 1 of the trial resulted in proof of safety and tolerability of PfSPZ Vaccine in the protocol specified dose ranges in infants, which allowed us to proceed into the efficacy trial in infants (Part 2).</p>\n<ol style=\"list-style-type: lower-alpha;\">\n <li value=\"4\">\n <strong>Challenges and lessons learned</strong>:</li>\n</ol>\n<ol>\n <li>\n Study start was delayed by about 3 months due to a delay in getting approval from the regulatory authorities and a clinical hold imposed on the sponsor by the FDA in the US.</li>\n</ol>\n<p style=\"margin-left: 0.5in;\">\n We expected about a rate of 25% screening failures and the final screening failure rate was 41%. About 30% of the screening failures were due to consent withdrawals by fathers before vaccination, and in most cases even before screening. The mothers had consented but when they reached home with the consent, fathers did not want their children to participate in the study, mostly because of the associated blood draws.</p>\n<p>\n <strong>Primary objectives Part 2</strong>:  <em>Safety and efficacy trial in infants (5-12M inclusive) living in an area of high malaria transmission: </em>1. Measure the safety, tolerability and immunogenicity of the highest safe and well tolerated dose of PfSPZ Vaccine administered by DVI in 3 doses to infants 5-12M inclusive of age.  Dosage has been determined to be 4.5x10⁵, 9.0x10⁵ and 1.8 x 10⁶ PfSPZ Vaccine during the age de-escalation and dose escalation trial (Part 1) based on safety and tolerability. 2. Determine whether PfSPZ Vaccine administered by DVI to infants 5-12M inclusive of age at a pre-specified well tolerated dose level provides high-level (point estimate <u>></u> 60%) protection against naturally acquired Pf infection, measured by blood smear microscopy, during 6 months following the last vaccine dose when compared to a control (placebo) group. </p>\n<ol style=\"list-style-type: lower-alpha;\">\n <li>\n <strong>Status: </strong> All primary vaccinations have been given as of 15 AUG2017. Twelve months of follow up for safety, immunogenicity and efficacy have been completed for all participants on 15AUG2018. Data lock occurred on 15OCT2018. Data analysis is ongoing. PCR assays to detect malaria are still ongoing at the KEMRI/CDC laboratories in Kisumu. Specific antibody assays and cell assays for assessment of parasite-specific T cell responses are ongoing at laboratories of our collaborators in the United States. Epstein Barr Virus serological assays are ongoing at the University of Massachusetts. Parasite genotyping is ongoing at the University of Maryland.</li>\n <li>\n <strong>Major findings/accomplishments:</strong></li>\n</ol>\n<p style=\"margin-left: 0.25in;\">\n <u>Recruitment:</u> In December 2016, multiple meetings with members of the communities in Siaya and Wagai (our satellite study clinic) took place. We concentrated on the issues we had encountered during Part 1 of the study and explained the blood draws and the vaccination procedure in detail. Study start for part 2 was on 03 January 2017. Consenting of the last participant took place on 10APR2017, and a total of 548 parents of potential participants were consented. Of these, 212 (38.7%) are confirmed screening failures. A total of 337 participants were enrolled and randomized, although one mother withdrew consent after randomization, leaving 336 participants who were vaccinated.</p>\n<p style=\"margin-left: 0.25in;\">\n <u>Vaccinations:</u>  Vaccinations in part 2 started on 23JAN2017, and the last enrolment (i.e. the last vaccination 1) took place on 13 April 2017.  The last vaccination 3 was given on 15AUG2017.</p>\n<p style=\"margin-left: 0.25in;\">\n <u>Safety:</u> Final unblinded safety evaluations showed no related serious adverse events; unrelated serious adverse events occurred in 38/252 (15.1%) of vaccine participants and in 8/84 (9.5%) of those who had received placebo. One child (placebo recipient) died at home due to bee attack. Grade 3 unsolicited adverse events included simple febrile seizures, considered to be adverse events of special interest which did not fulfil SAE criteria and were reported throughout the study period; at least one febrile seizure was reported in 14/252 (5.6%) of vaccinees compared to 4/84 (4.8%) of placebo recipients. Unsolicited adverse events which were considered possibly or probably related occurred in 15/252 (6%) of vaccine recipients compared to 4/84 (4.8%) of placebo recipients; all were of mild severity. Solicited local adverse events occurred in 11.9% of vaccine recipients and in 16.7% of placebo recipients after a total of 980 vaccinations: 2 participants(0.6%) one a vaccine recipient and the other a placebo recipient had severe swelling at the injection site, and one of those was withdrawn from further vaccination. There was a clear trend that injection site swelling was less common at vaccinations 2 and 3. Overall, 45.6% of vaccine recipients and 45.2% of placebo recipients experienced solicited systemic adverse events like fever, drowsiness, irritability or loss of appetite during the first week post vaccination, but most of these were related to other infections and thus unlikely related to the vaccine. Possibly and probably related solicited systemic reactions were observed in 24/252 (9.5%) of vaccine recipients and in 7/84 (8.3%) of placebo recipients after a total of 980 vaccinations, with one Grade 3 reaction in the placebo group (one spike of fever to 40.1 ⁰Celsius) which was considered possibly related in the absence of another explanation. There was no trend showing that solicited systemic events increased after second or third doses.</p>\n<p style=\"margin-left: 0.25in;\">\n <u>Feasibility:</u> In a total of 980 injections, 95.2% were successful with one needle stick. Children did not cry during 15.8% of injections with vaccine versus 18.2% of injections with placebo.</p>\n<p style=\"margin-left: 0.25in;\">\n <u>Efficacy: </u> The 6 month endpoint of vaccine efficacy (VE) by proportional analysis was 12% by proportional  analysis and 30.1% by survival analysis method in infants who had received 3 doses of 18 x 10⁵PfSPZ. In the 9.0 x 10⁵ PfSPZ group VE was -6.5% by proportional analysis and 3.3% by survival analysis, and in the 4.5 x 10⁵ PfSPZ group proportional analysis showed VE of 0.8% and survival analysis of 13.5%. None of these results were statistically significant. Thus the efficacy needed per protocol to allow for a booster dose was not reached.</p>\n<p style=\"margin-left: 0.25in;\">\n <u>Immunogenicity: </u>The vaccine was immunogenic in all 3 dose groups in terms of circumsporozoite antibody titers 2 weeks after vaccination 3. Those who did not become infected had significantly higher response to PfCSP in the 18x10⁵ and 4.5x10⁵ PfSPZ groups</p>\n<ol style=\"list-style-type: lower-alpha;\">\n <li value=\"3\">\n <strong>Significance of those findings/accomplishments:</strong></li>\n</ol>\n<p style=\"margin-left: 0.25in;\">\n Feasibility of intravenous inoculation by DVI in infants was assessed during all vaccinations. In total, several very experienced injectors managed to vaccinate 95.2% of the infants in Part 2 by 1 direct venous inoculation. This is an improvement compared to Part 1, where only 75% of the infants were vaccinated by 1 single injection. The injector performance improved significantly over time and this finding is important also for other future vaccinations which have to be given to infants via the intravenous route. </p>\n<p style=\"margin-left: 0.25in;\">\n The vaccine was overall safe and well tolerated, but the efficacy did not reach the expected levels while circumsporozoite antibody titers were increased in all dose groups 2 weeks after vaccination 3. Further immunological evaluation and parasite genotyping may provide the answer why the vaccination in infants did not show the same levels of efficacy as in malaria naïve adults. </p>\n<ol style=\"list-style-type: lower-alpha;\">\n <li value=\"4\">\n <strong>Challenges and lessons learned</strong>:</li>\n</ol>\n<p style=\"margin-left: 0.25in;\">\n Recruitment of participants was a challenge. Consent withdrawals before screening contributed in about 50% to the screening failures, mostly by fathers.  The original sample size of 416 participants was not reached, but the previously expected minimum number of 320 participants was exceeded and we enrolled 336 participants. 98.2% of the scheduled follow up visits were completed. We retained 303 children in the study, however only 260 participants remained in the ATP cohort, falling short of our original aim to retain 280 children in the ATP cohort.  46 participants have dropped out of the study for various reasons, including consent withdrawals (14) and migration out of the study area (26).</p>\n<div>\n  </div>\n
      • implication_results
      • quantity_imported136 Vials(450,000 PfSPZ/vial) + 2290 vials(150,000 PfSPZ/vial)
      • quantity_dispensed63 Vials(150,000 PfSPZ/vial) + 2123 vials(450,000 PfSPZ/vial)
      • quantity_destroyedNone
      • quantity_exported73 Vials(150,000 PfSPZ/vial) + 240 vials(450,000 PfSPZ/vial)
      • balance_siteNone
      • final_date0000-00-00
      • modified2025-01-28 11:57:45
      • created2015-10-22 10:52:37
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id291
        • application_id436
        • given_nameMartina
        • middle_name
        • family_nameOneko
        • qualificationMD
        • professional_addressKEMRI Center for Global Health Research, P.O.Box 1578-40100, Kisumu, Kenya
        • telephone+254 717 747279
        • emailmoneko@kemricdc.org
        • created2015-10-22 10:58:47
        • modified2020-12-15 14:25:12
      • 1(array)
        • id292
        • application_id436
        • given_nameMary
        • middle_nameJ
        • family_nameHamel
        • qualificationMD
        • professional_addressCenters for Disease Control and Prevention, Atlanta, GA, USA
        • telephone+ 1 404 3886811
        • emailmlh8@cdc.gov
        • created2015-10-22 11:05:01
        • modified2020-12-15 14:25:12
    • SiteDetail(array)
      • 0(array)
        • id349
        • application_id436
        • county_id41
        • site_nameSiaya County Referral Hospital
        • physical_addressSiaya Town
        • contact_details+254 717 747279
        • contact_personDr Martina Oneko
        • site_capacity(null)
        • misc(null)
        • created2015-10-22 10:58:47
        • modified2020-12-15 14:25:12
        • County(array)
          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
      • 1(array)
        • id358
        • application_id436
        • county_id41
        • site_nameWagai Health Center
        • physical_addressWagai Market
        • contact_details+254 717 747279
        • contact_personDr Martina Oneko
        • site_capacity(null)
        • misc(null)
        • created2015-11-06 11:39:05
        • modified2020-12-15 14:25:12
        • County(array)
          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
    • Sponsor(array)
      • 0(array)
        • id227
        • application_id436
        • sponsorSanaria
        • sponsor_typeIndustry
        • contact_personStephen L. Hoffman
        • address9800 Medical Center Dr A209, Rockville, MD 20850, United States
        • telephone_number+1 301-770-3222
        • fax_number
        • cell_number+1 301-770-3222
        • email_addresssanaria@sanaria.com
        • created2015-10-22 10:58:47
        • modified2020-12-15 14:25:12
  • 1(array)
    • Application(array)
      • id814
      • user_id81
      • trial_status_id3
      • abstract_of_study<p>\n In the era of anti-malaria drug resistance and resistance to insecticide treated bed nets, there is an urgent need for a highly efficacious vaccine. We plan to evaluate the immunogenicity and efficacy of candidate malaria vaccines incorporating the sporozoite antigen R21 (<em>P. falciparum</em> circumsporozoite protein co-expressed with hepatitis B antigen) administered as protein-in-adjvuvant with the Matrix M and viral-vectored vaccines expressing the liver antigen TRAP (<em>P. falciparum</em> multiple epitope thrombospondin adhesion protein, ME-TRAP expressed in Chimpanzee Adenovirus 63 and Modified Vaccinia Ankara administered in a heterologous prime-boost regimen). There is evidence of safety and immunogenicity utilising these two vaccines. We plan to conduct a phase IIb trial in malaria-exposed individuals to assess the immunogenicity and efficacy of the two vaccines in the context of controlled human malaria infection<em>. P. falciparum</em> sporozoite challenge, PfSPZ Challenge.</p>\n<p>\n Healthy adults aged between 18-45 years will be recruited to participate in the study after a process of information giving and sensitisation about the study. Those that provide informed consent to participate in the study will be screened to ensure they are in good health based on clinical assessment and laboratory results. Each participant will have blood tests undertaken, and physical and clinical examination to ensure suitability prior to vaccination and PfSPZ Challenge. A total of 64 participants will be enrolled for challenge and divided into four groups as follows: 20 participants to receive R21/Matrix M (R21/MM) with intradermal PfSPZ Challenge; 20 participants to receive viral-vectored ME-TRAP with intradermal PfSPZ Challenge; 10 participants to receive R21/MM with direct venous inoculation PfSPZ Challenge; and 14 participants comprising of the control group with intradermal PfSPZ Challenge. Blood tests and clinical assessments will be conducted to screen out participants with health conditions that may impact participation in the study.</p>\n<p>\n Blood samples will be taken at screening and a day prior to vaccine and PfSPZ Challenge enrolment. Blood will also be taken prior to each vaccination as well as after PfSPZ Challenge administration until diagnosis with malaria, endpoint. A set threshold for malaria diagnosis will be met and once this is achieved, participants will be treated with the recommended anti-malaria drug treatment. Blood samples to assess immunogenicity will be taken prior to vaccination, and throughout the study to assess vaccine-induced immune responses. Efficacy will be assessed in relation to the control group with serial quantitative polymerase chain reaction (PCR) monitoring of parasitaemia during PfSPZ Challenge. A day before PfSPZ Challenge, participants will be enrolled residents at Pwani University where they will be monitored daily up to a period of 25 days depending on when they are diagnosed with malaria. There will be follow-up after exit from residence for up to 90 days after PfSPZ Challenge.</p>\n
      • study_title<p>\n Safety, immunogenicity, and efficacy of R21/Matrix M (R21/MM) and ChAd63/MVA-ME-TRAP in the context of controlled human malaria infection: A Phase IIb Trial in Kenyan Adults.</p>\n
      • laymans_summary<div>\n Lay Title: A study to determine if candidate malaria vaccines are safe, effective, and induce immunity among Kenyan adults.</div>\n<div>\n What is the problem/background? Malaria deaths have fallen with the advent of new drug combinations and widespread use of insecticide treated bed nets, but the hope of malaria eradication is threatened by emerging resistance to these drugs and insecticides. RTS,S, is the only malaria vaccine in advanced clinical development albeit with low efficacy. It is being evaluated for use in an infant vaccine schedule recommended by WHO, while determining the significance of any safety concerns. However, with RTS,S only a small proportion of the vaccine is made up of the malaria parasite protein. We have developed a malaria vaccine candidate, R21, which is also based on the same protein in RTS,S. The majority of RTS,S is composed of the Hepatitis B surface protein which may interfere with the immune response in infants; whereas R21 has very little of this protein on its surface. R21 also induces a good immune response and there is a good case for further clinical development of this vaccine.</div>\n<div>\n What questions are we trying to answer? We plan to evaluate whether the malaria vaccine candidates R21 administered with Matrix M (MM) and ChAd63/MVA-ME-TRAP, are safe and effective in a Controlled Human Malaria Infection (CHMI) and induce good vaccine responses in healthy Kenyan adults (aged 18-45 years). We plan to investigate the immune responses following vaccination and CHMI.</div>\n<div>\n Where is the study taking place, how many people does it involve and how are they selected? The study is taking place in Kilifi County (Ngerenya) as well as at KEMRI-CGMRC where we will recruit and screen healthy adult volunteers. A total number of 64 eligible volunteers will be required after assessment of eligibility at the screening visit to be enrolled for the vaccine efficacy study. This will be done after a programme of sensitization and information giving about the study.</div>\n<div>\n What does the study involve for those who are in it? The following procedures are involved for those who volunteer to participate in the study. Blood samples will be taken at screening, a day prior to vaccine enrolment, prior to each vaccination, and post vaccination, a day before malaria infection, during infection and after infection treatment.</div>\n<div>\n Screening Procedures: For individuals who are screened for potential participation, 8ml of blood will be drawn at the screening visit for serology; haematology; biochemistry and malaria testing. Medical history will also be obtained and a clinical assessment including a check of the functioning of the heart to exclude any significant heart problems. Those that pass screening will be invited to attend a pre-enrolment visit. At the enrolment visit, all eligible volunteers will be re-assessed and a blood sample of 37ml taken for haematology, biochemistry, malaria testing, and immunology.</div>\n<div>\n Vaccine Enrolment and Vaccination Procedures: On the day of enrolment, a total of 64 eligible volunteers will be randomised into one of 4 groups as follows: group 1, receiving R21/MM (N=20); group 2 receiving ChAd63/MVA-ME-TRAP (N=20); group 3, receiving R21/Matrix M (N=10); and group 4 receiving no vaccine (control group). The R21/MM vaccine will be administered as a three-dose regimen at intervals of 28 days (days 0, 28 and 56) whilst the ChAd63/MVA-ME-TRAP will be administered as a prime-boost regimen at days 0 and 56. At each vaccination visit (except for day 0), a blood sample of 33ml will be taken from each of the volunteers. All volunteers in the vaccination groups (groups 1 to 3). Two weeks after each vaccine administration, a blood sample will be taken from each volunteer (30ml or 34ml after the final vaccination). Repeat blood samples may be taken to verify abnormal results. If volunteers are found to have malaria 2 weeks after the final vaccination (day 70), they will be given anti-malarial monotherapy and a blood sample taken post-treatment to test for malaria (4ml). A blood sample from the volunteers in the control group will also be collected at (day 70) for the purposes of checking for malaria and treatment initiated if found positive with a post-treatment sample taken to ensure malaria infection has been cleared.</div>\n<div>\n Malaria Infection Procedures: A clinical assessment will be repeated a day before infection including collection of a urine sample and measurement of weight and height. At this visit, volunteers will be enrolled as residents at Pwani University under medical supervision for up to 25days depending on when they are diagnosed with malaria. This will also include volunteers from the control group who did not go through the vaccination procedures (group 4, N=14). The malaria infection will be given either via the intradermal route-into the skin (groups 1, 2, and 4) or via direct venous injection (into the blood stream) (group 3) of PfSPZ Challenge, which leads to a blood-stage malaria infection after 6.5 days of incubation in the liver. Blood samples will also be taken: a day before the malaria infection (57mls); day five after infection (32mls); twice daily every day from day seven after infection up to the time that signs and symptoms of malaria are detected and malaria treatment initiated and completed (usually between seven to twenty-four days, 238ml); and on days thirty-five and ninety after infection (35ml at each of these time points). A total of 308ml of blood per volunteer will be drawn during this period. Observed treatment for malaria will be administered on the day of diagnosis or after twenty-one days for those who do not develop an infection.</div>\n<div>\n What are the benefits and risks/costs of the study for those involved? Participants may benefit from receipt of the vaccine if it demonstrates that the efficacy in a Kenyan population is favourable and the vaccine is safe. Participants will also have close oversight and treatment support from the study team although this will primarily be for risk monitoring. There will also be wider benefit in the field of malaria vaccine research in building on data available on safety, efficacy and immune responses to R21/MM and ChAd63/MVA ME-TRAP. Controlled human malaria infection challenge via the intradermal route and direct venous injection has been conducted in seventy-eight and one hundred and eighty-four individuals respectively and has been safe and well-tolerated. The first ever controlled malaria infection study in Kenya by intramuscular injection was safely conducted in Nairobi with twenty-eight individuals. We have since conducted a controlled malaria infection study in Kenya by direct venous injection in another one hundred and sixty-one individuals in Kilifi. The risks relate to the possibility of developing an allergic reaction upon administration of the malaria infection. In addition, participants may develop signs and symptoms of malaria after infection which are unpleasant and may develop some side effects to the drugs used to treat the infection. During malaria infection, volunteers are required to be resident in a guest-house for safety monitoring and reduce the risk of acquiring field malaria infections. This is a considerable cost to the volunteers on their time but is a requirement for the study to be successful. There are no direct benefits to individuals participating in this study other than information about their health. There might be a perception of benefit from receipt of a vaccine, clinical assessment and laboratory screening.</div>\n<div>\n How will the study benefit society? Controlled human malaria infection provides a way of studying immunity to malaria in a very detailed way that is not possible using natural infections, and we believe that this step is now necessary to inform vaccine design. This study will also evaluate promising malaria vaccine candidates, which will inform the design of a phase III study, contribute further to the area of malaria research and hopefully provide a possible tool to contribute to future eradication.</div>\n<div>\n When does the study start and finish? </div>\n<div>\n The study will start upon receipt of ethical and regulatory approval; data collection, analysis and write up will take place over 2 years.</div>\n
      • short_titleA study to determine if candidate malaria vaccines are safe, effective, and induce immunity among Kenyan adults.
      • protocol_noECCT/19/11/01
      • version_noVersion 1.1
      • date_of_protocol17-05-2019
      • study_drugR21/MM, ChAd/MVA-ME-TRAP PfSPZ Challenge
      • disease_conditionMalaria
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines1
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressregulatory@kemri-wellcome.org
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries0
      • applicant_addendum0
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantMelissa Kapulu
      • declaration_date104-11-2019
      • declaration_principal_investigatorMelissa Kapulu
      • declaration_date204-11-2019
      • placebo_presentNo
      • study_objectives<div>\n 2.2. Primary objective(s)</div>\n<div>\n 1. To assess the safety and tolerability of adjuvanted R21/MM and heterologous prime- boost regime of ChAd63-MVA ME-TRAP in healthy adult volunteers.</div>\n<div>\n 2. To assess the safety of intradermal sporozoite infection dose in semi-immune healthy adult volunteers.</div>\n<div>\n 3. To assess the efficacy (occurrence of P. falciparum parasitemia, (assessed by qPCR) of adjuvanted R21 and heterologous prime- boost regime of ChAd63-MVA ME-TRAP against malaria sporozoite challenge, in healthy adult volunteers.</div>\n<div>\n <div>\n 2.3. Secondary objective(s)</div>\n <div>\n 1. To assess humoral immunogenicity generated in individuals of adjuvanted R21(R21/MM) and heterologous prime-boost regime of ChAd63-MVA ME-TRAP at different time points.</div>\n <div>\n 2. To assess cell-mediated immunogenicity by IFN-Æ´ ELISPOT generated in individuals of heterologous prime-boost regime of ChAd63-MVA ME-TRAP at different time points.</div>\n <div>\n 3. To assess any differences in efficacy estimates with ID versus DVI challenge in individuals receiving R21/MM by assessing parasite density dynamics by qPCR.</div>\n <div>\n 4. To measure and compare the parasite growth rates and liver to blood inoculum in individuals receiving DVI versus ID sporozoite challenge in relation to naturally acquired immunity.</div>\n <div>\n 2.4. Tertiary objective(s)</div>\n <div>\n To evaluate cell-mediated immunogenicity using flow cytometry with intracellular cytokine staining and other exploratory immunological end points.</div>\n</div>\n<p>\n  </p>\n
      • principal_inclusion_criteria<p>\n • Healthy adults aged 18 to 45 years</p>\n<p>\n • Able and willing (in the Investigator’s opinion) to comply with all study requirements</p>\n<p>\n • Non-pregnant, non-lactating adult female or adult male</p>\n<p>\n • Agreement to refrain from blood donation during the study</p>\n<p>\n • Use of effective method of contraception for the duration of study for female participants. For those with no contraception, they will be referred for contraception at the relevant health facility. For female participants, we will ask them to attend with their family planning records for verification. Effective contraception is defined as a contraceptive method with failure rate of less than 1% per year when used consistently and correctly, in accordance with the product label. Examples of these include: combined oral contraceptives; injectable progestogen; implants of etenogestrel or levonorgestrel; intrauterine device or intrauterine system; male condom combined with a vaginal spermicide (foam, gel, film, cream or suppository); and male condom combined with a female diaphragm, either with or without a vaginal spermicide (foam, gel, film, cream, or suppository)</p>\n<p>\n • Provide written informed consent</p>\n<p>\n • Plan to remain resident in the study area for 1 year following first dose of vaccination</p>\n
      • principal_exclusion_criteria<p>\n • Clinically significant congenital abnormalities as judged by the study clinicians</p>\n<p>\n • Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed).</p>\n<p>\n • Sickle cell disease</p>\n<p>\n • Any history of anaphylaxis in relation to vaccination</p>\n<p>\n • Clinically significant laboratory abnormality as judged by the study clinician</p>\n<p>\n • Blood transfusion within one month of enrolment</p>\n<p>\n • Haemoglobin less than 11.3 g/dl for men and less than 10g/dl for in women, where judged to be clinically significant in the opinion of the investigator.</p>\n<p>\n • Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate</p>\n<p>\n • Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period
</p>\n<p>\n • Seropositive for hepatitis B surface antigen (HBsAg) or hepatitis C (HCV IgG)</p>\n<p>\n • Use of systemic antibiotics with known antimalarial activity within 30 days of administration of PfSPZ Challenge (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones and azithromycin)</p>\n<p>\n • Women only; pregnancy, or an intention to become pregnant a day before challenge i.e. at C-1</p>\n<p>\n • Any significant disease, disorder or situation which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant’s ability to participate in the trial</p>\n<p>\n • Confirmed parasite positive by PCR a day before challenge i.e. at C-1.</p>\n<p>\n • Exclusion criteria on day of challenge Acute disease, defined as moderate or severe illness with or without fever (temperature >37.5°C)</p>\n
      • primary_end_points<p>\n Safety:</p>\n<p>\n The specific endpoints for safety and reactogenicity will be actively and passively collected data on adverse events. The following parameters will be assessed for all study groups</p>\n<p>\n 1. Occurrence of solicited local reactogenicity signs and symptoms for 7 days following the vaccination</p>\n<p>\n 2. Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following the vaccination and occurrence of unsolicited adverse events for 28 days following the vaccination</p>\n<p>\n 3. Change from baseline for safety laboratory measures</p>\n<p>\n 4. Occurrence of serious adverse events during the whole study duration including safety with regards to PfSPZ Challenge administration.</p>\n<p>\n Efficacy:</p>\n<p>\n Venous blood samples will be taken at each study visit during the post-CHMI follow-up period as described above for quantitative PCR (qPCR) for P. falciparum nucleic acids which will be processed within 6 hours of collection. A diagnosis of malaria infection will be made and treatment with anti-malarials commenced immediately for a volunteer satisfying one of the following criteria:</p>\n<p>\n 1. The density of infection rises past a threshold of 500 parasites per µl</p>\n<p>\n 2. The volunteer develops symptoms or signs of illness and an immediate blood film examination shows any evidence of detectable malaria parasites</p>\n<p>\n 3. The volunteer reaches day 21 of monitoring, at which point CHMI will be completed The investigators are able to treat any volunteer for malaria regardless of the qPCR result if they are clinically concerned (and have discussed the case with the Chief Investigator), or a volunteer wishes to withdraw from the study.</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory1
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n Medical officer-1<br />\n Clinical officer - 3<br />\n Nurses -2<br />\n Fieldworkers - 6<br />\n Assistant Research Officer - 1 and Research Officer - 1<br />\n Study Coordinator -1<br />\n Pharmacisit-1<br />\n Data Manager-1<br />\n Data Clerk-2<br />\n The inpatient facility is already staffed with 3 clincians, 1 paediatrician and 20 nurses.<br />\n All staff are trained in basic life support and resuscitation facilitaties are available</p>\n
      • other_details_explanation<p>\n Not Applicable</p>\n
      • other_details_regulatory_notapproved<p>\n Not applicable with only PPB providing regulatory oversight and approval.</p>\n
      • other_details_regulatory_approved<p>\n Not applicable.</p>\n
      • other_details_regulatory_rejected<p>\n Not applicable.</p>\n
      • other_details_regulatory_halted<p>\n Not applicable.</p>\n
      • estimated_duration2 years
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorChAd63/MVA-ME-TRAP and no
      • design_controlled_other_medicinalYes
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKEMRI-Wellcome Trust Research Programme (KWTRP) Centre for Geographic Medical Research - Coast (CGMRC), Kilifi, Kenya.
      • single_site_physical_addressKEMRI-Wellcome Trust Research Programme, Off Bofa Road, Kilifi County Hospital, Kilifi, Kenya
      • single_site_contact_personMelissa Kapulu
      • single_site_telephone+254717501319
      • multiple_sites_member_stateNo
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites
      • multi_country_list
      • data_monitoring_committeeYes
      • total_enrolment_per_site64
      • total_participants_worldwide64
      • 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_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_nameMelissa
      • investigator1_middle_nameChola
      • investigator1_family_nameKapulu
      • investigator1_qualificationBSc MSc DPhil
      • investigator1_professional_addressKEMRI-Wellcome Trust Research Programme, P. O. Box 230, Kilifi, Kenya 80108
      • investigator1_telephone+254709983463
      • investigator1_emailmkapulu@kemri-wellcome.org
      • organisations_transferred_No
      • number_participants64
      • notification
      • approval_date07-08-2021
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted15-12-2021
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonApplication approved by the experts
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2024-08-02 17:52:27
      • created2019-07-17 16:47:36
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id504
        • application_id814
        • given_nameMelissa
        • middle_name
        • family_nameKapulu
        • qualificationBSc MSc DPhil
        • professional_addressKEMRI-Wellcome Trust Research Programme, P. O. Box 230, Kilifi, Kenya 80108
        • telephone+254709983463
        • emailmkapulu@kemri-wellcome.org
        • created2019-07-17 16:51:47
        • modified2021-12-15 04:41:06
    • SiteDetail(array)
      • 0(array)
        • id663
        • application_id814
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2019-07-17 16:51:47
        • modified2021-12-15 04:41:06
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id394
        • application_id814
        • sponsorUniversity of Oxford
        • sponsor_typeResearch Institution
        • contact_personAdrian Hill (Chief Invetigator)
        • addressUniversity Offices, Wellington Square, Oxford, OX1 2JD, UK
        • telephone_number+44 (0)1865 611418
        • fax_number
        • cell_number+44 (0)1865 611418
        • email_addressadrian.hill@ndm.ox.ac.uk
        • created2019-07-17 16:51:47
        • modified2021-12-15 04:41:06
  • 2(array)
    • Application(array)
      • id425
      • user_id613
      • trial_status_id7
      • abstract_of_study<p>\n The Human Immunodeficiency Virus (HIV) epidemic presents the most serious infectious<br />\n disease threat worldwide. The global incidence of new human immunodeficiency virus (HIV)<br />\n infections peaked in the mid-1990s, and a reduction in this incidence has been observed. In 2012<br />\n there were 2.3 million new cases, down from 3.4 million in 2001. The reduction of HIV<br />\n incidence is due to multiple factors that include prevention and treatment programs. The wider<br />\n availability of antiretroviral therapy (ART), prevention of mother-to-child transmission<br />\n programs, and a diverse array of other interventions have all contributed to turning the tide of the<br />\n epidemic. Long-term use of antiretroviral therapy (ART) in HIV-positive persons may be<br />\n challenged by the need for high-level life long adherence to a daily regimen, development of<br />\n drug resistance and cross-resistance, short and long-term toxicities, and cost. Administration of<br />\n broadly neutralizing monoclonal antibodies has the potential to treat HIV infection by preventing<br />\n viral spread, by facilitating clearance of virus particles and mediating destruction of virusproducing<br />\n cells. This may decrease the viral reservoir and limit chronic immune activation. This<br />\n is a multi-centre, double-blinded, placebo-controlled study of the safety and impact of broadly<br />\n neutralizing monoclonal antibody therapy with VRC01 on viremia in acute HIV infection, alone<br />\n or in combination with antiretroviral therapy (ART). A total of twenty four participants will be<br />\n enrolled, with Kericho site enrolling about six participants. Participants will be randomized to<br />\n three groups; 1, 2 and 3. Group 1 will receive immediate ART only (n=8), Group 2 will receive<br />\n immediate ART and mAb therapy (n=8) and Group 3 will receive immediate mAb therapy and<br />\n subsequent ART from day 7 (n=8). Other sites participating include Uganda, Tanzania and<br />\n Thailand. Participants from the RV217 High Risk Cohort study who become acutely infected<br />\n with HIV will be screened and enrolled into this study. The study duration is 25 weeks. Results<br />\n obtained from this study may inform considerations for the development of broadly neutralizing<br />\n monoclonal antibodies for use in therapeutic settings.</p>\n
      • study_title<p>\n Safety  and  Virologic Effect  Of  A  Human   Monoclonal   Antibody,   VRC-HIVmAb060-00-Ab  (VRCOl),   With Broad  HIV-1  Neutralizing Activity, Administered Intravenously to Adults  During Early Acute HIV Infection.</p>\n
      • laymans_summary<div>\n The Human Immunodeficiency Virus (HIV) epidemic presents the most serious infectious</div>\n<div>\n disease threat worldwide. The global incidence of new human immunodeficiency virus (HIV)</div>\n<div>\n infections peaked in the mid-1990s, and a reduction in this incidence has been observed. In 2012</div>\n<div>\n there were 2.3 million new cases, down from 3.4 million in 2001. The reduction of HIV</div>\n<div>\n incidence is due to multiple factors that include prevention and treatment programs. The wider</div>\n<div>\n availability of antiretroviral therapy (ART), prevention of mother-to-child transmission</div>\n<div>\n programs, and a diverse array of other interventions have all contributed to turning the tide of the</div>\n<div>\n epidemic. Long-term use of antiretroviral therapy (ART) in HIV-positive persons may be</div>\n<div>\n challenged by the need for high-level life long adherence to a daily regimen, development of</div>\n<div>\n drug resistance and cross-resistance, short and long-term toxicities, and cost. Administration of</div>\n<div>\n broadly neutralizing monoclonal antibodies has the potential to treat HIV infection by preventing</div>\n<div>\n viral spread, by facilitating clearance of virus particles and mediating destruction of virusproducing</div>\n<div>\n cells. This may decrease the viral reservoir and limit chronic immune activation. This</div>\n<div>\n is a multi-centre, double-blinded, placebo-controlled study of the safety and impact of broadly</div>\n<div>\n neutralizing monoclonal antibody therapy with VRC01 on viremia in acute HIV infection, alone</div>\n<div>\n or in combination with antiretroviral therapy (ART). A total of twenty four participants will be</div>\n<div>\n enrolled, with Kericho site enrolling about six participants. Participants will be randomized to</div>\n<div>\n three groups; 1, 2 and 3. Group 1 will receive immediate ART only (n=8), Group 2 will receive</div>\n<div>\n immediate ART and mAb therapy (n=8) and Group 3 will receive immediate mAb therapy and</div>\n<div>\n subsequent ART from day 7 (n=8). Other sites participating include Uganda, Tanzania and</div>\n<div>\n Thailand. Participants from the RV217 High Risk Cohort study who become acutely infected</div>\n<div>\n with HIV will be screened and enrolled into this study. The study duration is 25 weeks. Results</div>\n<div>\n obtained from this study may inform considerations for the development of broadly neutralizing</div>\n<div>\n monoclonal antibodies for use in therapeutic settings.</div>\n
      • short_titleVRC01 Monoclonal HIV Antibodies Study
      • protocol_noECCT/15/10/01
      • version_no2.0
      • date_of_protocol29-04-2015
      • study_drugVRC01 Monoclonal Antibodies
      • disease_conditionHIV
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals1
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorYes
      • comparator_nameNormal Saline
      • comparator_registeredYes
      • comparator_countriesKenya
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressjosphat.kosgei@usamru-k.org
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries1
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd0
      • applicant_prev_data0
      • applicant_stability_data0
      • applicant_analysis_cert0
      • applicant_pictorial_sample0
      • applicant_gcp_training0
      • applicant_dsmb_charter0
      • applicant_detailed_budget0
      • applicant_indemnity_pi0
      • applicant_practice_license0
      • applicant_registration_ctr(null)
      • applicant_pan_african0
      • applicant_hard_copies(null)
      • applicant_signed_checklist0
      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantDr josphat Kosgei
      • declaration_date108-10-2015
      • declaration_principal_investigatorDr Josphat Kosgei
      • declaration_date208-10-2015
      • placebo_presentYes
      • study_objectives<div>\n PRIMARY OBJECTIVES</div>\n<div>\n 1. Safety of VRC01 in acutely HIV-infected viremic individuals</div>\n<div>\n 2. Impact of VRC01 on plasma viremia in each mAb arm compared to the ART plus</div>\n<div>\n placebo control at day 7 (+/- 1 day)</div>\n<div>\n 3.2 SECONDARY OBJECTIVES</div>\n<div>\n 1. Impact of VRC01 on viral dynamics in plasma over the course of 24 weeks.</div>\n<div>\n 2. Impact of VRC01 on HIV reservoir measures in peripheral blood mononuclear cells and</div>\n<div>\n plasma</div>\n<div>\n 3. Impact of VRC01 on clinical outcomes/characteristics of AHI</div>\n<div>\n 4. Impact of VRC01 on CD4 + T cell count</div>\n<div>\n 5. Pharmacokinetics of VRC01 in AHI in peripheral blood</div>\n<div>\n 3.3 EXPLORATORY OBJECTIVES</div>\n<div>\n 1. Impact of VRC01 on reservoir measures in CSF, mucosal, and tissue compartments</div>\n<div>\n 2. Comparison of peripheral blood reservoir measures to those in the CSF, mucosal and</div>\n<div>\n tissue compartments</div>\n<div>\n 3. Impact of VRC01 on reservoir measures in T cell subsets</div>\n<div>\n 4. Pharmacokinetics of VRC01 in CSF and mucosal compartments</div>\n<div>\n 5. Anti-VRC01 antibody detection</div>\n<div>\n 6. Impact of VRC01 on immune responses and activation</div>\n<div>\n 7. Effect of VRC01 on viral sequence, phenotype, and evolution</div>\n<div>\n 8. Predictors of favorable viral dynamics, immune responses, and reservoir seeding</div>\n<div>\n 9. Impact of VRC01 on neuropsychological testing outcomes</div>\n
      • principal_inclusion_criteria<p>\n 1. Able and willing to complete the informed consent process.<br />\n 2. Passes Test of Understanding<br />\n 0 20 40 60 80 100<br />\n 0<br />\n 2<br />\n 4<br />\n 6<br />\n 8<br />\n 10<br />\n Days From First RNA Positive<br />\n VL (log10 cps/ml)<br />\n days to Nadir<br />\n day to EIA<br />\n days to peak<br />\n 42<br />\n 15<br />\n 13<br />\n 4.2<br />\n 6.7<br />\n RV 398/WRAIR 2166 Version 2.0<br />\n 29 April 2015<br />\n Page 26 of 79<br />\n 3. 18 to 50 years of age.<br />\n 4. Experiencing early acute HIV-1 infection as defined by blood samples on at least two<br />\n separate days positive by nucleic acid testing within 21 days of a negative nucleic acid<br />\n HIV-1 test.<br />\n 5. No history of antiretroviral therapy for any indication<br />\n 6. In general good health<br />\n 7. Willing to have blood samples collected and stored.<br />\n 8. Able to participate for 25 weeks for study visits<br />\n 9. Willing to have photo or fingerprint taken for identification purposes<br />\n Female-specific Criteria:<br />\n 10. Agrees not to become pregnant from the time of study enrollment until the last study<br />\n visit. If a woman has no history of hysterectomy, tubal ligation or menopause, she must<br />\n agree to use an effective birth control method: abstinence; male or female condoms;<br />\n diaphragm or cervical cap with spermicide; intrauterine device; contraceptive hormones<br />\n delivered by pills, patch, injections, or vaginally; and hormonal implants under the skin;<br />\n or a male partner who has previously undergone a vasectomy.<br />\n 11. Negative β-HCG (human chorionic gonadotropin) pregnancy test (urine or serum) on day<br />\n of enrollment for any woman unless she is post-menopause for 24 consecutive months or<br />\n has undergone a surgical procedure that precludes pregnancy.</p>\n
      • principal_exclusion_criteria<p>\n Exclusion Criteria<br />\n 1. Weight < 46 kg or >115kg<br />\n 2. Previous receipt of humanized or human monoclonal antibody whether licensed or<br />\n investigational.<br />\n 3. Ongoing AIDS-related opportunistic infection (including oral thrush or active<br />\n tuberculosis).<br />\n 4. Severe acute retroviral syndrome (as defined in Appendix 1) or other clinical condition<br />\n constituting an indication for immediate antiretroviral therapy per local country<br />\n guidelines.<br />\n 5. Active injection drug use within previous 12 months.<br />\n 6. History of a severe allergic reaction with generalized urticaria, angioedema or<br />\n anaphylaxis in the 2 years prior to enrollment.<br />\n 7. History of chronic urticaria<br />\n 8. Physical finding on examination considered indicative of significant disease such as<br />\n murmur (other than functional), hepatosplenomegaly, focal neurological deficit.<br />\n 9. Hypertension that is not well controlled by medication.<br />\n 10. Positive Hepatitis B surface antigen at any time in the past<br />\n RV 398/WRAIR 2166 Version 2.0<br />\n 29 April 2015<br />\n Page 27 of 79<br />\n 11. History of hepatitis C infection<br />\n 12. Untreated syphilis infection<br />\n 13. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2x the upper<br />\n limit of normal (ULN).<br />\n 14. Absolute neutrophil count (ANC) <740 cells/mm3<br />\n 15. Estimated GFR < 50 ml/min within the past 90 days<br />\n 16. Breast-feeding.<br />\n 17. Pregnancy<br />\n 18. Receipt of licensed vaccine or other investigational study agent within 28 days prior to<br />\n enrollment or past participation in an investigational HIV vaccine study with receipt of<br />\n active product.<br />\n 19. Current or planned participation in another interventional clinical trial during the study<br />\n period.<br />\n 20. Chronic or recurrent use of medications that modify host immune response, e.g., oral or<br />\n parenteral steroids, cancer chemotherapy.<br />\n 21. Any other chronic or clinically significant medical condition that in the opinion of<br />\n investigator would jeopardize the safety or rights of the volunteer. Including, but not<br />\n limited to: diabetes mellitus type I, chronic hepatitis, renal failure; OR clinically<br />\n significant forms of: drug or alcohol abuse, mental illness, severe asthma, autoimmune<br />\n disease, psychiatric disorders, heart disease, or cancer.<br />\n 22. Study site employee</p>\n
      • primary_end_points<p>\n 1. Safety: mAb related - grade 3 or greater reactogenicity and product related AEs<br />\n <br />\n 2. Log change in plasma viral load from day 0 to day 7</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology1
      • trial_administration_humans1
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n Site Principal Investigator<br />\n Josphat Kosgei,<br />\n MBChB, MSc<br />\n Kenya Medical Research Institute/Walter Reed Project HIV Program<br />\n Hospital Road, P.O. Box 1357, Kericho, 20200; Kenya<br />\n Office: (254-52) 30686, 30388, Fax: (254-52) 30546<br />\n Mobile phone: 254-729-110122, E-mail: josphat.kosgei@usamru-­â€k.org<br />\n Study Coordinator<br />\n Elizabeth Ngetich,<br />\n BSN<br />\n Kenya Medical Research Institute/Walter Reed Project HIV Program<br />\n Hospital Road, P.O. Box 1357, Kericho, 20200; Kenya<br />\n Office: (254-52) 30686, 30388, Fax: (254-52) 30546<br />\n E-mail: elizabeth.ngetich@usamru-­â€k.org<br />\n Associate Investigators<br />\n Fredrick Sawe,<br />\n MBChB, MMed.<br />\n Senior Deputy Director,<br />\n Kenya Medical Research Institute/Walter Reed Project HIV Program<br />\n Hospital Road, P.O. Box 1357, Kericho, 20200; Kenya<br />\n Office: (254-52) 30686, 30388, Fax: (254-52) 30546<br />\n Mobile phone: 254-724-255-623, E-mail: fredrick.sawe@usamru-­â€k.org<br />\n Samuel Sinei,<br />\n MBChB, MMed<br />\n Program Director<br />\n Kenya Medical Research Institute/Walter Reed Project HIV Program<br />\n Hospital Road, P.O. Box 1357, Kericho, 20200; Kenya<br />\n Office: (254-52) 30686, 30388, Fax: (254-52) 30546<br />\n Mobile phone: 254-727-531-396, E-mail: samuel.sinei@usamru-­â€k.org<br />\n Deborah Chepng’eno<br />\n Langat, MBChB,<br />\n MSc<br />\n Kenya Medical Research Institute/Walter Reed Project HIV Program<br />\n Hospital Road, P.O. Box 1357, Kericho, 20200; Kenya<br />\n Office: (254-52) 30686, 30388, Fax: (254-52) 30546<br />\n E-mail: Deborah.langat@usamru-­â€k.org<br />\n RV 398b/WRAIR 2166b Page 2 of 4 Version 2.0<br />\n Protocol Team Roster 08 June 2015<br />\n Lucy C. Koech,<br />\n MBChB<br />\n Kenya Medical Research Institute/Walter Reed Project HIV Program<br />\n Pharmacy Head, &Hospital Road, P.O. Box 1357, Kericho, 20200;<br />\n Kenya<br />\n Office: (254-52) 30686, 30388, Fax: (254-52) 30546<br />\n Mobile phone: 254-726-290103, E-mail: lucy.koech@usamru-­â€k.org<br />\n Faith Riziki, B.<br />\n Pharm, MSc<br />\n Pharmacist of Record<br />\n Kenya Medical Research Institute/Walter Reed Project HIV Program<br />\n Pharmacy Head, &Hospital Road, P.O. Box 1357, Kericho, 20200;<br />\n Kenya<br />\n Office: (254-52) 30686, 30388, Fax: (254-52) 30546<br />\n Mobile phone: 254-726-290103, E-mail: Faith.Riziki@usamru-­â€k.org<br />\n Joseph Oundo, MSc,<br />\n PhD<br />\n Laboratory Director,<br />\n Kenya Medical Research Institute/Walter Reed Project HIV Program<br />\n Clinical Research Center Laboratory.<br />\n Hospital Road, P.O. Box 1357, Kericho, 20200; Kenya<br />\n Office: (254-52) 30686, 30388, Fax: (254-52) 30546<br />\n E-mail: joseph.oundo@usamru-­â€k.org<br />\n Ignatius Kiptoo, BSc,<br />\n MSc<br />\n Information Technology Department Head.<br />\n Kenya Medical Research Institute/Walter Reed Project HIV Program<br />\n Hospital Road, P.O. Box 1357, Kericho, 20200; Kenya<br />\n Office: (254-52) 30686, 30388, Fax: (254-52) 30546<br />\n Mobile phone:254-727-531375; E-mail: ignatius.kiptoo@usamru-­â€k.org<br />\n DoD Research Monitors<br />\n Jonah Maswai,<br />\n MBChB, MPH<br />\n Kenya Medical Research Institute/Walter Reed Project HIV Program<br />\n Hospital Road, P.O. Box 1357, Kericho, 20200; Kenya<br />\n Office: (254-52) 30686, 30388, Fax: (254-52) 30546<br />\n Mobile phone:254-716-430271; E-mail: jonah.maswai@usamru-­â€k.org<br />\n Appolonia Aoko,<br />\n MBChB, MPH<br />\n Kenya Medical Research Institute/Walter Reed Project HIV Program<br />\n Hospital Road, P.O. Box 1357, Kericho, 20200; Kenya<br />\n Office: (254-52) 30686, 30388, Fax: (254-52) 30546<br />\n Mobile phone:254-715-551234; E-mail: appolonia.aoko@usamru-­â€k.org</p>\n
      • other_details_explanation<p>\n The source cohort study for this study is not being carried out in the USA, hence only the countries with the source cohort are participating. Two protocols (VRC 601 and VRC 602) utiling the same experimental product as this study are being carried out in the USA.</p>\n
      • other_details_regulatory_notapproved<p>\n None.</p>\n
      • other_details_regulatory_approved<p>\n KEMRI. One site in Kenya. Approval date - 21 september 2015.</p>\n
      • other_details_regulatory_rejected<p>\n None.</p>\n
      • other_details_regulatory_halted<p>\n Not Applicable.</p>\n
      • estimated_duration25 Weeks
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorPlacebo, 0.9% Saline
      • design_controlled_other_medicinalYes
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKEMRI Walter Reed Project Kericho
      • single_site_physical_addressHospital Road
      • single_site_contact_personDr Josphat Kosgei
      • single_site_telephone+254 729 110 122
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states4
      • number_of_sites
      • multi_country_listKenya, Uganda, Tanzania, Thailand
      • data_monitoring_committeeYes
      • total_enrolment_per_site6
      • total_participants_worldwide24
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male0
      • subjects_healthyNo
      • subjects_patientsNo
      • subjects_vulnerable_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_nameElizabeth
      • investigator1_middle_nameC
      • investigator1_family_nameNgetich
      • investigator1_qualificationBSc Nursing
      • investigator1_professional_addressKEMRI/WRP Kericho
      • investigator1_telephone+254 713 603 217
      • investigator1_emailelizabeth.ngetich@usamru-k.org
      • organisations_transferred_Yes
      • number_participants6
      • notification
      • approval_date20-03-2016
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted01-07-2020
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report<div>\n <strong>To:</strong> The Registrar,</div>\n<div>\n Pharmacy and Poisons Board,</div>\n<div>\n P.O. Box 27663- 00506</div>\n<div>\n NAIROBI. KENYA.</div>\n<div>\n  </div>\n<div>\n <strong>Attn: Expert Committee on Clinical Trials</strong></div>\n<div>\n  </div>\n<div>\n From: Josphat Kosgei, MBChB; MSc, DLSHTM</div>\n<div>\n Principal Investigator PPB/ECCT/15/10/01</div>\n<div>\n KEMRI/WRP HIV Program</div>\n<div>\n P.O Box 1357- 20200 Kericho, Kenya</div>\n<div>\n Tel; 052 5220 36100</div>\n<div>\n Email: Josphat.Kosgei@usamru-k.org</div>\n<div>\n  </div>\n<div>\n <strong>SUBJECT</strong>: Submission of the Study's Close Out Executive Summary Report for ECCT/15/10/01 protocol titled: “Safety and Virologic Effect Of A Human Monoclonal Antibody, VRC-HIVmAb060-00-Ab (VRCOl), With Broad HIV-1 Neutralizing Activity, Administered Intravenously to Adults During Early Acute HIV Infection.’’(RV 398b).</div>\n<div>\n  </div>\n<div>\n The purpose of this memo is to submit the close out executive summary report for the above-mentioned study for PPB/ECCT notification and acknowledgement.</div>\n<div>\n  </div>\n<div>\n <strong>1. INTRODUCTION:</strong></div>\n<div>\n This was a placebo-controlled study of the safety and impact of broadly neutralizing monoclonal antibody (mAb) therapy with VRC01 on viral dynamics in acute HIV infection, alone or in combination with antiretroviral therapy (ART). Subjects were enrolled during early acute HIV infection (AHI): defined as two positive nucleic acid amplification tests (NAATs) for HIV-1 RNA within 21 days of a prior negative NAAT. They were randomized to one of three groups:</div>\n<div>\n • Group 1, Immediate ART and placebo infusion (n=8): start ART with a single infusion of placebo on day 0 during AHI .</div>\n<div>\n • Group 2, Immediate ART and mAb Therapy (n=8): start ART with a single infusion of 40 milligrams/kilograms (mg/kg) VRC01 on day 0 during AHI</div>\n<div>\n • Group 3, Immediate mAb Therapy and Subsequent ART (n=8): a single infusion of 40 mg/kg VRC01 on day 0 during AHI followed by ART initiation on day 7</div>\n<div>\n  </div>\n<div>\n <strong>2. RESEARCH OBJECTIVES:</strong></div>\n<div>\n a) <strong>Primary Objective</strong></div>\n<div>\n 1. Safety of VRC01 in acutely HIV-infected individuals.</div>\n<div>\n 2. Impact of VRC01 on plasma viremia in each mAb arm compared to the ART plus placebo control at day 7 (+/- 1 day).</div>\n<div>\n 3. <strong>SUMMARY OF STUDY RESULTS:</strong></div>\n<div>\n For groups 1 and 2, participants and study team were blinded to active mAb vs. placebo infusion. After day 7, all groups were on ART and followed for 24 weeks.</div>\n<div>\n US Army Medical Research Directorate-Africa</div>\n<div>\n From 11 December 2016 to 31 May 2018, fifteen subjects were enrolled in RV398 at 3 sites in East Africa and 1 site in Thailand. All fifteen have completed their follow-up. RV217, the source protocol for recruiting acutely HIV-infected participants into RV398, was closed on 30 September 2018. No further study activities have since occurred at the East African sites. From 01 June 2018 to 12 February 2020, there were no enrollments into RV398 as the protocol was modified to recruit acutely HIV-infected participants enrolling in RV254 and to add a new study site, South East Asia Research Collaboration in HIV (SEARCH) Clinic, Thai Red Cross AIDS Research Center (TRCARC), Bangkok, Thailand. Since 13 February 2020 when enrollment began at SEARCH, nine participants have been enrolled into RV398.</div>\n<div>\n The study has now enrolled 24 of the 24 subjects permitted by the protocol. With the onset of the COVID-19 outbreak, the SEARCH team adopted enhanced infection prevention and control measures to mitigate risk and allow for continued low volume enrollment in the RV254 source cohort and in RV398 while pausing optional invasive procedures for study participants.</div>\n<div>\n In Kenya Kericho, the site was originally approved to enroll 6 participants. 6 participants were enrolled, and all participants completed all study activities.</div>\n<div>\n Infusions have been well tolerated. A summary of the data and adverse events for the overall study was just reviewed by the Safety Monitoring Committee (SMC) in the 13 January 2021 SMC Report (Attached).</div>\n<div>\n The cumulative deviation log, which includes all major and minor deviations that occurred in the study, is attached herein and the same have been uploaded on the ECCT portal.</div>\n<div>\n 4. List publications arising from study (attach copies of the manuscript(s).</div>\n<div>\n A summary of the data and adverse events for the overall study was reviewed by the Safety Monitoring Committee (SMC) in the 13 January 2021 and 13 July 2020 SMC Reports Attached herein.</div>\n<div>\n 5. Confirm destruction of each study participant’s identifiers and provide an assurance/evidence that the destruction has occurred (send copies of the blacked-out books).</div>\n<div>\n Data obtained from the conduct of this study are housed in a secure database maintained by the DCAC, MHRP, WRAIR. DCAC serves as the central data management facility for MHRP research protocols. Data managed by DCAC are entered into and maintained in a password-protected database accessible only to participating sites, DCAC and Information Technology staff authorized to work on the protocol. The database is located at the Bethesda campus of MHRP and is protected by a firewall. This data does not contain participant names or national identification number, but is referenced only by the study identification number. The clinical database is currently locked, and DCAC will maintain it indefinitely or until there is a regulatory requirement or sponsor instructions to destroy it. At the Kericho site the PI maintained research records of participants’ participation for this study. All participants received study numbers that were known only to the investigators and clinic staff. Clinical tests were identified by the study number and the specimen bag was identified by the study number and bar code only. The subject ID does not contain any identifiable information or any information which can be used to identify a study participant either directly or indirectly. These identification numbers were used for medical records, all laboratory tests or samples stored for testing in future studies. The study participants’ medical records were stored at the Clinical Research Center (CRC) archive room which is access controlled and double locked. The study documents have now been transferred to a safe, secured, long-term archive room within the Kericho CRC that is only accessible to regulatory personnel. All other research staff do not have access to this archive room. Destruction approval will be obtained from the sponsor and the IRBs will be notified when this is done. Any publication of this study will not use the study participant’s name or identify him/her personally. Efforts will be made to keep the study participants’ personal information confidential. The personal information may be disclosed if required by law. Clinical and research records may be reviewed by the representative of the KEMRI SERU, DAIDS, USAMRMC, WRAIR, representatives of the USAMRMC ORP,</div>\n<div>\n US Army Medical Research Directorate-Africa</div>\n<div>\n representatives of the FDA, OHRP, the product and device providers, and other regulatory agencies as part of their responsibilities for insuring the protection of research participants. Every effort will be made to keep the records as confidential as possible within the limits of the law. All data and medical information obtained about participants, as individuals will be considered privileged and held in confidence. Identification photographs did not contain participants’ names, but only a four-digit Study Number. A file copy of the photograph was kept in a secure location with other study documents and was only accessible to study staff. Research and clinical information relating to participants was shared with other investigators and the scientific community through presentation or publication; however, participants were NOT identified by name or social security number. Electronic data will be stored at least as long as the IND remains open. All participants received an emergency card indicating their status as a clinical trial participant. All participants were counseled periodically regarding the potential for testing positive on routine screening tests for HIV-1 as a consequence of participation in this trial and receiving this vaccine product. All participants were offered further confirmatory testing and certification as to the nature of their vaccine trial participation whenever needed to address complications arising at home, at work, or in the community, which could arise from routine screening for HIV.</div>\n<div>\n 6. Destruction of each study participant’s identifiers and provide an assurance/evidence that the destruction has occurred (send copies of the blacked-out books).</div>\n<div>\n Study documents have been transferred to a safe, secured, long-term archive room that is only accessible to two regulatory personnel. All other research staff does not have access to this archive room. Access to study documents is controlled and restricted and the site is responsible for ensuring that any access is accurately recorded and any documents accessed/removed and returned are recorded. Destruction approval will be obtained from the sponsor and the IRBs will be notified when this is done.</div>\n<div>\n 7. Plan for future use of data from the study (if applicable)</div>\n<div>\n All work for this study is complete. There are no future plans and any future use of individually coded data will have to be approved by the IRB. No further use of specimens or data can occur until a new protocol is approved and authorized by the WRAIR Institutional Review Board (IRB) and KEMRI SERU.</div>\n<div>\n 8. Confirm destruction of surplus investigational agents and provide an assurance/evidence that the destruction has occurred (if applicable).</div>\n<div>\n Attached is RV 398 Investigation Products Destruction Authorization Documents.</div>\n<div>\n 9. Detail the plan for the destruction, storage, or future use of biological specimens obtained as part of this study (include number of samples being destroyed or stored).</div>\n<div>\n All the samples that were not for safety testing were shipped out with the approval Scientific and Ethics Review Unit for analysis. The site is not storing any study samples</div>\n<div>\n  </div>\n<div>\n <strong>Find below the summary.</strong></div>\n<div>\n US Army Medical Research Directorate-Africa</div>\n<div>\n RV 398 -Sample Shipment</div>\n<div>\n Aliquot type</div>\n<div>\n Quantity</div>\n<div>\n Lymph Node fixed</div>\n<div>\n 11</div>\n<div>\n Rectal BX Fixed</div>\n<div>\n 6</div>\n<div>\n CSF Large Cells</div>\n<div>\n 15</div>\n<div>\n CSF Small Cells</div>\n<div>\n 48</div>\n<div>\n CSF Supernatant</div>\n<div>\n 246</div>\n<div>\n PBMC</div>\n<div>\n 294</div>\n<div>\n Plasma</div>\n<div>\n 387</div>\n<div>\n Recatal Bx VRC01 Lv1</div>\n<div>\n 2</div>\n<div>\n REctal Bx RNA Later</div>\n<div>\n 32</div>\n<div>\n Rectal Bx VRC01 Lv1</div>\n<div>\n 4</div>\n<div>\n Rectal Sponge</div>\n<div>\n 19</div>\n<div>\n Serum</div>\n<div>\n 151</div>\n<div>\n Soft Cup</div>\n<div>\n 61</div>\n<div>\n TOTAL</div>\n<div>\n 1276</div>\n<div>\n  </div>\n<div>\n Thank you for your time and review.</div>\n<div>\n  </div>\n<div>\n <strong>Included in this submission are the following:</strong></div>\n<div>\n a) Initial ECCT approval letter dated 08 January 2016.</div>\n<div>\n b) ECCT annual approval letter dated 22 January 2021.</div>\n<div>\n c) Safety Monitoring Committee (SMC) Report Dated 13 January 2021.</div>\n<div>\n d) Safety Monitoring Committee (SMC) Report Dated 13 July 2021.</div>\n<div>\n e) WRAIR# 2166B Closeout Acceptance Memo Dec 2020.</div>\n<div>\n f) KEMRI SERU#3096 Closeout Acceptance Memo dated 03 May 2021.</div>\n<div>\n g) Cumulative Deviation Log.</div>\n<div>\n h) RV 398 Investigation Products Destruction Authorization Documents.</div>\n<div>\n  </div>\n<div>\n The point of contact for this action is <strong>Dr. Josphat Kosgei</strong> at the Kenya Medical Research Institute-US Army Medical Research Directorate-Africa, who can be reached by email at <strong>josphat.kosgei@usamru-k .org.</strong></div>\n<div>\n  </div>\n<div>\n  </div>\n
      • implication_results<p>\n  </p>\n<p>\n <span style=\"font-size:14px;\">Yes,VRC01 intervention during early acute HIV infection was seen to be well tolerated and thus to ensure and determine whether it could significantly play a vital role in viral suppression, it may be imperative to encourage further development of it together with other immunotherapies for HIV directed against unique therapeutic targets.</span></p>\n
      • quantity_imported1. VRC-HIVmAb060-00-Ab (VRCOl) = 80 (2) 0.9%Sodium Chloride Inj USP 50ml = 24
      • quantity_dispensed1. VRC-HIVmAb060-00-Ab (VRCOl) = 45 (2) 0.9%Sodium Chloride Inj USP 50ml = 2
      • quantity_destroyed1. VRC-HIVmAb060-00-Ab (VRCOl) = 35 (2) 0.9%Sodium Chloride Inj USP 50ml = 22
      • quantity_exported1. VRC-HIVmAb060-00-Ab (VRCOl) = 0 (2) 0.9%Sodium Chloride Inj USP 50ml = 0
      • balance_site1. VRC-HIVmAb060-00-Ab (VRCOl) = 0 (2) 0.9%Sodium Chloride Inj USP 50ml = 0
      • final_date0000-00-00
      • modified2024-12-17 15:41:52
      • created2015-10-07 16:37:05
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id288
        • application_id425
        • given_nameJosphat
        • middle_nameK
        • family_nameKosgei
        • qualificationMBChB, MSc, DLSHTM.
        • professional_addressKEMRI/WRP Kericho
        • telephone+254 729 110 122
        • emailjosphat.kosgei@usamru-k.org
        • created2015-10-07 16:41:59
        • modified2020-07-01 11:51:32
    • SiteDetail(array)
      • 0(array)
        • id342
        • application_id425
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2015-10-07 16:41:59
        • modified2020-07-01 11:51:32
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id225
        • application_id425
        • sponsorNational Institute of Allergy and Infectious Diseases (NIAID), Division of AIDS (DAIDS), National Institutes of Health (NIH) Bethesda, Maryland
        • sponsor_typeOthers
        • contact_personJulie Ake
        • address6720A Rockledge Drive, Suite 400 Bethesda, MD 20817
        • telephone_number301-500-3621
        • fax_number
        • cell_number240-506-1915
        • email_addressjake@hivresearch.org
        • created2015-10-07 16:41:59
        • modified2020-07-01 11:51:32
  • 3(array)
    • Application(array)
      • id858
      • user_id71
      • trial_status_id7
      • abstract_of_study<p>\n This is a Phase 1/2 study to evaluate the safety and tolerability of two broadly neutralizing monoclonal human antibodies (bNAbs), 3BNC117-LS-J, which targets the CD4 binding site on HIV-1 envelope protein, and 10-1074-LS-J which targets the V3 loop of HIV-1 envelope protein. The hypothesis is that the two antibodies will be safe for healthy American and African adults when co-administered subcutaneously or intravenously and, after subcutaneous administration in the optimal ratio, each antibody will maintain trough serum levels >10 µg/ml at steady state. Primary Objectives 1.To evaluate the safety and tolerability of two broadly neutralizing monoclonal human antibodies, 3BNC117-LS-J and 10-1074-LS-J, when given alone and in combination, intravenously (IV) or subcutaneously (SC) to healthy American and African adults. 2.To evaluate the pharmacokinetic profile of two broadly neutralizing monoclonal human antibodies, 3BNC117-LS-J and 10-1074-LS-J, when given alone or in combination, IV or SC to healthy American and African adults. 3.To identify a regimen of the two antibodies that, when given SC every 3 months, will maintain a trough level of > 10 µg/ml for each antibody in >80% of study population. Secondary Objectives 1.To evaluate the effect of participant characteristics (e.g. sex, body weight or body mass index ) on pharmacokinetic parameters. 2.To conduct pharmacokinetic modelling to assess the effect of dose, dose ratio, dosing frequency and loading dose on serum trough levels of each antibody. 3.To assess the incidence and titers of anti-drug antibodies (ADA) against each antibody</p>\n
      • study_title<p>\n Safety and Pharmacokinetics of the Combination Broadly Neutralizing Antibodies, 3BNC117-LS-J and 10-1074-LS-J, in Healthy American and African Adults</p>\n
      • laymans_summary<p>\n This is a clinical research study in which 2 experimental study products either given separately or together are being tested to see if they are safe, and to understand how long they stay in the human body. We hope to learn what kind of side effects one may experience after receiving the study product(s). The two study products being tested are called 3BNC117-LS-J and 10-1074-LS-J. They are human antibodies against HIV that have been made in a laboratory. HIV is the virus that causes Acquired Immunodeficiency Syndrome (AIDS). Scientists are hoping that one day, these antibodies can be used to help prevent HIV infection in people</p>\n
      • short_titleIAVI C100
      • protocol_noECCT/20/06/01
      • version_noVersion 2.0
      • date_of_protocol13-12-2019
      • study_drug3BNC117-LS-J and 10-1074-LS-J
      • disease_conditionHIV
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines1
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressjnyange@kaviuon.org
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter0
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd0
      • 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_african0
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan0
      • applicant_contractual_agreement0
      • declaration_applicantProf Walter Jaoko
      • declaration_date104-06-2020
      • declaration_principal_investigatorN/A
      • declaration_date204-06-2020
      • placebo_presentYes
      • study_objectives<p>\n Primary Objectives 1. To evaluate the safety and tolerability of two broadly neutralizing monoclonal human antibodies, 3BNC117-LS-J and 10-1074-LS-J, when given alone and in combination, intravenously (IV) or subcutaneously (SC) to healthy American and African adults. 2. To evaluate the pharmacokinetic profile of two broadly neutralizing monoclonal human antibodies, 3BNC117-LS-J and 10-1074-LS-J, when given alone or in combination, IV or SC to healthy American and African adults. 3. To identify a regimen of the two antibodies that, when given SC every 3 months, will maintain a trough level of > 10 µg/ml for each antibody in >80% of study population. Secondary Objectives 1. To evaluate the effect of participant characteristics (e.g. sex, body weight or body mass index ) on pharmacokinetic parameters. 2. To conduct pharmacokinetic modelling to assess the effect of dose, dose ratio, dosing frequency and loading dose on serum trough levels of each antibody. 3. To assess the incidence and titers of anti-drug antibodies (ADA) against each antibody</p>\n
      • principal_inclusion_criteria<p>\n INCLUSION CRITERIA 1. Healthy male and female individuals, as assessed by a medical history, physical exam, and laboratory tests 2. At least 18 years of age on the day of screening and have not reached their 46th birthday on the day of the first administration 3. Willing to undergo HIV testing, risk reduction counseling and receive HIV test results; committed to maintaining low-risk behavior for the trial duration 4. Willing to comply with the requirements of the protocol and available for follow-up for the planned duration of the study; 5. In the opinion of the Principal Investigator or designee and based on Assessment of Understanding results, has understood the information provided and potential impact and/or risks linked to investigational product administration and participation in the trial; written informed consent will be obtained from the participant before any study-related procedures are performed; 6. All male and female participants of reproductive potential who are engaging in sexual activity that could lead to pregnancy must commit to use an effective method of contraception from enrolment until 9months after last administration. 7. All participants born female and of reproductive potential who are not heterosexually active at screening must agree to utilize an effective method of contraception if they become heterosexually active as outlined above. 8. All participants born female and of reproductive potential must be willing to undergo urine pregnancy tests at time points indicated in the Schedule of Procedures 9. Willing to forgo donations of blood, or any other tissues during the study and, for those who test HIV-positive due to antibody-induced seropositivity, until the anti-HIV antibody titers become undetectable on HIV tests used in the community</p>\n
      • principal_exclusion_criteria<p>\n EXCLUSION CRITERIA 1. Confirmed HIV infection 2. Reported risk for HIV infection within 6months prior to investigational product administration as specified by the protocol 3. Any clinically relevant abnormality on history or examination, including history of immunodeficiency or autoimmune disease; use of systemic corticosteroids (the use of topical or inhaled steroids is permitted), immunosuppressive, anticancer, anti-tuberculosis or other medications considered significant by the investigator within the previous 6 months. Limited exceptions are permitted and are described in detail in the protocol. 4. Any clinically significant acute or chronic medical condition that is considered progressive or in the opinion of the investigator makes the participant unsuitable for participation in the study 5. Asthma that is not well controlled 6. If female, pregnant or planning a pregnancy during the study period of enrolment until 9months after final IP administration; or lactating 7. Bleeding disorder diagnosed by a physician (e.g., factor deficiency, coagulopathy or platelet disorder that requires special precautions) 8. History of splenectomy 9. Any of the following abnormal hematological, chemistry and urine laboratory parameters as detailed in the protocol 10. Infectious disease diagnosis: • Hepatitis B infection as measured by HbsAg and/or PCR • Hepatitis C infection Africa: HCV Ab positive and/or PCR; • Active syphilis (positive RPR confirmed by TPHA) 11. Receipt of blood transfusion or blood-derived products within the previous 3 months 12. Participation in another clinical trial of an investigational product currently, within the previous 3 months or expected participation during this study 13. Prior receipt of any investigational HIV vaccine candidate, or HIV monoclonal antibody, 14. History of severe local or systemic reactions to blood or immunoglobulin products or constituents of investigational product (e.g., anaphylaxis, respiratory difficulties, angioedema) 15. Psychiatric condition that compromises safety of the participant and precludes compliance with the protocol. 16. Seizure disorder: A participant who has had a seizure in the last 3 years is excluded. 17. History of malignancy in the past 5 years or ongoing malignancy 18. Body mass index (BMI) >40 19. Active tuberculosis 20. If, in the opinion of the Principal Investigator, it is not in the best interest of the participant to participate in the trial</p>\n
      • primary_end_points<p>\n Primary:</p>\n<p>\n Safety and Tolerability: 1. Proportion of participants with solicited and IP-related unsolicited adverse events that are Grade 2 and above (including confirmed laboratory abnormalities) and their duration. 2. Proportion of participants with solicited and IP-related unsolicited adverse events that are Grade 3 and above (including confirmed laboratory abnormalities) and their duration. 3. Proportion of participants with serious adverse events (SAEs) throughout the study period that are considered related to investigational product and their duration. Pharmacokinetics (PK) 4. The ratio of 3BNC117-LS-J to 10-1074-LS-J that, when injected SC, will maintain similar levels of each bNAb at steady state.</p>\n<p>\n Secondary: 1. Serum concentration of the bNAb in each group at multiple timepoints along with participant characteristics (e.g. sex, weight, and BMI). 2. Serum concentration of 3BNC117-LS-J and 10-1074-LS-J in each group at multiple timepoints along with dose, dose ratio, dosing frequency and loading dose. 3. Serum concentration of anti-3BNC117-LS-J and anti-10-1074-LS-J antibodies in each group at multiple timepoints.</p>\n<p>\n Exploratory: 1. Serum concentration of the bNAb in each group at multiple timepoints along with geographical region, immunoglobulin levels and the subcutaneous site of injection (abdomen vs. arm). 2. Magnitude of serum neutralization of virus isolates sensitive to each antibody at 7 days and 12 weeks after SC administration in selected participants in America and Africa. 3. Proportion of participants with reduction in bNAb half-life concomitant with ADA. 4. Proportion of participants with reduction in bNAb neutralization potency concomitant with ADA. 5. Proportion of participants with pIMDs throughout the study period that are considered related to investigational product and their duration. 6. Relationship of solicited and unsolicited adverse events and pIMDs to ADA. 7. bNAb concentrations in mucosal secretions at selected sites.</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy0
      • scope_pharmacokinetic1
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology1
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n <strong>Number of Staff:</strong> 1 physician, I pharmacist, 2 pharmacy staff, 2 trial clinicians, 3 nurse counselors, 2 community staff, 1 data IT/Data manager, 3 Data staff and 8 lab staff, I labaratory Manager</p>\n<p>\n <strong>Core Staff:</strong></p>\n<p>\n 1. Prof. Omu Anzala MBChB PhD, Co-Investigator,Virologist & Senior Research Scientist 2. Dr. Marianne Mureithi PhD, C100 Mucosal Study team leader 3. Dr Moses Masika MBChB MSc.Laboratory Manager 4.  Ms. Hilda Ogutu BsN, KPHN, KRM,KRN,Study Coordinator 6. Jacquelyn Nyange RN, BA, MSc. Clinical PSY Regulatory compliance</p>\n<p>\n <strong>Site Facities</strong>: Clinic, Labaratory, data and  Pharmacy  space available on site</p>\n<p>\n <strong>Emergency Facities:</strong> Well equiped Emergecy room in the clinic</p>\n
      • other_details_explanation<p>\n N/A</p>\n
      • other_details_regulatory_notapproved<p>\n N/A</p>\n
      • other_details_regulatory_approved<p>\n N/A</p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration24 months
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_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_states1
      • number_of_sites2
      • multi_country_listKenya \nUSA\nRwanda\nUganda\nSouth Africa
      • data_monitoring_committeeYes
      • total_enrolment_per_site24
      • total_participants_worldwide225 HIV-uninfected participants
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultNo
      • 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_nameN/A
      • investigator1_middle_nameN/A
      • investigator1_family_nameN/A
      • investigator1_qualificationN/A
      • investigator1_professional_addressN/A
      • investigator1_telephoneN/A
      • investigator1_emailgmutua@kaviuon.org
      • organisations_transferred_No
      • number_participants24
      • notification
      • approval_date02-12-2020
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted07-12-2021
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonApplication approved by the expert committee
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2024-04-02 09:06:41
      • created2020-03-06 10:44:03
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id528
        • application_id858
        • given_nameProf Walter Jaoko
        • middle_nameGodfrey
        • family_nameJaoko
        • qualificationMBChB, MTropMed, PhD, PGD (Health Research Ethics)
        • professional_addressP.O Box 19676
        • telephone0727555254
        • emailwjaoko@kaviuon.org
        • created2020-03-06 11:27:32
        • modified2021-12-07 12:35:37
    • SiteDetail(array)
      • 0(array)
        • id703
        • application_id858
        • county_id47
        • site_nameKAVI-Insitute of Clinical Research, KNH site
        • physical_addressCollege of health Sciences, University of Nairobi, Kenyatta National Hospital
        • contact_detailsP.O Box 19676, 00202 KNH
        • contact_personDr Gaudensia Nzembi Mutua
        • site_capacity(null)
        • misc(null)
        • created2020-03-06 11:27:32
        • modified2021-12-07 12:35:37
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
    • Sponsor(array)
      • 0(array)
        • id415
        • application_id858
        • sponsorInternational AIDS Vaccine Initiative (IAVI)
        • sponsor_typeOthers
        • contact_personDagna Laufer, MD
        • address125 Broad Street, 9th Floor
        • telephone_number+1 212-328-7459
        • fax_numberN/A
        • cell_number+1 212-328-7459
        • email_addressdlaufer@iavi.org
        • created2020-03-06 11:27:32
        • modified2021-12-07 12:35:37
  • 4(array)
    • Application(array)
      • id131
      • user_id70
      • trial_status_id5
      • abstract_of_study<p>\n  </p>\n<div>\n The RTS,S/AS01E candidate malaria vaccine is being developed for the routine immunization of infants and children living in malaria-endemic areas. The RTS,S/AS01E candidate malaria vaccine consists of sequences of the  ircumsporozoite (CS) protein and hepatitis B surface antigen (HBsAg) with the proprietary adjuvant AS01E (proprietary liposomes, MPL and Stimulon QS21 immunostimulants). The vaccine also induces a strong immune response against hepatitis B.</div>\n<div>\n In studies completed to date, the RTS,S candidate malaria vaccine adjuvanted with GSK’s proprietary Adjuvants  systems has consistently demonstrated efficacy in the pediatric population in malaria endemic countries. It has a favorable safety profile when given to young children and infants in co-administration with EPI routine vaccines.</div>\n<div>\n In order for the RTS,S candidate vaccine to be recommended for vaccination in children and infants in sub-Saharan Africa, safety of the vaccine needs to be demonstrated in HIV positive children, given the HIV disease burden in some parts of Africa.</div>\n<div>\n Approximately 2-3 million children live with HIV in sub- Saharan Africa; about 1500 children are newly infected each day.</div>\n<div>\n Vertical transmission rates are approximately 12-40%, and down to 2% in the context of optimal Prevention of Mother-to-Child Transmission (PMCT).</div>\n<div>\n Although HIV infected children have defective immunity and low immune response to some vaccines, the WHO recommends</div>\n<div>\n that children who are, or are s uspected of being, infected with HIV but are not yet symptomatic should be given all vaccines as recommended by the national EPI program. It is only the BCG and, where applicable, yellow fever vaccine - two live attenuated vaccines - that are contra-indicated in children with symptomatic</div>\n<div>\n HIV infection, because of the risk of disseminated invasive disease post vaccination. In all other situations, benefits of</div>\n<div>\n vaccination by far outweigh any associated risk. For non-live vaccines, HIV infection has not been shown to be associated with an increased risk of adverse vaccine-related event. On the contrary, because of HIV-infected children’s susceptibility towards infections, vaccination is strongly advocated.</div>\n<div>\n As HIV infected children are more susceptible to malaria they may potentially gain additional benefits from receiving the</div>\n<div>\n malaria candidate vaccine. Among HIV-infected children up to 5 years of age, rates of parasitemia and parasite densities are higher than in those without HIV. HIV-infected infants are also at increased risk for severe anemia and for hospitalization due to malaria. Furthermore, malaria episodes can transiently increase viral load, and thus could theoretically have an impact on HIV disease progression and HIV transmission.</div>\n<div>\n This study will assess the safety and immunogenicity of the RTS,S/AS01E candidate malaria vaccine in HIV-infected infants and children. It will also describe the malaria experience, HIV viral load and CD4+ cell count of subjects. Through the monitoring of markers of HIV disease progression we will determine whether a reduction of malaria attacks in these</div>\n<div>\n children translates to a lower rate of HIV disease progression.</div>\n<div>\n We will also be able to exclude a potential detrimental effect of the vaccine on HIV disease progression.</div>\n<div>\n The clinical development of the RTS,S candidate malaria vaccine is conducted under a partnership agreement with the PATH Malaria Vaccine Initiative (MVI) and is guided by a joint MVI/GSK Steering Committee.</div>\n<div>\n This study is overseen by a formally constituted IDMC operating under a charter.</div>\n<div>\n  </div>\n<div>\n <div>\n <u><strong>Detailed Title</strong></u></div>\n <div>\n A Phase III randomized, double blind (observer blinded), controlled study of the safety and immunogenicity of GlaxoSmithKline Biologicals’ candidate Plasmodium falciparum malaria vaccine RTS,S/AS01E (0.5 mL dose), administered IM according to a 0, 1, 2-month vaccination schedule in HIV infected infants and children living in a</div>\n <div>\n malaria-endemic region. Indication Primary immunization of HIV infected male and female infants</div>\n <div>\n and children (between and including 6 weeks and 17 months of age), if eligible according to inclusion and exclusion criteria.</div>\n <div>\n  </div>\n <div>\n <u><strong>Rationale for the study and study design</strong></u></div>\n <div>\n The RTS,S/AS01E candidate malaria vaccine is being developed for the routine immunization of infants and children</div>\n <div>\n living in malaria-endemic areas. The RTS,S/AS01E candidate malaria vaccine consists of sequences of the circumsporozoite (CS) protein and hepatitis B surface antigen (HBsAg) with the proprietary adjuvant AS01E (proprietary liposomes, MPL and Stimulon QS21 immunostimulants). The vaccine also induces a strong immune response against hepatitis B.</div>\n <div>\n In studies completed to date, the RTS,S candidate malaria vaccine adjuvanted with GSK’s proprietary Adjuvants Systems has consistently demonstrated efficacy in the pediatric population in malaria endemic countries. It has a favorable safety profile when given to young children and infants in co-administration with EPI routine vaccines.</div>\n <div>\n In order for the RTS,S candidate vaccine to be recommended for vaccination in children and infants in sub-Saharan Africa, safety of the vaccine needs to be demonstrated in HIV positive children, given the HIV disease burden in some parts of Africa.</div>\n <div>\n Approximately 2-3 million children live with HIV in sub- Saharan Africa; about 1500 children are newly infected each day.</div>\n <div>\n Vertical transmission rates are approximately 12-40%, and down to 2% in the context of optimal Prevention of Mother-to-Child Transmission (PMCT).</div>\n <div>\n Although HIV infected children have defective immunity and low immune response to some vaccines, the WHO recommends that children who are, or are suspected of being, infected with HIV but are not yet symptomatic should be given all vaccines as recommended by the national EPI program. It is only the BCG and, where applicable, yellow fever vaccine - two live attenuated vaccines - that are contra-indicated in children with symptomatic HIV infection, because of the risk of disseminated invasive disease post vaccination. In all other situations, benefits of vaccination by far  outweigh any associated risk. For non-live vaccines, HIV infection has not been shown to be associated with</div>\n <div>\n an increased risk of adverse vaccine-related event. On the contrary, because of HIV-infected children’s susceptibility</div>\n <div>\n towards infections, vaccination is strongly advocated. </div>\n <div>\n As HIV infected children are more susceptible to malaria they may potentially gain additional benefits from receiving the</div>\n <div>\n malaria candidate vaccine. Among HIV-infected children up to 5 years of age, rates of parasitemia and parasite densities are higher than in those without HIV. HIV-infected infants are also at increased risk for severe anemia and for hospitalization due to malaria. Furthermore, malaria episodes can transiently increase viral load, and thus could theoretically have an impact on HIV disease progression and HIV transmission. This study will assess the safety and immunogenicity of the RTS,S/AS01E candidate malaria vaccine in HIV-infected infants and children. It will also describe the malaria experience, HIV viral load and CD4+ cell count of subjects. Through the monitoring of markers of HIV disease progression we will determine whether a reduction of malaria attacks in these children translates to a lower rate of HIV disease progression. </div>\n <div>\n We will also be able to exclude a potential detrimental effect of the vaccine on HIV disease progression. The clinical development of the RTS,S candidate malaria vaccine is conducted under a partnership agreement with the PATH</div>\n <div>\n Malaria Vaccine Initiative (MVI) and is guided by a joint MVI/GSK Steering Committee. </div>\n <div>\n This study is overseen by a formally constituted IDMC operating under a charter.</div>\n <div>\n  </div>\n <div>\n <u><strong>Objectives</strong></u></div>\n <div>\n  </div>\n <div>\n <strong><em>Primary: Safety</em></strong></div>\n <div>\n ï‚· To describe the safety (occurrence of SAEs) of RTS,S/AS01E when administered on a 0, 1, 2-month schedule to</div>\n <div>\n HIV-infected infants and children, until 14 months post Dose 1.</div>\n <div>\n <em><strong>Secondary :Safety</strong></em></div>\n <div>\n ï‚· To describe the reactogenicity profile (occurrence of solicited symptoms) of RTS,S/AS01E when administered on a 0, 1, 2-month schedule to HIVinfected infants and children, during 7 days (day of vaccination and 6 subsequent days) after each vaccination.</div>\n <div>\n ï‚· To describe the safety (occurrence of unsolicited AEs) of RTS,S/AS01E when administered on a 0, 1, 2-month</div>\n <div>\n schedule to HIV-infected infants and children over a 30 day period after each vaccination.</div>\n <div>\n ï‚· To describe the occurrence of non-malaria-related SAEs in HIV infected infants and children vaccinated with RTS,S/AS01E when  dministered on a 0, 1, 2-month schedule, until 14 months post Dose 1.</div>\n <div>\n Immunogenicity</div>\n <div>\n ï‚· To assess the antibody responses to CS and  HBs antigens for RTS,S/AS01E when administered on a 0, 1, 2-month schedule to HIV-infected infants and children up to 12 months post Dose 3.</div>\n <div>\n Malaria monitoring</div>\n <div>\n ï‚· To monitor and describe the occurrence of   malaria disease in HIV infected infants and children occurring during the study period.</div>\n <div>\n <em><strong>Progression of HIV disease</strong></em></div>\n <div>\n ï‚· To describe the evolution of CD4+ cell counts (CD4 % and absolute counts), HIV viral load and HIV WHO clinical classification for  RTS,S/AS01E when administered on a 0, 1,</div>\n <div>\n 2-month schedule to HIV-infected infants and children up to 14 months post Dose 1.</div>\n <div>\n <em><strong>Growth</strong></em></div>\n <div>\n To describe growth in HIV infected infants and children during the study period.</div>\n <div>\n Study design ï‚· Experimental design: Phase III, double blind (observer blind), randomized (1:1 ratio) controlled trial with two groups, one vaccinated with the experimental malaria</div>\n <div>\n candidate vaccine RTS,S/AS01E, the other one with the rabies control vaccine.</div>\n <div>\n ï‚· Parents/Legally Acceptable Representatives (LARs) of HIV-infected infants and children will be identified at HIV clinics and will be informed about the study. If interested, and if the infant/child is eligible based on the inclusion and</div>\n <div>\n exclusion criteria, the parents/LARs will be asked to consent for study participation.</div>\n <div>\n ï‚· Route of vaccine administration: intramuscular (IM) route in the left antero-lateral thigh for infants < 5 months and left deltoid for infants/children  5 months of age.</div>\n <div>\n ï‚· The experimental vaccines will be given outside the context of co-administration with other vaccines. Standard EPI vaccine delivery will be allowed 1 week apart from study vaccines.</div>\n <div>\n <div>\n ï‚· Each subject will be observed for at least 60 minutes after vaccination to evaluate and treat any acute adverse events (AEs).</div>\n <div>\n ï‚· There will be a 7-day follow-up period for solicited AEs post-vaccination. Day 0 evaluation will be carried out by the study clinician at the study center. Subsequently, trained field workers will visit the infants and children to solicit AEs on Days 1 to 5 after each vaccination.</div>\n <div>\n Evaluation on Day 6 post vaccination which will be carried out by the study clinician at the study center.</div>\n <div>\n ï‚· There will be a 30-day (day of vaccination and 29 subsequent days) follow-up after each vaccine dose for reporting unsolicited symptoms.</div>\n <div>\n ï‚· SAEs will be recorded throughout the study period. Prior to vaccination, any SAE due directly to study procedures will be recorded. All SAEs will be recorded beginning with the administration of the first dose and ending 14 months after the first dose of study vaccine. Monthly clinic visits will contribute to maximal capture of SAEs.</div>\n <div>\n ï‚· Safety blood samples for assessment of hematology, hepatic and renal function will be collected at baseline, 6 days post Dose 1, one month post Dose 3, 6 months post Dose 3 and 12 months post Dose 3. (Amended 26 January 2011).</div>\n <div>\n ï‚· IDMC reports:</div>\n <div>\n Safety reports will be sent at three time points after 30 subjects have completed the 7 days of follow-up post Dose</div>\n <div>\n 1, post Dose 2 and post Dose 3. The IDMC will review the data to authorize continuation of enrolment and</div>\n <div>\n vaccinations.</div>\n <div>\n ï‚· Long-lasting insecticide impregnated bednets and directions for use will be distributed at screening, regardless of the decision of parents/LARs to participate in the study or not. </div>\n <div>\n ï‚· Children and infants will be followed passively for the occurrence of clinical malaria for the duration of their participation in the study. Cases will be detected at all</div>\n <div>\n study health facilities.</div>\n <div>\n ï‚· P. falciparum parasitemia will be determined on a crosssectional sample in all study participants at study end (Month 14).</div>\n <div>\n ï‚· This study will be conducted in the context of access to an HIV management unit with availability of Voluntary Counseling and Testing (VCT),pediatric Highly Active Antiretroviral Therapy (HAART), daily  trimethoprimsulfamethoxasole prophylaxis (co-trimoxazole: CTX) for the prevention of opportunistic infections, Prevention of Mother-to-Child Transmission (PMCT) and HIV clinical follow up, including immunology monitoring, according to the national HIV control guidelines. CTX prophylaxis and antiretroviral therapy</div>\n <div>\n (ART) will be monitored during the trial.</div>\n <div>\n ï‚· Subjects with Grade III or IV AIDS, with an acute illness resulting in deferment of vaccination past the 30-day window, or with an abnormal laboratory value at the time of enrolment will not be able to participate in the study  (see exclusion criteria). However, in case the health of the subject improves, he or she might be re-onsidered</div>\n <div>\n for enrolment. In that case, a new ICF should be signed and all screening procedures should be repeated, except possibly the HIV DNA PCR test. (Amended 26 January 2011).</div>\n <div>\n ï‚· There will be a balanced randomization to ensure that both groups are comparable in terms of age and CD4 %</div>\n <div>\n levels. An equivalent number of children of age categories 6 weeks to 4 months and 5 months to 17 months, and with various CD4 % levels (<10%, 10-14%, 15-19%, 20%) will be enrolled in both study groups. Children can be enrolled whether or not they are on ART at enrollment. However all enrolled children will be provided ART and daily septrin, according to national guidelines.</div>\n <div>\n ï‚· Data collection: this study will use electronic case report forms (eCRF) by remote data entry (RDE).</div>\n <div>\n ï‚· Study duration will be approximately 14 months per subject. </div>\n <div>\n ï‚· The final analysis of the study will be conducted on all data collected up to Month 14 (Clinic Visit 19).</div>\n <div>\n <em><strong>Number of subjects </strong></em></div>\n <div>\n 200 infants and children aged 6 weeks to 17 months will be</div>\n <div>\n enrolled.</div>\n <div>\n <em><strong>Primary endpoint :Safety</strong></em></div>\n <div>\n ï‚· Serious adverse events Occurrence of SAEs from the time of first vaccination until 14 months post Dose 1.</div>\n <div>\n <div>\n <em><strong>Secondary endpoints Safety</strong></em></div>\n <div>\n ï‚· Solicited local and general symptoms Occurrence of general and local solicited symptoms over a 7-day follow-up period (day of vaccination and 6 subsequent days) after each vaccination.</div>\n <div>\n ï‚· Unsolicited adverse events Occurrence of unsolicited symptoms over a 30-day followup period (day of vaccination and 29 subsequent days) after each vaccination.</div>\n <div>\n ï‚· Non-malaria-related serious adverse events Occurrence of non-malaria-related SAEs from the time of first vaccination until 14 months post Dose 1.</div>\n <div>\n <em><strong>Immunogenicity</strong></em></div>\n <div>\n ï‚· Immunogenicity of a primary course of investigational vaccine Anti-CS antibody titers prior to vaccination and one month post Dose 3.</div>\n <div>\n Anti-HBs antibody titers prior to vaccination and one month post Dose 3.</div>\n <div>\n Anti-CS antibody titers at 12 months post Dose 3.</div>\n <div>\n Anti-HBs antibody titers at 12 months post Dose 3.</div>\n <div>\n <em><strong>Malaria monitoring</strong></em></div>\n <div>\n ï‚· Malaria disease:Occurrence of malaria disease according to specific case definitions.</div>\n <div>\n ï‚· Malaria parasitemia:Asexual P. falciparum parasitemia prevalence and density at 12 months post Dose 3. Progression of HIV disease</div>\n <div>\n ï‚· HIV viral load:Viral load (copies/mL) at baseline and at 1 month, 6 months and 12 months post Dose 3.</div>\n <div>\n ï‚· T-cell counts CD4+ % and absolute cell counts at baseline and at 1 month, 6 months and 12 months post Dose 3. </div>\n <div>\n ï‚· HIV clinical classification progression:WHO HIV clinical classification at baseline, 1 month, 6 months and 12 months post Dose 3.</div>\n <div>\n <em><strong>Growth</strong></em></div>\n <div>\n ï‚· Growth parameters:Weight, age/length and middle upper arm circumference for age score at baseline and study end.</div>\n </div>\n </div>\n</div>\n<p>\n  </p>\n
      • study_title<p>\n SAFETY AND IMMUNOGENICITY STUDY OF GSK BIOLOGICALS' <em>Plasmondium falciparum </em>MALARIA VACCINE 257049 ADMINISTERED TO HIV INFECTED INFANTS AND CHILDREN</p>\n
      • laymans_summary(null)
      • short_titleMAL-58 Study: Protocol no. 112745: SAFETY AND IMMUNOGENICITY STUDY OF GSK BIOLOGICALS\' Plasmondium falciparum MALARIA VACCINE 257049 ADMINISTERED TO HIV INFECTED INFANTS AND CHILDREN
      • protocol_noECCT/09/09/02
      • version_noFINAL PROTOCOL
      • date_of_protocol11-08-2009
      • study_drugRTS,S/AS01E
      • disease_conditionMALARIA
      • 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_addressHarun.N.Aketch@gsk.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter0
      • applicant_statement1
      • applicant_participating_countries0
      • applicant_addendum0
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd(null)
      • applicant_prev_data(null)
      • applicant_stability_data(null)
      • applicant_analysis_cert(null)
      • applicant_pictorial_sample(null)
      • applicant_gcp_training(null)
      • applicant_dsmb_charter(null)
      • applicant_detailed_budget(null)
      • applicant_indemnity_pi(null)
      • applicant_practice_license(null)
      • applicant_registration_ctr(null)
      • applicant_pan_african(null)
      • applicant_hard_copies(null)
      • applicant_signed_checklist(null)
      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantHARUN NJAGO AKETCH
      • declaration_date121-05-2013
      • declaration_principal_investigator DECLARATION BY PRINCIPAL INVESTIGATOR Name: Title of the study: A Phase III randomized, double blind (observer blinded), controlled study of the safety and immunogenicity of GlaxoSmithKline Biological’ candidate Plasmodium falci
      • declaration_date216-07-2013
      • placebo_presentNo
      • study_objectives(null)
      • principal_inclusion_criteria<p>\n  </p>\n<div>\n ï‚· A male or female infant or child between and including 6 weeks to 17 months of</div>\n<div>\n age, at the time of first vaccination.</div>\n<div>\n ï‚· Signed or thumb-printed informed consent obtained from the parent(s)/LAR(s)</div>\n<div>\n of the infant or child. Where parents/LARs are illiterate, the consent form will</div>\n<div>\n be countersigned by a witness.</div>\n<div>\n ï‚· Subjects who the investigator believes that their parents/LARs can and will</div>\n<div>\n comply with the requirements of the protocol should be enrolled in the study.</div>\n<div>\n ï‚· Subjects who are known to be HIV-infected (documented positive DNA PCR),</div>\n<div>\n whether taking HIV antiretroviral treatment (ART) or not.</div>\n<div>\n ï‚· Subjects who are born following a normal gestation period (i.e. gestation period</div>\n<div>\n of minimum 36 weeks and maximum 42 weeks).</div>\n
      • principal_exclusion_criteria<p>\n  </p>\n<div>\n ï‚· Acute disease at the time of enrolment (acute disease is defined as the presence</div>\n<div>\n of a moderate or severe illness with or without fever). However, the presence of</div>\n<div>\n an illness listed as Grade I or Grade II (WHO pediatric AIDS clinical staging;</div>\n<div>\n see Appendix B) will not of itself constitute an exclusion criterion. Enrolment</div>\n<div>\n should be deferred if axillary temperature is  37.5°C.</div>\n<div>\n ï‚· Grade III or Grade IV abnormality on screening laboratory blood sample (see</div>\n<div>\n Table 7).</div>\n<div>\n ï‚· Grade III or IV AIDS at the time of enrolment (WHO pediatric AIDS clinical</div>\n<div>\n staging; see Appendix B).</div>\n<div>\n ï‚· Major congenital defects.</div>\n<div>\n ï‚· Planned administration/administration of a vaccine not foreseen by the study</div>\n<div>\n protocol prior to or within 7 days of study vaccine.</div>\n<div>\n ï‚· Use of any investigational or non-registered product (drug or vaccine) other than</div>\n<div>\n the study vaccine 30 days preceding Dose 1 of study vaccine, or planned use</div>\n<div>\n during the study period.</div>\n<div>\n ï‚· Previous participation in any other malaria vaccine trial.</div>\n<div>\n ï‚· Simultaneous participation in another clinical trial including administration of</div>\n<div>\n experimental treatment.</div>\n<div>\n ï‚· Same sex twins.</div>\n<div>\n ï‚· History of allergic reactions (significant IgE-mediated events) or anaphylaxis to</div>\n<div>\n previous immunizations.</div>\n<div>\n <div>\n History of allergic disease or reactions likely to be exacerbated by any</div>\n <div>\n component of the study vaccine.</div>\n <div>\n ï‚· Child in care.</div>\n</div>\n<p>\n  </p>\n
      • primary_end_points<p>\n  </p>\n<div>\n Safety</div>\n<div>\n ï‚· To describe the safety (occurrence of SAEs) of RTS,S/AS01E when administered on a 0, 1, 2-month schedule to</div>\n<div>\n HIV-infected infants and children, until 14 months post Dose 1.</div>\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_specifySAFETY AND IMMUNOGENICITY
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other1
      • trial_other_specifySafety and immunogenicity, Phase 3
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n -</p>\n
      • other_details_explanation<p>\n THIS TRIAL IS CONDUCTED IN KENYA SINCE THE PRESENCE AND PREVALENCE OF MALARIA HAS BEEN NOTED TO BE HIHG HERE AND NOT THE APPLICANT'S /SPONSOR HOST COUNTRY. </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 N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration200
      • 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_comparatorRABIES VACCINE
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites2
      • multi_country_list
      • data_monitoring_committeeYes
      • total_enrolment_per_siteONE HUNDRED PARTICIPANTS PER SITE
      • total_participants_worldwide200
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerYes
      • population_childrenNo
      • population_adolescentNo
      • population_above_18No
      • population_adultNo
      • 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_nameBERNHARD
      • investigator1_middle_name
      • investigator1_family_nameOGUTU
      • investigator1_qualificationMBCHB,MMED,PAED
      • investigator1_professional_addressKEMRI/Walter Reed Project, P.O. Box 54-40100, kISUMU
      • investigator1_telephone+254-57-22942
      • investigator1_emailbogutu@wrp-ksm.org
      • organisations_transferred_No
      • number_participantsTWO HUNDRED
      • notification
      • approval_date24-06-2010
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted19-07-2013
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2018-07-10 15:46:31
      • created2013-04-30 14:35:52
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id79
        • application_id131
        • given_nameLUCAS
        • middle_nameOTIENO
        • family_nameTINA
        • qualificationMBCHB MPH,
        • professional_addressKEMRI/Walter Reed Project, P.O. Box 54-40100, kISUMU
        • telephone+254-57-22942
        • emailotienol@wrp-ksm.org
        • created2013-04-30 14:50:01
        • modified2013-07-19 16:25:12
      • 1(array)
        • id80
        • application_id131
        • given_nameMARY
        • middle_name
        • family_nameHAMEL
        • qualificationMD,INTERNAL MED.
        • professional_address+254-57-22923
        • telephoneKEMRI-CDC RESEARCH STATION, KISIAN, KISUMU BUSIA ROAD
        • emailmlh8@cdc.gov
        • created2013-04-30 15:32:27
        • modified2013-07-19 16:25:12
    • SiteDetail(array)
      • 0(array)
        • id100
        • application_id131
        • county_id41
        • site_nameKEMRI-CDC,
        • physical_addressKEMRI-CDC RESEARCH STATION,KISIAN,KISUMU-BUSIA ROAD
        • contact_detailsP O Box 1578-40100,KISUMU;TEL +254-57-22923
        • contact_personDR. MARY HAMEL
        • site_capacity(null)
        • misc(null)
        • created2013-04-30 14:50:01
        • modified2013-07-19 16:25:12
        • County(array)
          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
      • 1(array)
        • id101
        • application_id131
        • county_id42
        • site_nameKEMRI-WRP
        • physical_addressNEXT TO NEW NYANZA PROVINCIAL GENERAL HOSPITAL,KONDELE ,KISUMU
        • contact_detailsWalter Reed Project, Kombewa Clinical Research Center. P.0.Box 54-40100, Kisumu, Kenya , Tel:+254-57-2022942
        • contact_personDR. LUCAS OTIENO
        • site_capacity(null)
        • misc(null)
        • created2013-04-30 15:50:10
        • modified2013-07-19 16:25:12
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
    • Sponsor(array)
      • 0(array)
        • id62
        • application_id131
        • sponsorGlaxosmithkline
        • sponsor_type(null)
        • contact_personHarun Njago Aketch
        • address78392-00507
        • telephone_number+254 20 6933200/314
        • fax_number
        • cell_number+254 725669143
        • email_addressHarun.N.Aketch@gsk.com
        • created2013-04-30 14:50:01
        • modified2013-07-19 16:25:12
• page_options(array)
  • 55
  • 1010
• redir
• $request->data(array)
  • Application(array)
    • approved2
• $this->validationErrors(array)
  • Permission(empty)
  • Aro(empty)
  • Aco(empty)
  • Application(empty)
  • User(empty)
  • TrialStatus(empty)
  • InvestigatorContact(empty)
  • Sponsor(empty)
  • SiteDetail(empty)
  • County(empty)
• Loaded Helpers(array)
  • 0Html
  • 1Form
  • 2Session
  • 3Text
  • 4Number
  • 5SimpleGraph
  • 6Paginator
  • 7DebugTimer
  • 8Toolbar
  • 9HtmlToolbar

App Constants

CakePHP Constants

PHP Environment

Included Files

Include Paths

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

Included Files

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