Clinical trial NCT02564523: Safety, Tolerability and Immunogenicity Study of 3 Prime-boost Regimens for Ebola Vaccines Ad26.ZEBOV/MVA-BN-Filo in Healthy Adults, Children and Human Immunodeficiency Virus Positive (HIV+) Adults
Official title: A Randomized, Observer-blind, Placebo-controlled, Phase 2 Study to Evaluate the Safety, Tolerability and Immunogenicity of Different Prime-boost Regimens of the Candidate Prophylactic Vaccines for Ebola Ad26.ZEBOV and MVA-BN-Filo in Healthy Adults, Including Elderly Subjects, HIV-infected Subjects, and Healthy Children in Two Age Strata in Africa
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hemorrhagic Fever, Ebola
Keywords: Healthy
Vaccine
Ebola viruses
Ebola virus disease (EVD)
Filoviruses
Hemorrhagic fever
Monovalent vaccine
Human adenovirus serotype 26 (Ad26) expressing the Ebola virus Mayinga variant glycoprotein (Ad26.ZEBOV)
Modified Vaccinia Virus Ankara - Bavarian Nordic (MVA-BN) Filo-vector
Safety
Immunogenicity
Inserm, Centre Muraz
Lead sponsor: Janssen Vaccines & Prevention B.V.
Sponsor class: INDUSTRY
Collaborators: name: EBOVAC2 Consortium
name: Institut National de la Santé Et de la Recherche Médicale, France
name: Centre Muraz
First posted: 2015-09-30
Enrollment: 1075
Sex: ALL
Minimum age (years): 4
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to assess the safety, tolerability and immunogenicity of three heterologous prime-boost regimens for Ebola vaccines Ad26.ZEBOV and MVA-BN-Filo. The study will include healthy adults and elderly participants, HIV infected participants and healthy children in 2 age strata.

Detailed description: This is a randomized, observer-blind, placebo-controlled, parallel-group, multicenter, Phase 2 study evaluating the safety, tolerability and immunogenicity of 3 heterologous prime-boost regimens using Ad26.ZEBOV as prime and MVA-BN-Filo as boost vaccination, administered at 28-, 56- and 84-day (Group 1, 2 and 3 as above) intervals, in healthy adults and elderly participants. A 28- and 56-day (Groups 1 and 2, as above) schedule will be evaluated in HIV-infected participants and in healthy children in 2 age strata. The study consists of a screening phase of up to 8 weeks, a vaccination phase in which participants will be vaccinated at baseline (Day 1) followed by a boost vaccination on Day 29, 57 or 85, a post-vaccination phase and long-term follow-up phase until Day 365. Participants in Cohort 1 substudy (Group 1 and 2) who received Ad26.ZEBOV and MVA-BN-Filo (at selected sites) will receive Ad26.ZEBOV as third vaccination and who received placebo will receive placebo as third vaccination (at least 1 year post prime vaccination). All participants within a cohort will be followed in a blinded manner by the site until the last subject in that cohort has completed the study. This study will be conducted in Africa and the enrollment will take place sequentially in three cohorts: the first cohort will consist of healthy participants (18 - 70 years); the second cohort (2a) will include HIV-infected participants (18 to 50 years) and healthy children 12 to 17 years (cohort 2b); the third cohort will include children aged 4 to 11 years inclusive will be enrolled. Within each cohort, participants will be randomized in a 5:1 ratio to receive active vaccine versus placebo. Safety evaluations will include assessments of adverse events, an electrocardiogram (ECG) for adult participants at screening, physical examination, vital signs (blood pressure, pulse/heart rate, body temperature), clinical laboratory and pregnancy testing. An independent data monitoring committee (IDMC) will be established to monitor data on a regular basis to ensure the continuing safety of the participants enrolled in the study.

Eligibility criteria: Inclusion Criteria:

Criteria for healthy adults and elderly participants:

* Participant must be healthy in the investigator's clinical judgment on the basis of clinical laboratory tests, medical history, ECG, physical examination and vital signs performed at screening. Participants with hemoglobin values outside the local laboratory reference ranges may be included if the hemoglobin is above the age/gender specific limits
* Female participants of childbearing potential must use adequate birth control measures, must have a negative pregnancy test at screening and immediately prior to each study vaccination
* A man who is sexually active with a woman of childbearing potential must be willing to use condoms for sexual intercourse beginning prior to enrollment, unless a vasectomy was performed more than 1 year prior to screening
* Participant must pass the test of understanding (TOU)
* Participant must be available and willing to participate for the duration of the study visits and follow-up, provide verifiable identification, and have a means to be contacted Additional Inclusion Criteria HIV-infected Participants
* Participant must be between 18 to 50 years of age and must have a documented HIV-infection for at least 6 months prior to screening
* Participant must be on a stable 3 drug regimen of Highly Active Antiretroviral Therapy for at least 4 weeks prior to screening and having a CD4 positive cell count of \>350 cells/microliter. Also participant must be in an otherwise reasonable good medical condition Additional Inclusion Criteria Children Participants
* Parent/legal guardian must pass the TOU before signing the inform consent form. Informed assent must be obtained from adolescents and older children, depending on local regulations and practice
* Pediatric participant's age on the day of randomization must be within one of the 2 age strata: 12-17 years or 4-11 years (all ages inclusive)
* Pediatric participants must have received all routine immunizations appropriate for his or her age as reported by the parent(s)/legal guardian, according to local routine vaccination schedules

Exclusion criteria:

* Diagnosed with Ebola virus disease or previously exposed to Ebola virus including travel to epidemic Ebola areas less than 1 month prior to screening
* Having received any candidate Ebola vaccine or any experimental candidate Ad26- or MVA-based vaccine in the past
* Having HIV type 1 or type 2 infection (for healthy adults/elderly/children)
* Pediatric participants with weight-per-height below 10th percentile according to the Centers for Disease Control and Prevention (CDC) growth charts (4- to 11-year-olds)
* A woman who is pregnant, breast-feeding or planning to become pregnant while enrolled in the study or within at least 3 months after the prime vaccination or up to 1 month after the boost vaccination (whichever takes longer) or within at least 3 months after the third vaccination
* For HIV+ adults, no AIDS-defining illnesses

Primary outcomes:
measure: Number of Participants With Adverse Events (Day 29)
timeFrame: Up to 28 days post-dose 1 (Day 29)
measure: Number of Participants With Adverse Events (AEs) (28-Day Interval)
timeFrame: Up to 28 days post-dose 2 (Day 57 for Cohorts 1, 2a, 2b and 3 [28-Day Interval])
measure: Number of Participants With Adverse Events (56-day Interval)
timeFrame: Up 28 days post-dose 2 (Day 85 for Cohorts 1, 2a, 2b and 3 [56-Day Interval])
measure: Number of Participants With Adverse Events (84-day Interval)
timeFrame: Up to 28 days post-dose 2 (Day 113 for Cohort 1 [84-Day Interval])
measure: Number of Participants With Adverse Events Post-dose 3 (Day 393)
timeFrame: Up 28 days post-dose 3 (Day 393)
measure: Number of Participants With Serious Adverse Events
timeFrame: Up to 3 years and 3 months
measure: Number of Participants With Immediate Reportable Events (IREs)
timeFrame: Up to 3 years and 3 months
measure: Number of Participants With Solicited Local Adverse Events (Day 8)
timeFrame: 7 days post-dose 1 (Day 8)
measure: Number of Participants With Solicited Local Adverse Events (28-day Interval)
timeFrame: Up to 7 days post-dose 2 (Day 36 for Cohort 1, 2a, 2b and 3 [28-Day Interval])
measure: Number of Participants With Solicited Local Adverse Events Post-dose 2 (56-day Interval)
timeFrame: Up to 7 days post-dose 2 (Day 64 for Cohort 1, 2a, 2b and 3 [56-Day Interval])
measure: Number of Participants With Solicited Local Adverse Events (84-day Interval)
timeFrame: Up to 7 days post-dose 2 (Day 92 for Cohort 1 [84-Day Interval])
measure: Number of Participants With Solicited Local Adverse Events (Day 372)
timeFrame: Up 7 days post-dose 3 (Day 372)
measure: Number of Participants With Solicited Systemic Adverse Events (Day 8)
timeFrame: Up to 7 days post-dose 1 (Day 8)
measure: Number of Participants With Solicited Systemic Adverse Events (28-Day Interval)
timeFrame: Up to 7 days post-dose 2 (Day 36 for Cohorts 1, 2a, 2b and 3 [28-Day Interval])
measure: Number of Participants With Solicited Systemic Adverse Events (56-Day Interval)
timeFrame: Up 7 days post-dose 2 (Day 64 for Cohort 1, 2a, 2b and 3 [56-Day Interval])
measure: Number of Participants With Solicited Systemic Adverse Events (84-Day Interval)
timeFrame: Up 7 days post-dose 2 (Day 92 for Cohort 1 [84-Day Interval])
measure: Number of Participants With Solicited Systemic Adverse Events (Day 372)
timeFrame: Up to 7 days post-dose 3 (Day 372)
Secondary outcomes:
measure: Geometric Mean Concentrations (GMCs) of Binding Antibody Levels Against Ebola Virus Glycoprotein (EBOV GP) Measured Using Filovirus Animal Non-Clinical Group (FANG) Enzyme-linked Immunosorbent Assay
timeFrame: 21-days post-dose 2 (Day 50 for Cohorts 1, 2a, 2b, 3 [28-day interval] , Day 78 for Cohort 1, 2a, 2b, 3 [56-day interval] and Day 106 Cohort 1 [84-day interval]
measure: Number of Participants With Serious Adverse Events Post-dose 3
timeFrame: Up 28 days post-dose 3 (Day 393)
Other outcomes:
Locations:
city: BoboDioulasso
country: Burkina Faso
city: Ouagadougou
country: Burkina Faso
city: Abidjan
country: Côte D'Ivoire
city: Toupah/Ousrou
country: Côte D'Ivoire
city: Nairobi
country: Kenya
city: Entebbe
country: Uganda
city: Kampala
country: Uganda
Study officials:
affiliation: Janssen Vaccines & Prevention B.V.
name: Janssen Vaccines & Prevention B.V. Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Anywaine Z, Barry H, Anzala O, Mutua G, Sirima SB, Eholie S, Kibuuka H, Betard C, Richert L, Lacabaratz C, McElrath MJ, De Rosa SC, Cohen KW, Shukarev G, Katwere M, Robinson C, Gaddah A, Heerwegh D, Bockstal V, Luhn K, Leyssen M, Thiebaut R, Douoguih M; EBL2002 Study group. Safety and immunogenicity of 2-dose heterologous Ad26.ZEBOV, MVA-BN-Filo Ebola vaccination in children and adolescents in Africa: A randomised, placebo-controlled, multicentre Phase II clinical trial. PLoS Med. 2022 Jan 11;19(1):e1003865. doi: 10.1371/journal.pmed.1003865. eCollection 2022 Jan.
citation: Barry H, Mutua G, Kibuuka H, Anywaine Z, Sirima SB, Meda N, Anzala O, Eholie S, Betard C, Richert L, Lacabaratz C, McElrath MJ, De Rosa S, Cohen KW, Shukarev G, Robinson C, Gaddah A, Heerwegh D, Bockstal V, Luhn K, Leyssen M, Douoguih M, Thiebaut R; EBL2002 Study group. Safety and immunogenicity of 2-dose heterologous Ad26.ZEBOV, MVA-BN-Filo Ebola vaccination in healthy and HIV-infected adults: A randomised, placebo-controlled Phase II clinical trial in Africa. PLoS Med. 2021 Oct 29;18(10):e1003813. doi: 10.1371/journal.pmed.1003813. eCollection 2021 Oct.