Clinical trial NCT02509494: Staged Phase 3 Study to Assess the Safety and Immunogenicity of Ebola Candidate Vaccines Ad26.ZEBOV and MVA-BN-Filo
Official title: A Staged Phase 3 Study, Including a Double-Blinded Controlled Stage to Evaluate the Safety and Immunogenicity of Ad26.ZEBOV and MVA-BN-Filo as Candidate Prophylactic Vaccines for Ebola
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Ebola Virus Disease
Keywords: Vaccine
Ebola
Ebola virus disease
EVD
Hemorrhagic fever
Sierra Leone
Human adenovirus serotype 26 (Ad26) encoding the Ebola virus Mayinga variant glycoprotein (Ad26.ZEBOV)
Safety
Immunogenicity
Modified Vaccinia Virus Ankara - Bavarian Nordic Filo-vector
(MVA-BN Filo)
Lead sponsor: Janssen Vaccines & Prevention B.V.
Sponsor class: INDUSTRY
Collaborators: name: London School of Hygiene and Tropical Medicine
name: Ministry of Health and Sanitation, Sierra Leone
name: University of Sierra Leone
name: University of Oxford
name: Institut National de la Santé Et de la Recherche Médicale, France
name: Grameen Foundation
name: World Vision, Ireland
First posted: 2015-07-28
Enrollment: 1023
Sex: ALL
Minimum age (years): 1
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 the evaluation of the safety and immunogenicity of two candidate Ebola vaccines Ad26.ZEBOV and MVA-BN-Filo, in a 2-dose heterologous regimen.

Detailed description: This is staged Phase 3 study to gather information on the safety and immunogenicity of a 2-dose heterologous regimen. In this regimen, Ad26.ZEBOV will be administered as a Dose 1 vaccination followed by the candidate vaccine MVA-BN-Filo (Dose 2 56 days later) and a booster dose of A26.ZEBOV will be administered 2 years post Dose 1 vaccination to participants in Stage 1 who consent to this. The study will take place in Sierra Leone and will consist of a screening phase, an active phase (vaccination) and a follow-up phase. The active phase of the study will be conducted initially in two stages. In the first stage approximately 40 adults aged 18 years or older will be vaccinated to gain information about the safety and immunogenicity of the 2-dose heterologous vaccine regimen. In stage 2 a larger group of approximately 976 individuals will be vaccinated to further evaluate the safety and immunogenicity of the 2 dose heterologous vaccine regimen across different age groups. In this stage, children aged 1 year or older, adolescents and adults will be included. Solicited local and systemic adverse events will be collected until 7 days after the Dose 1 and Dose 2 vaccination. Unsolicited adverse events will be collected from signing of the informed consent form (ICF) onwards until 56 days after the Dose 2 vaccination in Stage 1 and then again from the day of the booster vaccination until 28 days after the booster vaccination, and until 28 days after each vaccination in stage 2. Serious adverse events will be collected from signing of the ICF onwards until 12 and 36 months after the Dose 1 vaccination in Stage 2 and Stage 1, respectively. These data will be reviewed by an independent data monitoring committee (IDMC) to assess whether initiation of vaccination in the next stage or age group can be provided. Safety evaluations will include assessment of adverse events, which will be monitored throughout the study. Participants in Stage 2 will be followed up for safety and immunogenicity until 12 months (children and adolescents) or 24 months (adults) after the Dose 1 vaccination. Participants in Stage 1 will be followed up for safety and immunogenicity until 36 months after the Dose 1 vaccination or until 1 year after the booster vaccination.

Eligibility criteria: Inclusion Criteria Stage 1 and 2:

* Documented community engagement from community leader and a signed inform consent form (ICF) from each participant must be available
* Participant Stage 1 must be 18 years or older at screening and be resident in selected study community with no intention to move from study area within the next 5 months
* Participant must be healthy with no abnormalities in laboratory screening tests within 28 days before Dose 1 vaccination
* Female participants of childbearing potential must use adequate birth control measures and must have a negative pregnancy test at screening and immediately prior to each study vaccination
* Participant must pass the test of understanding (TOU)

Additional Inclusion criteria Stage 2:

* One year or older at screening (children of enrolled parents are eligible)
* Parent/legal guardian (for children) must pass the TOU before signing the ICF
* Subjects aged 7 years and older will be asked to give positive assent in the presence of a witness

Exclusion Criteria:

* Diagnosed with EVD or under quarantine/exposed to Ebola or body temperature equal of \>= 38 degree Celsius (fever)
* Having an acute illness (mild in nature that can be treated at home) or any clinically significant acute/chronic medical condition or having a decreased number of red blood cells/hemoglobin in the blood (anemia)
* Previously participated in another Ebola interventional study or received any Ad26/MVA-based candidate vaccine
* Vaccinated with live attenuated vaccines within 30 days or with inactivated vaccines 15 days before Dose 1 vaccination
* Treated with an immunosuppressive drug at the time of screening

Additional exclusion criteria:

- Children up to 5 years of age with severe malnutrition (underweight or Z-score weight \<2)

Primary outcomes:
measure: Stages 1 and 2: Number of Participants With Solicited Local Adverse Events (AEs) (Day 8)
timeFrame: 7 days post dose 1 (Day 8)
measure: Stages 1 and 2: Number of Participants With Solicited Local AEs (Day 64)
timeFrame: 7 days post dose 2 (Day 64)
measure: Stage 1: Number of Participants With Solicited Local AEs (Day 738)
timeFrame: 7 days post dose 3 (Day 738)
measure: Stages 1 and 2: Number of Participants With Solicited Systemic AEs (Day 8)
timeFrame: 7 days post dose 1 (Day 8)
measure: Stages 1 and 2: Number of Participants With Solicited Systemic AEs (Day 64)
timeFrame: 7 days post dose 2 (Day 64)
measure: Stage 1: Number of Participants With Solicited Systemic AEs (Day 738)
timeFrame: 7 days post dose 3 (Up to Day 738)
measure: Stages 1: Number of Participants With Serious Adverse Events (SAEs)
timeFrame: Up to 36 months
measure: Stages 2: Number of Participants With SAEs
timeFrame: Up to 24 months
measure: Stage 1: Number of Participants With Unsolicited AEs (Day 759)
timeFrame: 28 days post booster dose (Day 759)
measure: Stage 1: Number of Participants With Unsolicited AEs (Day 29)
timeFrame: 28 days post dose 1 (Day 29)
measure: Stage 2: Number of Participants With Unsolicited AEs (Day 29)
timeFrame: 28 days post dose 1 (Day 29)
measure: Stage 1: Number of Participants With Unsolicited AEs (Day 85)
timeFrame: 28 days post dose 2 (Day 85)
measure: Stage 2: Number of Participants With Unsolicited AEs (Day 85)
timeFrame: 28 days post dose 2 (Day 85)
measure: Stage 1: Number of Participants With Deaths
timeFrame: Up to 36 months
measure: Stage 2: Number of Participants With Deaths (Children and Adolescents)
timeFrame: Up to 12 months
measure: Stage 2: Number of Participants With Deaths (Adults)
timeFrame: Up to 24 months
measure: Stage 1: Number of Participants With Immediate Reportable Event (IREs)
timeFrame: Up to 36 months
measure: Stage 2: Number of Participants With IREs (Children and Adolescents)
timeFrame: Up to 12 months
measure: Stage 2: Number of Participants With IREs (Adults)
timeFrame: Up to 24 months
Secondary outcomes:
measure: Stages 1 and 2: Geometric Mean Concentrations (GMCs) of Binding Antibody Levels Against Ebola Virus Glycoprotein (EBOV GP) Measured Using Enzyme-linked Immunosorbent Assay (ELISA)
timeFrame: 21 days post-dose 2 (Day 78)
Other outcomes:
Locations:
city: Freetown
country: Sierra Leone
Study officials:
affiliation: Janssen Vaccines & Prevention B.V.
name: Janssen Vaccines & Prevention B.V. Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Ishola D, Manno D, Afolabi MO, Keshinro B, Bockstal V, Rogers B, Owusu-Kyei K, Serry-Bangura A, Swaray I, Lowe B, Kowuor D, Baiden F, Mooney T, Smout E, Kohn B, Otieno GT, Jusu M, Foster J, Samai M, Deen GF, Larson H, Lees S, Goldstein N, Gallagher KE, Gaddah A, Heerwegh D, Callendret B, Luhn K, Robinson C, Leyssen M, Greenwood B, Douoguih M, Leigh B, Watson-Jones D; EBL3001 study group. Safety and long-term immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in adults in Sierra Leone: a combined open-label, non-randomised stage 1, and a randomised, double-blind, controlled stage 2 trial. Lancet Infect Dis. 2022 Jan;22(1):97-109. doi: 10.1016/S1473-3099(21)00125-0. Epub 2021 Sep 13.
citation: Afolabi MO, Ishola D, Manno D, Keshinro B, Bockstal V, Rogers B, Owusu-Kyei K, Serry-Bangura A, Swaray I, Lowe B, Kowuor D, Baiden F, Mooney T, Smout E, Kohn B, Otieno GT, Jusu M, Foster J, Samai M, Deen GF, Larson H, Lees S, Goldstein N, Gallagher KE, Gaddah A, Heerwegh D, Callendret B, Luhn K, Robinson C, Greenwood B, Leyssen M, Douoguih M, Leigh B, Watson-Jones D; EBL3001 study group. Safety and immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in children in Sierra Leone: a randomised, double-blind, controlled trial. Lancet Infect Dis. 2022 Jan;22(1):110-122. doi: 10.1016/S1473-3099(21)00128-6. Epub 2021 Sep 13.
citation: Mooney T, Smout E, Leigh B, Greenwood B, Enria L, Ishola D, Manno D, Samai M, Douoguih M, Watson-Jones D. EBOVAC-Salone: Lessons learned from implementing an Ebola vaccine trial in an Ebola-affected country. Clin Trials. 2018 Oct;15(5):436-443. doi: 10.1177/1740774518780678. Epub 2018 Jun 12.