Staged Phase 3 Study to Assess the Safety and Immunogenicity of Ebola Candidate Vaccines Ad26.ZEBOV and MVA-BN-Filo

Janssen Vaccines & Prevention B.V.1,023 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

DOUBLE

Enrollment

1,023

Conditions

Ebola Virus Disease

Interventions

Ad26.ZEBOVBIOLOGICAL

Ebola Zaire vaccine, replication incompetent vaccine, sterile suspension of 0.5 milliliter (mL) intramuscular (IM) injection of 5\*10\^10 viral particles.

MVA-BN-FiloBIOLOGICAL

MVA-BN-Filo- is a non-replicating vaccine, 0.5 mL IM injection of 1\*10\^8 Infectious Unit (Inf. U.).

MenACWYBIOLOGICAL

MenACWY is a WHO-prequalified Meningococcal Group A, C, W135 and Y conjugate vaccine.

Eligibility

Sex: ALLMin age: 1 YearHealthy volunteers:

Medical Language ↔ Plain English

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)

Locations (1)

Unnamed facility

Freetown, Sierra Leone

Outcomes

Primary Outcomes

Stages 1 and 2: Number of Participants With Solicited Local Adverse Events (AEs) (Day 8)

Number of participants with solicited local AEs were reported. Solicited local AEs were pre-defined local (at the injection site) AEs for which participants were specifically questioned and which were noted by participants in their diary for 7 days post vaccination. Solicited local AEs were: injection site pain/tenderness, erythema, induration/swelling, itching at the vaccination site.

Time frame: 7 days post dose 1 (Day 8)

Stages 1 and 2: Number of Participants With Solicited Local AEs (Day 64)

Time frame: 7 days post dose 2 (Day 64)

Stage 1: Number of Participants With Solicited Local AEs (Day 738)

Time frame: 7 days post dose 3 (Day 738)

Stages 1 and 2: Number of Participants With Solicited Systemic AEs (Day 8)

Number of participants with solicited systemic AEs were reported. Solicited systemic AEs included body temperature, vomiting, reduced activity, somnolence, fatigue, irritability/fussiness/crying/screaming, and loss of appetite (for preverbal children/infants) and body temperature, nausea/vomiting, fatigue/malaise, muscle pain, chills, joint pain and headache (for young children, adolescents, and adults).