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

NCT ID: NCT02509494

Last Updated: 2022-07-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1023 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-30
• Study Completion Date: 2019-07-03

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.

Conditions

Ebola Virus Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Stage 1: Active vaccination

Ad26.ZEBOV will be administered as a 0.5 milliliter (mL) intramuscular (IM) injection (Dose 1); MVA-BN-Filo will be administered as a 0.5 mL IM injection (Dose 2). The booster vaccination using Ad26.ZEBOV will be administered as a 0.5 mL IM injection (2 years post Dose 1).

Group Type: EXPERIMENTAL

Ad26.ZEBOV

Intervention Type: BIOLOGICAL

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

MVA-BN-Filo

Intervention Type: BIOLOGICAL

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

Stage 2: Active vaccination

Ad26.ZEBOV will be administered as a 0.5 mL IM injection (Dose 1); MVA-BN-Filo will be administered as a 0.5 mL IM injection (Dose 2).

Group Type: EXPERIMENTAL

Ad26.ZEBOV

Intervention Type: BIOLOGICAL

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

MVA-BN-Filo

Intervention Type: BIOLOGICAL

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

Stage 2: Active vaccination for children

Ad26.ZEBOV will be administered as a 0.5 mL IM injection (Dose 1); MVA-BN-Filo will be administered as a 0.5 mL IM injection (Dose 2). Children aged less than 2 years at randomization will receive a booster dose of vaccination at 3 months post Dose 2 with Placebo.

Group Type: EXPERIMENTAL

Ad26.ZEBOV

Intervention Type: BIOLOGICAL

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

MVA-BN-Filo

Intervention Type: BIOLOGICAL

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

Stage 2: Control vaccination

MenACWY will be administered as a 0.5 mL IM injection on Day 1 (Dose 1) and placebo on Day 57 (Dose 2).

Group Type: ACTIVE_COMPARATOR

MenACWY

Intervention Type: BIOLOGICAL

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

Placebo

Intervention Type: BIOLOGICAL

0.9% saline for injection.

Stage 2: Control vaccination for children

MenACWY will be administered as a 0.5 mL IM injection on Day 1 (Dose 1) and placebo on Day 57 (Dose 2). Children aged less than 2 years at randomization will receive a booster dose of MenACWY vaccination at 3 months post Dose 2 with MenACWY.

Group Type: ACTIVE_COMPARATOR

MenACWY

Intervention Type: BIOLOGICAL

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

Placebo

Intervention Type: BIOLOGICAL

0.9% saline for injection.

Interventions

Ad26.ZEBOV

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

Intervention Type: BIOLOGICAL

MVA-BN-Filo

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

Intervention Type: BIOLOGICAL

MenACWY

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

Intervention Type: BIOLOGICAL

Placebo

0.9% saline for injection.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• 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)

• 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

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

• Minimum Eligible Age: 1 Year
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

London School of Hygiene and Tropical Medicine

OTHER

Sponsor Role: collaborator

Ministry of Health and Sanitation, Sierra Leone

OTHER_GOV

Sponsor Role: collaborator

University of Sierra Leone

OTHER

Sponsor Role: collaborator

University of Oxford

OTHER

Sponsor Role: collaborator

Institut National de la Santé Et de la Recherche Médicale, France

OTHER_GOV

Sponsor Role: collaborator

Grameen Foundation

OTHER

Sponsor Role: collaborator

World Vision, Ireland

OTHER

Sponsor Role: collaborator

Janssen Vaccines & Prevention B.V.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Vaccines & Prevention B.V. Clinical Trial

Role: STUDY_DIRECTOR

Janssen Vaccines & Prevention B.V.

Locations

Freetown, , Sierra Leone

Countries

Sierra Leone

References

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Reference Type: DERIVED

PMID: 38603720 (View on PubMed)

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Reference Type: DERIVED

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Reference Type: DERIVED

PMID: 34529963 (View on PubMed)

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Reference Type: DERIVED

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Reference Type: DERIVED

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Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

VAC52150EBL3001

Identifier Type: OTHER

Identifier Source: secondary_id

115854 EBOVAC1

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

2019-000691-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR107372

Identifier Type: -

Identifier Source: org_study_id