Effectiveness and Safety of a Heterologous, Two-dose Ebola Vaccine in the DRC

NCT ID: NCT04152486

Last Updated: 2021-11-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

20426 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-11-14

Study Completion Date

2022-02-28

Brief Summary

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A single arm, open-label, non-randomized, interventional phase 3 study to measure safety and effectiveness of a heterologous, two dose preventative vaccine (Ad26. ZEBOV, MVA-BN®-Filo) against Ebola Virus Disease.

Detailed Description

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Ebola Virus Disease (EVD) is an acute, systemic, febrile syndrome caused by Ebola viruses. EVD has a case fatality ranging from 30% to 90% and spreads by direct contact with body fluids of symptomatic patients.

During the 2013-16 Ebola outbreak in Guinea, a Phase 3 cluster-randomised ring-vaccination trial using single-dose rVSV-ZEBOV-GP investigational vaccine reported 100% efficacy in protection against EVD. In 2016, the WHO Strategic Advisory Group of Experts (SAGE) on Immunization recommended the rapid deployment of rVSV-ZEBOV-GP in case of an EVD outbreak under an Expanded Access (compassionate use) protocol, with informed consent and Good Clinical Practice (GCP) compliance.

A new EVD outbreak started in North Kivu and Ituri provinces in the Democratic Republic of Congo in July 2018. Despite extensive control measures, including vaccination with rVSV-ZEBOV-GP in active outbreak areas, the outbreak has continued and WHO declared the outbreak a Public Health Emergency of International Concern on 17 July 2019. The ongoing outbreak has prompted consideration of additional vaccine candidates that might assist in preventing the spread of this infection to currently unaffected communities.

This study will investigate population-level vaccination with a two-dose prophylactic vaccine against Ebola, the Ad26.ZEBOV, MVA-BN-Filo vaccine that has been extensively studied in 11 previous safety and immunogenicity trials. This will be done by offering vaccination first to communities that neighbour the outbreak area or that are located on transport routes from the edge of the outbreak area to major centres like Goma.

In this study, approximately 500,000 healthy adults and children will be given the two-dose candidate vaccine regimen VAC52150 that consists of two vaccines, Ad26.ZEBOV and MVA-BN®-Filo, administered at an interval of 56 days (-14 day +28 day). Safety will be assessed in a safety subset of 1000 individuals and a pregnancy subset of up to 500 pregnant women will be followed to delivery. The first 100 infants born to these pregnant participants will be given a clinical examination at 3 months post-delivery. The study will estimate vaccine coverage of dose 1 and dose 2 overall and in different target groups and will also examine the knowledge and perceptions of persons eligible for large-scale delivery of a preventative Ebola vaccine with a two-dose vaccine strategy. The effectiveness of the vaccination on EVD will be determined through a test-negative case control study. The target sample size for the primary effectiveness evaluation is 110 laboratory-confirmed EVD cases.

An exploratory objective is to assess the immune response at before the second dose and 21 days after the second dose (MVN-BN-Filo) in a subgroup of 50 adults and 50 children who receive dose 2 beyond the recommended 56-day interval.

Conditions

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Ebola Virus Disease

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Single arm, open-label, non-randomized interventional trial of the two dose, Ad26.ZEBOV, MVA-BN-Filo Ebola preventative vaccine
Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Intervention arm

The vaccine Ad26.ZEBOV (5x10\^10 viral particles (vp)) will be given as the first dose and the vaccine MVA-BN-Filo (1x10\^8 infectious units (Inf U)) will be given as the second dose 56 (-14 day +28 day) days later.

Group Type EXPERIMENTAL

Ad26.ZEBOV, MVA-BN-Filo vaccine

Intervention Type BIOLOGICAL

Ad26.ZEBOV: a monovalent vaccine expressing the full-length glycoprotein (GP) from Ebola virus (EBOV) Mayinga. The vaccine is produced in the human cell line PER.C6®.

MVA-mBN226B: further referred to as Modified Vaccinia Ankara (MVA)-BN®-Filo. This is a multivalent vaccine expressing the EBOV GP, the Sudan virus (SUDV) GP, the Marburg virus (MARV) Musoke GP, and the Taï Forest virus (TAFV, formerly known as Côte d'Ivoire ebolavirus) nucleoprotein (NP). The EBOV GP expressed by MVA BN Filo has 100% homology with the one expressed by Ad26.ZEBOV.

Interventions

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Ad26.ZEBOV, MVA-BN-Filo vaccine

Ad26.ZEBOV: a monovalent vaccine expressing the full-length glycoprotein (GP) from Ebola virus (EBOV) Mayinga. The vaccine is produced in the human cell line PER.C6®.

MVA-mBN226B: further referred to as Modified Vaccinia Ankara (MVA)-BN®-Filo. This is a multivalent vaccine expressing the EBOV GP, the Sudan virus (SUDV) GP, the Marburg virus (MARV) Musoke GP, and the Taï Forest virus (TAFV, formerly known as Côte d'Ivoire ebolavirus) nucleoprotein (NP). The EBOV GP expressed by MVA BN Filo has 100% homology with the one expressed by Ad26.ZEBOV.

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

1. Must provide a written or witnessed (if illiterate) informed consent form indicating that he or she understands the reasons for the study and is willing to participate in the study and be vaccinated. If less than 18 years old, must have a parent or guardian that is able to meet this criterion.
2. Must be aged 1 year or older.
3. Must be healthy in the investigator's clinical judgment as assessed on the day of vaccination.
4. Must be willing to have a photograph taken.
5. Participant must be available and willing to participate for duration of study visits and follow up.

Exclusion Criteria

1. Known history of Ebola virus disease.
2. Has received any experimental Ebola vaccine less than one month prior to Visit 1.
3. Known allergy or history of anaphylaxis or other serious adverse reactions to vaccines or vaccine products, egg and egg proteins or gentamicin.
4. Presence of acute illness (excluding minor illnesses such as mild diarrhea or mild upper respiratory tract infection) or temperature ≥38.0ºC at Visit 1 (dose 1 visit). Participants with such symptoms will be temporarily excluded from vaccination at that time but may be rescheduled for vaccination at a later date if feasible.
5. Presence of significant conditions or clinically significant findings at the vaccination visit for which, in the opinion of the investigator, vaccination would not be in the best interest of the participant.
6. History of recurrent generalized hives.
Minimum Eligible Age

1 Year

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Epicentre

OTHER

Sponsor Role collaborator

Ministère de la Santé de la RDC

UNKNOWN

Sponsor Role collaborator

Médecins Sans Frontières, France

OTHER

Sponsor Role collaborator

Coalition for Epidemic Preparedness Innovations

OTHER

Sponsor Role collaborator

Janssen Vaccines & Prevention B.V.

INDUSTRY

Sponsor Role collaborator

Public Health England

OTHER_GOV

Sponsor Role collaborator

London School of Hygiene and Tropical Medicine

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jean-Jacques Muyembe-Tamfum, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

L'Institut National de Recherche Biomédicale RDC

Daniel Bausch, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

London School of Hygiene and Tropical Medicine

Deborah Watson-Jones, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

London School of Hygiene and Tropical Medicine

Locations

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L'Institut National de Recherche Biomédicale RDC

Kinshasa, , Democratic Republic of the Congo

Site Status

Countries

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Democratic Republic of the Congo

References

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Watson-Jones D, Kavunga-Membo H, Grais RF, Ahuka S, Roberts N, Edmunds WJ, Choi EM, Roberts CH, Edwards T, Camacho A, Lees S, Leyssen M, Spiessens B, Luhn K, Douoguih M, Hatchett R, Bausch DG, Muyembe JJ; DRC-EB-001 protocol writing team. Protocol for a phase 3 trial to evaluate the effectiveness and safety of a heterologous, two-dose vaccine for Ebola virus disease in the Democratic Republic of the Congo. BMJ Open. 2022 Mar 8;12(3):e055596. doi: 10.1136/bmjopen-2021-055596.

Reference Type DERIVED
PMID: 35260458 (View on PubMed)

Other Identifiers

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DRC-EB-001

Identifier Type: -

Identifier Source: org_study_id