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

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ClinicalTrials.gov Identifier: NCT04152486
Recruitment Status : Recruiting
First Posted : November 5, 2019
Last Update Posted : December 2, 2019
Sponsor:
Collaborators:
Epicentre
Ministère de la Santé de la RDC
Médecins Sans Frontières, France
Coalition for Epidemic Preparedness Innovations
Janssen Vaccines & Prevention B.V.
Public Health England
Information provided by (Responsible Party):
London School of Hygiene and Tropical Medicine

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Ebola Virus Disease Biological: Ad26.ZEBOV, MVA-BN-Filo vaccine Phase 3

Detailed Description:

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 500 individuals and pregnant women will be followed to 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.

Depending on logistical and community constraints, one exploratory objective is to assess the immune response at T0 before vaccination and 21 days after the second dose (MVN-BN-Filo) in a subgroup of adults and children.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 500000 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Single arm, open-label, non-randomized interventional trial of the two dose, Ad26.ZEBOV, MVA-BN-Filo Ebola preventative vaccine
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Evaluation of a Heterologous, Two-dose Preventive Ebola Vaccine for Effectiveness and Safety in the Democratic Republic of the Congo
Actual Study Start Date : November 14, 2019
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : November 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Ebola

Arm Intervention/treatment
Experimental: 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.
Biological: 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.





Primary Outcome Measures :
  1. Numbers and odds of vaccination status in Ebola Virus Diseases cases and in EVD-negative controls. [ Time Frame: Through study completion, an average of 2 years. ]
    Test negative case control study of 110 laboratory confirmed EVD cases matched to controls who test negative for EVD. Effectiveness is derived from the odds ratio for vaccination in cases compared to controls to calculate vaccine effectiveness.

  2. Number and proportion of adults and children with solicited and unsolicited serious adverse events. [ Time Frame: From date of first vaccination to the one month post-dose 2 assessment of the last vaccinated participant. ]
    Data on SAEs within one month post-dose 2 that are considered related to vaccination with Ad26. ZEBOV, MVA-BN®-Filo vaccine in adults and children.


Secondary Outcome Measures :
  1. Number and proportion of pregnant participants with solicited and unsolicited serious adverse events including congenital abnormalities in their infants. [ Time Frame: From date of first vaccination to the six months post-dose 2 or the 3 month post-delivery assessment for the last pregnant participant vaccinated, whichever comes first. ]
    SAEs and birth outcome data in participants who were pregnant at the time of vaccination or who become pregnant within one month of vaccination.

  2. Number and proportion of adults and children receiving dose 1. [ Time Frame: From date of first vaccination up to month 12. ]
    Vaccine uptake

  3. Number and proportion of adults and children receiving dose 2. [ Time Frame: From date of first vaccination up to month 12. ]
    Vaccine coverage

  4. Number of participants participating in in-depth interviews and focus group discussions [ Time Frame: Through to study completion at month 24. ]
    Focus group discussions and in-depth interviews on participant and community perceptions of the trial and on vaccine acceptability.



Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04152486


Contacts
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Contact: Jean-Jacques Muyembe-Tamfum, MD, PhD +243 898949289 jjmuyembet@inrb.net
Contact: Hugo Kavunga, MD, PhD +243 823875153 hugokavunga@inrb.net

Locations
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Congo, The Democratic Republic of the
L'Institut National de Recherche Biomédicale RDC Recruiting
Kinshasa, Congo, The Democratic Republic of the
Contact: Jean-Jacques Muyembe-Tamfum, MD, PhD    +243 898949289    jjmuyembet@inrb.net   
Contact: Hugo Kavunga, MD, PhD    +243 823875153    hugokavunga@inrb.net   
Sponsors and Collaborators
London School of Hygiene and Tropical Medicine
Epicentre
Ministère de la Santé de la RDC
Médecins Sans Frontières, France
Coalition for Epidemic Preparedness Innovations
Janssen Vaccines & Prevention B.V.
Public Health England
Investigators
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Principal Investigator: Jean-Jacques Muyembe-Tamfum, MD, PhD L'Institut National de Recherche Biomédicale RDC
Principal Investigator: Daniel Bausch, MD, PhD London School of Hygiene and Tropical Medicine
Principal Investigator: Deborah Watson-Jones, MD, PhD London School of Hygiene and Tropical Medicine
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Responsible Party: London School of Hygiene and Tropical Medicine
ClinicalTrials.gov Identifier: NCT04152486    
Other Study ID Numbers: DRC-EB-001
First Posted: November 5, 2019    Key Record Dates
Last Update Posted: December 2, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hemorrhagic Fever, Ebola
Virus Diseases
Hemorrhagic Fevers, Viral
RNA Virus Infections
Filoviridae Infections
Mononegavirales Infections