Effectiveness and Safety of a Heterologous, Two-dose Ebola Vaccine in the DRC
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|ClinicalTrials.gov Identifier: NCT04152486|
Recruitment Status : Active, not recruiting
First Posted : November 5, 2019
Last Update Posted : June 29, 2021
|Condition or disease||Intervention/treatment||Phase|
|Ebola Virus Disease||Biological: Ad26.ZEBOV, MVA-BN-Filo vaccine||Phase 3|
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.
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 adults and children who receive dose 2 beyond the recommended 56-day interval.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||20426 participants|
|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)|
|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 :||January 31, 2022|
|Estimated Study Completion Date :||February 28, 2022|
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.
- 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.
- 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.
- 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.
- Number and proportion of adults and children receiving dose 1. [ Time Frame: From date of first vaccination up to month 12. ]Vaccine uptake
- Number and proportion of adults and children receiving dose 2. [ Time Frame: From date of first vaccination up to month 12. ]Vaccine coverage
- 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.
- Samples collected for immunogenicity subset at 2 time points [ Time Frame: From date of dose 2 through to 21 days post-dose 2. ]Level of immunoglobulin G binding antibodies at dose 2 and 21 days post-dose 2
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
|Congo, The Democratic Republic of the|
|L'Institut National de Recherche Biomédicale RDC|
|Kinshasa, Congo, The Democratic Republic of the|
|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|