Clinical trial NCT04152486: Effectiveness and Safety of a Heterologous, Two-dose Ebola Vaccine in the DRC
Official title: Evaluation of a Heterologous, Two-dose Preventive Ebola Vaccine for Effectiveness and Safety in the Democratic Republic of the Congo
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Ebola Virus Disease
Lead sponsor: London School of Hygiene and Tropical Medicine
Sponsor class: OTHER
Collaborators: name: Epicentre
name: Ministère de la Santé de la RDC
name: Médecins Sans Frontières, France
name: Coalition for Epidemic Preparedness Innovations
name: Janssen Vaccines & Prevention B.V.
name: Public Health England
First posted: 2019-11-05
Enrollment: 20426
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single arm, open-label, non-randomized interventional trial of the two dose, Ad26.ZEBOV, MVA-BN-Filo Ebola preventative vaccine
Primary purpose: PREVENTION

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.

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 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.

Eligibility 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.

Primary outcomes:
measure: Numbers and odds of vaccination status in Ebola Virus Diseases cases and in EVD-negative controls.
timeFrame: Through study completion, an average of 2 years.
Secondary outcomes:
measure: Number and proportion of adults and children with solicited and unsolicited serious adverse events.
timeFrame: From date of first vaccination to the one month post-dose 2 assessment of the last vaccinated participant.
measure: Number and proportion of adults and children receiving dose 1.
timeFrame: From date of first vaccination up to month 12.
measure: Number and proportion of adults and children receiving dose 2.
timeFrame: From date of first vaccination up to month 12.
measure: Number of participants participating in in-depth interviews and focus group discussions
timeFrame: Through to study completion at month 24.
Other outcomes:
measure: Samples collected for immunogenicity subset at 2 time points
timeFrame: From date of dose 2 through to 21 days post-dose 2.
Locations:
city: Kinshasa
country: Congo, The Democratic Republic of the
facility: L'Institut National de Recherche Biomédicale RDC
Study officials:
affiliation: L'Institut National de Recherche Biomédicale RDC
name: Jean-Jacques Muyembe-Tamfum, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: London School of Hygiene and Tropical Medicine
name: Daniel Bausch, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: London School of Hygiene and Tropical Medicine
name: Deborah Watson-Jones, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.