Durability of Immunity Induced by the Ebolavirus Vaccine VSV-EBOV and As-sessment of a Booster Dose for Pre-Exposure Prophylaxis in Individuals at Potential Occupational Risk for Ebolavirus Exposure
Trial Snapshot
- Phase
- Phase 3
- Status
- Withdrawn
- Enrollment
- 70
- Locations
- 4
- Primary Endpoint
- 1. Binding anti-EBOV antibody titers I. The course of anti-EBOV immunoglobulin as measured by EBOV ELISA titers during the 24 months following primary vaccination II. Anti-EBOV immunoglobulin as measured by EBOV ELISA titers at 12 and 24 months follow-up
Study Overview
Brief Summary
This study is a multi-center, open label, randomized phase 3b trial to assess the durability of Immunity induced by the Ebolavirus Vaccine VSV-EBOV ( with or without booster vaccination) in individuals at potential occupational risk for ebolavirus exposure
Detailed Description
All participants will receive a single dose of ERVEBO® (≥72 million pfu) on Day 0. The participants will receive a diary to document local and defined systemic adverse events for 14 days after vaccination. We will collect grade 3 and 4 adverse events after vaccination and at Month 1 and Month 7, and seri-ous adverse events (SAE) for the duration of the study, and assess the immune response at Months 1, 3, 6, 7, 12, 18, 24. In a subgroup (Innate Subgroup) we are also going to assess innate immune response at Day 1 and 3 and Month 6 + Day 1 and Month 6 + Day 3.
A single booster immunization with the same dose as the primary dose (≥72 million pfu/mL) will be given to those randomized to the booster arm of the trial six months after primary vaccination.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 64 years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Adults age ≥18 years.
- •Signed informed consent for the trial.
- •At risk of occupational exposure to Ebola virus through laboratory, clinical contact, or field work, in the judgment of the investigator.
- •Females of child-bearing potential (FOCP) must be willing to use effective methods of con-traception as per the requirements of the protocol (9.3.7) from at least 30 days prior to vac-cination through 2 months following vaccination/booster.
- •Willing to avoid blood and body fluid exposure to high-risk individuals (i.e., immunocompro-mised individuals, individuals receiving immunosuppressive therapy and pregnant or breast-feeding women, children <1 year of age) for at least 6 weeks after vaccination/booster. This includes:
- •Use of effective barrier prophylaxis, such as latex condoms, during any sexual inter-action (regardless of childbearing status or sexual orientation)
- •Avoiding the sharing of needles, razors, eating utensils, drinking from the same cup, or toothbrushes
- •Avoiding open-mouth kissing
- •Use of universal precautions in the health-care setting The investigator can be counseled and may determine when individuals are classified as "immuno-compromised" and what therapy is defined as immunosuppressive therapy in this context.
- •Willing to forgo blood donation 30 days prior to first vaccination until end of study.
- •Willing to accept randomization (boost versus no boost) at month 6 (time window -1 month) visit.
Exclusion Criteria
- •Any condition that would, in the eyes of the investigator, limit the ability of the participant to meet protocol requirements or would place the participant at unreasonable risk. This includes:
- •I) Clinically significant medical condition, physical examination findings, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health, per the investigator. A clinically significant condition or process includes but is not limited to:
- •A process that would adversely affect the systemic immune response
- •A process that would require medication that might adversely affect the systemic immune re-sponse
- •Any contraindication to repeated injections or blood draws
- •A condition that requires active medical intervention or monitoring to avert grave danger to the participant's health or well-being during the study period
- •A condition or process for which signs or symptoms could be confused with reactions to vaccine
- •II) Presence of any pre-existing illness or clinical history that, in the opinion of the investigator, would place the participant at an unreasonably increased risk through participation in this study. This in-cludes but is not limited to:
- •Active malignancy
- •History of Guillain-Barré Syndrome
- •History of neurological disorder that may increase risk (history of encephalitis, stroke, or sei-zure)
- •Active autoimmune disorder requiring systemic immunosuppressive treatment
- •III) Any concomitant medication for which reported side effects or adverse events, in the judg-ment of the investigator, may interfere with assessment of safety.
- •IV) Participants who, in the judgment of the investigator, will be unlikely or unable to comply with the requirements of this protocol.
- •Pregnant or breast feeding (must have negative pregnancy test on the day of vaccination, prior to vaccination)
- •Known allergy to the components of the rVSV∆G-ZEBOV-GP vaccine (ERVEBO®) vaccine product (VSV, albumin, tris, rice).
- •History of severe local or systemic reactions to any vaccination.
- •Received killed vaccines 14 days before, or intention to receive within 7 days following vac-cination (Day 0)/booster (Month 6).
- •Received live virus vaccines within 30 days before, or intention to receive live virus vaccines within 30 days following, vaccination (Day 0)/booster (Month 6).
- •Received immunoglobulins and/or any blood products within the 120 days preceding vaccina-tion (Day 0)/booster (Month 6).
- •Received allergy treatment with antigen injections within 30 days before vaccination (Day 0)/booster (Month 6).
- •Clinical evidence (e.g. oral temperature >38.0 degrees Celsius, systemic symptoms) of a sys-temic infection or other acute intercurrent illness at the proposed time of vaccination (Day 0)/booster (Month 6).
- •Prior receipt of a vaccine against EVD or prior EVD in medical history.
- •Participation in a clinical trial or use of an investigational product within 30 days or five times the half-life of the investigational product -whichever is longer- prior to receiving the first dose within this study.
Outcomes
Primary Outcomes
1. Binding anti-EBOV antibody titers I. The course of anti-EBOV immunoglobulin as measured by EBOV ELISA titers during the 24 months following primary vaccination II. Anti-EBOV immunoglobulin as measured by EBOV ELISA titers at 12 and 24 months follow-up
1. Binding anti-EBOV antibody titers I. The course of anti-EBOV immunoglobulin as measured by EBOV ELISA titers during the 24 months following primary vaccination II. Anti-EBOV immunoglobulin as measured by EBOV ELISA titers at 12 and 24 months follow-up
2. Anti-EBOV neutralizing antibody titers I. The course of anti-EBOV neutralizing antibody titers during the 24 months following primary vaccination II. Anti-EBOV neutralizing titers at 12 and 24 months follow-up
2. Anti-EBOV neutralizing antibody titers I. The course of anti-EBOV neutralizing antibody titers during the 24 months following primary vaccination II. Anti-EBOV neutralizing titers at 12 and 24 months follow-up
Secondary Outcomes
- Occurrence of Grade ≥ 3 AE until one month after primary and booster vaccination
- Occurrence of SAE throughout the study
Investigators
Svenja Hardtke
Scientific
University Medical Center Hamburg-Eppendorf