Clinical trial NCT06126822: Safety and Immunogenicity of Ervebo® and Zabdeno® Booster Vaccines Against Ebola Virus Following Previous Vaccination with the Zabdeno/Mvabea® or Ervebo® Vaccine Schedules in DRC
Official title: Safety and Immunogenicity of Ervebo® and Zabdeno® Booster Vaccines Against Ebola Virus Following Previous Vaccination with the Zabdeno/Mvabea® or Ervebo® Vaccine Schedules in DRC: a Mix-and-match Phase II RCT
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Ebola Virus Disease
Keywords: Ebola vaccines
Lead sponsor: Institute of Tropical Medicine, Belgium
Sponsor class: OTHER
Collaborators: name: Institut National pour la Recherche Biomedicale (INRB)
First posted: 2023-11-13
Enrollment: 624
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The goal of this randomized controlled trial is to investigate whether individuals in DRC previously vaccinated with Zabdeno/Mvabea® or Ervebo® vaccine schedules against Ebola virus can be safely and adequately boosted with homologous or heterologous vaccine schedules.

Participants will be randomized to receive either a homologous or heterologous vaccine schedule and will be asked to come to the clinic at prespecified timepoints over a period of 6 months to collect blood samples for comparison of immunological responses against Ebola virus between both schedules. Safety and tolerability of the vaccines will be evaluated by recording Adverse Events (AE's) and grading physical and vital signs evaluations.

Detailed description: The aim of this randomized controlled with four arms is to investigate whether individuals previously vaccinated with Zabdeno/Mvabea® or Ervebo® vaccine schedules against Ebola virus can be safely and adequately boosted with homologous and heterologous vaccine schedules. We hypothesize that heterologous booster vaccine schedules generate a non-inferior boosting in antibodies and cellular responses against Ebola virus as compared to homologous schedules and incite a similar safety profile.

Based on the predefined variables (living place and time since vaccination), the research team will pre-select and re-contact individuals previously included in the Phase III EBOVAC vaccine database, EBOSURV participant database, and the Programme Élargi de Vaccination (PEV) database. Participants will be contacted by phone and, if they agree to participate, they are scheduled on predefined screening/recruitment days taken place at the 2 recruitment sites: INRB Goma and INRB Kinshasa.

A total of 624 participants will be included, 312 will be previously vaccinated with Zabdeno/Mvabea® and 312 participants with Ervebo®. Within those two groups, half of the participants (n=156) will be randomized to a single Ervebo® booster vaccine and the other half (n=156) to a single Zabdeno® booster vaccine. Participants will be asked to come to the clinic at prespecified timepoints over a period of 6 months to collect blood samples for comparison of antibody- and cellular response against EBOV between homologous and heterologous schedules. Safety and tolerability of the vaccines will be evaluated by recording Adverse Events (AE's) and grading physical and vital signs evaluations. An additional 50 non-vaccinated participants will be recruited in Kinshasa for assay optimization.

In case of insufficient participants living close to the recruitment centers, a community outreach will be undertaken with a lower amount of visits for logistical reasons.

Eligibility criteria: Inclusion Criteria:

* Subjects who received either the Ervebo® vaccine (MSD), or the full Zabdeno, Mvabea® vaccine regimen (J\&J) more than 4 months prior to recruitment
* Subjects between 18 and 50 years of age at time of randomization
* Subject must be willing and able to provide informed consent
* The subject must be in possession of an identification card (or other identification document)
* Agreement to refrain from blood donation and other vaccinations 30 days after booster vaccination
* Agreement to share and discuss participant's medical history, medical records and concomitant medications when relevant

Exclusion Criteria:

* Participants who previously experienced active Ebola Virus Disease (EVD)
* Receipt of any vaccine (licensed or experimental) within 30 days prior to recruitment
* Receipt of an additional booster dose of either Ervebo®, Zabdeno®, or any experimental Ebola vaccine
* Incorrect or incomplete primary vaccination scheme with the Zabdeno, Mvabea® (J\&J) vaccine
* Administration of immunoglobulins and/or any blood products within three months prior to recruitment.
* Fever (\>38°C) within last 24 hours prior to recruitment.
* Any confirmed or suspected immunosuppressive or immunodeficient state (incl. cancer and HIV); asplenia; recurrent severe infections and use of immunosuppressant medication within the last 6 months, except topical or short-term oral steroids.
* Severe and/or uncontrolled cardiovascular disease, respiratory disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder and neurological illness (mild/moderate well controlled comorbidities are allowed)
* History of anaphylaxis, allergic disease or reactions to any component of the study vaccines
* History of bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venipuncture
* History of any thrombotic disorder, thrombocytopenia, thrombotic thrombocytopenia syndrome (TTP), or heparin-induced thrombocytopenia and thrombosis (HITT)
* Any other significant disease, disorder, planned surgery, or finding which may significantly affect the ability of the volunteer to participate in the study or impair interpretation of the study data
* Suspected or known alcohol or drug dependency
* Subject is not readily available by telephone, email or physical address

The non-vaccinated control group will also adhere to all the above in- and exclusion criteria, with exemption of:

* Agreement to refrain from blood donation and other vaccinations 30 days after study vaccination
* Subjects who received either the Ervebo® vaccine, or the full Zabdeno, Mvabea® vaccine regimen more than 4 months prior to recruitment

The latter is rather introduced as an additional exclusion criteria:

* Subjects who received either the Ervebo® vaccine or the full Zabdeno, Mvabea® vaccine regimen

Primary outcomes:
measure: To assess non-inferiority in EBOV-specific IgG levels elicited by a heterologous to a homologous booster vaccine schedule, by type of primary vaccination, 21 days after administration of the booster.
timeFrame: Day 21 after booster vaccination = Day 21
Secondary outcomes:
measure: To assess the safety of heterologous and homologous booster vaccine schedules, by type of primary vaccine schedule
timeFrame: Day 7, Day 21 and Month 6
measure: To compare the EBOV-specific IgG levels at D21 across all vaccine combinations
timeFrame: Day 21
measure: To compare the fold change between D0 and D21 across all vaccine combinations
timeFrame: Day 0 and Day 21
measure: To compare the EBOV-specific binding and neutralizing antibodies to the glycoproteins of different EBOV variants across all vaccine combinations and timepoints
timeFrame: Day 0, Day 3, Day 7, Day 21, Month 6
measure: To compare the EBOV-specific binding and neutralizing antibodies to the glycoproteins of different EBOV variants across all vaccine combinations and timepoints
timeFrame: Day 0, Day 21, Month 6
measure: To compare the EBOV-specific effector-memory T cell response across all vaccine combinations and timepoints
timeFrame: Day 0, Day 7, Day 21 and Month 6
measure: To compare the EBOV-specific effector-memory B cell response across all vaccine combinations and timepoints
timeFrame: Day 0, Day 7, Day 21 and Month 6
measure: To characterize the phenotype and polyfunctionality of the vaccine-induced T and B cell response by vaccine combination
timeFrame: at Day 0 and Day 21
measure: To assess the impact of the participant age and sex on the vaccine-induced EBOV-specific bAbs
timeFrame: Day 21
measure: To assess the impact of the participant age and sex on the vaccine-induced EBOV-specific bAbs
timeFrame: Day 0, Day 3, Day 7, Day 21 and Month 6
measure: To assess the impact of the participant age and sex on the vaccine-induced EBOV-specific nAbs
timeFrame: Day 0, Day 21 and Month 6
measure: To assess the impact of the participant age and sex on the vaccine-induced EBOV-specific T cells
timeFrame: Day 0, Day 7, Day 21 and Month 6
measure: To assess the impact of the participant age and sex on the vaccine-induced EBOV-specific B cells
timeFrame: Day 0, Day 7, Day 21 and Month 6
measure: To assess the impact of the participant age and sex on the vaccine-induced EBOV-specific T cells
timeFrame: Day 0, Day 21
Other outcomes:
Locations:
city: Goma
country: Congo, The Democratic Republic of the
facility: Institut National de Recherche Biomédicale (INRB)
city: Kinshasa
country: Congo, The Democratic Republic of the
facility: Institut National de Recherche Biomédicale (INRB)
Study officials:
affiliation: Institute of Tropical Medicine
name: Wim Adriaensen, Prof.
role: PRINCIPAL_INVESTIGATOR
References: