Ebola Virus Disease Clinical Trial
— EBO-BOOSTOfficial 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
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.
Status | Not yet recruiting |
Enrollment | 624 |
Est. completion date | October 2026 |
Est. primary completion date | October 2025 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 18 Years to 50 Years |
Eligibility | 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 |
Country | Name | City | State |
---|---|---|---|
Congo, The Democratic Republic of the | Institut National de Recherche Biomédicale (INRB) | Goma | |
Congo, The Democratic Republic of the | Institut National de Recherche Biomédicale (INRB) | Kinshasa |
Lead Sponsor | Collaborator |
---|---|
Institute of Tropical Medicine, Belgium | Institut National pour la Recherche Biomedicale (INRB) |
Congo, The Democratic Republic of the,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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. | FANG ELISA units/mL of anti-EBOV IgG | Day 21 after booster vaccination = Day 21 | |
Secondary | To assess the safety of heterologous and homologous booster vaccine schedules, by type of primary vaccine schedule | The occurrence of solicited local Adverse Events (AEs) [Up to Day 7]
The occurrence of solicited systemic AEs [Up to Day 7] The occurrence of unsolicited AEs [Up to Day 21] The occurrence of Serious Adverse Events (SAE's) [Up to Month 6] |
Day 7, Day 21 and Month 6 | |
Secondary | To compare the EBOV-specific IgG levels at D21 across all vaccine combinations | - FANG ELISA units/mL of anti-EBOV IgG at D21 after vaccination | Day 21 | |
Secondary | To compare the fold change between D0 and D21 across all vaccine combinations | - Fold change in FANG ELISA units/mL of anti-EBOV IgG between D0 and D21 | Day 0 and Day 21 | |
Secondary | To compare the EBOV-specific binding and neutralizing antibodies to the glycoproteins of different EBOV variants across all vaccine combinations and timepoints | - The Mean Fluorescence Intensity (MFI) IgG levels against the GP variants [multiplexed Luminex assay - at D0, D3, D7, D21, M6] | Day 0, Day 3, Day 7, Day 21, Month 6 | |
Secondary | To compare the EBOV-specific binding and neutralizing antibodies to the glycoproteins of different EBOV variants across all vaccine combinations and timepoints | - The 50% neutralizing titer (NT50) levels of the GP-specific antibodies [at D0, D21, M6] | Day 0, Day 21, Month 6 | |
Secondary | To compare the EBOV-specific effector-memory T cell response across all vaccine combinations and timepoints | - The IFN-y, TNF-a and IL-2 Spot Forming Units (SFU) after T cell stimulation with GP peptide pools [at D0, D7, D21, M6] | Day 0, Day 7, Day 21 and Month 6 | |
Secondary | To compare the EBOV-specific effector-memory B cell response across all vaccine combinations and timepoints | - The IgG1, IgG2, IgG3 Spot Forming Units (SFU) after B cell stimulation with recombinant GPs [at D0, D7, D21, M6] | Day 0, Day 7, Day 21 and Month 6 | |
Secondary | To characterize the phenotype and polyfunctionality of the vaccine-induced T and B cell response by vaccine combination | Proportions of EBOV GP-specific cell phenotypes and polyfunctional cells | at Day 0 and Day 21 | |
Secondary | To assess the impact of the participant age and sex on the vaccine-induced EBOV-specific bAbs | - FANG ELISA units/mL of anti-EBOV IgG at D21 after vaccination | Day 21 | |
Secondary | To assess the impact of the participant age and sex on the vaccine-induced EBOV-specific bAbs | - The Mean Fluorescence Intensity (MFI) IgG levels against the GP variants and VP40 [multiplexed Luminex assay - at D0, D3, D7, D21, M6] | Day 0, Day 3, Day 7, Day 21 and Month 6 | |
Secondary | To assess the impact of the participant age and sex on the vaccine-induced EBOV-specific nAbs | - The 50% neutralizing titer (NT50) levels of the GP-specific antibodies [at D0, D21, M6] | Day 0, Day 21 and Month 6 | |
Secondary | To assess the impact of the participant age and sex on the vaccine-induced EBOV-specific T cells | - The IFN-y, TNF-a and IL-2 Spot Forming Units (SFU) after T cell stimulation with GP peptide pools [at D0, D7, D21, M6] | Day 0, Day 7, Day 21 and Month 6 | |
Secondary | To assess the impact of the participant age and sex on the vaccine-induced EBOV-specific B cells | - The IgG1, IgG2, IgG3 Spot Forming Units (SFU) after B cell stimulation with recombinant GPs [at D0, D7, D21, M6] | Day 0, Day 7, Day 21 and Month 6 | |
Secondary | To assess the impact of the participant age and sex on the vaccine-induced EBOV-specific T cells | - Proportions of EBOV GP-specific cell phenotypes and polyfunctional cells [at D0, D21] | Day 0, Day 21 |
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