Clinical trial NCT05130398: Safety and Immunogenicity of the rVSVΔG-ZEBOV-GP Ebola Virus Vaccine Candidate in Children Living in Lambaréné, Gabon
Official title: A Phase 1/2, Randomized, Controlled Open-label Trial to Evaluate the Safety and Immunogenicity of the rVSVΔG-ZEBOV-GP Ebola Virus Vaccine Candidate in Healthy Children Aged 1 to 12 Years and in Their Relatives Living in Lambaréné, Gabon
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Ebola Virus Disease
Keywords: Sub-Saharan Africa Africa ,
Children
rVSV-ZEBOV-GP vaccine
Shedding
Safety
Tolerability
Lead sponsor: Centre de Recherche Médicale de Lambaréné
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2021-11-23
Enrollment: 120
Sex: ALL
Minimum age (years): 1
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A Phase 1/2, randomized, controlled, open label clinical trial.
Primary purpose: PREVENTION

Brief summary: LA rVSVΔG-ZEBOV-GP -02-PED is a Phase 1/2, randomized, controlled open label trial. The LA rVSVΔG-ZEBOV-GP -02-PED trial aims primarily to assess the clinical significance of shedding of the rVSV RNA following vaccination with the rVSVΔG-ZEBOV-GP vaccine in children. The vaccine doses of ≥7.8 x 107 pfu will be evaluated and compared to vaccination with varicella vaccine as a control. In addition, the closest contact persons of the vaccinees will be monitored for possible transmission of the viral vaccine vector.

The study will enroll children of two age groups living in Lambaréné, Gabon. Children will be followed-up for 12 months post vaccination.

The 1-2 closest contact persons of each participant will be involved in the monitoring of rVSV transmission. They will be followed until day 56 post- vaccination of their children/ sibling.

Detailed description: LA-rVSVΔG-ZEBOV-GP -02-PED is a Phase 1/2, randomized, controlled, open label, trial and is designed to generate further safety, tolerability and immunogenicity data of the 7.8 x 107 PFU rVSVΔG-ZEBOV-GP vaccine in children aged 1 -12 years living in a sub-Saharan Africa. The study will enroll participants into two age groups. A total of 120 children will be enrolled and followed-up for 12 months post injection. In addition, a maximum of 240 relatives of the study participants will be enrolled to assess the transmission of the rVSVΔG-ZEBOV-GP vaccine.

Group 1: 60 participants aged 6-12 years will be randomized in group 1. 40 participants will receive a single intramuscular dose of 7.8 x 107 pfu rVSVΔG-ZEBOV-GP vaccine. 20 participants will receive a single subcutaneous dose of varicella vaccine The participants will be allocated to each treatment at a ratio of 2:1 respectively Group 2: 60 participants aged 1 -5 years will be randomized into group 2. 40 will receive a single intramuscular dose of 7.8 x 107 pfu of rVSV-ZEBOV vaccine. 20 participants will receive a single subcutaneous dose of varicella vaccine The participants will be allocated to each treatment at a ratio of 2:1 respectively

Vaccinations will start in group 2 after the first 10 participants of group 1 have completed the day 28 post vaccination visit and the SMC has done a review of safety data until that point.

For each vaccinee there will be a 365 -day period of follow-up after vaccination. The contact persons of the vaccinees will be followed-up until day 56 after the vaccination of their relative.

Eligibility criteria: Inclusion Criteria:

* Healthy children aged 1 to 12 years (inclusive) at the time of inclusion.
* Willingness of parent or legal guardian to provide written informed consent prior to screening procedures.
* Willingness of the relatives of the participant to provide written informed consent if they are ≥ 18 years (or an assent when they are 13 to 17 years old).
* Available, able, and willing to participate in all study visits and procedures

Exclusion Criteria:

* History of severe local or systemic reactions to any vaccination or a history of severe allergic reactions, or known allergy to the components of the vaccines.
* Ongoing participation in another clinical trial
* Participation in previous Ebola vaccine trials
* Receipt of a licensed vaccine within 14 days of planned study immunization (30 days for live vaccines)
* Presence of any febrile illness (fever \>38°C) or any moderate to severe illness within one week prior to vaccination;
* Administration of immunoglobulins and/or any blood products within the 120 days preceding study entry or planned administration during the study period
* Any other significant finding that in the opinion of the investigator would increase the risk of the individual having an adverse outcome from participating in this study.

Primary outcomes:
measure: Concentration of viral vector in blood, saliva and urine in vaccinees
timeFrame: at days 0, 1, 2/3, 7, 14 and 28
measure: Prevalence and relative risk of sollicited adverse events in vaccinees
timeFrame: until day 14 post vaccination
measure: Prevalence and relative risk of unsolicited adverse events and serious adverse events in vaccinees
timeFrame: until day 28 after vaccination
Secondary outcomes:
measure: Prevalence and relative risk of serious adverse events
timeFrame: until day 365
measure: Transmission intensity of the viral vector in blood, saliva and urine among the the relatives of the vaccinees
timeFrame: days 0, 1, 3, 14, 28, 56
measure: Titres of ZEBOV-GP-specific binding antibody
timeFrame: days 0, 1, 3, 14, 21, 28, 56, 84, 180, 365
measure: Affinity/Avidity of antibody induced by vaccination
timeFrame: days 28 and 180
measure: Concentration of IL-1RN (IL-1Ra), IL-6, TNF-α, IL-10, MCP-1/CCL2, and MIP-1β/CCL4
timeFrame: days 0, 1 and 2 or 3
measure: Prevalence of miRNAs
timeFrame: at days 0, 1, 2/3, 7
measure: Concentration of Lipids, glutamine, Alanine, Aspargine
timeFrame: at day 0, day 1, day 2/3 and day 7
measure: Concentrations Nitric oxides species
timeFrame: days 0, 1, 2/3, 7, 28, 56, 90, 180, 365
measure: Concentration of metabolites of gut bacteria
timeFrame: days 0, 7, 28, 56, 90
measure: Titres of antibody induced by diphtheria, tetanus, Bordetella, poliomyelitis, hepatitis B, measles, yellow fever ( EPI vaccines)
timeFrame: days 0, 7, 14, 28, 90, 180, 365
measure: Concentration of bystander cytokines
timeFrame: days 0, 1, 2/3, 7, 28, 90
Other outcomes:
Locations:
city: Lambarene
country: Gabon
facility: Centre de Recherches Médicales de Lambaréné
state: Moyen-Ogooué
Study officials:
References: