Safety and Immunogenicity of the rVSVΔG-ZEBOV-GP Ebola Virus Vaccine Candidate in Children Living in Lambaréné, Gabon

Centre de Recherche Médicale de Lambaréné120 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Interventions

rVSVΔG-ZEBOV-GP, V920BIOLOGICAL

The experimental vaccine is the rVSVΔG-ZEBOV-GP, an Ebola vaccine.

Fibre and equilibrate breakfast and lunchDIETARY_SUPPLEMENT

Participants receive fibres and caloric equilibrate diet during breakfast and lunch every day for 21 consecutive days.

Active detection and treatment of pathogensDIAGNOSTIC_TEST

Monthly diagnostic and treatment of childhood infections Active detection and treatment of pathogens.

Fibre and equilibrate breakfast and lunch plus Active detection and treatment of pathogensCOMBINATION_PRODUCT

Participants receive fibres and caloric equilibrate diet during breakfast and lunch every day for 21 consecutive days and diagnostic and treatment of childhood infections Active detection and treatment of pathogens every month for 12 months

Chikenpox or Varicella vaccine (VARILRIX)BIOLOGICAL

The active comparator vaccine, a Varicella vaccine (VARILRIX®)

PlaceboOTHER

About 30 children do not receive diet, nor active pathogen detection

Eligibility

Sex: ALLMin age: 1 YearMax age: 12 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Concentration of viral vector in blood, saliva and urine in vaccinees

Concentration of rVSVΔG-ZEBOV-GP in blood, urine, or saliva as detected by RT-PCR and expressed as copy number in vaccinees

Time frame: at days 0, 1, 2/3, 7, 14 and 28

Prevalence and relative risk of sollicited adverse events in vaccinees

Proportion (percent) of participants experiencing sollicited adverse events in vaccinees groups

Time frame: until day 14 post vaccination

Prevalence and relative risk of unsolicited adverse events and serious adverse events in vaccinees

Proportion (percent ) of participant experiencing unsollicited adverse event (AEs) and serious adverse events (SAEs) and relative risk of AEs and SAEs in participant by vaccine groups

Time frame: until day 28 after vaccination

Secondary Outcomes

Prevalence and relative risk of serious adverse events

Proportion (percent) of participants experiencing SAEs and relative risk of SAEs in until study last visit (at 365 days)

Time frame: until day 365

Transmission intensity of the viral vector in blood, saliva and urine among the the relatives of the vaccinees

Concentration of rVSVΔG-ZEBOV-GP in blood, urine, or saliva as detected by RT-PCR and expressed as copy number in the close relatives of the vaccinees

Time frame: days 0, 1, 3, 14, 28, 56

Titres of ZEBOV-GP-specific binding antibody

Titres of ZEBOV-GP-specific binding antibody by ELISA expressed in geometric mean titres (GMTs)

Time frame: days 0, 1, 3, 14, 21, 28, 56, 84, 180, 365

Affinity/Avidity of antibody induced by vaccination

Affinity/avidity of GP-specific serum antibodies as assessed by Surface Plasmon Resonance platform at D28 and D180 expressed as percent of affinity maturation

Time frame: days 28 and 180

Concentration of IL-1RN (IL-1Ra), IL-6, TNF-α, IL-10, MCP-1/CCL2, and MIP-1β/CCL4

Cytokines (IL-1RN (IL-1Ra), IL-6, TNF-α, IL-10), chemokines and soluble adhesion molecules (MCP-1/CCL2, and MIP-1β/CCL4) plasma expressed in microgram per milliliter .

Time frame: days 0, 1 and 2 or 3

Prevalence of miRNAs

Proportion (percent) of circulating miRNAs using the Human miRNome PCR array v.21 in serum samples

Time frame: at days 0, 1, 2/3, 7

Concentration of Lipids, glutamine, Alanine, Aspargine

Proportion (percent ) and concentration ( microgram/ mililiter) of Lipids, glutamine, Alanine, Aspargine in plasma samples

Time frame: at day 0, day 1, day 2/3 and day 7

Concentrations Nitric oxides species

Profiling nitric oxides species according to vaccines, diet and pathogens

Time frame: days 0, 1, 2/3, 7, 28, 56, 90, 180, 365

Concentration of metabolites of gut bacteria

Measurement of gut metabolites

Time frame: days 0, 7, 28, 56, 90

Titres of antibody induced by diphtheria, tetanus, Bordetella, poliomyelitis, hepatitis B, measles, yellow fever ( EPI vaccines)

Concentration of antibody of EPI vaccines

Time frame: days 0, 7, 14, 28, 90, 180, 365

Concentration of bystander cytokines

Concentration of cytokines that may induce heterologous vaccine induced immune responses

Time frame: days 0, 1, 2/3, 7, 28, 90