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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Ebola Virus Disease

Intervention / Treatment
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* Biological: rVSVΔG-ZEBOV-GP, V920
* Dietary Supplement: Fibre and equilibrate breakfast and lunch
* Diagnostic Test: Active detection and treatment of pathogens
* Combination Product: Fibre and equilibrate breakfast and lunch plus Active detection and treatment of pathogens
* Biological: Chikenpox or Varicella vaccine (VARILRIX)
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A Phase 1/2, randomized, controlled, open label clinical trial.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: the rVSVΔG-ZEBOV-GP vaccine<br>Participants of the experimental arm will receive a single intramuscular dose of ≥7.8 x 107 pfu of the rVSVΔG-ZEBOV-GP vaccine. In total, 80 participants will receive the experimental vaccine: 40 participants aged 6-12 years and 40 aged 1-5 years. | Biological: rVSVΔG-ZEBOV-GP, V920<br>* The experimental vaccine is the rVSVΔG-ZEBOV-GP, an Ebola vaccine.<br>|
| Active Comparator: The Chikenpox or Varicella (Varilix) vaccine<br>The control arm consists of the chickenpox vaccine. Forty children will receive a single subcutaneous dose of Varilix, the active comparator vaccine, 20 aged 6-12 years and 20 aged 1-5 years | Biological: Chikenpox or Varicella vaccine (VARILRIX)<br>* The active comparator vaccine, a Varicella vaccine (VARILRIX®)<br>|
| Experimental: Fibre and equilibrate diet<br>Participants were assigned to receive two meals daily ( breakfast and lunch) for 21 days. About 30 children are randomly assigned to fibre and equilibrate diet. | Dietary Supplement: Fibre and equilibrate breakfast and lunch<br>* Participants receive fibres and caloric equilibrate diet during breakfast and lunch every day for 21 consecutive days.<br>|
| Experimental: Active detection and treatment of pathogens according to standard of care<br>The following pathogens: P. falciparum, Ascaris lumbricoides, Trichuris trichiura, Necator americanus, intestinal protozoa, BG+, BG- colonies and pathogens, SARS-CoV2 are actively detected and treated according to the standard of care every month. About 30 children are randomly assigned to this arm. | Diagnostic Test: Active detection and treatment of pathogens<br>* Monthly diagnostic and treatment of childhood infections Active detection and treatment of pathogens.<br>|
| Experimental: Diet plus Active detection and treatment of pathogens according to standard of care<br>Participants were assigned to receive two meals daily ( breakfast and lunch) for 21 days and concomitantly assigned to active detection of P. falciparum, Ascaris lumbricoides, Trichuris trichiura, Necator americanus, intestinal protozoa, BG+, BG- colonies and pathogens, SARS-CoV2 every month. About 30 children are assigned to receive combined interventions | Combination Product: Fibre and equilibrate breakfast and lunch plus Active detection and treatment of pathogens<br>* 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<br>|
| Placebo Comparator: No diet and no pathogen detection<br>About 30 children received no diet and no active detection of pathogens | Other: Placebo<br>* About 30 children do not receive diet, nor active pathogen detection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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 | 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 | until day 28 after vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 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 | 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) | 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 | 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 . | 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 | 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 | 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 | days 0, 1, 2/3, 7, 28, 56, 90, 180, 365 | 
| Concentration of metabolites of gut bacteria | Measurement of gut metabolites | 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 | days 0, 7, 14, 28, 90, 180, 365 | 
| Concentration of bystander cytokines | Concentration of cytokines that may induce heterologous vaccine induced immune responses | days 0, 1, 2/3, 7, 28, 90 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sub-Saharan Africa Africa ,, Children, rVSV-ZEBOV-GP vaccine, Shedding, Safety, Tolerability