Ebola Virus Disease
Conditions
Keywords
Sub-Saharan Africa Africa ,, Children, rVSV-ZEBOV-GP vaccine, Shedding, Safety, Tolerability
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.
Interventions
BIOLOGICALrVSVΔG-ZEBOV-GP, V920
The experimental vaccine is the rVSVΔG-ZEBOV-GP, an Ebola vaccine.
DIETARY_SUPPLEMENTFibre and equilibrate breakfast and lunch
Participants receive fibres and caloric equilibrate diet during breakfast and lunch every day for 21 consecutive days.
DIAGNOSTIC_TESTActive detection and treatment of pathogens
Monthly diagnostic and treatment of childhood infections Active detection and treatment of pathogens.
COMBINATION_PRODUCTFibre and equilibrate breakfast and lunch plus Active detection and treatment of pathogens
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
BIOLOGICALChikenpox or Varicella vaccine (VARILRIX)
The active comparator vaccine, a Varicella vaccine (VARILRIX®)
OTHERPlacebo
About 30 children do not receive diet, nor active pathogen detection
Sponsors
Merck Sharp & Dohme LLC
Centre de Recherche Médicale de Lambaréné
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Masking description
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.
Intervention model description
A Phase 1/2, randomized, controlled, open label clinical trial.
Eligibility
Sex/Gender
ALL
Age
1 Years to 12 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Concentration of viral vector in blood, saliva and urine in vaccinees | at days 0, 1, 2/3, 7, 14 and 28 | Concentration of rVSVΔG-ZEBOV-GP in blood, urine, or saliva as detected by RT-PCR and expressed as copy number in vaccinees |
| Prevalence and relative risk of sollicited adverse events in vaccinees | until day 14 post vaccination | Proportion (percent) of participants experiencing sollicited adverse events in vaccinees groups |
| Prevalence and relative risk of unsolicited adverse events and serious adverse events in vaccinees | until day 28 after vaccination | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Affinity/Avidity of antibody induced by vaccination | days 28 and 180 | Affinity/avidity of GP-specific serum antibodies as assessed by Surface Plasmon Resonance platform at D28 and D180 expressed as percent of affinity maturation |
| Concentration of IL-1RN (IL-1Ra), IL-6, TNF-α, IL-10, MCP-1/CCL2, and MIP-1β/CCL4 | days 0, 1 and 2 or 3 | 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 . |
| Prevalence of miRNAs | at days 0, 1, 2/3, 7 | Proportion (percent) of circulating miRNAs using the Human miRNome PCR array v.21 in serum samples |
| Concentration of Lipids, glutamine, Alanine, Aspargine | at day 0, day 1, day 2/3 and day 7 | Proportion (percent ) and concentration ( microgram/ mililiter) of Lipids, glutamine, Alanine, Aspargine in plasma samples |
| Prevalence and relative risk of serious adverse events | until day 365 | Proportion (percent) of participants experiencing SAEs and relative risk of SAEs in until study last visit (at 365 days) |
| Concentration of metabolites of gut bacteria | days 0, 7, 28, 56, 90 | Measurement of gut metabolites |
| Titres of antibody induced by diphtheria, tetanus, Bordetella, poliomyelitis, hepatitis B, measles, yellow fever ( EPI vaccines) | days 0, 7, 14, 28, 90, 180, 365 | Concentration of antibody of EPI vaccines |
| Concentration of bystander cytokines | days 0, 1, 2/3, 7, 28, 90 | Concentration of cytokines that may induce heterologous vaccine induced immune responses |
| Concentrations Nitric oxides species | days 0, 1, 2/3, 7, 28, 56, 90, 180, 365 | Profiling nitric oxides species according to vaccines, diet and pathogens |
| Transmission intensity of the viral vector in blood, saliva and urine among the the relatives of the vaccinees | days 0, 1, 3, 14, 28, 56 | 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 |
| Titres of ZEBOV-GP-specific binding antibody | days 0, 1, 3, 14, 21, 28, 56, 84, 180, 365 | Titres of ZEBOV-GP-specific binding antibody by ELISA expressed in geometric mean titres (GMTs) |
Countries
Gabon
Outcome results
None listed