Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202005733552021 Date of Approval: 21/05/2020
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public 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 adults and/or children relatives living in Lambaréné, Gabon.
Official scientific 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 adults and/or children relatives living in Lambaréné, Gabon.
Brief summary describing the background and objectives of the trial During the Western African EVD outbreak, about 14% of the cases occurred in children under 15 years, with a case fatality rate of 73%. Most Ebola vaccine trials have been conducted in adults aged 18 years and above. The first rVSVΔG-ZEBOV-GP vaccine trial in children enrolled 20 adolescents and 20 children in Gabon showed that the vaccine had no major safety concerns and was immunogenic in these age groups. It was however noted that in this paediatric cohort the rVSV RNA replicated beyond the protocol-assessed timeline of 7 days, with children and adolescents shedding viral rVSV RNA in saliva and urine and displaying a correspondingly higher viremia compared to adults. The clinical significance of the rVSV shedding in vaccines and the implications for contact with individuals in the community needs to be investigated. Therefore, this rVSVΔG-ZEBOV-GP vaccine trial aims to assess shedding beyond seven days and further explore the safety and immunogenicity of the rVSVΔG-ZEBOV-GP vaccine in children. 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 to assess the clinical significance of shedding 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 the 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 enrol 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 monitoring rVSV transmission. They will be followed until day 56, post-vaccination of their children/siblings. Exploratory objectives investigate the effects of diet and health status on vaccine-induced immunity.
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Ebola
Purpose of the trial Prevention: Vaccines
Anticipated trial start date 04/01/2021
Actual trial start date 09/04/2021
Anticipated date of last follow up 09/06/2022
Actual Last follow-up date 09/08/2022
Anticipated target sample size (number of participants) 120
Actual target sample size (number of participants) 120
Recruitment status Completed
Publication URL https://www.journalofinfection.com/article/S0163-4453(24)00171-3/fulltext
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Permuted block randomization Sealed opaque envelopes Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Intervention group a single intramuscular dose of 7.8 x 107 pfu rVSVΔG-ZEBOV-GP vaccine follow-up for 12 months post injection The vaccine is supplied individually packaged in sterile single dose vials. Each vial contains vaccine virus frozen in a mixture of USP water for injection, human serum albumin (2.5g/L, USP) and 10 mM Tris, ph 7.2. After thawing, the content of the vials is a colourless to slightly brownish-yellow liquid with no particulates visible. The vaccine concentrations in the vials are formulated as: the nominal dose 2 x 107 pfu/ml and are intended to be administered as is in a volume of 1.0 mL without dilution. 1.0 mL of vaccine is administered to the deltoid intramuscularly using a 3cc syringe with a #25-gauge needle. 80
Control Group control group a single subcutaneous dose of varicella vaccine VARILRIX® vaccine 0.5 x 1033pfu follow-up for 12 months post injection VARILRIX® vaccine is an active immunization for the prevention of varicella in individuals from the age of 9 months. VARILRIX® is lyophilized vaccine with diluent syringe or ampoule included for the preparation of the live attenuated Oka strain of varicella zoster virus. Each 0.5ml dose of the reconstituted vaccine contains no less than 10 3.3 plaque forming units (PFU) of the varicella- zoster virus. The vaccine also contains amino acids, human albumin, lactose, mannitol and sorbitol. VARILRIX® does not contain a preservative. Neomycin sulphate is present as a residual from the manufacturing process. The VARILIX® vaccine is administered by subcutaneous injection into the upper arm (deltoid region). In children aged 9 months to 12 years, one dose is administered. 40 Active-Treatment of Control Group
Experimental Group Diet group Two meals per day ( breakfast and lunch) for 21 days. Twenty one consécutive days A healthy diet with fibre and calories 30
Experimental Group Active detection of infectious diseases plus treatment according to local guidelines Monthly active detection 12 months The pathogens are actively detected: P. falciparum, Ascaris lumbricoides, Trichuris trichiura, Necator americanus, intestinal protozoa, BG+, BG- colonies and pathogens, SARS-CoV2 30
Experimental Group Diet and Health status Twenty one day of healthy diet plus monthly detection of infectious diseases and treatment 21 days for diet and monthly pathogen detection and treatment for 12 months. A healthy diet and pathogen detection plus treatment. 30
Control Group No diet No pathogen detection 12 months follow up No diet, no pathogen detection but vaccine administration 30 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Healthy children, aged 1to 12 years(inclusive) at the time of screening 2. Willingness of parent or legal guardian to provide written informed consent prior to screening procedures. 3. 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). 4. Available, able, and willing to participate in all study visits and procedures 1. History of severe local or systemic reactions to any vaccination or a history of severe allergic reactions, or known allergy to components of the study vaccines 2. Ongoing participation in another clinical trial 3. Participation in previous Ebola vaccine trial 4. Receipt of licensed vaccines within 30 days of planned study immunization 5. Presence of any febrile illness (fever >38°C) or any moderate to severe illness within one week prior to vaccination 6. Acute or chronic, clinically significant disease 7. Known history of varicella 8. Known hepatitis B, C or HIV infection. 9. Receipt of blood products or immunoglobulin (IVIg or IMIg) within three (3) months of study entry/baseline serologic evaluation 10. Administration of immunoglobulins and/or any blood products within the 120 days preceding study entry or planned administration during the study period 11. Any other significant finding that in the opinion of the investigator would increase the risk to the individual of suffering an adverse outcome from participating in the study Child: 6 Year-12 Year,Preschool Child: 2 Year-5 Year 1 Year(s) 12 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 07/11/2019 Comite National dEthique pour la Recherche au Gabon
Ethics Committee Address
Street address City Postal code Country
avenue du colonel parent Libreville 00546 Gabon
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome • Concentration of rVSV in blood, urine, or saliva as detected by RT-PCR at days 0, 1, 2/3, 7, 14, 21, 28. The frequency and severity of adverse events (AEs) and/or serious adverse events (SAEs) associated with administration of ≥7.8 x 107 PFU rVSVΔG-ZEBOV-GP measured as follow: • Frequency and severity of local signs and symptoms until day 14 post vaccination (solicited local symptoms). • Frequency and severity of systemic signs and symptoms until day 14 post vaccination (solicited systematic symptoms). • Frequency of adverse events (AEs), severity and assessed relationship to study vaccines until day 28 post vaccination (unsolicited AE). • Detailed description of all serious adverse events (SAEs) until day 28 post vaccination. • Values of safety laboratory measures at baseline and at follow-up visits post-vaccination until day 28 post vaccination (reference ranges will be age appropriate). days 0, 1, 2/3, 7, 14, 21, 28.
Secondary Outcome Description of all serious adverse events (SAEs) until the study's last visit (at 365 days). The concentration of rVSVΔG-ZEBOV-GP in blood, urine, or saliva of vaccinees in close contact persons as detected by RT-PCR. The concentration of ZEBOV-GP-specific binding antibody by ELISA Affinity/avidity of GP-specific serum antibodies as assessed by Surface Plasmon Resonance platform at D28 and D180 (affinity maturation) Neutralizing epitopes on the Ebola virus GP by an in-house competitive Surface Plasmon Resonance assay, Cytokines, chemokines and soluble adhesion molecules in fresh frozen plasma Profile and quantify circulating miRNAs using the Human miRNome PCR array Transcriptomic profiles of the immune response following rVSVΔG-ZEBOV-GP immunization. Analysis of adaptive cellular immune responses Metabolomics analysis of plasma samples Characterize the immunogenicity and immune responses induced by vaccination according to diet and health status Characterize the profile of Nitric Oxides species before and after vaccination, diet and health status To assess the translocation of gut microbial molecules in the peripheral blood • To assess the state of cytokine secretions in all groups according to diet and reduction/elimination of the effects of pathogens • To assess the vaccine-induced immune responses according to the states of immune activation within the causal groups • To profile the type and quality of diets among the participants day 0 to day 365 post immunization
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Centre de Recherches Medicales de Lambarene Quartier Schweitzer Lambarene 00242 Gabon
FUNDING SOURCES
Name of source Street address City Postal code Country
The Innovative Medicines Initiative European Union, Brussels Belgium
European Developing Countries Clinical Trial Partnership EDCTP Anna van Saksenlaan 51 The Hague 51 2593 H Netherlands
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor centre de recherches medicales de lambarene quartier schweitzer lambarene 00242 Gabon Individual
COLLABORATORS
Name Street address City Postal code Country
Claire Anne Siegrist 4 rue Gabrielle-Perret-Gentil Geneva 0014 Switzerland
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Selidji Todagbe AGNANDJI agnandjis@cermel.org +24177353114 quartier Swcheitzer, Lambarene
City Postal code Country Position/Affiliation
Lambarene 00242 Gabon Principal Investigator
Role Name Email Phone Street address
Public Enquiries Selidji Todagbe AGNANDJI agnandjis@cermel.org 0024177353114 quartier Schweitzer,Lambarene
City Postal code Country Position/Affiliation
Lambarene 00242 Gabon Scientist
Role Name Email Phone Street address
Scientific Enquiries Selidji Todagbe AGNANDJI agnandjis@cermel.org 0024177353114 quartier Schweitzer, Lambarene
City Postal code Country Position/Affiliation
Lambarene 00242 Gabon Scientist
Role Name Email Phone Street address
Public Enquiries Ferdie Chyssie AGNANDJI chryssie.mihindou@cermel.org +24162944813 Campus CERMEL
City Postal code Country Position/Affiliation
Lambarene BP 242 Gabon Project manager
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes The study protocol, documentation, data and all other information generated will be held in strict confidence. No information concerning the study or the data will be released to any unauthorized third party, without prior written approval of the trial sponsor Clinical Study Report,Informed Consent Form,Statistical Analysis Plan,Study Protocol The site owns the data and it is agreed that these will be shared or publication in a timely manner during the 15 years all biological material will be stored securely at CERMEL . No information concerning the study or the data will be released to any unauthorized third party, without prior written approval of the trial sponsor
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information