Randomised, Double-Blind, Controlled Phase 3 Trial to Evaluate the Efficacy, Safety and Immunogenicity of MTBVAC in Healthy HIV Unexposed (HU) and HIV Exposed Uninfected (HEU) Newborns in Tuberculosis-Endemic Regions of Sub-Saharan Africa
The objective of this project is to demonstrate safety, immunogenicity and improved efficacy of the new live attenuated M. tuberculosis vaccine called MTBVAC in a Phase 3 efficacy trial in HIV-uninfected infants born to HIV-infected and HIV-uninfected mothers as compared to standard of care BCG vaccination. The proposal builds upon a group of TB vaccine development partners in Europe and sub-Saharan Africa established in a previous EDCTP-supported project. It creates an expanded consortium of clinical trial partners for the optimal implementation of a large infant efficacy trial of MTBVAC in high TB incidence settings. New capacity for efficacy trials in infants will be a valuable resource for the TB vaccine development community. The proposal will create a network of institutions in three TB endemic African countries with enhanced laboratory capacity to conduct TB vaccine immunology studies and to bio-bank samples to discover immune correlates of vaccine-mediated protection.
• Male or female newborns within seven days of birth.
• Written informed maternal consent, including permission to access maternal antenatal, postnatal, and infant medical records.
• Infant participants and their caregivers available for trial follow-up and display the willingness and capacity to comply with trial procedures.
• Newborns must be in good general health during pregnancy and delivery, as assessed by medical history and targeted physical examination.
• Birth weight ≥ 2450 grams.
• Apgar score at 5 minutes ≥ 7.
• A maternal HIV test result (rapid test, enzyme-linked immunosorbent assay (ELISA), or Polymerase chain reaction (PCR)) taken within 30 days of delivery, or within seven days post-partum must be available and documented if HIV uninfected. If the mother is HIV infected, then she must be on antiretroviral (ARV) therapy as per in-country guidelines with a viral load of \<50 copies/mL (within six months of labour).
• Estimated gestational age ≥ 37 weeks.
• Mother has not participated in a clinical trial within three months prior to the infant's birth.
• Mother has never participated in a TB vaccine trial before.
• Infant may not participate in any other clinical trials.