Efficacy, Safety and Immunogenicity Evaluation of MTBVAC in Newborns in Sub-Saharan Africa
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
Biofabri, S.L
7,120 participants
Oct 17, 2022
INTERVENTIONAL
Conditions
Summary
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.
Eligibility
Inclusion Criteria11
- 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.
Exclusion Criteria10
- Receipt of BCG vaccination prior to enrolment.
- Significant antenatal, intrapartum, or postpartum complications that may affect the health of the newborn.
- Skin condition, bruising or birth mark at the intended injection site.
- Maternal HIV test (rapid test, ELISA, or PCR) result not available.
- HIV exposed Newborn's HIV PCR result positive or not available.
- Maternal history of TB during pregnancy.
- History of close/household contact with a TB patient, antenatal or postnatal, whether maternal, other family member or another household member who has not yet completed TB treatment.
- Clinically suspected neonatal sepsis.
- Any severe congenital malformation.
- History or evidence of any systemic disease on examination, or any illness that in the opinion of the Investigator may interfere with the evaluation of the safety and immunogenicity of the vaccine. Neonatal jaundice not considered clinically significant is not an exclusion.
Interventions
MTBVAC is a novel TB vaccine candidate based on an attenuated M. tuberculosis clinical isolate of the Euro-American lineage. Attenuation is based on two independent, stable genetic deletions of the genes phoP and fadD26 coding for two major virulence factors, the transcription factor PhoP and the cell-wall lipids PDIM, respectively. We hypothesize that MTBVAC will provide improved protection, as individuals latently infected with live M.tuberculosis have an 80% lower chance of developing TB, and as MTBVAC contains most of the genes deleted from BCG and presents a wider collection of antigens to the host immune system. Preclinical studies in different animal models indicated that MTBVAC is safe and is able to induce an improved protection compared to BCG.
BCG is a live attenuated M. bovis strain developed 100 years ago and is used as a preventive vaccine against tuberculosis. It is administered at birth.
Locations(1)
View Full Details on ClinicalTrials.gov
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NCT04975178