Evaluating a new tuberculosis vaccine in newborns in 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

This study is testing a new tuberculosis vaccine for newborns in Africa to see if it works better than the standard vaccine and is safe for babies who don't have HIV.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 7120 (estimated)
• Ages: 5 Minutes to 7 Days
• Sex: All
• Sponsor: Biofabri, S.L (industry)
• Locations: 1 site (Worcester, Western Cape)
• Trial ID: NCT04975178 on ClinicalTrials.gov

What this trial studies

This project aims to assess the safety, immunogenicity, and efficacy of a new live attenuated tuberculosis vaccine called MTBVAC in HIV-uninfected infants. The trial compares MTBVAC to the standard BCG vaccination in high tuberculosis incidence settings in sub-Saharan Africa. It involves a consortium of clinical trial partners and aims to enhance laboratory capacity for conducting TB vaccine studies. The study will also bio-bank samples to identify immune correlates of vaccine-mediated protection.

Who should consider this trial

Good fit: Ideal candidates for this study are newborns within seven days of birth, born to HIV-infected or uninfected mothers, and in good general health.

Not a fit: Patients who may not benefit include those with HIV infection not on effective antiretroviral therapy or those with health complications at birth.

Why it matters

Potential benefit: If successful, this vaccine could significantly reduce the incidence of tuberculosis in newborns, contributing to global efforts to eliminate the disease.

How similar studies have performed: Other studies have shown promise with similar vaccine approaches, but this specific trial represents a novel effort in the context of newborn vaccination.

Eligibility criteria

Inclusion Criteria:

* 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 Criteria:

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.

Where this trial is running

Worcester, Western Cape

• South African Tuberculosis Initiative, Brewelskloof Hospital — Worcester, Western Cape, South Africa (RECRUITING)

Study contacts

• Principal investigator: Mark Hatherill — University of Cape Town, Faculty of Health Sciences
• Study coordinator: Ingrid Murillo Jelsbak

Conditions: Tuberculosis