Efficacy, Safety and Immunogenicity Evaluation of MTBVAC in Newborns in Sub-Saharan Africa

NCT04975178
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Phase
Phase 3
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Recruitment status
Recruiting
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Participants
7,120
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Lead sponsor
Biofabri, S.L
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Start date
2022-10-17
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Number of sites
1
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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.
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Acronym
MTBVACN3
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Short title
Efficacy, Safety and Immunogenicity Evaluation of MTBVAC in Newborns in Sub-Saharan Africa
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Official title
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
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Control arm
Active comparator
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 3
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Study type
Interventional
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Completion date
2029-02-01
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First posted
2021-07-23
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Registry last updated
2025-02-10
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Primary completion date
2029-02-01
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Start date
2022-10-17
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Participants
7,120
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Participant count basis
Estimated
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Planned participants
7,120
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Protocol amendments
3
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Number of sites
1
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
Biofabri, S.L
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Source registry
ClinicalTrials.gov
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Registry ID
NCT04975178
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ClinicalTrials.gov ID
NCT04975178
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Prevention
Masking
Quadruple masking
Masking description
MTBVAC and BCG vaccine will be prepared, and allocation concealed by the site pharmacist. All other site staff will be blinded to vaccine allocation, throughout the follow-up period. Data pertaining to the MTBVAC vaccine and to BCG control will be collected in an observer-blinded manner. Blinding will be maintained throughout the vaccination and follow-up portions of the vaccine trial. No set of individual codes will be held at Biofabri's Headquarters. Biofabri's Headquarters will be able to access the individual randomization code from the SATVI Pharmacy randomization register. The code will be broken by the Site's Pharmacist (Study Contact for Emergency Code Break) only in the case of medical events that the investigator/physician in charge of the participant feels cannot be treated without knowing the identity of the study vaccine(s). The Site's Pharmacist is responsible for unblinding the treatment assignment in accordance with specified time frames for expedited reporting of SAEs.
Masked roles
Participants, Care providers, Investigators, Outcome assessors
Sources for study design
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  1. To demonstrate efficacy in terms of incidence of MTBVAC against TB disease in healthy HU and HEU newborns compared to BCG

    Timeframe: Minimum of 24 months to a maximum 80 months; or until study end in South Africa.

    Primary: Time from vaccination to diagnosis of first confirmed or unconfirmed TB disease, which might be right-censored due to loss to follow-up, death, or successful completion of the study without acquiring TB disease from day of vaccination. Secondary: Confirmed TB disease, which might be right-censored due to loss to follow-up, death, or successful completion of the study without acquiring TB from day of vaccination. Exploratory: i) Time from vaccination to diagnosis of first unconfirmed or unlikely TB disease, which might be right-censored due to loss to follow-up, death, or successful completion of the study without acquiring TB disease from day of vaccination. ii) Confirmed or unconfirmed TB, which might be right-censored due to loss to follow-up, death, or successful completion of the study without acquiring TB carried out with a washout period of 90 days after vaccination. iii) Confirmed TB disease; iv) Unconfirmed or unlikely TB disease (ver ii for iii and iv).

  1. To assess the safety and reactogenicity of MTBVAC in healthy HU and HEU newborns compared to BCG.

    Timeframe: Minimum of 24 months to a maximum 80 months; or until study end in South Africa.

    Incidence and severity of: Solicited AEs; Local solicited AEs (injection-site reactions): pain, erythema (redness), swelling, and induration (collected up to Day 10), and ulceration, drainage/discharge, and scarring (collected up to Day 56); Systemic solicited AEs: fever, irritability, vomiting, diarrhea, and skin rash (collected up to Day 10). Unsolicited AEs: MAAEs; Medically un-attended AEs. Solicited AEs with onset after Day 10: Local solicited AEs (injection-site reactions): pain, erythema (redness), swelling, and induration. Systemic solicited AEs: fever, irritability, vomiting, diarrhea, and skin rash. Solicited AEs with onset after Day 56: ulceration, drainage/discharge, and scarring; AESIs, SAEs

Sources for outcomes
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Sex
All
Age groups
Children
Minimum age
5 Minutes
Maximum age
7 Days
Healthy volunteers
Yes

  • 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.

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.
Sources for eligibility
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  • South African Tuberculosis Initiative, Brewelskloof HospitalWorcester, South AfricaRecruiting
Sources for sites
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Sources for references
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Related records

Drugs (1)

Collaborators (8)

Lead sponsors (1)

Conditions (1)