NCT03536117

Brief Summary

A Phase 2a dose-defining study of MTBVAC to evaluate the safety, reactogenicity, immunogenicity, and potential for IGRA conversion and reversion, of MTBVAC in South African newborns. Ninety-nine HIV unexposed, BCG naïve newborns will be randomized to receive either BCG 2.5 x 105 CFU (n=24) or MTBVAC at one of three dose levels (n=75). Allocation will be double blind. Enrolment will be sequential into 3 cohorts of increasing MTBVAC dose (Cohort 1: n=25 MTBVAC 2.5 x 10E+04 and n=8 BCG; Cohort 2: n=25 MTBVAC 2.5 x 10E+05 and n=8 BCG; Cohort 3: n=25 MTBVAC 2.5 x 10E+06 and n=8 BCG). Dose escalation will be staggered to allow gradual evaluation of safety; final selection of the dose for Cohort 3 will be based on all available safety and immunogenicity data.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
99

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Feb 2019

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 16, 2018

Completed
3 months until next milestone

First Posted

Study publicly available on registry

May 24, 2018

Completed
9 months until next milestone

Study Start

First participant enrolled

February 12, 2019

Completed
3.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 17, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 17, 2022

Completed
Last Updated

April 27, 2025

Status Verified

April 1, 2025

Enrollment Period

3.3 years

First QC Date

February 16, 2018

Last Update Submit

April 23, 2025

Conditions

Tuberculosis

Outcome Measures

Primary Outcomes (2)

  • Number of participants with treatment-related adverse events as defined in protocol.

    * Solicited systemic adverse events: fever, irritability, vomiting, diarrhea, drowsiness, poor feeding, skin rash. * Solicited injection site reaction adverse events: pain, redness, swelling, ulceration, drainage, and regional lymphadenopathy * Unsolicited adverse events and serious adverse events

    365 days post-vaccination

  • Immunogenicity analysis in infants

    Measure of CD4 and CD8 T cells expressing specific cytokines in whole blood.

    365 days post-vaccination

Secondary Outcomes (1)

  • MTBVAC-induced QFT conversion and reversion kinetics

    365 days post-vaccination

Study Arms (4)

MTBVAC Group 1

EXPERIMENTAL

MTBVAC intermediate dose 2.5 x 10E+04 CFU/0.05 mL

Biological: MTBVAC

MTBVAC Group 2

EXPERIMENTAL

MTBVAC high dose 2.5 x 10E+05 CFU/0.05 mL

Biological: MTBVAC

MTBVAC Group 3

EXPERIMENTAL

MTBVAC highest dose 2.5 x 10E+06 CFU/0.05 mL

Biological: MTBVAC

BCG Group 4

ACTIVE COMPARATOR

BCG control 2.5 x 10E+05 CFU/0.05 mL

Biological: BCG

Interventions

MTBVACBIOLOGICAL

Live-attenuated Mycobacterium tuberculosis based on the deletion of phoP and fadD26 virulence genes

MTBVAC Group 1MTBVAC Group 2MTBVAC Group 3
BCGBIOLOGICAL

Live-attenuated Mycobacterium bovis obtained by subculture passaging in ox-bile and glycerated potatoes between 1908-1921 by Albert Calmette and Camille Guerin. BCG is the only licensed vaccine today against tuberculosis (TB) mainly used in TB-endemic countries.

Also known as: Licensed BCG
BCG Group 4

Eligibility Criteria

AgeUp to 96 Hours
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17)

You may qualify if:

  • Newborns of mothers who provided informed consent will be enrolled within 96 hours of birth if they are in general good health during pregnancy and delivery
  • Weight ≥2450 grams at birth
  • Apgar score at 5 minutes ≥7
  • Estimated gestational age ≥37 weeks.

You may not qualify if:

  • If received routine BCG vaccination prior to enrolment
  • Have any significant antenatal or intrapartum or postpartum complications
  • Have unknown or positive maternal HIV test; or
  • Have prior history of close contact with a TB patient, antenatal or postnatal, whether maternal, other family member or other household member.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

SATVI: Worcester

Worcester, Western Cape, 6850, South Africa

Location

Related Publications (6)

  • Arbues A, Aguilo JI, Gonzalo-Asensio J, Marinova D, Uranga S, Puentes E, Fernandez C, Parra A, Cardona PJ, Vilaplana C, Ausina V, Williams A, Clark S, Malaga W, Guilhot C, Gicquel B, Martin C. Construction, characterization and preclinical evaluation of MTBVAC, the first live-attenuated M. tuberculosis-based vaccine to enter clinical trials. Vaccine. 2013 Oct 1;31(42):4867-73. doi: 10.1016/j.vaccine.2013.07.051. Epub 2013 Aug 17.

    PMID: 23965219BACKGROUND

  • Spertini F, Audran R, Chakour R, Karoui O, Steiner-Monard V, Thierry AC, Mayor CE, Rettby N, Jaton K, Vallotton L, Lazor-Blanchet C, Doce J, Puentes E, Marinova D, Aguilo N, Martin C. Safety of human immunisation with a live-attenuated Mycobacterium tuberculosis vaccine: a randomised, double-blind, controlled phase I trial. Lancet Respir Med. 2015 Dec;3(12):953-62. doi: 10.1016/S2213-2600(15)00435-X. Epub 2015 Nov 17.

    PMID: 26598141BACKGROUND

  • Aguilo N, Uranga S, Marinova D, Monzon M, Badiola J, Martin C. MTBVAC vaccine is safe, immunogenic and confers protective efficacy against Mycobacterium tuberculosis in newborn mice. Tuberculosis (Edinb). 2016 Jan;96:71-4. doi: 10.1016/j.tube.2015.10.010. Epub 2015 Nov 30.

    PMID: 26786657BACKGROUND

  • Clark S, Lanni F, Marinova D, Rayner E, Martin C, Williams A. Revaccination of Guinea Pigs With the Live Attenuated Mycobacterium tuberculosis Vaccine MTBVAC Improves BCG's Protection Against Tuberculosis. J Infect Dis. 2017 Sep 1;216(5):525-533. doi: 10.1093/infdis/jix030.

    PMID: 28329234BACKGROUND

  • Marinova D, Gonzalo-Asensio J, Aguilo N, Martin C. MTBVAC from discovery to clinical trials in tuberculosis-endemic countries. Expert Rev Vaccines. 2017 Jun;16(6):565-576. doi: 10.1080/14760584.2017.1324303. Epub 2017 May 12.

    PMID: 28447476BACKGROUND

  • Tameris M, Rozot V, Imbratta C, Geldenhuys H, Mendelsohn SC, Kany Luabeya AK, Shenje J, Tredoux N, Fisher M, Mulenga H, Bilek N, Young C, Veldsman A, Botes N, Thole J, Fritzell B, Mukherjee R, Jelsbak IM, Rodriguez E, Puentes E, Doce J, Marinova D, Gonzalo-Asensio J, Aguilo N, Martin C, Scriba TJ, Hatherill M; MTBVAC 202 study team. Safety, reactogenicity, and immunogenicity of MTBVAC in infants: a phase 2a randomised, double-blind, dose-defining trial in a TB endemic setting. EBioMedicine. 2025 Apr;114:105628. doi: 10.1016/j.ebiom.2025.105628. Epub 2025 Mar 17.

    PMID: 40101388RESULT

MeSH Terms

Conditions

Tuberculosis

Interventions

MTBVAC vaccine

Condition Hierarchy (Ancestors)

Mycobacterium InfectionsActinomycetales InfectionsGram-Positive Bacterial InfectionsBacterial InfectionsBacterial Infections and MycosesInfections

Study Officials

  • Michele Tameris, MD

    Study Principal Investigator South African Tuberculosis Vaccine Initiative

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
SEQUENTIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 16, 2018

First Posted

May 24, 2018

Study Start

February 12, 2019

Primary Completion

May 17, 2022

Study Completion

May 17, 2022

Last Updated

April 27, 2025

Record last verified: 2025-04

Locations

ZA(1)