Dose-Defining Safety and Immunogenicity Study of MTBVAC in South African Neonates (MTBVAC-03)

June 16, 2023 updated by: Biofabri, S.L

Phase 2a Dose-Defining Safety and Immunogenicity Study of MTBVAC in South African Neonates Living in a High-Burden Tuberculosis-Endemic Region

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

new effective tuberculosis (TB) vaccine is essential to achieve World Health Organization (WHO) End TB goals and eliminate TB by 2050. The optimal long-term strategy would be a combination of serial mass campaigns in adults, coupled with universal newborn vaccination. Newborns are the only human population without prior mycobacterial exposure in TB endemic countries and as such, live attenuated mycobacterial vaccines may offer better protection to this naïve population compared to adults.

MTBVAC is a novel TB vaccine candidate generated by genetically attenuating an M. tuberculosis clinical isolate of the EuroAmerican lineage. MTBVAC is based on two independent, stable genetic deletions of the genes coding for two major virulence factors, phoP coding for the transcription factor PhoP and fadD26 coding for the synthesis of PDIM. Since MTBVAC contains most of the genes deleted from BCG, it presents a wider collection of mycobacterial antigens to the host immune system. Safety and immunogenicity of MTBVAC has been demonstrated in BCG naive adults; and MTBVAC appears safe in a small ongoing Phase 1b study in South African newborns. Definitive demonstration of safety and immunogenicity at the optimal MTBVAC dose is key to progression into multi-centre efficacy trials in newborns.

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.

Study Type

Interventional

Enrollment (Actual)

99

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • South Africa
    • Western Cape
      • Worcester, Western Cape, South Africa, 6850
        • SATVI: Worcester

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 4 days (Child)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria of Newborns:

  • 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.

Exclusion Criteria of Newborns:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: MTBVAC Group 1
MTBVAC intermediate dose 2.5 x 10E+04 CFU/0.05 mL
Biological: MTBVAC
Live-attenuated Mycobacterium tuberculosis based on the deletion of phoP and fadD26 virulence genes
Experimental: MTBVAC Group 2
MTBVAC high dose 2.5 x 10E+05 CFU/0.05 mL
Biological: MTBVAC
Live-attenuated Mycobacterium tuberculosis based on the deletion of phoP and fadD26 virulence genes
Experimental: MTBVAC Group 3
MTBVAC highest dose 2.5 x 10E+06 CFU/0.05 mL
Biological: MTBVAC
Live-attenuated Mycobacterium tuberculosis based on the deletion of phoP and fadD26 virulence genes
Active Comparator: BCG Group 4
BCG control 2.5 x 10E+05 CFU/0.05 mL
Biological: BCG
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.
Other Names:
  • Licensed BCG

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with treatment-related adverse events as defined in protocol.
Time Frame: 365 days post-vaccination
  • 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
Time Frame: 365 days post-vaccination
Measure of CD4 and CD8 T cells expressing specific cytokines in whole blood.
365 days post-vaccination

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
MTBVAC-induced QFT conversion and reversion kinetics
Time Frame: 365 days post-vaccination
Quantitative and qualitative results of the QFT Gold Plus assay up to day 365 post-vaccination.
365 days post-vaccination

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Biofabri, S.L

Collaborators

South African Tuberculosis Vaccine Initiative
TuBerculosis Vaccine Initiative
Universidad de Zaragoza

Investigators

  • Principal Investigator: Michele Tameris, MD, Study Principal Investigator South African Tuberculosis Vaccine Initiative

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 12, 2019

Primary Completion (Actual)

May 19, 2022

Study Completion (Actual)

May 19, 2022

Study Registration Dates

First Submitted

February 16, 2018

First Submitted That Met QC Criteria

May 14, 2018

First Posted (Actual)

May 24, 2018

Study Record Updates

Last Update Posted (Estimated)

June 19, 2023

Last Update Submitted That Met QC Criteria

June 16, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MTBVAC-03

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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