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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03536117
Recruitment Status : Completed
First Posted : May 24, 2018
Last Update Posted : August 29, 2022
Sponsor:
Collaborators:
South African Tuberculosis Vaccine Initiative
Universidad de Zaragoza
TuBerculosis Vaccine Initiative
Information provided by (Responsible Party):
Biofabri, S.L

Study Description
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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.

Condition or disease Intervention/treatment Phase
Tuberculosis Biological: MTBVAC Biological: BCG Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 99 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Phase 2a Dose-Defining Safety and Immunogenicity Study of MTBVAC in South African Neonates Living in a High-Burden Tuberculosis-Endemic Region
Actual Study Start Date : February 11, 2019
Actual Primary Completion Date : March 8, 2021
Actual Study Completion Date : March 7, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Tuberculosis

Arms and Interventions
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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 Name: Licensed BCG


Outcome Measures
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Primary Outcome Measures :
  1. 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

  2. Immunogenicity analysis in infants [ Time Frame: 365 days post-vaccination ]
    Measure of CD4 and CD8 T cells expressing specific cytokines in whole blood.


Secondary Outcome Measures :
  1. 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.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   up to 96 Hours   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03536117


Locations
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South Africa
SATVI: Worcester
Worcester, Western Cape, South Africa, 6850
Sponsors and Collaborators
Biofabri, S.L
South African Tuberculosis Vaccine Initiative
Universidad de Zaragoza
TuBerculosis Vaccine Initiative
Investigators
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Principal Investigator: Michele Tameris, MD Study Principal Investigator South African Tuberculosis Vaccine Initiative
More Information
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Publications:

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Responsible Party: Biofabri, S.L
ClinicalTrials.gov Identifier: NCT03536117    
Other Study ID Numbers: MTBVAC-03
First Posted: May 24, 2018    Key Record Dates
Last Update Posted: August 29, 2022
Last Verified: August 2022

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
 Bacterial Infections
Bacterial Infections and Mycoses
Infections