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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

99 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-02-12

Study Completion Date

2022-05-17

Brief Summary

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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.

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Detailed Description

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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.

Conditions

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Tuberculosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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MTBVAC Group 1

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

Group Type EXPERIMENTAL

MTBVAC

Intervention Type BIOLOGICAL

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

MTBVAC Group 2

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

Group Type EXPERIMENTAL

MTBVAC

Intervention Type BIOLOGICAL

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

MTBVAC Group 3

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

Group Type EXPERIMENTAL

MTBVAC

Intervention Type BIOLOGICAL

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

BCG Group 4

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

Group Type ACTIVE_COMPARATOR

BCG

Intervention Type BIOLOGICAL

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.

Interventions

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MTBVAC

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

Intervention Type 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.

Intervention Type BIOLOGICAL

Other Intervention Names

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Licensed BCG

Eligibility Criteria

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Inclusion Criteria

* 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

* 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.

Maximum Eligible Age

96 Hours

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes