TuberculosisPhase 2MTBVAC-03NCT03536117
Dose-Defining Safety and Immunogenicity Study of MTBVAC in South African Neonates
A Phase 2 study testing MTBVAC and BCG in people with Tuberculosis, run by Biofabri, S.L at 1 site in South Africa.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 96 hoursHealthy volunteers can take part
- Conditions the study is for
- Tuberculosis
- What is being tested?
- MTBVAC and BCG
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 99 participants
- Where
- 1 siteSouth Africa
- Study dates
- 12 Feb 2019to 17 May 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 96 hours
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Tuberculosis
- Being tested
- MTBVAC, BCG
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MTBVACBiological
Live-attenuated Mycobacterium tuberculosis based on the deletion of phoP and fadD26 virulence genes
BCGBiological
Also called Licensed 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.
| Study group | Role | What they receive |
|---|---|---|
| MTBVAC Group 1 | Experimental | MTBVAC intermediate dose 2.5 x 10E+04 CFU/0.05 mL Receives: Biological: MTBVAC |
| MTBVAC Group 2 | Experimental | MTBVAC high dose 2.5 x 10E+05 CFU/0.05 mL Receives: Biological: MTBVAC |
| MTBVAC Group 3 | Experimental | MTBVAC highest dose 2.5 x 10E+06 CFU/0.05 mL Receives: Biological: MTBVAC |
| BCG Group 4 | Active comparator | BCG control 2.5 x 10E+05 CFU/0.05 mL Receives: Biological: BCG |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 365 days post-vaccination
Immunogenicity analysis in infants
Measure of CD4 and CD8 T cells expressing specific cytokines in whole blood.
Measured: 365 days post-vaccination
Secondary outcomes (1)
MTBVAC-induced QFT conversion and reversion kinetics
Quantitative and qualitative results of the QFT Gold Plus assay up to day 365 post-vaccination.
Measured: 365 days post-vaccination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2018
- Study start12 Feb 2019
- Primary completion17 May 2022
- Study completion17 May 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 99 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biofabri, S.L
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- South African Tuberculosis Vaccine Initiative, Universidad de Zaragoza, TuBerculosis Vaccine Initiative
- Responsible party
- Sponsor
- Investigators
- Michele Tameris, MD, Principal investigator, Study Principal Investigator South African Tuberculosis Vaccine Initiative
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03536117
- Sponsor's protocol ID
- MTBVAC-03
- Acronym
- MTBVAC-03
- Status last verified
- Apr 2025
- First submitted
- 16 Feb 2018
- Last updated
- 27 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 23965219Spertini 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.
PubMed 26598141Aguilo 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.
PubMed 26786657Clark 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.
PubMed 28329234Marinova 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.
PubMed 28447476Tameris 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.
PubMed 40101388
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2a Dose-Defining Safety and Immunogenicity Study of MTBVAC in South African Neonates Living in a High-Burden Tuberculosis-Endemic Region
- ClinicalTrials.gov ID
- NCT03536117
- Acronym / sponsor ID
- MTBVAC-03 / MTBVAC-03
- Conditions
- Tuberculosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 99 participants (actual)
- Lead sponsor
- Biofabri, S.LIndustry (pharma, biotech, devices)
- Collaborators
- South African Tuberculosis Vaccine Initiative, Universidad de Zaragoza, TuBerculosis Vaccine Initiative
- Study start
- 12 Feb 2019 (actual)
- Primary completion
- 17 May 2022 (actual)
- Study completion
- 17 May 2022 (actual)
- First posted
- 24 May 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| MTBVAC Group 1 | Experimental | Biological: MTBVACMTBVAC intermediate dose 2.5 x 10E+04 CFU/0.05 mL |
| MTBVAC Group 2 | Experimental | Biological: MTBVACMTBVAC high dose 2.5 x 10E+05 CFU/0.05 mL |
| MTBVAC Group 3 | Experimental | Biological: MTBVACMTBVAC highest dose 2.5 x 10E+06 CFU/0.05 mL |
| BCG Group 4 | Active comparator | Biological: BCGBCG control 2.5 x 10E+05 CFU/0.05 mL |
Who may qualify
- Ages
- Up to 96 hours
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MTBVACLive-attenuated Mycobacterium tuberculosis based on the deletion of phoP and fadD26 virulence genes | Biological | MTBVAC Group 1, MTBVAC Group 2, MTBVAC Group 3 |
| BCGAlso: Licensed BCGLive-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. | Biological | BCG Group 4 |
Primary outcome
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
Immunogenicity analysis in infants
Time frame: 365 days post-vaccination
Measure of CD4 and CD8 T cells expressing specific cytokines in whole blood.
1 secondary outcome
MTBVAC-induced QFT conversion and reversion kinetics
Time frame: 365 days post-vaccination
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2025.
- Background: PubMed 23965219Arbues 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.
- Background: PubMed 26598141Spertini 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.
- Background: PubMed 26786657Aguilo 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.
- Background: PubMed 28329234Clark 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.
- Background: PubMed 28447476Marinova 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.
- Results publication: PubMed 40101388Tameris 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michele Tameris, MD principal investigator
Study Principal Investigator South African Tuberculosis Vaccine Initiative
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MTBVAC and BCG in people with Tuberculosis, run by Biofabri, S.L at 1 site in South Africa.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with treatment-related adverse events as defined in protocol. (time frame: 365 days post-vaccination). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03536117, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2025; AzTrials last refreshed its copy on 7 Nov 2026.