Evaluating the Safety and Immunogenicity of MTBVAC
HVTN605A5421
A Phase 2a Clinical Trial to Evaluate the Safety and Immunogenicity of MTBVAC
3 other identifiers
interventional
276
1 country
16
Brief Summary
The purpose of this study is to evaluate the safety and immunogenicity of MTBVAC in adolescents and adults living with and without HIV in South Africa
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Jan 2024
Typical duration for phase_2
16 active sites
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
June 30, 2023
CompletedFirst Posted
Study publicly available on registry
July 17, 2023
CompletedStudy Start
First participant enrolled
January 30, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 5, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
April 5, 2027
March 12, 2026
March 1, 2026
3.2 years
June 30, 2023
March 10, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (8)
Number of unsolicited adverse events
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017 (exceptions apply).
Through study week 48
Number of solicited adverse events
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017 (exceptions apply).
Through study week 16
Number of Grade 3 or higher adverse events
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017 (exceptions apply).
Through study week 48
Number of serious adverse events
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017 (exceptions apply).
Through study week 48
Frequency and response of MTBVAC-reactive CD4+ cells expressing Th1 and/or Th17 cytokines
Measured by intracellular cytokine staining (ICS) and flow cytometry on cryopreserved peripheral blood mononuclear cells
At baseline and study weeks 4
Frequency and response of MTBVAC-reactive CD4+ cells expressing Th1 and/or Th17 cytokines
Measured by intracellular cytokine staining (ICS) and flow cytometry on cryopreserved peripheral blood mononuclear cells
At baseline and study weeks10
Frequency and response of MTBVAC-reactive CD8+ T cells expressing Th1 and/or Th17 cytokines
Measured by intracellular cytokine staining (ICS) and flow cytometry on cryopreserved peripheral blood mononuclear cells
At baseline and study weeks 4
Frequency and response of MTBVAC-reactive CD8+ T cells expressing Th1 and/or Th17 cytokines
Measured by intracellular cytokine staining (ICS) and flow cytometry on cryopreserved peripheral blood mononuclear cells
At baseline and study weeks10
Secondary Outcomes (19)
Number of unsolicited adverse events
Through study week 48
Number of solicited adverse events
Through study week 16
Number of Grade 3 or higher adverse events
Through study week 48
Number of serious adverse events
Through study week 48
Frequency and response of BCG-reactive CD8+ T cells expressing Th1 and/or Th17 cytokines
At baseline and study week 4
- +14 more secondary outcomes
Study Arms (12)
1.1a - Adolescents and adults without HIV and negative interferon-gamma release assay
EXPERIMENTALParticipants will receive MTBVAC as a 0.1 mL intradermal (ID) injection, in the upper arm once at Week 0.
1.1b - Adolescents and adults without HIV and negative interferon-gamma release assay
EXPERIMENTALParticipants will receive BCG as a 0.1 mL intradermal (ID) injection, in the upper arm once at Week 0.
1.2a - Adolescents and adults without HIV and positive interferon-gamma release assay
EXPERIMENTALParticipants will receive MTBVAC as a 0.1 mL intradermal (ID) injection, in the upper arm once at Week 0.
1.2b - Adolescents and adults without HIV and positive interferon-gamma release assay
EXPERIMENTALParticipants will receive BCG as a 0.1 mL intradermal (ID) injection, in the upper arm once at Week 0.
2.1 a- Adolescents and adults with well-controlled HIV and negative interferon-gamma release assay
EXPERIMENTALParticipants will receive MTBVAC as a 0.1 mL intradermal (ID) injection, in the upper arm once at Week 0.
2.1.b - Adolescents and adults with well-controlled HIV and negative interferon-gamma release assay
EXPERIMENTALParticipants will receive BCG as a 0.1 mL intradermal (ID) injection, in the upper arm once at Week 0.
2.2 a- Adolescents and adults with well-controlled HIV and positive interferon-gamma release assay
EXPERIMENTALParticipants will receive MTBVAC as a 0.1 mL intradermal (ID) injection, in the upper arm once at Week 0.
2.2 b- Adolescents and adults with well-controlled HIV and positive interferon-gamma release assay
EXPERIMENTALParticipants will receive BCG as a 0.1 mL intradermal (ID) injection, in the upper arm once at Week 0.
3.1 a- Adults with well-controlled HIV and negative interferon-gamma release assay
EXPERIMENTALParticipants will receive MTBVAC as a 0.1 mL intradermal (ID) injection, in the upper arm once at Week 0.
3.1 b- Adults with well-controlled HIV and negative interferon-gamma release assay
EXPERIMENTALParticipants will receive BCG as a 0.1 mL intradermal (ID) injection, in the upper arm once at Week 0.
3.2 a- Adults with well-controlled HIV and positive interferon-gamma release assay
EXPERIMENTALParticipants will receive MTBVAC as a 0.1 mL intradermal (ID) injection, in the upper arm once at Week 0.
3.2 b- Adults with well-controlled HIV and positive interferon-gamma release assay
EXPERIMENTALParticipants will receive BCG as a 0.1 mL intradermal (ID) injection, in the upper arm once at Week 0.
Interventions
The MTBVAC vaccine is a freeze-dried lyophilized pellet containing live attenuated strain MTBVAC01 derived from Mycobacterium tuberculosis (M.tb). Excipients include sucrose and sodium glutamate.
The active substance in BCG vaccine is a freeze-dried powder containing live attenuated Mycobacterium bovis BCG, Danish strain 1331 and sodium glutamate as a stabilizer. The powder is white and crystalline and may be difficult to see due to the small amount contained in each vial.
Eligibility Criteria
You may qualify if:
- Age of 12 through 55 years, on the day of enrollment.
- Access to a participating HVTN or ACTG CRS and willingness to be followed for the planned duration of the study.
- For volunteers 18 years of age or older: ability and willingness to provide informed consent.
- For volunteers less than 18 years of age: parent or legal guardian is willing and able to provide informed consent for potential participant's study participation; in addition, when applicable per ethics committee policies and procedures, potential participant is willing and able to provide written assent for study participation.
- Assessment of Understanding (AoU): volunteer demonstrates understanding of this study and completes a questionnaire prior to vaccination with verbal demonstration of understanding of all questionnaire items answered incorrectly.
- Prior receipt of BCG vaccine in infancy as determined by the site investigator.
- Agrees not to enroll in another study of an investigational study product until after the last scheduled clinic visit. If a potential participant is already enrolled in another clinical trial, approvals from the other trial sponsor and the HVTN 605/A5421 PSRT are required prior to enrollment into HVTN 605/A5421.
- Good general health as shown by medical history, physical exam, and screening laboratory tests and assessed by the site investigator.
- Willingness to receive HIV-related test results.
- For volunteers living without HIV:
- Negative HIV-1 and -2 blood test: Non-US sites may use locally available assays that have been approved by HVTN Laboratory Operations
- Assessed by the clinic staff as having a low likelihood of acquiring HIV and is committed to maintaining behavior that is consistent with a lower likelihood of acquiring HIV through the last required protocol clinic visit
- Willingness to discuss their potential for HIV acquisition and is amenable to HIV risk reduction counseling
- For volunteers living with HIV:
- For both Cohorts 2 and 3: Completed one course of tuberculosis preventive treatment (TPT) as determined by the site investigator.
- +12 more criteria
You may not qualify if:
- Weight less than 40 kg
- Known significant exposure to TB or receipt of tuberculin skin test in the six months prior enrollment, as determined by the site investigator based on potential participant/parent/guardian report and available medical records. \[Note: Significant exposure is defined as close contact with a person who has active TB and has not completed TB treatment. Close contact is defined as sleeping in the same contiguous house/dwelling, and/or working or socializing in close proximity in an enclosed space frequently (eg, several times a week).\]
- History of prior active TB disease, as determined by the site investigator based on participant/parent/guardian report and available medical, laboratory or radiographic records.
- Evidence of active TB disease as determined by the site investigator based on participant/parent/guardian report and available medical records, results from physical examination, two-view chest X-ray, and M.tb nucleic acid testing from an expectorated sputum, including a review of any available radiography; and, for volunteers living with HIV and a CD4 count \<200 cells/mm3, a positive urine LAM test.
- For volunteers living with HIV: current active AIDS-defining condition as determined by the site investigator based on participant/parent/guardian report and available medical records
- Blood products received within 120 days before vaccination.
- Investigational study products (non-vaccine) received within 28 days before vaccination.
- Pregnant or breastfeeding.
- Investigational TB vaccine(s) received in a prior TB vaccine trial or BCG vaccination outside infancy. For volunteers who have received control/placebo in a TB vaccine trial, the HVTN 605/A5421 PSRT will determine eligibility on a case-by-case basis.
- Investigational non-TB vaccine(s) received within the last 1 year in a prior vaccine trial. Exceptions may be made by the HVTN 605/A5421 PSRT for vaccines that have subsequently undergone licensure by the FDA or by the national regulatory authority where the volunteer is enrolling. For volunteers who have received control/placebo in an experimental vaccine trial, the HVTN 605/A5421 PSRT will determine eligibility on a case-by-case basis. For volunteers who have received an experimental vaccine(s) greater than 1 years ago, eligibility for enrollment will be determined by the HVTN 605/A5421 PSRT on a case-by-case basis.
- Live attenuated vaccines received within 28 days before first vaccination or scheduled within 28 days after injection (eg, measles, mumps, and rubella \[MMR\]; oral polio vaccine \[OPV\]; varicella; yellow fever; live attenuated influenza vaccine).
- Any vaccines that are not live attenuated vaccines and were received within 14 days prior to first vaccination (eg, tetanus, pneumococcal, Hepatitis A or B).
- Allergy treatment with antigen injections within 28 days before first vaccination or that are scheduled within 14 days after first vaccination.
- Serious adverse reactions to vaccines or to vaccine components including history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain. (Not excluded from participation: a volunteer who had a non-anaphylactic adverse reaction to pertussis vaccine as a child).
- Immunoglobulin received within 90 days before vaccination.
- +16 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- HIV Vaccine Trials Networklead
- Biofabri, S.Lcollaborator
- National Institute of Allergy and Infectious Diseases (NIAID)collaborator
- Fred Hutchinson Cancer Centercollaborator
Study Sites (16)
Soweto - Gauteng
Johannesburg, Gauteng, 1862, South Africa
Johannesburg - CHRU
Westdene, Gauteng, 2092, South Africa
Durban - Botha's Hill CRS
Durban, KwaZulu-Natal, 4001, South Africa
Durban - Wentworth
Durban, KwaZulu-Natal, 4052, South Africa
Cape Town - UCTLI
Cape Town, Western Cape, 7700, South Africa
Cape Town - Emavundleni
Cape Town, Western Cape, 7750, South Africa
Cape Town - Groote Schuur
Cape Town, Western Cape, 7784, South Africa
Worcester - SATVI
Worcester, Western Cape, 6850, South Africa
Cape Town - Khayelitsha
Cape Town, South Africa
Durban - Chatsworth
Chatsworth, South Africa
Durban eThekwini
Durban, South Africa
Durban - Isipingo
Isipingo, South Africa
Klerksdorp
Klerksdorp, South Africa
Ladysmith
Ladysmith, South Africa
Rustenburg CRS
Rustenburg, South Africa
Soshanguve
Soshanguve, South Africa
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Mark Hatherill
South African Tuberculosis Vaccine Initiative
- STUDY CHAIR
Limakatso Lebina
Africa Health Research Institute (AHRI)
Central Study Contacts
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
- NETWORK
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 30, 2023
First Posted
July 17, 2023
Study Start
January 30, 2024
Primary Completion (Estimated)
April 5, 2027
Study Completion (Estimated)
April 5, 2027
Last Updated
March 12, 2026
Record last verified: 2026-03