Safety and Immunogenicity of VPM1002 Vaccination or BCG Revaccination Against TB in Pre-Adolescents Living With and Without HIV in South Africa

NCT05539989 | Withdrawn Phase 1 DMC

• 5 other identifiers: IMPAACT 2035/HVTN 604UM1AI068632UM1AI068616UM1AI106716HHSN275201800001I
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 9

Brief Summary

The purpose of this study is to assess whether Mycobacterium bovis rBCGΔureC::hly (VPM1002) vaccination and Mycobacterium bovis bacille Calmette-Guérin (BCG) revaccination are safe and immunogenic in pre-adolescents with and without HIV and with and without Mycobacterium tuberculosis (M.tb) sensitization.

Conditions

Tuberculosis; HIV Infections

Keywords

Bacterial and fungal diseases; Tuberculosis; Vaccine; Live vaccine; rBCG

Outcome Measures

Primary Outcomes (6)

• All adverse events

  Proportion of participants, based on the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017

  Through Week 48

• Solicited adverse events

  Proportion of participants, based on the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017

  Through Week 16

• Grade 3 or higher adverse events

  Proportion of participants, based on the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017

  Through Week 48

• Serious adverse events

  Proportion of participants, based on the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017

  Through Week 48

• Adverse pregnancy outcomes

  Proportion of participants, based on the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017

  Through Week 48 or delivery or other pregnancy outcome, whichever occurs later

• Frequency and response of VPM1002-specific and BCG-specific CD4+ and CD8+ T cells expressing Th1 and/or Th17 cytokines

  Measured by ICS and flow cytometry on cryopreserved PBMCs

  Through Week 10

Secondary Outcomes (9)

• Frequency and response of VPM1002-specific and BCG-specific CD4+ and CD8+ T cells expressing Th1 and/or Th17 cytokines

  Weeks 24 and 48

• Mycobacteria-specific IgA, IgG, and IgM binding antibodies

  Entry and Weeks 4, 10, 24, and 48

• Association of HIV and IGRA with primary safety outcomes (All AEs, solicitated AEs, grade 3 or higher AEs, serious adverse events, adverse pregnancy outcomes).

  Through Week 48 or delivery or other pregnancy outcome, whichever occurs later

• Cellular immunogenicity outcome measures associated with HIV and IGRA status

  Through Week 48

• Humoral immunogenicity outcome measures associated with HIV and IGRA status

  Through Week 48

Study Arms (3)

VPM1002 Vaccine Arm

EXPERIMENTAL

Participants stratified by HIV and M.tb sensitization status.

Biological: VPM1002 Vaccine

BCG Vaccine Arm

EXPERIMENTAL

Participants stratified by HIV and M.tb sensitization status.

Biological: BCG Vaccine

Placebo Arm

PLACEBO COMPARATOR

Participants stratified by HIV and M.tb sensitization status.

Drug: Placebo

Interventions

VPM1002 Vaccine BIOLOGICAL

0.1 mL (2-8x10\^5 CFU)

VPM1002 Vaccine Arm

BCG Vaccine BIOLOGICAL

0.1mL (0.075 Mycobacterium bovis)

BCG Vaccine Arm

Placebo DRUG

0.1 mL (sodium chloride for injection 0.9%)

Placebo Arm

Eligibility Criteria

• Age: 8 Years - 14 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Parent or legal guardian is willing and able to provide written informed consent; when applicable potential participant is willing and able to provide written assent
• Age 8-14 years (inclusive) at entry
• Received birth dose of BCG vaccine
• Has a negative nucleic acid test result for M.tb at screening and no other evidence of current active TB disease at screening
• M.tb sensitization status (positive or negative) determined based on IGRA testing at screening
• HIV status determined
• For participants living with HIV: has been receiving antiretroviral therapy for at least six months prior to study entry, has a CD4+ cell count of at least 200 cells/mm\^3 at screening, has had a suppressed HIV viral load for at least three months prior to entry
• Has normal or grade 1 results for all of the following at screening: Hemoglobin, White blood cell count, Platelet count, Creatinine, ALT, AST, Total bilirubin
• Has a normal temperature and no signs or symptoms of acute illness
• For participants assigned female sex at birth or who could otherwise become pregnant: not pregnant
• For participants assigned female sex at birth or who could otherwise breastfeed: not breastfeeding
• Expected to be available for 48 weeks of study participation
• Not expected to participate in any other study of an investigational agent during the 48 weeks of study participation

You may not qualify if:

• Known significant exposure to TB or receipt of tuberculin skin test in the six months prior to study entry
• Receipt of treatment for active TB disease in the 24 months prior to study entry
• Receipt of TB preventive therapy within 30 days prior to study entry or expected to initiate TB preventive therapy within the 48 weeks following study entry
• For participants living with HIV, current active AIDS-defining condition
• Receipt of any of the following: Any investigational TB vaccine, More than 14 consecutive days of systemic immunosuppressants or other immune-modifying therapy within the six months prior to study entry, Any immunoglobulin or other blood product within the three months prior to study entry,
• Receipt of any vaccine within the 30 days prior to study entry or is expected to receive any vaccine between study entry and the Week 4 Visit
• Receipt of allergy treatment with an antigen injection within the 30 days prior to study entry or is expected to receive one or more antigen injections between study entry and the Week 48 Visit
• History of any of the following: serious adverse reaction to any vaccine, allergy or hypersensitivity to BCG vaccine, allergy or hypersensitivity to the components of VPM1002 vaccine, anaphylaxis, generalized urticaria, autoimmune disease, diabetes mellitus type 1 or type 2, mild persistent, moderate, or severe asthma, bleeding disorder, malignancy, any condition resulting in the absence of a functional spleen (asplenia), including but not limited to sickle cell disease
• History of seizure or use of any medication to prevent or treat seizure within the three years prior to entry
• History of suspected or confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection diagnosed within the 30 days prior to entry
• Any other documented or suspected clinically significant medical, psychiatric, or behavioral condition or any other condition that, in the opinion of the site investigator, would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives

Sponsors & Collaborators

• International Maternal Pediatric Adolescent AIDS Clinical Trials Group: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• National Institute of Mental Health (NIMH): collaborator

Study Sites (9)

Soweto IMPAACT CRS

Johannesburg, Gauteng, 1862, South Africa

Location

Setshaba Research Centre CRS

Soshanguve, Gauteng, South Africa

Location

Isipingo CRS

Soshanguve, KwaZulu-Natal, South Africa

Location

Klerksdorp CRS

Klerksdorp, North West, South Africa

Location

Desmond Tutu TB Centre - Stellenbosch University (SU) CRS

Cape Town, Western Cape, South Africa

Location

Emavundleni CRS

Cape Town, Western Cape, South Africa

Location

Umlazi CRS

Durban, South Africa

Location

Wits RHI Shandukani Research CRS

Johannesburg, South Africa

Location

Family Clinical Research Unit (FAM-CRU) CRS

Tygerberg Hills, South Africa

Location

MeSH Terms

Conditions

Tuberculosis; HIV Infections; Mycoses

Interventions

VPM1002 recombinant BCG vaccine; BCG Vaccine

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Tuberculosis Vaccines; Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Lisa Marie Cranmer, MD, MPH

  Emory University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2022
• First Posted: September 14, 2022
• Study Start: December 31, 2025
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: August 17, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months following publication and available throughout period of funding of the International Maternal Pediatric Adolescent AIDS Clinical Trial (IMPAACT) Network by NIH.
• Access Criteria: * With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the IMPAACT Network. * For what types of analyses? To achieve aims in the proposal approved by the IMPAACT Network. * By what mechanism will data be made available? Researchers may submit a request for access to data using the IMPAACT "Data Request" form at: https://www.impaactnetwork.org/studies/submit-research-proposal. Researchers of approved proposals will need to sign an IMPAACT Data Use Agreement before receiving the data.

Locations

ZA (9)