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

Phase I/II Randomized, Placebo-Controlled Study of the Safety and Immunogenicity of VPM1002 Vaccination or BCG Revaccination Against Tuberculosis in Pre-Adolescents Living With and Without HIV in South Africa

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.

Study Overview

• Status: Withdrawn
• Conditions: HIV Infections; Tuberculosis
• Intervention / Treatment: Biological: VPM1002 Vaccine; Biological: BCG Vaccine; Drug: Placebo

Detailed Description

Phase I/II, double-blinded, placebo-controlled, randomized (1:1:1) multi-center study. Randomization will be stratified by HIV status and M.tb sensitization status. The study will enroll approximately 480 pre-adolescents (8-14 years of age inclusive) with or without HIV and with or without M.tb sensitization who received BCG vaccination at birth. Participants with HIV will be immunocompetent and virologically suppressed on antiretroviral therapy.

Participants will be randomized to one of three study product arms: VPM1002 Vaccine, BCG Vaccine, or Placebo. Each participant will receive a single intradermal injection of the assigned study product.

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• South Africa
  • Durban, South Africa
    • Umlazi CRS
  • Johannesburg, South Africa
    • Wits RHI Shandukani Research CRS
  • Tygerberg Hills, South Africa
    • Family Clinical Research Unit (FAM-CRU) CRS
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 1862
      • Soweto IMPAACT CRS
    • Soshanguve, Gauteng, South Africa
      • Setshaba Research Centre CRS
  • Kwa Zulu Natal
    • Soshanguve, Kwa Zulu Natal, South Africa
      • Isipingo CRS
  • North West Province
    • Klerksdorp, North West Province, South Africa
      • Klerksdorp CRS
  • Western Cape
    • Cape Town, Western Cape, South Africa
      • Desmond Tutu TB Centre - Stellenbosch University (SU) CRS
    • Cape Town, Western Cape, South Africa
      • Emavundleni CRS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 14 years (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VPM1002 Vaccine Arm; Participants stratified by HIV and M.tb sensitization status.	Biological: VPM1002 Vaccine; 0.1 mL (2-8x10^5 CFU)
Experimental: BCG Vaccine Arm; Participants stratified by HIV and M.tb sensitization status.	Biological: BCG Vaccine; 0.1mL (0.075 Mycobacterium bovis)
Placebo Comparator: Placebo Arm; Participants stratified by HIV and M.tb sensitization status.	Drug: Placebo; 0.1 mL (sodium chloride for injection 0.9%)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 PBMC	Weeks 24 and 48
Mycobacteria-specific IgA, IgG, and IgM binding antibodies	Measured using BAMA	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).	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
Cellular immunogenicity outcome measures associated with HIV and IGRA status	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 48
Humoral immunogenicity outcome measures associated with HIV and IGRA status	Mycobacteria-specific IgA, IgG, and IgM binding antibodies, measured using BAMA	Through Week 48
Gene expression profiles	Measured by RNA-seq in whole blood	Entry and Weeks 1, 4, and 10
Differential leukocyte count and immunophenotype	Measured in cryopreserved ex vivo whole blood (DLC-ICE) by flow cytometry	Entry and Weeks 1, 4, and 10
Measurement of soluble proinflammatory mediators	Based on serum measurement	Entry and Weeks 1, 4, and 10
Acceptability of the study products	Based on scores derived from questionnaire responses	Week 24

Collaborators and Investigators

• Sponsor: International Maternal Pediatric Adolescent AIDS Clinical Trials Group
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institute of Mental Health (NIMH)
• Investigators: Study Chair: Lisa Marie Cranmer, MD, MPH, Emory University

Study record dates

Study Major Dates

• Study Start (Estimated): December 31, 2025
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: September 9, 2022
• First Submitted That Met QC Criteria: September 9, 2022
• First Posted (Actual): September 14, 2022

Study Record Updates

• Last Update Posted (Actual): August 17, 2025
• Last Update Submitted That Met QC Criteria: August 13, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Vaccine; Tuberculosis; Live vaccine; Bacterial and fungal diseases; rBCG
• Additional Relevant MeSH Terms: Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Immunologic Factors; Physiological Effects of Drugs; Adjuvants, Immunologic; BCG Vaccine; Vaccines
• Other Study ID Numbers: IMPAACT 2035/HVTN 604; UM1AI068632 (U.S. NIH Grant/Contract); UM1AI068616 (U.S. NIH Grant/Contract); UM1AI106716 (U.S. NIH Grant/Contract); HHSN275201800001I (Other Identifier: Eunice Kennedy Shriver National Institute of Child Health and Human Development)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie results in the publication, after deidentification.
• IPD Sharing 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.

IPD Sharing 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.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No