Clinical trial NCT05539989: Safety and Immunogenicity of VPM1002 Vaccination or BCG Revaccination Against TB in Pre-Adolescents Living With and Without HIV in South Africa
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Tuberculosis
HIV Infections
Keywords: Bacterial and fungal diseases
Tuberculosis
Vaccine
Live vaccine
rBCG
Lead sponsor: International Maternal Pediatric Adolescent AIDS Clinical Trials Group
Sponsor class: NETWORK
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: National Institute of Mental Health (NIMH)
First posted: 2022-09-14
Enrollment: 0
Sex: ALL
Minimum age (years): 8
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: All adverse events
timeFrame: Through Week 48
measure: Solicited adverse events
timeFrame: Through Week 16
measure: Grade 3 or higher adverse events
timeFrame: Through Week 48
measure: Serious adverse events
timeFrame: Through Week 48
measure: Adverse pregnancy outcomes
timeFrame: Through Week 48 or delivery or other pregnancy outcome, whichever occurs later
measure: Frequency and response of VPM1002-specific and BCG-specific CD4+ and CD8+ T cells expressing Th1 and/or Th17 cytokines
timeFrame: Through Week 10
Secondary outcomes:
measure: Frequency and response of VPM1002-specific and BCG-specific CD4+ and CD8+ T cells expressing Th1 and/or Th17 cytokines
timeFrame: Weeks 24 and 48
measure: Mycobacteria-specific IgA, IgG, and IgM binding antibodies
timeFrame: Entry and Weeks 4, 10, 24, and 48
measure: Association of HIV and IGRA with primary safety outcomes (All AEs, solicitated AEs, grade 3 or higher AEs, serious adverse events, adverse pregnancy outcomes).
timeFrame: Through Week 48 or delivery or other pregnancy outcome, whichever occurs later
measure: Cellular immunogenicity outcome measures associated with HIV and IGRA status
timeFrame: Through Week 48
measure: Humoral immunogenicity outcome measures associated with HIV and IGRA status
timeFrame: Through Week 48
measure: Gene expression profiles
timeFrame: Entry and Weeks 1, 4, and 10
measure: Differential leukocyte count and immunophenotype
timeFrame: Entry and Weeks 1, 4, and 10
measure: Measurement of soluble proinflammatory mediators
timeFrame: Entry and Weeks 1, 4, and 10
measure: Acceptability of the study products
timeFrame: Week 24
Other outcomes:
Locations:
city: Johannesburg
country: South Africa
facility: Soweto IMPAACT CRS
state: Gauteng
city: Soshanguve
country: South Africa
facility: Setshaba Research Centre CRS
state: Gauteng
city: Soshanguve
country: South Africa
facility: Isipingo CRS
state: Kwa Zulu Natal
city: Klerksdorp
country: South Africa
facility: Klerksdorp CRS
state: North West Province
city: Cape Town
country: South Africa
facility: Desmond Tutu TB Centre - Stellenbosch University (SU) CRS
state: Western Cape
city: Cape Town
country: South Africa
facility: Emavundleni CRS
state: Western Cape
city: Durban
country: South Africa
facility: Umlazi CRS
city: Johannesburg
country: South Africa
facility: Wits RHI Shandukani Research CRS
city: Tygerberg Hills
country: South Africa
facility: Family Clinical Research Unit (FAM-CRU) CRS
Study officials:
affiliation: Emory University
name: Lisa Marie Cranmer, MD, MPH
role: STUDY_CHAIR
References: