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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05539989
• Other study ID #: IMPAACT 2035/HVTN 604
• Secondary ID: UM1AI068632UM1AI
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: December 31, 2024
• Est. completion date: July 31, 2027

Study information

• Verified date: March 2024
• Source: International Maternal Pediatric Adolescent AIDS Clinical Trials Group
• Contact: Emily Brown, MA
• Phone: 919-321-3806
• Email: embrown[@]fhi360.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 480
• Est. completion date: July 31, 2027
• Est. primary completion date: July 31, 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 8 Years to 14 Years

Eligibility

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

Related Conditions & MeSH terms

• HIV Infections
• Tuberculosis

Intervention

Biological:
• VPM1002 Vaccine
0.1 mL (2-8x10^5 CFU)
• BCG Vaccine
0.1mL (0.075 Mycobacterium bovis)

Drug:
• Placebo
0.1 mL (sodium chloride for injection 0.9%)

Locations

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

Sponsors (4)

Lead Sponsor	Collaborator
International Maternal Pediatric Adolescent AIDS Clinical Trials Group	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

South Africa, 

Outcome

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