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

• Sponsor: International Maternal Pediatric Adolescent AIDS Clinical Trials Group (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05539989
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID) (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH), National Institute of Mental Health (NIMH) (NIH)
• Enrollment: 480
• Locations: 9
• Arms: 3
• Anticipated Duration (Months): 30
• Patients Per Site: 53.3
• Patients Per Site Per Month: 1.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Tuberculosis; HIV Infections	Biological: VPM1002 Vaccine; Biological: BCG Vaccine; Drug: Placebo	Phase 1/Phase 2

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 480 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• 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
• Anticipated Study Start Date: Mar 31, 2023
• Anticipated Primary Completion Date: Sep 30, 2025
• Anticipated Study Completion Date: Sep 30, 2025

Arms and Interventions

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%)

Outcome Measures

Primary Outcome Measures

1. All adverse events [Through Week 48]

   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

2. Solicited adverse events [Through Week 16]

   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

3. Grade 3 or higher adverse events [Through Week 48]

   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

4. Serious adverse events [Through Week 48]

   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

5. Adverse pregnancy outcomes [Through Week 48 or delivery or other pregnancy outcome, whichever occurs later]

   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

6. Frequency and response of VPM1002-specific and BCG-specific CD4+ and CD8+ T cells expressing Th1 and/or Th17 cytokines [Through Week 10]

   Measured by ICS and flow cytometry on cryopreserved PBMCs

Secondary Outcome Measures

1. Frequency and response of VPM1002-specific and BCG-specific CD4+ and CD8+ T cells expressing Th1 and/or Th17 cytokines [Weeks 24 and 48]

   Measured by ICS and flow cytometry on cryopreserved PBMC

2. Mycobacteria-specific IgA, IgG, and IgM binding antibodies [Entry and Weeks 4, 10, 24, and 48]

   Measured using BAMA

3. 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]

   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

4. Cellular immunogenicity outcome measures associated with HIV and IGRA status [Through Week 48]

   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

5. Humoral immunogenicity outcome measures associated with HIV and IGRA status [Through Week 48]

   Mycobacteria-specific IgA, IgG, and IgM binding antibodies, measured using BAMA

6. Gene expression profiles [Entry and Weeks 1, 4, and 10]

   Measured by RNA-seq in whole blood

7. Differential leukocyte count and immunophenotype [Entry and Weeks 1, 4, and 10]

   Measured in cryopreserved ex vivo whole blood (DLC-ICE) by flow cytometry

8. Measurement of soluble proinflammatory mediators [Entry and Weeks 1, 4, and 10]

   Based on serum measurement

9. Acceptability of the study products [Week 24]

   Based on scores derived from questionnaire responses

Eligibility Criteria

Criteria

• Ages Eligible for Study: 8 Years to 14 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Soweto IMPAACT CRS	Johannesburg	Gauteng	South Africa	1862
2	Setshaba Research Centre CRS	Soshanguve	Gauteng	South Africa
3	Isipingo CRS	Soshanguve	Kwa Zulu Natal	South Africa
4	Klerksdorp CRS	Klerksdorp	North West Province	South Africa
5	Desmond Tutu TB Centre - Stellenbosch University (SU) CRS	Cape Town	Western Cape	South Africa
6	Emavundleni CRS	Cape Town	Western Cape	South Africa
7	Umlazi CRS	Durban		South Africa
8	Wits RHI Shandukani Research CRS	Johannesburg		South Africa
9	Family Clinical Research Unit (FAM-CRU) CRS	Tygerberg Hills		South Africa

Sponsors and Collaborators

• International Maternal Pediatric Adolescent AIDS Clinical Trials Group
• 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 Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: International Maternal Pediatric Adolescent AIDS Clinical Trials Group
• ClinicalTrials.gov Identifier: NCT05539989
• Other Study ID Numbers: IMPAACT 2035/HVTN 604; UM1AI068632; UM1AI068616; UM1AI106716; HHSN275201800001I
• First Posted: Sep 14, 2022
• Last Update Posted: Sep 16, 2022
• Last Verified: Sep 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• 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
• Keywords provided by International Maternal Pediatric Adolescent AIDS Clinical Trials Group: Bacterial and fungal diseases; Tuberculosis; Vaccine; Live vaccine; rBCG
• Additional relevant MeSH terms: Tuberculosis; Vaccines; BCG Vaccine

Study Results

No Results Posted as of Sep 16, 2022