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.

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.

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