A Phase 1a, Dose-finding, Open-label Trial Followed by a Phase 1b, Double-blind, Randomised, Placebo-controlled Trial to Evaluate the Safety, Reactogenicity, and Immunogenicity of the Tuberculosis Subunit Vaccine H107e/CAF®10b in Adults (nTB-01)

NCT06050356 Phase 1 ACTIVE_NOT_RECRUITING

Tuberculosis (TB) is an infection caused by bacteria passed from one person to another through the air when an infected person for instance coughs, speaks, or sneezes. This study tests the safety and vaccine-induced immune response of a new preventive TB vaccine called H107e/CAF®10b. H107e is a copy of protein parts from the bacterium causing tuberculosis, Mycobacterium tuberculosis, which are also called antigens. CAF®10b is an adjuvant which helps the body discover the antigen. The adjuvant and antigen are mixed together to formulate the final vaccine. The final formulated vaccine enhances the immune system's response against the antigen. This is a first-in-human study, meaning this vaccine is being given to people for the first time. The primary objective is to evaluate the safety of the vaccine and its components; however, the study will also evaluate the specific immune responses generated by the new vaccine. The study is divided into two parts, phase 1a and phase 1b. Phase 1a investigates unadjuvanted H107e, CAF®10b adjuvant, H107e/CAF®10b vaccine (low adjuvant dose), and H107e/CAF®10b vaccine (full adjuvant dose). The trial products are administered twice intramuscularly. H107e is also administered intranasally in one of the groups on Day 85. Phase 1b investigates H107e/CAF®10b, H107e/CAF®10b+Bacillus Calmette-Guérin (BCG), BCG, and placebo. A placebo is a look-alike substance that contains no active drug. All groups in phase 1b receive H107e intranasally on Day 211. A preventive TB vaccine such as H107e/CAF®10b should be able to introduce the body's immune system to antigens from Mycobacterium tuberculosis. This will result in memory in the immune system, meaning that when a person gets infected with Mycobacterium tuberculosis, the immune system will recognise and target the bacteria to prevent disease, thereby avoiding the need for antibiotic treatment and/or other treatments and their side effects.

Details

Lead sponsor	Statens Serum Institut
Phase	Phase 1
Status	ACTIVE_NOT_RECRUITING
Enrolment	140
Start date	2024-03-14
Completion	2026-12

Conditions

• Healthy

Interventions

• H107e
• CAF®10b
• H107e/CAF®10b - low adjuvant dose
• H107e/CAF®10b - full adjuvant dose
• Low dose intranasal H107e
• Full dose intranasal H107e
• H107e/CAF®10b
• i.m. placebo
• BCG
• i.d. placebo

Primary outcomes

• Percentage of participants with solicited injection site reactions recorded up to seven days after each i.m. vaccination (phase 1a) — Up to Day 8 (7 days after first dose) and Day 29 up to Day 36 (7 days after second dose)
• Percentage of participants with solicited systemic reactions recorded up to seven days after each i.m. vaccination (phase 1a) — Up to Day 8 (7 days after first dose) and Day 29 up to Day 36 (7 days after second dose)
• Percentage of participants with unsolicited adverse events occurring up to 28 days after last i.m. vaccination (phase 1a) — Up to Day 57 (28 days after second dose)
• Percentage of participants with adverse events of special interest occurring up to last visit (phase 1a) — Up to Day 197 (196 days after first dose)
  Adverse events of special interest represent a subset of AEs that include autoimmune diseases and other systemic disorders of interest which could potentially have an autoimmune etiology
• Percentage of participants with serious adverse events (SAEs) occurring up to last visit (phase 1a) — Up to Day 197 (196 days after first dose)
• Percentage of participants with solicited adverse events occurring up to seven days after i.n. mucosal recall (phase 1a) — Day 85 up to Day 92 (7 days after mucosal recall)
  This outcome is only measured for phase 1a Arm 4a and Arm 4b. Solicited adverse events related to mucosal recall consist of local and systemic reactions

Countries

South Africa