NCT03912207

Investigating Immune Responses to Aerosol BCG Challenge in Healthy UK Adults

A Human Challenge Study to Evaluate Innate and Adaptive Immune Responses to a Controlled Human Infection With BCG Administered by the Intradermal or Aerosol Inhaled Route in Healthy, BCG-naïve or Historically BCG-vaccinated, UK Adult Volunteers

• Status: Unknown
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 94 (estimated)
• Sponsor: University of Oxford · Academic / Other
• Sex: All
• Age: 18 Years – 50 Years
• Healthy volunteers: Accepted

Summary

TB043 is a clinical challenge trial primarily to evaluate the safety of BCG challenge administered by the aerosol inhaled route in healthy, BCG naive (Group 1-7) as well as historically BCG vaccinated UK adults (Group 8) . The trial will also look to evaluate and compare the amount of BCG recovered from the lungs as various points after challenge.

Detailed description

Mycobacterium tuberculosis (M.tb) is a pathogen with worldwide preponderance that infects humans and causes the transmissible disease tuberculosis (TB). An estimated one-third of the world's population is latently infected with M.tb, carrying a 10% lifetime risk of developing active life-threatening disease. In 2016, there were 10 million new cases worldwide and 1.7 million people died of TB. Co-infection with human immunodeficiency virus (HIV) greatly increases the risk of TB reactivation and death. Diagnosis is challenging and drug treatment is often harmful, costly and complex. For these reasons, it is essential to develop a more effective vaccine against TB. An improved understanding of the nature of protective immunity in humans would significantly improve rational vaccine development. Whilst host immunity, particularly systemic adaptive immunity, has been well characterized in murine models, the understanding of the immunological events that occur in humans during acute infection is limited. In particular, the knowledge of human mucosal responses to M.tb. is limited. This is primarily due to the difficulties in studying early disease processes in the lung. Consequently, the majority of human studies have investigated immune responses ex-vivo in peripheral blood or after in-vitro infection of cell lines. A better understanding of the immune components that exist at the respiratory mucosal surfaces in humans could lead to interventions that prevent infection at the point of entry. TB043 is a clinical challenge trial primarily to evaluate the safety of BCG challenge administered by the aerosol inhaled route in healthy, BCG naive (Group 1-7) as well as historically BCG vaccinated UK adults (Group 8) . The trial will also look to evaluate and compare the amount of BCG recovered from the lungs as various points after challenge, allowing investigation into the immune components at mucosal surfaces.

Conditions

• Tuberculosis

Interventions

Type	Name	Description
BIOLOGICAL	BCG Danish	BCG Danish 1331 is on the WHO list of pre-qualified vaccines and has a well-defined side effect profile. BCG is licensed for delivery via the intradermal route. It is not licensed for delivery via the aerosol route.
OTHER	Saline placebo	Saline is a routinely used placebo.

Timeline

• Start date: 2019-04-19
• Primary completion: 2024-06-01
• Completion: 2024-06-01
• First posted: 2019-04-11
• Last updated: 2024-01-03

Locations

2 sites across 1 country: United Kingdom