NCT05443178

Safety and Tolerability of Chlorquine in Addition to Anti-tuberculosis Therapy

Open Label, Single Center, Phase 1 Dose Escalation and Extension Trial to Evaluate Safety and Tolerability of Chlorquine as Adjuvant Drug to Standard 4-drug Anti-tuberculosis Therapy in Healthy Volunteers

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 16 (estimated)
• Sponsor: University of Zurich · Academic / Other
• Sex: All
• Age: 18 Years – 50 Years
• Healthy volunteers: Accepted

Summary

In vitro and in vivo data show promising results of adjunctive use of Chloroquine to standard tuberculosis therapy as Chloroquine enhances animicrobial effectiveness against intracellular MTB. To date, no safety data of the concurrent use of both treatments is availble. In a phase I trial, the investigators aim to evaluate safety and tolerability of the concurrent use of Chloroquine and standard anti-TB drug in healthy volunteers.

Detailed description

Even though tuberculosis (TB) remains one of the top 10 causes of death worldwide in 2019, there exists a gap in development of new diagnostics and treatments. There is a substantial need for new TB regimens, which would ideally be shorter, more tolerable and more efficient in eradicating all subpopulations of mycobacterium tuberculosis (MTB). In this regard, a promising TB drug pipeline emerges through re-use of marketed non TB-drugs, re-engineering of existing anti-TB compounds and discovery of new compounds. In vitro data showed that Chloroquine (CQ) inhibits an efflux pump expressed on macrophages. Inhibition of this pump increases intracellular concentration of Isoniazid and Pyrazinamide and enhances antimicrobial effectiveness against intracellular MTB. Recently published in vivo mouse model data confirmed the positive effect of CQ combined with the standard anti-TB therapy. In line with global attempts to enhance effectiveness and shorten TB therapy, the investigators propose to evaluate this combination in a clinical setting. The absence of clinical study data showing safety and tolerability of CQ administered with first-line anti-TB drugs in humans shows the need for the research team to conduct this study. the investigators hypothesize that additional CQ to standard 4-drug anti-TB therapy is safe and increases the efficacy against intracellular MTB, leading to a pronounced reduction of the intracellularly hiding bacteria and overall to an accelerated reduction of bacterial load. The major advantages of this new combination with CQ and the 4-drug anti-TB therapy are, that all substances are long-term approved, commercially available drugs and that effective CQ concentrations are well achievable in humans. Primary objective of the study is to investigate the safety and tolerability of a combination of standard doses of Nivaquine® (Chloroquine) with standard doses of Rimstar® (4-drug anti-TB therapy) in healthy volunteers. Secondary objective of the study is to assess drug concentration of the new combination (Nivaquine® and Rimstar®) in healthy volunteers over time.

Conditions

• Tuberculosis Infection

Interventions

Type	Name	Description
DRUG	Nivaquine ® (Chloroquine)	dose escalation and extension trial

Timeline

• Start date: 2022-01-04
• Primary completion: 2024-10-04
• Completion: 2025-06-01
• First posted: 2022-07-05
• Last updated: 2024-07-01

Locations

1 site across 1 country: Switzerland