Evaluating the safety of Chloroquine with tuberculosis treatment

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

This study is testing if adding Chloroquine to regular tuberculosis treatment is safe for healthy volunteers and could make the treatment work better.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 16 (estimated)
• Ages: 18 Years to 50 Years
• Sex: All
• Sponsor: University of Zurich (Academic / other)
• Locations: 1 site (Zurich)
• Trial ID: NCT05443178 on ClinicalTrials.gov

What this trial studies

This phase 1 trial investigates the safety and tolerability of Chloroquine when used alongside standard anti-tuberculosis therapy in healthy volunteers. The study is motivated by promising in vitro and in vivo data suggesting that Chloroquine enhances the effectiveness of existing TB treatments by increasing the intracellular concentration of key anti-TB drugs. The trial aims to fill the gap in clinical data regarding the concurrent use of these treatments, which could lead to improved TB management strategies.

Who should consider this trial

Good fit: Ideal candidates for this study are healthy volunteers aged 18 to 50 years who can provide informed consent.

Not a fit: Patients who are pregnant, lactating, or have contraindications to Chloroquine will not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to a more effective treatment regimen for tuberculosis, potentially shortening therapy duration and improving patient outcomes.

How similar studies have performed: While this approach is novel in the context of tuberculosis treatment, previous studies have shown promise in using adjunctive therapies to enhance the effectiveness of existing treatments.

Eligibility criteria

Inclusion criteria:

1. Informed study-specific consent (including possible pharmacogenetic analysis) as documented by signature
2. Healthy volunteers aged between 18 and 50 years of age (significantly increased risk of side effects from 50 years of age with Rimstar®)

Exclusion criteria:

1. Lack of highly effective contraception during the study treatment and for 8 months after the last dose of study treatment (until Day 254, visit 7) according to 11.4 with the following consideration for participating women:

   * From Day 1 (visit 2) up to Day 30 (visit 6) hormonal contraception is insufficient due to lower concentrations of estrogen and/or gestagen during and up to 14 days after Rimstar® intake. The hormonal contraception must be supplemented with a barrier method (preferably male condom).
   * From Day 30 (visit 6) up to Day 254 (visit 7) hormonal contraceptive methods can be used and are considered highly effective.
2. Pregnant or lactating females
3. Contraindications to the class of drugs under study, e.g. known hypersensitivity or allergy to class of drugs or the investigational product, glucose-6-phosphate dehydrogenase insufficiency (favism)
4. Regular treatment with drugs in the last 14 days prior to first intake of study drug (except for Paracetamol and Vitamin B6 (pyridoxine), see 8.7).
5. History of or concurrent, clinically significant cardiac, immunological, pulmonary, neurological, renal, gastrointestinal, dermatological, endocrinological or other major disease as determined by the Investigator and/or his representative
6. History of or presence of any clinically significant abnormality in vital signs, ECG, or laboratory test results or has any medical or psychiatric condition that, in the opinion of the Investigator, may interfere with the study procedures or compromise subject safety
7. History of or currently present retinopathy or other disturbances of the field of vision or the retina according to the Investigator
8. History of alcohol or substance abuse for the last 3 months prior to Screening, as determined by the Investigator
9. Weight less than 55kg
10. Intake of grapefruit juice or grapefruits within 2 weeks before the first study drug administration and during treatment phase
11. Donation of blood or blood products within a 30-day period prior to Screening
12. Current enrolment or a plan to enroll in any interventional clinical study in which an investigational treatment or approved therapy for investigational use is administered within 3 months of participation to the Clear trial.
13. Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant
14. The investigator, his/her family members, employees and other dependent persons

Where this trial is running

Zurich

• Clinical Trial Center — Zurich, Switzerland (Recruiting)

Study contacts

• Principal investigator: Marisa Kaelin, Dr. med. — University of Zurich
• Study coordinator: Khadija M'Rabet, Dr. med.

Conditions Tuberculosis Infection; Safety and tolerability; Chloroquin as adjuvant to standard 4-drug anti-TB therapy; Healthy volunteers; Phase I trial