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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05443178
Other study ID # Clear TB
Secondary ID
Status Recruiting
Phase Phase 1
First received
Last updated
Start date January 4, 2022
Est. completion date December 1, 2024

Study information

Verified date December 2023
Source University of Zurich
Contact Khadija M'Rabet, Dr. med.
Phone +41 44 255 13 65
Email Khadija.MRabet-Bensalah@usz.ch
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 16
Est. completion date December 1, 2024
Est. primary completion date July 4, 2024
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 18 Years to 50 Years
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Nivaquine ® (Chloroquine)
dose escalation and extension trial

Locations

Country Name City State
Switzerland Clinical Trial Center Zurich

Sponsors (1)

Lead Sponsor Collaborator
University of Zurich

Country where clinical trial is conducted

Switzerland, 

Outcome

Type Measure Description Time frame Safety issue
Primary Physicial examination 1.1 Heart auscultation (normal/abnormal) day 14
Primary Physicial examination 1.2 Heart auscultation (normal/abnormal) day 30
Primary Physicial examination 2.1 lung auscultation (normal, abnormal) day 14
Primary Physicial examination 2.2 lung auscultation (normal, abnormal) day 30
Primary Physicial examination 3.1 abdominal examination (normal, abnormal) day 14
Primary Physicial examination 3.2 abdominal examination (normal, abnormal) day 30
Primary Physicial examination 4.1 lymph node palpation (normal, abnormal) day 14
Primary Physicial examination 4.2 lymph node palpation (normal, abnormal) day 30
Primary Physicial examination 5.1 reflex testing (normal, abnormal) day 14
Primary Physicial examination 5.2 reflex testing (normal, abnormal) day 30
Primary Physicial examination 6.1 test vibration sense with tuning fork (mallelor left and right X/8) day 14
Primary Physicial examination 6.2 test vibration sense with tuning fork (mallelor left and right X/8) day 30
Primary Vital Signs 1.1 heart rate (beats/min) day 1
Primary Vital Signs 1.2 heart rate (beats/min) day 7
Primary Vital Signs 1.3 heart rate (beats/min) day 14
Primary Vital Signs 1.4 heart rate (beats/min) day 15
Primary Vital Signs 1.5 heart rate (beats/min) day 30
Primary Vital Signs 2.1 blood pressure (mmHg) day 1
Primary Vital Signs 2.2 blood pressure (mmHg) day 7
Primary Vital Signs 2.3 blood pressure (mmHg) day 14
Primary Vital Signs 2.4 blood pressure (mmHg) day 15
Primary Vital Signs 2.5 blood pressure (mmHg) day 30
Primary Vital Signs 3.1 temperature (°C) day 1
Primary Vital Signs 3.2 temperature (°C) day 7
Primary Vital Signs 3.3 temperature (°C) day 14
Primary Vital Signs 3.4 temperature (°C) day 15
Primary Vital Signs 3.5 temperature (°C) day 30
Primary Safety Laboratory samples Panel 1.1 Sodium (mmol/l) day 1
Primary Safety Laboratory samples Panel 1.2 Sodium (mmol/l) day 7
Primary Safety Laboratory samples Panel 1.3 Sodium (mmol/l) day 14
Primary Safety Laboratory samples Panel 1.4 Sodium (mmol/l) day 30
Primary Safety Laboratory samples Panel 2.1 Potassium (mmol/l) day 1
Primary Safety Laboratory samples Panel 2.2 Potassium (mmol/l) day 7
Primary Safety Laboratory samples Panel 2.3 Potassium (mmol/l) day 14
Primary Safety Laboratory samples Panel 2.4 Potassium (mmol/l) day 30
Primary Safety Laboratory samples Panel 3.1 Calcium (mmol/l) day 1
Primary Safety Laboratory samples Panel 3.2 Calcium (mmol/l) day 7
Primary Safety Laboratory samples Panel 3.3 Calcium (mmol/l) day 14
Primary Safety Laboratory samples Panel 3.4 Calcium (mmol/l) day 30
Primary Safety Laboratory samples Panel 4.1 Creatinine (umol/l) day 1
Primary Safety Laboratory samples Panel 4.2 Creatinine (umol/l) day 7
Primary Safety Laboratory samples Panel 4.3 Creatinine (umol/l) day 14
Primary Safety Laboratory samples Panel 4.4 Creatinine (umol/l) day 30
Primary Safety Laboratory samples Panel 5.1 Total Bilirubin (umol/l) day 1
Primary Safety Laboratory samples Panel 5.2 Total Bilirubin (umol/l) day 7
Primary Safety Laboratory samples Panel 5.3 Total Bilirubin (umol/l) day 14
Primary Safety Laboratory samples Panel 5.4 Total Bilirubin (umol/l) day 30
Primary Safety Laboratory samples Panel 6.1 ALT (U/l) day 1
Primary Safety Laboratory samples Panel 6.2 ALT (U/l) day 7
Primary Safety Laboratory samples Panel 6.3 ALT (U/l) day 14
Primary Safety Laboratory samples Panel 6.4 ALT (U/l) day 30
Primary Safety Laboratory samples Panel 7.1 Glucose (mmol/l) day 1
Primary Safety Laboratory samples Panel 7.2 Glucose (mmol/l) day 7
Primary Safety Laboratory samples Panel 7.3 Glucose (mmol/l) day 14
Primary Safety Laboratory samples Panel 7.4 Glucose (mmol/l) day 30
Primary Safety Laboratory samples Panel 8.1 CRP (mg/l) day 1
Primary Safety Laboratory samples Panel 8.2 CRP (mg/l) day 7
Primary Safety Laboratory samples Panel 8.3 CRP (mg/l) day 14
Primary Safety Laboratory samples Panel 8.4 CRP (mg/l) day 30
Primary Safety Laboratory samples Panel 9.1 Haemoglobin (g/l) day 1
Primary Safety Laboratory samples Panel 9.2 Haemoglobin (g/l) day 7
Primary Safety Laboratory samples Panel 9.3 Haemoglobin (g/l) day 14
Primary Safety Laboratory samples Panel 9.4 Haemoglobin (g/l) day 30
Primary Safety Laboratory samples Panel 10.1 Platlets (G/l) day 1
Primary Safety Laboratory samples Panel 10.2 Platlets (G/l) day 7
Primary Safety Laboratory samples Panel 10.3 Platlets (G/l) day 14
Primary Safety Laboratory samples Panel 10.4 Platlets (G/l) day 30
Primary Safety Laboratory samples Panel 11.1 White blood cell (G/l) day 1
Primary Safety Laboratory samples Panel 11.2 White blood cell (G/l) day 7
Primary Safety Laboratory samples Panel 11.3 White blood cell (G/l) day 14
Primary Safety Laboratory samples Panel 11.4 White blood cell (G/l) day 30
Primary Safety Laboratory samples Panel 12.1 Blood pregnancy test (Blood beta-hCG) day 7
Primary Safety Laboratory samples Panel 12.2 Blood pregnancy test (Blood beta-hCG) day 30
Primary Urinanalysis 1.1 Dipstick: protein negative/+/++/+++ day 1
Primary Urinanalysis 1.2 Dipstick: protein negative/+/++/+++ day 7
Primary Urinanalysis 1.3 Dipstick: protein negative/+/++/+++ day 14
Primary Urinanalysis 1.4 Dipstick: protein negative/+/++/+++ day 30
Primary Urinanalysis 2.1 Dipstick: white blood cells negative/+/++/+++ day 1
Primary Urinanalysis 2.2 Dipstick: white blood cells negative/+/++/+++ day 7
Primary Urinanalysis 2.3 Dipstick: white blood cells negative/+/++/+++ day 14
Primary Urinanalysis 2.4 Dipstick: white blood cells negative/+/++/+++ day 30
Primary Urinanalysis 3.1 Dipstick: red blood cells negative/+/++/+++ day 1
Primary Urinanalysis 3.2 Dipstick: red blood cells negative/+/++/+++ day 7
Primary Urinanalysis 3.3 Dipstick: red blood cells negative/+/++/+++ day 14
Primary Urinanalysis 3.4 Dipstick: red blood cells negative/+/++/+++ day 30
Primary Urinanalysis 4.1 Dipstick: Glucose negative/+/++/+++ day 1
Primary Urinanalysis 4.2 Dipstick: Glucose negative/+/++/+++ day 7
Primary Urinanalysis 4.3 Dipstick: Glucose negative/+/++/+++ day 14
Primary Urinanalysis 4.4 Dipstick: Glucose negative/+/++/+++ day 30
Primary Safety 12 lead ECG 1.1 Rate/min day 7
Primary Safety 12 lead ECG 1.2 Rate/min 30
Primary Safety 12 lead ECG 2.1 Rhythm (regular/irregular) day 7
Primary Safety 12 lead ECG 2.2 Rhythm (regular/irregular) day 30
Primary Safety 12 lead ECG 3.1 PQ interval (ms) day 7
Primary Safety 12 lead ECG 3.3 PQ interval (ms) day 30
Primary Safety 12 lead ECG 4.1 QRS interval (ms) day 7
Primary Safety 12 lead ECG 4.2 QRS interval (ms) day 30
Primary Safety 12 lead ECG 5.1 ST Segment (normal/elevation/depression) day 7
Primary Safety 12 lead ECG 5.2 ST Segment (normal/elevation/depression) day 30
Primary Safety ophtalmological examination 1.1 Slit lamp examaniation both sides (normal/abnormal) day 30
Primary Safety ophtalmological examination 1.2 Refraction both sides (+/-) day 30
Primary Safety ophtalmological examination 1.3 Biomicroscopy of the central fundus both sides(normal/abnormal) day 30
Primary Safety ophtalmological examination 1.4 Applanation tonometry and stereoscopic papilla evaluation bilateral (normal/abnormal), Color sense test according to Panel D-15 right and left side (normal/abnormal) day 30
Primary Safety ophtalmological examination 1.5 Color sense test according to Panel D-15 bilateral (normal/abnormal) day 30
Primary Occurence of adverse events and serious adverse events 1.1 according to GCP Guideline day 1
Primary Occurence of adverse events and serious adverse events 1.2 according to GCP Guideline day 7
Primary Occurence of adverse events and serious adverse events 1.3 according to GCP Guideline day 14
Primary Occurence of adverse events and serious adverse events 1.4 according to GCP Guideline day 15
Primary Occurence of adverse events and serious adverse events 1.5 according to GCP Guideline day 30
Primary Occurence of adverse events and serious adverse events 1.6 according to GCP Guideline day 256
Secondary Drug concentration over time measured by the pharmacokinetics drug concentration (mg/l) of Rifampicin, Isoniazid, 25-O-Desacetylrifampicin, Ethambutol, Pyrazinamide, Chloroquine, Desethylchloroquine day 14 prior to dosing (-15 until -5 minutes) and 1, 2, 4, 6 and 24 hours after dosing
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