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RecruitingNCT05443178Updated Jul 1, 2024

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

A Phase 1 interventional study of Nivaquine ® (Chloroquine) in Tuberculosis Infection, sponsored by University of Zurich. Recruiting at 1 site in Switzerland. Open to participants aged 18 Years to 50 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-07-01.

Sponsored by University of Zurich · Phase 1, Interventional, and Treatment

From the registry’s dates

  • Primary completion was expected by Oct 2024, 2 years ago, but the record still lists the study as recruiting.
  • Started Jan 2022; still recruiting 4 years 9 months later.
Phase
Phase 1
Study type
Interventional
Enrollment
16
Allocation
Non-randomized
Ages
18 Years to 50 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Tuberculosis Infection

Keywords

  • Safety and tolerability
  • Chloroquin as adjuvant to standard 4-drug anti-TB therapy
  • Healthy volunteers
  • Phase I trial
03

In context

Tuberculosis

1,417 studies on the registry are indexed under Tuberculosis; 208 are open to participants now.

This study's planned enrollment of 16 is below the median of 150 across 952 interventional studies indexed under Tuberculosis.

Browse Tuberculosis studies →

Lead sponsor

University of Zurich is the lead sponsor of 1,030 studies on the registry; 130 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 50 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

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

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
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
16 participants (estimated)

Study arms

  • Experimental
    Cohort 1

    100 mg Nivaquine and 4 Tabl Rimstar peroral once daily before breakfast for 14 days

    Drug: Nivaquine ® (Chloroquine)

  • Experimental
    Cohort 2

    200 mg Chloroquine and 4 Tabl Rimstar peroral once daily before breakfast for 14 days

    Drug: Nivaquine ® (Chloroquine)

  • Experimental
    Cohort 3

    300 mg Chloroquine and 4 Tabl Rimstar peroral once daily before breakfast for 14 days

    Drug: Nivaquine ® (Chloroquine)

  • Experimental
    Dose extension group

    Dose escalation: XX mg Chloroquine (depending on results) and 4 Tabl Rimstar peroral once daily before breakfast for 14 days

    Drug: Nivaquine ® (Chloroquine)

Interventions

  • DrugNivaquine ® (Chloroquine)

    dose escalation and extension trial

    Also known as: Rimstar ® (Rifampicin, Isoniazid, Ethambutol, Pyrazinamid)

06

What researchers measure

Primary outcomes

  1. Physicial examination 1.1

    Heart auscultation (normal/abnormal)

    Time frame: day 14

  2. Physicial examination 1.2

    Heart auscultation (normal/abnormal)

    Time frame: day 30

  3. Physicial examination 2.1

    lung auscultation (normal, abnormal)

    Time frame: day 14

  4. Physicial examination 2.2

    lung auscultation (normal, abnormal)

    Time frame: day 30

  5. Physicial examination 3.1

    abdominal examination (normal, abnormal)

    Time frame: day 14

  6. Physicial examination 3.2

    abdominal examination (normal, abnormal)

    Time frame: day 30

  7. Physicial examination 4.1

    lymph node palpation (normal, abnormal)

    Time frame: day 14

  8. Physicial examination 4.2

    lymph node palpation (normal, abnormal)

    Time frame: day 30

  9. Physicial examination 5.1

    reflex testing (normal, abnormal)

    Time frame: day 14

  10. Physicial examination 5.2

    reflex testing (normal, abnormal)

    Time frame: day 30

  11. Physicial examination 6.1

    test vibration sense with tuning fork (mallelor left and right X/8)

    Time frame: day 14

  12. Physicial examination 6.2

    test vibration sense with tuning fork (mallelor left and right X/8)

    Time frame: day 30

  13. Vital Signs 1.1

    heart rate (beats/min)

    Time frame: day 1

  14. Vital Signs 1.2

    heart rate (beats/min)

    Time frame: day 7

  15. Vital Signs 1.3

    heart rate (beats/min)

    Time frame: day 14

  16. Vital Signs 1.4

    heart rate (beats/min)

    Time frame: day 15

  17. Vital Signs 1.5

    heart rate (beats/min)

    Time frame: day 30

  18. Vital Signs 2.1

    blood pressure (mmHg)

    Time frame: day 1

  19. Vital Signs 2.2

    blood pressure (mmHg)

    Time frame: day 7

  20. Vital Signs 2.3

    blood pressure (mmHg)

    Time frame: day 14

  21. Vital Signs 2.4

    blood pressure (mmHg)

    Time frame: day 15

  22. Vital Signs 2.5

    blood pressure (mmHg)

    Time frame: day 30

  23. Vital Signs 3.1

    temperature (°C)

    Time frame: day 1

  24. Vital Signs 3.2

    temperature (°C)

    Time frame: day 7

  25. Vital Signs 3.3

    temperature (°C)

    Time frame: day 14

  26. Vital Signs 3.4

    temperature (°C)

    Time frame: day 15

  27. Vital Signs 3.5

    temperature (°C)

    Time frame: day 30

  28. Safety Laboratory samples Panel 1.1

    Sodium (mmol/l)

    Time frame: day 1

  29. Safety Laboratory samples Panel 1.2

    Sodium (mmol/l)

    Time frame: day 7

  30. Safety Laboratory samples Panel 1.3

    Sodium (mmol/l)

    Time frame: day 14

  31. Safety Laboratory samples Panel 1.4

    Sodium (mmol/l)

    Time frame: day 30

  32. Safety Laboratory samples Panel 2.1

    Potassium (mmol/l)

    Time frame: day 1

  33. Safety Laboratory samples Panel 2.2

    Potassium (mmol/l)

    Time frame: day 7

  34. Safety Laboratory samples Panel 2.3

    Potassium (mmol/l)

    Time frame: day 14

  35. Safety Laboratory samples Panel 2.4

    Potassium (mmol/l)

    Time frame: day 30

  36. Safety Laboratory samples Panel 3.1

    Calcium (mmol/l)

    Time frame: day 1

  37. Safety Laboratory samples Panel 3.2

    Calcium (mmol/l)

    Time frame: day 7

  38. Safety Laboratory samples Panel 3.3

    Calcium (mmol/l)

    Time frame: day 14

  39. Safety Laboratory samples Panel 3.4

    Calcium (mmol/l)

    Time frame: day 30

  40. Safety Laboratory samples Panel 4.1

    Creatinine (umol/l)

    Time frame: day 1

  41. Safety Laboratory samples Panel 4.2

    Creatinine (umol/l)

    Time frame: day 7

  42. Safety Laboratory samples Panel 4.3

    Creatinine (umol/l)

    Time frame: day 14

  43. Safety Laboratory samples Panel 4.4

    Creatinine (umol/l)

    Time frame: day 30

  44. Safety Laboratory samples Panel 5.1

    Total Bilirubin (umol/l)

    Time frame: day 1

  45. Safety Laboratory samples Panel 5.2

    Total Bilirubin (umol/l)

    Time frame: day 7

  46. Safety Laboratory samples Panel 5.3

    Total Bilirubin (umol/l)

    Time frame: day 14

  47. Safety Laboratory samples Panel 5.4

    Total Bilirubin (umol/l)

    Time frame: day 30

  48. Safety Laboratory samples Panel 6.1

    ALT (U/l)

    Time frame: day 1

  49. Safety Laboratory samples Panel 6.2

    ALT (U/l)

    Time frame: day 7

  50. Safety Laboratory samples Panel 6.3

    ALT (U/l)

    Time frame: day 14

  51. Safety Laboratory samples Panel 6.4

    ALT (U/l)

    Time frame: day 30

  52. Safety Laboratory samples Panel 7.1

    Glucose (mmol/l)

    Time frame: day 1

  53. Safety Laboratory samples Panel 7.2

    Glucose (mmol/l)

    Time frame: day 7

  54. Safety Laboratory samples Panel 7.3

    Glucose (mmol/l)

    Time frame: day 14

  55. Safety Laboratory samples Panel 7.4

    Glucose (mmol/l)

    Time frame: day 30

  56. Safety Laboratory samples Panel 8.1

    CRP (mg/l)

    Time frame: day 1

  57. Safety Laboratory samples Panel 8.2

    CRP (mg/l)

    Time frame: day 7

  58. Safety Laboratory samples Panel 8.3

    CRP (mg/l)

    Time frame: day 14

  59. Safety Laboratory samples Panel 8.4

    CRP (mg/l)

    Time frame: day 30

  60. Safety Laboratory samples Panel 9.1

    Haemoglobin (g/l)

    Time frame: day 1

  61. Safety Laboratory samples Panel 9.2

    Haemoglobin (g/l)

    Time frame: day 7

  62. Safety Laboratory samples Panel 9.3

    Haemoglobin (g/l)

    Time frame: day 14

  63. Safety Laboratory samples Panel 9.4

    Haemoglobin (g/l)

    Time frame: day 30

  64. Safety Laboratory samples Panel 10.1

    Platlets (G/l)

    Time frame: day 1

  65. Safety Laboratory samples Panel 10.2

    Platlets (G/l)

    Time frame: day 7

  66. Safety Laboratory samples Panel 10.3

    Platlets (G/l)

    Time frame: day 14

  67. Safety Laboratory samples Panel 10.4

    Platlets (G/l)

    Time frame: day 30

  68. Safety Laboratory samples Panel 11.1

    White blood cell (G/l)

    Time frame: day 1

  69. Safety Laboratory samples Panel 11.2

    White blood cell (G/l)

    Time frame: day 7

  70. Safety Laboratory samples Panel 11.3

    White blood cell (G/l)

    Time frame: day 14

  71. Safety Laboratory samples Panel 11.4

    White blood cell (G/l)

    Time frame: day 30

  72. Safety Laboratory samples Panel 12.1

    Blood pregnancy test (Blood beta-hCG)

    Time frame: day 7

  73. Safety Laboratory samples Panel 12.2

    Blood pregnancy test (Blood beta-hCG)

    Time frame: day 30

  74. Urinanalysis 1.1

    Dipstick: protein negative/+/++/+++

    Time frame: day 1

  75. Urinanalysis 1.2

    Dipstick: protein negative/+/++/+++

    Time frame: day 7

  76. Urinanalysis 1.3

    Dipstick: protein negative/+/++/+++

    Time frame: day 14

  77. Urinanalysis 1.4

    Dipstick: protein negative/+/++/+++

    Time frame: day 30

  78. Urinanalysis 2.1

    Dipstick: white blood cells negative/+/++/+++

    Time frame: day 1

  79. Urinanalysis 2.2

    Dipstick: white blood cells negative/+/++/+++

    Time frame: day 7

  80. Urinanalysis 2.3

    Dipstick: white blood cells negative/+/++/+++

    Time frame: day 14

  81. Urinanalysis 2.4

    Dipstick: white blood cells negative/+/++/+++

    Time frame: day 30

  82. Urinanalysis 3.1

    Dipstick: red blood cells negative/+/++/+++

    Time frame: day 1

  83. Urinanalysis 3.2

    Dipstick: red blood cells negative/+/++/+++

    Time frame: day 7

  84. Urinanalysis 3.3

    Dipstick: red blood cells negative/+/++/+++

    Time frame: day 14

  85. Urinanalysis 3.4

    Dipstick: red blood cells negative/+/++/+++

    Time frame: day 30

  86. Urinanalysis 4.1

    Dipstick: Glucose negative/+/++/+++

    Time frame: day 1

  87. Urinanalysis 4.2

    Dipstick: Glucose negative/+/++/+++

    Time frame: day 7

  88. Urinanalysis 4.3

    Dipstick: Glucose negative/+/++/+++

    Time frame: day 14

  89. Urinanalysis 4.4

    Dipstick: Glucose negative/+/++/+++

    Time frame: day 30

  90. Safety 12 lead ECG 1.1

    Rate/min

    Time frame: day 7

  91. Safety 12 lead ECG 1.2

    Rate/min

    Time frame: 30

  92. Safety 12 lead ECG 2.1

    Rhythm (regular/irregular)

    Time frame: day 7

  93. Safety 12 lead ECG 2.2

    Rhythm (regular/irregular)

    Time frame: day 30

  94. Safety 12 lead ECG 3.1

    PQ interval (ms)

    Time frame: day 7

  95. Safety 12 lead ECG 3.3

    PQ interval (ms)

    Time frame: day 30

  96. Safety 12 lead ECG 4.1

    QRS interval (ms)

    Time frame: day 7

  97. Safety 12 lead ECG 4.2

    QRS interval (ms)

    Time frame: day 30

  98. Safety 12 lead ECG 5.1

    ST Segment (normal/elevation/depression)

    Time frame: day 7

  99. Safety 12 lead ECG 5.2

    ST Segment (normal/elevation/depression)

    Time frame: day 30

  100. Safety ophtalmological examination 1.1

    Slit lamp examaniation both sides (normal/abnormal)

    Time frame: day 30

  101. Safety ophtalmological examination 1.2

    Refraction both sides (+/-)

    Time frame: day 30

  102. Safety ophtalmological examination 1.3

    Biomicroscopy of the central fundus both sides(normal/abnormal)

    Time frame: day 30

  103. 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)

    Time frame: day 30

  104. Safety ophtalmological examination 1.5

    Color sense test according to Panel D-15 bilateral (normal/abnormal)

    Time frame: day 30

  105. Occurence of adverse events and serious adverse events 1.1

    according to GCP Guideline

    Time frame: day 1

  106. Occurence of adverse events and serious adverse events 1.2

    according to GCP Guideline

    Time frame: day 7

  107. Occurence of adverse events and serious adverse events 1.3

    according to GCP Guideline

    Time frame: day 14

  108. Occurence of adverse events and serious adverse events 1.4

    according to GCP Guideline

    Time frame: day 15

  109. Occurence of adverse events and serious adverse events 1.5

    according to GCP Guideline

    Time frame: day 30

  110. Occurence of adverse events and serious adverse events 1.6

    according to GCP Guideline

    Time frame: day 256

Secondary outcomes

  1. Drug concentration over time measured by the pharmacokinetics

    drug concentration (mg/l) of Rifampicin, Isoniazid, 25-O-Desacetylrifampicin, Ethambutol, Pyrazinamide, Chloroquine, Desethylchloroquine

    Time frame: day 14 prior to dosing (-15 until -5 minutes) and 1, 2, 4, 6 and 24 hours after dosing

07

Study locations

1 of 1 sites recruiting
08

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 1, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT05443178
Lead sponsor
University of Zurich
Responsible party
Sponsor
First posted
Jul 5, 2022
Start date
Jan 4, 2022
Primary completion
Oct 4, 2024 (estimated)
Completion
Jun 1, 2025 (estimated)
Last update
Jul 1, 2024

Study contacts

Khadija M'Rabet, Dr. med.
Contact
Khadija.MRabet-Bensalah@usz.ch
+41 44 255 13 65
Jean Marc Hoffmann, Dr med.
Contact
Jean-Marc.Hoffmann@usz.ch
+41432532749
Marisa Kaelin, Dr. med.
principal investigator · University of Zurich

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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