| CTRI Number |
CTRI/2024/07/070677 [Registered on: 16/07/2024] Trial Registered Prospectively |
| Last Modified On: |
08/07/2024 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Multiple Arm Trial |
|
Public Title of Study
|
Safety Study on Chloroquine Based HREZ Combination Regimens in Adults with Pulmonary Tuberculosis |
|
Scientific Title of Study
|
A Phase 1b/2a Open Label Bridging Safety, Pharmacokinetics and Tolerability Studies on Chloroquine Based HREZ Combination Regimens in Adults with Pulmonary Tuberculosis |
| Trial Acronym |
NIL |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| TG/CLI/085, Version 1.0, 24 Feb 2024 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Deepti Krishnan |
| Designation |
Principal Investigator |
| Affiliation |
Hassan Institute of Medical Sciences |
| Address |
Room no:10, 1st floor, Department of pulmonary medicine, Hassan Institute of Medical Sciences, Hassan, Karnataka
Hassan
KARNATAKA
573201
India |
| Phone |
08867125414 |
| Fax |
|
| Email |
deeptihere@yahoo.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Deepti Krishnan |
| Designation |
Principal Investigator |
| Affiliation |
Hassan Institute of Medical Sciences |
| Address |
Room no:10, 1st floor, Department of pulmonary medicine, Hassan Institute of Medical Sciences, Hassan, Karnataka
Hassan
KARNATAKA
573201
India |
| Phone |
08867125414 |
| Fax |
|
| Email |
deeptihere@yahoo.com |
|
Details of Contact Person
Public Query
|
| Name |
Meena Dalal |
| Designation |
CRO representative |
| Affiliation |
TrialGuna Private Limited |
| Address |
TrialGuna Private Limited,
467, 2nd floor, 1st Main Rd, Royal Country, 8th Phase, Gottigere, Bengaluru, Karnataka
Bangalore
KARNATAKA
560083
India |
| Phone |
09972636265 |
| Fax |
|
| Email |
meena@trialguna.com |
|
|
Source of Monetary or Material Support
|
| Foundation for Neglected Disease Research
Plot No. 20A, KIADB Industrial Area,Veerapura, Doddaballapur,
Bangalore - 561203, Karnataka, India |
|
|
Primary Sponsor
|
| Name |
Foundation for Neglected Disease Research |
| Address |
Plot No. 20A, KIADB Industrial Area,Veerapura, Doddaballapur,
Bangalore - 561203, Karnataka, India |
| Type of Sponsor |
Research institution |
|
|
Details of Secondary Sponsor
|
| Name |
Address |
| Not Applicable |
Not Applicable |
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Deepti Krishnan |
Hassan Institute of Medical Sciences |
Room no 10, 1st floor, Department of Pulmonary medicine, Hassan Institute of Medical Sciences, Hassan
Hassan
KARNATAKA |
08867125414
deeptihere@yahoo.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Institutional Ethics Committee - HIMS |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: J158||Pneumonia due to other specified bacteria, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Chloroquine based HREZ combination regimens |
Route of Administration: Oral
Dosage range: 50,100,200 & 300 mg/day (Chloroquine)and Standard HREZ regimen for TB,
Frequency: Once daily
Duration: 14 days |
| Comparator Agent |
Standard HREZ regimen |
Route of Administration: Oral Dosage range: Standard HREZ regimen for TB based on the body weight of the patient
Frequency: Once daily
Duration: 6 months |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
60.00 Year(s) |
| Gender |
Both |
| Details |
1) Adult male and female subjects aged 18 years and above with body weight between 30-65 kg.
2) Individuals who are newly diagnosed with pulmonary tuberculosis through GeneXpert test. Individuals must be previously untreated and test positive for sputum GeneXpert.
3) Subjects must be susceptible to rifampicin as detected by a cartridge-based nucleic acid amplification test.
4) Willingness to undergo HIV testing.
5) Subjects must have never been treated with multidrug antituberculosis therapy for more than a week.
6) Willingness to attend the treatment center for supervised treatment and remain within the study area limit.
7) Willingness to give blood samples for PK analysis on day 1 and day 14.
8) Willingness to sign the informed consent form and adhere to study procedures and follow-up.
9) Willingness to join the Directly Observed Treatment, Short-Course (DOTS) program
10) Consent to home visits. |
|
| ExclusionCriteria |
| Details |
1) Female subjects who are pregnant, breastfeeding, or planning to conceive during the study.
2) Subjects with extra-pulmonary tuberculosis or drug-resistant tuberculosis (single drug resistance, H, or R).
3) Subjects with a body weight less than 30 kg or greater than 65 kg.
4) Subjects with a prior history of exposure to anti-tuberculosis treatment for more than a week.
5) Subjects with a history of liver disease or current Alanine aminotransferase levels greater than three times the upper limit of normal or total bilirubin concentration exceeding the upper limit of normal.
6) Subjects who test positive for hepatitis B virus surface antigen, hepatitis C virus antibody, and HIV.
7) Subjects with concomitant psychiatric illness or a history of seizures.
8) Anybody testing positive for malaria in the last two months prior to enrolment in the study.
9) Diagnosed cases of extrapulmonary tuberculosis.
10) Subjects who tested positive for COVID-19 with lung involvement.
11) Subjects receiving treatment for rheumatoid arthritis (RA)/autoimmune disorders and CQ/hydroxy-CQ therapy.
12) Subjects with malaria and Q-fever undergoing CQ/hydroxy-CQ therapy or have taken CQ/ hydroxy-CQ therapy 2 months prior to enrollment. |
|
|
Method of Generating Random Sequence
|
Permuted block randomization, fixed |
|
Method of Concealment
|
Centralized |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
a) Safety and tolerability of CQ. The assessment includes monitoring clinical manifestations and laboratory abnormalities in the blood.
b) Overall tolerability of the CQ-based combination regimens will be evaluated by assessing treatment emergent adverse events. |
Day 0, Day 1, Day 14 & Day 180 |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
a) Pharmacokinetics (PK) Assessment: Establishment of the PK profile of the CQ-based HREZ combination regimen.
b) Safe Dose Determination: Determination of safe CQ dose for the development of a
combination regimen.
c) Sputum Culture Conversion Evaluation: Determination of sputum culture conversion rates of CQ-based HREZ combination regimen compared to HREZ treatment alone by inoculating samples into MGIT and demonstrating the time to
culture positivity (TTP) |
Day 0, Day 1, Day 14 & Day 180 |
|
|
Target Sample Size
|
Total Sample Size="75"
Sample Size from India="75"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 2 |
|
Date of First Enrollment (India)
|
24/07/2024 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="2"
Months="0"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
Tuberculosis is a persistent and potentially lethal infectious disease caused by Mycobacterium tuberculosis (Mtb), a bacterium that primarily affects the lungs but can also impact other organs. Clinical research on tuberculosis has paved the way for the development and optimization of various drugs aimed at combating this infectious disease. The standard regimen for drug sensitive tuberculosis involves a combination of isoniazid, rifampicin, ethambutol, and pyrazinamide (HREZ), which has been a mainstay in tuberculosis treatment. Chloroquine (CQ), a well-known antimalarial drug, has garnered attention for its potential in
the treatment of tuberculosis through preclinical studies. The rationale for the above study lies in the need to address and optimize tuberculosis
treatment strategies, leveraging both established and potential interventions. The inclusion
of HREZ, a well-established and effective standard treatment for tuberculosis, serves as a
baseline for comparison. Exploring the intake of CQ with HREZ introduces a novel
component, aiming to capitalize on CQ’s antiviral properties and immunomodulatory
effects. This study seeks to comprehensively evaluate the safety, tolerability, and
pharmacokinetics of the CQ based HREZ combination regimen, considering its potential
benefits in enhancing the treatment outcome for tuberculosis. By conducting a thorough
examination of the risks and benefits associated with both HREZ and CQ, the study
endeavours to contribute valuable understandings into refining tuberculosis management
strategies, ultimately improving patient outcomes and advancing the field of infectious
disease therapeutics. |