Ignite Creation Date:
2025-12-25 @ 3:48 AM
Ignite Modification Date:
2025-12-31 @ 9:42 PM
Study NCT ID:
NCT04311502
Status:
TERMINATED
Last Update Posted:
2025-08-27
First Post:
2020-03-05
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Clofazimine- and Rifapentine-Containing Treatment Shortening Regimens in Drug-Susceptible Tuberculosis: The CLO-FAST Study
Sponsor:
National Institute of Allergy and Infectious Diseases (NIAID)
Organization:
Study Overview
Official Title:
A Phase IIc Trial of Clofazimine- and Rifapentine-Containing Treatment Shortening Regimens in Drug-Susceptible Tuberculosis: The CLO-FAST Study
Status:
TERMINATED
Status Verified Date:
2025-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Accrual was permanently closed due to futility in the experimental arm on June 22, 2023. Follow-up in the experimental arm was extended to 117 weeks.
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this study was to compare a 3-month rifapentine (RPT)/clofazimine (CFZ)-containing regimen with a CFZ loading dose with the 6-month standard of care (SOC) regimen for drug-susceptible (DS) tuberculosis (TB).
Detailed Description:
This study compared a 3-month rifapentine (RPT)/clofazimine (CFZ)-containing regimen with a CFZ loading dose with the 6-month standard of care (SOC) for drug-susceptible (DS) tuberculosis (TB).
Randomization was stratified based on HIV status and the presence of advanced disease as determined by chest X-ray.
Participants were randomized to one of three arms:
* Arm 1 (Experimental): rifapentine/isoniazid/pyrazinamide/ethambutol (PHZE) + CFZ 300 mg once daily for 2 weeks; then PHZE + CFZ 100 mg once daily for 6 weeks; then rifapentine/isoniazid/pyrazinamide (PHZ) + CFZ 100 mg once daily for 5 weeks
* Arm 2 (SOC): rifampicin/isoniazid/pyrazinamide/ethambutol (RHZE) for 8 weeks; then rifampicin/isoniazid (RH) for 18 weeks
* Arm C (PK-only subgroup): PHZE + CFZ 100 mg once daily for 4 weeks; then remain on study, off study medications and treated according to SOC (RHZE for 4 weeks; then RH for 18 weeks)
All participants received pyridoxine (vitamin B6) with each dose of isoniazid (INH) based on current local, national or international dosing guidelines.
Arm 1 participants were treated for 13 weeks (including a 2-week CFZ loading dose of 300 mg daily). Arm 2 participants were treated for 26 weeks, and Arm C participants were treated for 4 weeks.
All participants in Arms 1, 2, and C were followed from randomization to Week 65.
On June 1, 2023, the Data and Safety Monitoring Board (DSMB) recommended that the study permanently close to accrual because of the high rate of treatment failure and TB recurrence. The A5362 team, NIAID and DAIDS leadership, and ACTG leadership concurred with the DSMB's recommendation and the study was closed to accrual on June 2, 2023. A letter of amendment was created that extended follow-up to 117 weeks for some participants in Arm 1.
Due to the early close to accrual, a primary analysis report forming the basis of the primary trial manuscript used data collected at study visits up to and including the date when the last enrolled participant completed the week 26 study visit (September 25. 2023). Another final analysis was performed using data collected at study visits up to the date when the last enrolled participant completed the week 65 assessment.
Study visits included physical examinations; blood, urine, and/or sputum collection; chest X-rays; and electrocardiograms (ECG).
Randomization was stratified based on HIV status and the presence of advanced disease as determined by chest X-ray.
Participants were randomized to one of three arms:
* Arm 1 (Experimental): rifapentine/isoniazid/pyrazinamide/ethambutol (PHZE) + CFZ 300 mg once daily for 2 weeks; then PHZE + CFZ 100 mg once daily for 6 weeks; then rifapentine/isoniazid/pyrazinamide (PHZ) + CFZ 100 mg once daily for 5 weeks
* Arm 2 (SOC): rifampicin/isoniazid/pyrazinamide/ethambutol (RHZE) for 8 weeks; then rifampicin/isoniazid (RH) for 18 weeks
* Arm C (PK-only subgroup): PHZE + CFZ 100 mg once daily for 4 weeks; then remain on study, off study medications and treated according to SOC (RHZE for 4 weeks; then RH for 18 weeks)
All participants received pyridoxine (vitamin B6) with each dose of isoniazid (INH) based on current local, national or international dosing guidelines.
Arm 1 participants were treated for 13 weeks (including a 2-week CFZ loading dose of 300 mg daily). Arm 2 participants were treated for 26 weeks, and Arm C participants were treated for 4 weeks.
All participants in Arms 1, 2, and C were followed from randomization to Week 65.
On June 1, 2023, the Data and Safety Monitoring Board (DSMB) recommended that the study permanently close to accrual because of the high rate of treatment failure and TB recurrence. The A5362 team, NIAID and DAIDS leadership, and ACTG leadership concurred with the DSMB's recommendation and the study was closed to accrual on June 2, 2023. A letter of amendment was created that extended follow-up to 117 weeks for some participants in Arm 1.
Due to the early close to accrual, a primary analysis report forming the basis of the primary trial manuscript used data collected at study visits up to and including the date when the last enrolled participant completed the week 26 study visit (September 25. 2023). Another final analysis was performed using data collected at study visits up to the date when the last enrolled participant completed the week 65 assessment.
Study visits included physical examinations; blood, urine, and/or sputum collection; chest X-rays; and electrocardiograms (ECG).
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 30148 | REGISTRY | DAIDS-ES Registry Number | View |