A5362: A Phase IIc Trial of Clofazimine- and Rifapentine-Containing Treatment Shortening Regimens in Drug-Susceptible Tuberculosis: The CLO-FAST Study
Summary:
Primary Hypothesis
A 3-month regimen of rifapentine/isoniazid/pyrazinamide/ethambutol (PHZE) with clofazimine (CFZ) dosed as 100 mg daily with a 2-week 300 mg daily loading dose (Arm 1) will demonstrate early efficacy (time to 12-week liquid culture conversion) relative to standard of care (SOC) (RHZE; Arm 2), and will have acceptable safety and tolerability.
Primary Objective
- To compare time to 12-week liquid culture conversion for Arm 1 with SOC controls
- To compare adverse events (safety) over 65 weeks
Secondary Objectives
All Arm 1 vs. Arm 2 (SOC)
- To compare proportions of participants treated with RPT/CFZ-containing regimens who experience favorable composite efficacy outcome at 65 weeks with 6-month SOC controls To compare premature regimen discontinuation (tolerability)
- To estimate and compare CFZ-associated increases in QT interval with SOC (QTcF, using the Fridericia correction)
- To estimate and compare time to stable liquid and solid mycobacterial culture conversion
- To compare proportion of participants with liquid and solid culture conversion at weeks 8 and 12
- To compare days to positivity in automated liquid mycobacterial culture over treatment time
- To compare chest radiographic score (with specific attention to resolution of cavitary disease) between arms from baseline to end of treatment (Arm 1, week 13; SOC, week 26)
- To compare proportions of participants who experience a favorable clinical/bacteriologic treatment outcome at 65 weeks
- To estimate cumulative relapse and recurrence proportions up to week 65
- To determine CFZ pharmacokinetic (PK) parameters in plasma in Arm 1
- To compare PK parameters when CFZ is given with a loading dose in Arm 1 and without a loading dose in Arm C
- To objectively and subjectively assess CFZ-associated skin hyperpigmentation and compare with SOC