NCT06441006

Program for Rifampicin-Resistant Disease With Stratified Medicine for Tuberculosis

Program for Rifampicin-Resistant Disease With Stratified Medicine for Tuberculosis (PRISM-TB)

• Status: Recruiting
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 400 (estimated)
• Sponsor: University of California, San Francisco · Academic / Other
• Sex: All
• Age: 14 Years
• Healthy volunteers: Not accepted

Summary

PRISM-TB is an international, seamless, multicenter, open-label, randomized, controlled, pragmatic, stratified medicine, treatment shortening, multi-arm multi-stage (MAMS), noninferiority Phase 2/3 clinical trial for fluoroquinolone-susceptible multidrug-resistant/rifampin-resistant pulmonary tuberculosis (FQ-S MDR/RR-TB). In Stage 1, participants will be randomized among one of three treatment arms (one control and two experimental). Following the interim analysis (at the end of Stage 1) based on DOOR outcome comparisons and the entirety of the data, one of the four possible experimental strategies will be identified and continue into Stage 2. In Stage 2, participants will be randomized among one of two treatment arms (one control and one experimental). The trial objective is to identify, among participants with fluoroquinolone-susceptible multidrug-resistant/rifampicin-resistant tuberculosis (FQ-S MDR/RR-TB), the preferred BPaLM strategy of 13 or 17 weeks for participants stratified to receive shorter treatment and 17 or 24 weeks for participants stratified to receive longer treatment, as defined by a prespecified stratification algorithm, and to evaluate whether this BPaLM strategy has noninferior efficacy to the control strategy at Week 73.

Detailed description

At least 200 participants across three treatment arms (67 in each arm) will be enrolled in Stage 1 and at least an additional 200 participants across two treatment arms (100 in each arm) will be enrolled in Stage 2. Stage 1: After written informed consent, participants with FQ-S MDR/RR-TB will be randomly assigned to receive one of Stage 1 Strategies 1-3. Stage 1 Strategy 1 (control strategy): Control regimen for all with FQ-S MDR/RR-TB. The local standard of care (SOC) regimen consistent with preferred regimen(s) in international guidelines. In most cases this will be 24 weeks of bedaquiline, pretomanid, linezolid, and moxifloxacin (6BPaLM). Doses and durations of each component may change based on the latest international guidelines and the local SOC. Stage 1 Strategy 2 (investigational strategy): 4BPaLM for all with FQ-S MDR/RR-TB. 17 weeks of bedaquiline, pretomanid, linezolid, and moxifloxacin (4BPaLM). Stage 1 Strategy 3 (investigational strategy): 3BPaLM or 6BPaLM stratified medicine strategy for FQ-S MDR/RR-TB. 13 weeks of bedaquiline, pretomanid, linezolid, and moxifloxacin (3BPaLM) for participants stratified to receive shorter treatment and 24 weeks of bedaquiline, pretomanid, linezolid, and moxifloxacin (6BPaLM) for participants stratified to receive longer treatment. Stage 2: After written informed consent, participants with FQ-S MDR/RR-TB will be randomly assigned to receive one of the Stage 2 Strategies 1-2. Stage 2 Strategy 1 (control strategy): Control regimen for all with FQ-S MDR/RR-TB. The local standard of care (SOC) regimen consistent with preferred regimen(s) in international guidelines. In most cases this will be 24 weeks of bedaquiline, pretomanid, linezolid, and moxifloxacin (6BPaLM). Doses and durations of each component may change based on the latest international guidelines and the local SOC. Stage 2 Strategy 2 (investigational strategy): Preferred strategy from Stage 1 for FQ-S MDR/RR-TB. Number of weeks of bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) for participants stratified to receive shorter treatment and for participants stratified to receive longer treatment to be determined from the preferred strategy identified in Stage 1. The sites listed below are the planned sites for Stage 1 and/or Stage 2.

Conditions

• Tuberculosis, Pulmonary
• Tuberculosis, Multidrug-Resistant
• Tuberculosis, MDR

Interventions

Type	Name	Description
DRUG	Bedaquiline	Frequency: daily Route of administration: oral
DRUG	Linezolid	Frequency: daily Route of administration: oral
DRUG	Pretomanid	Frequency: daily Route of administration: oral
DRUG	Moxifloxacin	Frequency: daily Route of administration: oral
DRUG	Control Arm FQ-S MDR/RR-TB regimen, designed according to latest international guidelines	The local SOC regimen consistent with preferred regimen(s) in international guidelines. In most cases this will be 24 weeks of bedaquiline, pretomanid, linezolid, and moxifloxacin (6BPaLM). Doses and durations of each component may change based on the latest international guidelines and the local SOC.

Timeline

• Start date: 2025-10-03
• Primary completion: 2031-08-01
• Completion: 2031-08-01
• First posted: 2024-06-04
• Last updated: 2026-01-20

Locations

6 sites across 5 countries: Mongolia, Pakistan, Peru, Uganda, Vietnam

Regulatory

• FDA-regulated drug study