Program for Rifampicin-Resistant Disease With Stratified Medicine for Tuberculosis

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.

Conditions

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

Interventions

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.

Sponsors & Collaborators

• Johns Hopkins University

  collaborator OTHER

• University of California, San Francisco

  lead OTHER

Principal Investigators

• Gustavo E Velásquez, MD, MPH · University of California, San Francisco

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

14 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-10-03

Primary Completion

2031-08-31

Completion

2031-08-31

FDA Drug

Yes

Countries

• Mongolia
• Pakistan
• Peru
• Uganda
• Vietnam

Study Locations