Health Trials

Program for Rifampicin-Resistant Disease With Stratified Medicine for Tuberculosis

ConditionsTuberculosis, PulmonaryTuberculosis, Multidrug-ResistantTuberculosis, MDR
Trial statusRecruiting
Trial phasePhase 2, Phase 3
Trial typeInterventional
Biological sexAll
Age14+
SponsorUniversity of California, San Francisco

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Confirmed fluoroquinolone-susceptible rifampicin-resistant pulmonary tuberculosis, based on sputum Xpert MTB/RIF and Xpert MTB/XDR, and/or other validated molecular test, and/or phenotypic drug susceptibility testing.

Aged ≥ 14 years.

A verifiable address or residence location that is readily available for visiting, willingness to consent to home visits and phone calls, and willingness to inform the study team of any change of address during the treatment and follow-up period.

Ability and willingness of individual to provide written informed consent or written consent from a parent, guardian, or caregiver and assent of the child participant per local ethics committee guidance.

Disqualifiers

Known allergy/sensitivity, intolerance, or any hypersensitivity to components of study TB drugs or their formulation.

Absolute neutrophil count (ANC) < 1000/mm3.

Hemoglobin level < 8.0 g/dL.

Serum or plasma alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3 times the upper limit of normal.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Bedaquiline

    Drug

    Frequency: daily Route of administration: oral

  • Linezolid

    Drug

    Frequency: daily Route of administration: oral

  • Pretomanid

    Drug

    Frequency: daily Route of administration: oral

  • Moxifloxacin

    Drug

    Frequency: daily Route of administration: oral

  • Control Arm FQ-S MDR/RR-TB regimen, designed according to latest international guidelines

    Drug

    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.

Treatment groups

400 Participants
are divided into 3 treatment groups
Group A: Strategy 1: Control regimen for all with FQ-S MDR/RR-TBActive comparator 1 intervention
Group B: Strategy 2: 4BPaLM for all with FQ-S MDR/RR-TBExperimental treatment 4 interventions
Group C: Strategy 3: 3BPaLM or 6BPaLM stratified medicine strategy for those with FQ-S MDR/RR-TBExperimental treatment 4 interventions

Trial outcomes

Primary outcomes

1

Primary Efficacy Outcome: Desirability of Outcome Ranking (DOOR)

Desirability of outcome ranking (DOOR) outcome combining efficacy at the end of follow-up (a minimum of 28 weeks post-randomization) and safety at 28 weeks post-randomization. DOOR outcomes do not aggregate measures, but rather create distinct ordinal categories that participants will fall under. DOOR ordinal categories are as follows: 1. Cured or treatment completed by end of follow-up and no Grade 3+ AEs and treatment changes; 2. Cured or treatment completed by end of follow-up and no Grade 3+ with treatment change for any reason; 3. Cured or treatment completed by end of follow-up and at least one Grade 3+ AE; 4. Treatment failure or recurrence by end of follow-up and no Grade 3+ AE; 5. Treatment failure or recurrence by end of follow-up and at least one Grade 3+ AE; 6. Death by end of follow-up.

Time frame
73 weeks

Secondary outcomes

1

Mortality

Mortality

Time frame
73 weeks
2

All Grade 3 or Higher AEs up to 28 Weeks

All Grade 3 or higher AEs up to 28 weeks post-randomization.

Time frame
28 weeks
3

All AESIs up to 28 Weeks

All AESIs up to 28 weeks post-randomization.

Time frame
28 weeks

Other outcomes

Sponsors and contacts

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University of California, San Francisco

Lead sponsor

Johns Hopkins University

Collaborator

Source ClinicalTrials.gov
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