Trial of Novel Regimens for the Treatment of Pulmonary Tuberculosis

Summary

A5409/RAD-TB is an adaptive Phase 2 randomized, controlled, open-label, dose-ranging, platform protocol to evaluate the safety and efficacy of multidrug regimens for the treatment of adults with drug-susceptible pulmonary tuberculosis (TB).

A5409 hypothesizes that novel regimens for the treatment of pulmonary tuberculosis will result in superior early efficacy, as determined by longitudinal mycobacteria growth indicator tube (MGIT) liquid culture time to positivity (TTP) measurements over the first 6 weeks of treatment, and will have acceptable safety and tolerability over 8 weeks of treatment relative to standard of care \[(SOC) isoniazid/rifampicin/pyrazinamide/ethambutol (HRZE)\].

The study will run for 52 weeks, inclusive of 26 weeks of TB treatment comprised of 8 weeks of study treatment (experimental or SOC, based on treatment arm assignment) followed by 18 weeks of SOC continuation phase treatment with 45 participants in each experimental treatment arm and at least 90 participants in the SOC arm.

Conditions

• Pulmonary Tuberculosis

Interventions

DRUG

Isoniazid

INH 300 mg will be administered as one tablet orally once daily.

DRUG

Rifampicin

RIF 600 mg will be administered as two 300 mg capsules orally once daily on an empty stomach, 1 hour before or 2 hours after eating a meal.

DRUG

Pyrazinamide

PZA will be administered as 500 mg tablets, based on weight, orally once daily.

DRUG

Ethambutol

EMB will be administered as 400 mg tablets, based on weight, orally once daily.

DRUG

Bedaquiline

BDQ 400 mg will be administered as four 100 mg tablets orally once daily with a meal for the first 2 weeks followed by 200 mg (two 100 mg tablets) orally once daily with a meal for 6 weeks.

DRUG

Pretomanid

Pa 200 mg will be administered as one 200 mg tablet orally once daily with a meal.

DRUG

Linezolid

LZD 600 mg will be administered as one 600 mg tablet orally once daily.

DRUG

TBI-223

TBI-223 2400 mg once daily will be administered as four 600 mg tablets orally once daily with a meal.

DRUG

Sutezolid

SZD 1600 mg once daily will be administered as four 400 mg tablets orally once daily with a meal.

DRUG

TBI-223

TBI-223 1200 mg once daily will be administered as two 600 mg tablets orally with a meal.

DRUG

Sutezolid

SZD 800 mg once daily will be administered as two 400 mg tablets orally once daily with a meal.

Sponsors & Collaborators

• TB Alliance

  collaborator UNKNOWN

• National Institute of Allergy and Infectious Diseases (NIAID)

  lead NIH

Principal Investigators

• Radojka Savic, PharmD, PhD · University of California

• Kelly Dooley, MD, PhD · Vanderbilt University Medical Center

• Gustavo Velásquez, MD, MPH · University of California

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-03-11

Primary Completion

2026-11-11

Completion

2027-08-11

FDA Drug

Yes

Countries

• Botswana
• Brazil
• Haiti
• India
• Kenya
• Malawi
• Mexico
• Peru
• Philippines
• South Africa
• Thailand
• Uganda
• Vietnam
• Zimbabwe

Study Locations