Shorter and Safer Treatment Regimens for Latent TB

Summary

Our study rationale is based on:

1. Tuberculosis Preventive Treatment (TPT) is given to healthy people and needs to be safe;
2. Tuberculosis Preventive Treatment (TPT) with shorter regimens are superior with respect to acceptance, completion, and costs;
3. 4 months of Rifampin 10mg/kg (4R10) is the safest regimen, but is completed by \<80% of patients;
4. The safety of 2 months of Rifampin 20mg/kg (2R20) is similar to that of 4 months of Rifampin 10mg/kg (4R10), but completion is a concern;
5. 1-month regimens have promising efficacy;
6. Safety and tolerability must be carefully assessed with comparisons to 4 months of Rifampin 10mg/kg (4R10), and head-to-head with each other.

OBJECTIVES: The investigator will use a Bayesian adaptive Phase 2 randomized open-label trial design to test at least three experimental Tuberculosis Preventive Treatment (TPT) regimens to identify at least one regimen of ≤2 months duration that has non-inferior safety, completion, and tolerability in adults and children relative to the reference Tuberculosis Preventive Treatment (TPT) regimen. The shortest, safest, and best tolerated regimen identified in this Phase 2 trial will be tested for effectiveness and efficacy in a Phase 3 trial.

Specific Tuberculosis Preventive Treatment (TPT) regimens (All are daily and self-administered) Reference: Rifampin at a dose of 10 mg/kg/day for 4 months (4R10); Experimental: 1) Rifampin at 20 mg/kg/day for 2 months (2R20); (2) one month Levofloxacin and Rifapentine (1LP). At a later stage a 3rd experimental regimen will be selected and added: one another novel 1-2-month regimen identified from pre-clinical and clinical studies. When selected, this will be explained fully including preliminary data on safety and efficacy in an amended protocol and consent - which will be submitted for ethics and regulatory approval at that time).

Conditions

• Tuberculosis Infection, Latent

Interventions

DRUG

rifampin standard arm

120 doses daily self-administered rifampin at 10mg/kg/day (max 600mg/day)

DRUG

rifampin double dose

60 doses daily self-administered rifampin at 20 mg/kg (max. 1200 mg/day)

DRUG

levofloxacin and rifapentine

30 doses daily self-administered levofloxacin (15 mg/kg, max 750mg/day and rifapentine (10mg/kg, max: 600mg)

Sponsors & Collaborators

• Canadian Institutes of Health Research (CIHR)

  collaborator OTHER_GOV

• McGill University Health Centre/Research Institute of the McGill University Health Centre

  lead OTHER

Principal Investigators

• Dick Menzies, MD · RI-MUHC

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

5 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-06-10

Primary Completion

2027-04-01

Completion

2029-06-01

Countries

• Benin
• Brazil
• Canada
• Indonesia
• Vietnam

Study Locations