Re-evaluating the Duration in Children of TB Treatment

NCT07656012 | Not Yet Recruiting Phase 2 DMC

• 4 other identifiers: 2026-0205Protocol Version 2/10/26SMPH | Pediatrics - GPAM1U01AI192041-01
• Study Type: interventional
• Target: 230
• Locations: 1 country
• Sites: 1

Brief Summary

Current tuberculosis (TB) treatment is effective (works well), but it takes a long time to cure TB. This study will evaluate if TB treatment with a higher dose of rifampicin, one of the TB medicines, and shorter TB treatment duration is as effective and safe as the standard, TB treatment (with the usual rifampicin dose and usual duration). This study hopes to find a better shorter treatment that works as well as the current treatment (standard of care). This could benefit children worldwide who are getting TB treatment. Children 3 months to less than 10 years of age who have drug-susceptible TB (can be successfully treated with standard TB medicines) are eligible for this study.

Conditions

Tuberculosis

Keywords

children; rifampicin; duration randomization

Outcome Measures

Primary Outcomes (1)

• Step 2: Unfavorable TB treatment outcome

  A participant has unfavorable treatment outcomes if they fail to meet either of the following criteria: * No treatment extension or re-treatment for TB at any time up through 48 weeks after randomization. * TB recurrence-free cure or Probable TB recurrence-free cure

  48 weeks

Secondary Outcomes (10)

• Step 1: Safety measured by occurrence of Grade 3 to 5 Adverse Events after the first dose of study treatment by period in Lead-in PK study

  data collected from individual participants for 2 regimens of 4 weeks each, up to 8 weeks total

• Step 1: Tolerability Measured by discontinuation of at least one drug in Lead-in PK study

  data collected from individual participants for 2 regimens of 4 weeks each, up to 8 weeks total

• Step 1: Pharmacokinetics of optimized-dose rifampicin: (AUC0-24)

  data collected at week 4 (and week 8) visit lead-in PK study; pre-dose (0 hour), 1, 2, 4, 8 and 24 hour post dose

• Step 1: Pharmacokinetics of optimized-dose rifampicin: (Cmax)

  data collected at week 4 (and week 8) visit lead-in PK study; pre-dose (0 hour), 1, 2, 4, 8 and 24 hour post dose

• Step 1: Acceptability of optimized-dose rifampicin summarized by participant count

  baseline (at dose 1), week 4, week 8

Study Arms (7)

Arm 1: 8 week duration

EXPERIMENTAL

N = 40, 8 weeks of odRHZE

Drug: Rifampicin; Drug: Isoniazid; Drug: Pyrazinamide; Drug: Ethambutol

Arm 2: 11 week duration

EXPERIMENTAL

N = 40, 8 weeks of odRHZE followed by 3 weeks of odRH

Drug: Rifampicin; Drug: Isoniazid; Drug: Pyrazinamide; Drug: Ethambutol

Arm 3: 14 week duration

EXPERIMENTAL

N = 40, 8 weeks of odRHZE followed by 6 weeks of odRH

Drug: Rifampicin; Drug: Isoniazid; Drug: Pyrazinamide; Drug: Ethambutol

Arm 4: 17 week duration

EXPERIMENTAL

N = 40, 8 weeks of odRHZE followed by 9 weeks of odRH

Drug: Rifampicin; Drug: Isoniazid; Drug: Pyrazinamide; Drug: Ethambutol

Arm 5: Control (17 or 24 week duration)

ACTIVE COMPARATOR

N = 40, 8 week of RHZ(E) followed by 9 weeks (5a - non-severe TB) or 16 weeks (5b - severe TB) of RH

Drug: Isoniazid; Drug: Pyrazinamide; Drug: Ethambutol; Drug: Rifampicin

Step 1: PK - Dosing Schedule A > B

EXPERIMENTAL

N = 15 * Period 1 - odRIF Dosing Schedule A with HZE, PK sampling after 4 weeks followed by * Period 2 - odRIF Dosing Schedule B with HZE, PK sampling after 4 weeks Dosing schedules are by weight and age, with Schedule A a higher dose of RIF (totaling 250 - 1650mg) than Schedule B (totaling 200 - 1350mg)

Drug: Rifampicin; Drug: Isoniazid; Drug: Pyrazinamide; Drug: Ethambutol

Step 1: PK - Dosing Schedule B > A

EXPERIMENTAL

N = 15 * Period 1 - odRIF Dosing Schedule B with HZE, PK sampling after 4 weeks followed by * Period 2 - odRIF Dosing Schedule A with HZE, PK sampling after 4 weeks Dosing schedules are by weight and age, with Schedule A a higher dose of RIF (totaling 250 - 1650mg) than Schedule B (totaling 200 - 1350mg)

Drug: Rifampicin; Drug: Isoniazid; Drug: Pyrazinamide; Drug: Ethambutol

Interventions

Rifampicin DRUG

odR for main trial determined from Lead-in PK study 75 mg tablet, and 150 or 300 mg capsule, dosed by weight and age

Also known as: two optimized-doses (odR) rifampicin

Arm 1: 8 week duration; Arm 2: 11 week duration; Arm 3: 14 week duration; Arm 4: 17 week duration; Step 1: PK - Dosing Schedule A > B; Step 1: PK - Dosing Schedule B > A

Isoniazid DRUG

50 mg tablet, dosed by weight and age

Also known as: Isoniazid (H)

Arm 1: 8 week duration; Arm 2: 11 week duration; Arm 3: 14 week duration; Arm 4: 17 week duration; Arm 5: Control (17 or 24 week duration); Step 1: PK - Dosing Schedule A > B; Step 1: PK - Dosing Schedule B > A

Pyrazinamide DRUG

150 mg tablet, dosed by weight and age

Also known as: Pyrazinamide (Z)

Arm 1: 8 week duration; Arm 2: 11 week duration; Arm 3: 14 week duration; Arm 4: 17 week duration; Arm 5: Control (17 or 24 week duration); Step 1: PK - Dosing Schedule A > B; Step 1: PK - Dosing Schedule B > A

Ethambutol DRUG

100 mg tablet, dosed by weight and age

Also known as: Ethambutol (E)

Arm 1: 8 week duration; Arm 2: 11 week duration; Arm 3: 14 week duration; Arm 4: 17 week duration; Arm 5: Control (17 or 24 week duration); Step 1: PK - Dosing Schedule A > B; Step 1: PK - Dosing Schedule B > A

Eligibility Criteria

• Age: 3 Months - 9 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• months to less than 10 years of age
• Body weight greater than or equal to 3 kilograms (kg) and less than 45 kg at study entry
• Confirmed or clinically diagnosed intrathoracic (pulmonary) and/or some forms of extrathoracic (extrapulmonary) drug-susceptible TB:
• Confirmed intrathoracic (pulmonary) TB, based on chest radiograph and/or symptoms consistent with TB, and/or some forms of extrathoracic TB, with all of the following as determined by the site investigator:
• Microbiological confirmation of M. tuberculosis from any clinical specimen by either culture or molecular methods
• At least rifampicin-susceptibility demonstrated by genotypic (molecular) or phenotypic methods
• Documented clinical decision to treat for drug-susceptible TB
• Clinically diagnosed intrathoracic (pulmonary) TB, based on chest radiograph and/or symptoms consistent with TB, and/or some forms of extrathoracic TB, with all of the following as determined by the site investigator:
• Documented clinical decision to treat for drug-susceptible TB
• HIV positive or negative
• For participants living with HIV, they must be on a dolutegravir-based antiretroviral therapy regimen at the time of study entry

You may not qualify if:

• Received routine treatment for TB disease for greater than 5 days at the time of enrollment
• Exposure to a case of intrathoracic TB in the 12 months prior to enrollment with known or suspected resistance to any of the drugs in the treatment regimens OR confirmed resistance on molecular or phenotypic drug-susceptibility testing to any drugs in the treatment regimens
• Has greater than or equal to grade 3 results of any of the following during screening: creatinine, serum ALT, AST, total bilirubin
• Has hemoglobin less than 7.5 g/dL during screening
• Has TB meningitis, osteoarticular TB, or miliary TB as determined by the site investigator
• Severe renal, pulmonary, cardiac, gastrointestinal, neurologic or any other condition that in the judgement of the investigator would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving study objectives
• Use of any prohibited drug within 3 days of enrollment
• Severe acute malnutrition defined as weight-for-height/length z-score or BMI-for-age z-score less than -3
• Hypersensitivity to any of the study drugs (rifampicin, isoniazid, pyrazinamide or ethambutol)
• For Main Trial (Step 2) participants, previously enrolled in the Lead-in PK Study (Step 1)

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

Socios en Salud Sucursal Peru

Lima, Peru

Location

MeSH Terms

Conditions

Tuberculosis

Interventions

Rifampin; Isoniazid; Protons; Pyrazinamide; Ethambutol

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Hydrazines; Organic Chemicals; Isonicotinic Acids; Acids, Heterocyclic; Pyridines; Heterocyclic Compounds, 1-Ring; Cations, Monovalent; Cations; Ions; Electrolytes; Inorganic Chemicals; Hydrogen; Elements; Gases; Nucleons; Elementary Particles; Physical Phenomena; Pyrazines; Ethylenediamines; Diamines; Polyamines; Amines

Study Officials

• Anthony Garcia-Prats, MD, MSc, PhD

  UW School of Medicine and Public Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

UW Clinical Trials Institute

CONTACT

608.265.3132; info@clinicaltrials.wisc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a multi-arm open-label phase IIc trial with duration randomization, with a lead-in PK study. Children 3 months to less than 10 years of age with routinely diagnosed clinical or confirmed drug-susceptible TB will be screened and if eligible randomly assigned 1:1:1:1:1 to one of five arms (durations of TB treatment and control arm). Randomization will be stratified by age (3 months to less than 5 years of age vs 5 to less than 10 years of age). A total of 200 participants will be enrolled in the main trial, with 40 per study arm, with an additional 30 participants enrolled in a Lead-in PK study that has a crossover trial design.

Study Record Dates

• First Submitted: May 15, 2026
• First Posted: June 18, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2030
• Study Completion (Estimated): September 1, 2030
• Last Updated: June 18, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF

Locations

PE (1)