A Study of Daily Rifapentine Combined With Isoniazid (1HP) for Tuberculosis Prevention in Children Less Than 13 Years of Age With and Without HIV

NCT07124559 | Not Yet Recruiting Phase 1 FDA Drug

• 2 other identifiers: IMPAACT 202438747
• Study Type: interventional
• Target: 144
• Locations: 6 countries
• Sites: 11

Brief Summary

This study aims to find the proposed dose of Rifapentine (RPT) taken once daily with Isoniazid (INH) for 28 days to prevent tuberculosis (TB). The study will take place at multiple locations and children under 13 years old will be divided into two groups: one group will include children without HIV, and the other group will include children with HIV who are on antiretroviral treatment. Up to 144 children will participate, and participants in each group will be followed for 24 weeks.

Conditions

Tuberculosis

Keywords

HIV; Tuberculosis; Latent Tuberculosis

Outcome Measures

Primary Outcomes (14)

• Plasma concentration of Rifapentine (RPT) at specified time points among children with and without HIV

  Through Day 28

• Area Under the Curve (AUC)(0-inf) of RPT

  Through Day 28

• Maximum serum concentration (C(max)) of RPT

  Through Day 28

• Half-life (t1/2) of RPT

  Through Day 28

• Apparent oral clearance (CL/F) of RPT

  Through Day 28

• Apparent oral volume of distribution (V/F) of RPT

  Through Day 28

• Absorption rate (ka) of RPT

  Through Day 28

• Trough serum concentration (C(trough)) of DTG (Cohort 2 only)

  At study entry, Day 28 and Day 42

• CL/F of DTG (Cohort 2 only)

  At study entry, Day 28 and Day 42

• Proportion of participants experiencing Adverse Events (AEs)

  Through Day 28

• Proportion of participants experiencing Grade 3 or higher AEs

  Through Day 28

• Proportion of participants experiencing Grade 2 or higher AEs assessed as related to 1HP

  Through Day 28

• Proportion of participants experiencing Serious Adverse Events (SAEs) assessed as related to 1HP

  Through Day 28

• Proportion of participants experiencing AEs assessed as related to 1HP that led to permanent discontinuation of the regimen

  Through Day 28

Secondary Outcomes (12)

• Relative effects of significant covariates on RPT PK

  Through Day 28

• Proportion of participants experiencing AEs

  Through Day 168

• Proportion of participants experiencing Grade 3 or higher AEs

  Through Day 168

• Proportion of participants experiencing Grade 2 or higher AEs assessed as related to 1HP

  Through Day 168

• Proportion of participants experiencing SAEs assessed as related to 1HP

  Through Day 168

Study Arms (2)

Cohort 1: Children living without HIV

EXPERIMENTAL

Participants will be enrolled by weight bands across five weight groups.

Drug: Rifapentine; Drug: Isoniazid

Cohort 2: Children living with HIV

EXPERIMENTAL

Participants will be enrolled by weight bands across five weight groups.

Drug: Rifapentine; Drug: Isoniazid; Drug: Dolutegravir

Interventions

Rifapentine DRUG

Dispersible Tablet administered orally

Also known as: RPT

Cohort 1: Children living without HIV; Cohort 2: Children living with HIV

Isoniazid DRUG

Dispersible Tablet administered orally

Also known as: INH

Cohort 1: Children living without HIV; Cohort 2: Children living with HIV

Dolutegravir DRUG

Tablets and Tablets for oral suspension administered orally

Cohort 2: Children living with HIV

Eligibility Criteria

• Age: Up to 13 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• A parent or legal guardian must be willing and able to give written permission for the child to participate in the study. If required by local policies, the child must also be willing and able to give written assent to participate. All sites must follow local policies and procedures.
• Age requirements at entry:
• Cohort 1: Children under 13 years old.
• Cohort 2: Children aged 12 weeks to under 13 years old.
• For Cohort 1 participants under 28 days old: The child must have been born at or after 37 weeks of pregnancy, as determined by the site investigator using parent/guardian report or medical records.
• Weight requirements at entry:
• Cohort 1: 3 kg to under 45 kg.
• Cohort 2: 6 kg to under 45 kg.
• HIV status:
• Cohort 1: Must be living without HIV.
• Cohort 2: Must be living with HIV.
• At risk of TB disease, defined as meeting at least one of the following:
• Having close contact with someone with infectious pulmonary TB within the past six months.
• A positive tuberculin skin test (TST) or, for those over two years old, a positive interferon gamma release assay (IGRA) if TST is not available.
• For Cohort 2 only: Living in a high TB burden area (≥ 60 TB cases per 100,000 people per year).

You may not qualify if:

• The child has active TB, confirmed by medical records, parent/guardian report, or tests during screening, indicated by:
• Currently being treated for active TB.
• Symptoms like poor growth, poor weight gain, weight loss, cough for at least 11 days, or fever for at least eight days.
• X-ray or CT scan showing TB.
• Positive TB test results (e.g., culture, Xpert MTB/RIF Ultra, Truenat M.tb, other nucleic acid tests, urine tests).
• The child has been exposed to an adult with drug-resistant TB (resistant to Rifampicin or Isoniazid) within the past six months.
• The child has taken the following medications:
• Daily Isoniazid in the 28 days before entry.
• Any prohibited medications listed in the study within three days before entry.
• The child has any of the following conditions:
• Acute or chronic hepatitis.
• Allergy to Isoniazid or rifamycins.
• Porphyria.
• Severe peripheral neuropathy.
• The child has severe acute malnutrition (weight-for-height/length less than -3 z-scores of WHO standards). Note: Children who are stunted (height-for-age more than two standard deviations below WHO standards) are eligible.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• National Institute of Mental Health (NIMH): collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (11)

Gaborone (Site ID: 12701)

Gaborone, Botswana

Location

Molepolole (Site ID: 12702)

Gaborone, Botswana

Location

Les Centres GHESKIO (Site ID: 30022)

Port-au-Prince, HT-6110, Haiti

Location

Kenya Medical Research Institute, Walter Reed Project Clinical Research Center (Site ID: 5121)

Kericho, 20200, Kenya

Location

Siriraj Hospital, Mahidol University (Site ID: 5115)

Bangkok, Bangkoknoi, 10700, Thailand

Location

Chiangrai Prachanukroh Hospital (Site ID: 5116)

Chiang Rai, 57000, Thailand

Location

Baylor-Uganda (Site ID: 31798)

Kampala, Uganda

Location

MU-JHU Care Limited (Site ID: 5126)

Kampala, Uganda

Location

Harare Family Care (Site ID: 31890)

Belgravia, Harare, Zimbabwe

Location

Seke North (Site ID: 30306)

Belgravia, Harare, Zimbabwe

Location

St Mary's (Site ID: 30303)

Chitungwiza, Zimbabwe

Location

MeSH Terms

Conditions

Tuberculosis; Latent Tuberculosis

Interventions

rifapentine; Isoniazid; dolutegravir

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Hydrazines; Organic Chemicals; Isonicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Central Study Contacts

IMPAACT ClinicalTrials.gov Coordinator

CONTACT

Please email:; impaact.ctgov@fstrf.org

Sarah Bradford

CONTACT

919-321-3673; sbradford@fhi360.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Model Details: Cohort 1 will open to enrollment first and Cohort 2 will open following RPT dose confirmation in Cohort 1. Within each cohort, participants in all weight bands will be enrolled concurrently.

Study Record Dates

• First Submitted: August 8, 2025
• First Posted: August 15, 2025
• Study Start (Estimated): May 15, 2026
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): May 31, 2028
• Last Updated: February 3, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months following publication and available throughout period of funding of the International Maternal Pediatric Adolescent AIDS Clinical Trial (IMPAACT) Network by NIH.
• Access Criteria: * With whom? * Researchers who provide a methodologically sound proposal for use of the data that is approved by the IMPAACT Network. * For what types of analyses? * To achieve aims in the proposal approved by the IMPAACT Network. * By what mechanism will data be made available? * Researchers may submit a request for access to data using the IMPAACT "Data Request" form at: https://www.impaactnetwork.org/resources/study-proposals.htm. Researchers of approved proposals will need to sign an IMPAACT Data Use Agreement before receiving the data

Locations

TH (2); UG (2); ZI (3); BO (2); HA (1); KE (1)