Trial Outcomes & Findings for Tuberculosis Clinical Trials Consortium Study 35 (NCT NCT03730181)

Last Updated: 2026-07-24

Results Overview

Rifapentine exposure was assessed using population pharmacokinetic analysis incorporating pharmacokinetic samples collected during the 12-week treatment period. Reported AUC values are model-derived estimates from the overall pharmacokinetic analysis. The target median AUC was 522 mg·h/L, with an acceptable range of 392-914 mg·h/L.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

69 participants

Primary outcome timeframe

During the 12-week treatment period, based on pharmacokinetic samples collected during study treatment

Results posted on

2026-07-24

Participant Flow

Participants were recruited in South Africa at the Desmond Tutu TB Centre and Family Centre for Research with Ubuntu, Stellenbosch University, Cape Town, and the Perinatal HIV Research Unit, Johannesburg, between November 2019 and December 2023. Follow-up was completed in May 2024.

Tuberculosis Trials Consortium (TBTC) Study 35 was a phase I/II, open-label, multi-site, single-arm dose-finding study evaluating the pharmacokinetics, safety, and tolerability of once-weekly rifapentine plus isoniazid for 12 weeks (3HP) in children aged 0-12 years, including children living with HIV. Participants were enrolled sequentially into four age cohorts (18, 13, 19, and 19 participants, respectively) using a modified age de-escalation design before receiving the same study intervention.

Participant milestones

Participant milestones
Measure	3HP (Rifapentine Plus Isoniazid) Participants received once-weekly rifapentine plus isoniazid for 12 weeks (3HP) using age- and weight-based dosing with dispersible formulations.
Overall Study STARTED	69
Overall Study Completed Treatment	67
Overall Study COMPLETED	66
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Reasons for withdrawal
Measure	3HP (Rifapentine Plus Isoniazid) Participants received once-weekly rifapentine plus isoniazid for 12 weeks (3HP) using age- and weight-based dosing with dispersible formulations.
Overall Study Lost to Follow-up	1
Overall Study Withdrawal by caregiver/scheduling conflict	1
Overall Study Missing evaluable PK/safety data	1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	3HP (Rifapentine Plus Isoniazid) n=69 Participants Participants received once-weekly rifapentine plus isoniazid for 12 weeks (3HP) using age- and weight-based dosing with dispersible formulations.
Age, Continuous	22 months n=69 Participants
Sex: Female, Male Female	34 Participants n=69 Participants
Sex: Female, Male Male	35 Participants n=69 Participants
Region of Enrollment South Africa	69 participants n=69 Participants
Weight, Continuous	12 kg n=69 Participants

PRIMARY outcome

Timeframe: During the 12-week treatment period, based on pharmacokinetic samples collected during study treatment

Population: All participants who completed at least week 1 intensive pharmacokinetic sampling were included in the pharmacokinetic analysis. Overall pharmacokinetic analysis included all 69 enrolled participants.

Outcome measures

Outcome measures
Measure	3HP (Rifapentine Plus Isoniazid) n=69 Participants Participants received once-weekly rifapentine plus isoniazid for 12 weeks (3HP) using age- and weight-based dosing with dispersible formulations.
Rifapentine Pharmacokinetic Exposure (AUC) Following Weekly 3HP Administration Cohort 1	609 mg·h/L Interval 417.0 to 759.0
Rifapentine Pharmacokinetic Exposure (AUC) Following Weekly 3HP Administration Cohort 2	421 mg·h/L Interval 357.0 to 512.0
Rifapentine Pharmacokinetic Exposure (AUC) Following Weekly 3HP Administration Cohort 3	392 mg·h/L Interval 247.0 to 480.0
Rifapentine Pharmacokinetic Exposure (AUC) Following Weekly 3HP Administration Cohort 4	394 mg·h/L Interval 291.0 to 489.0

SECONDARY outcome

Timeframe: 12-week treatment period and 24-week follow-up

Safety and tolerability of 3HP were assessed through clinical and laboratory adverse event monitoring during treatment and follow-up.

Outcome measures

Outcome measures
Measure	3HP (Rifapentine Plus Isoniazid) n=69 Participants Participants received once-weekly rifapentine plus isoniazid for 12 weeks (3HP) using age- and weight-based dosing with dispersible formulations.
Incidence of Grade ≥3 Adverse Events Related to Study Treatment Participants developing TB disease	0 Participants
Incidence of Grade ≥3 Adverse Events Related to Study Treatment Participants with any Grade 3 adverse event	9 Participants
Incidence of Grade ≥3 Adverse Events Related to Study Treatment Participants with Grade ≥3 adverse event at least possibly related to study treatment	2 Participants
Incidence of Grade ≥3 Adverse Events Related to Study Treatment Serious adverse events	1 Participants
Incidence of Grade ≥3 Adverse Events Related to Study Treatment Grade 4 adverse events	0 Participants
Incidence of Grade ≥3 Adverse Events Related to Study Treatment Grade 5 adverse events (deaths)	0 Participants
Incidence of Grade ≥3 Adverse Events Related to Study Treatment Discontinuations due to adverse events	0 Participants

Adverse Events

3HP (Rifapentine Plus Isoniazid)

Serious events: 1 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	3HP (Rifapentine Plus Isoniazid) n=69 participants at risk Participants received once-weekly rifapentine plus isoniazid for 12 weeks (3HP) using age- and weight-based dosing with dispersible formulations.
Infections and infestations Bronchopneumonia	1.4% 1/69 • Number of events 1 • From first study drug dose through the Week 24 follow-up visit (approximately 24 weeks). Adverse events were assessed by clinical evaluation, laboratory testing, and systematic adverse event reporting from the first study drug dose through the Week 24 follow-up visit. All adverse events were collected. This module reports all-cause mortality, serious adverse events, and other adverse events meeting the prespecified reporting threshold.

Other adverse events

Other adverse events
Measure	3HP (Rifapentine Plus Isoniazid) n=69 participants at risk Participants received once-weekly rifapentine plus isoniazid for 12 weeks (3HP) using age- and weight-based dosing with dispersible formulations.
Skin and subcutaneous tissue disorders DERMATITIS DIAPER	10.1% 7/69 • Number of events 7 • From first study drug dose through the Week 24 follow-up visit (approximately 24 weeks). Adverse events were assessed by clinical evaluation, laboratory testing, and systematic adverse event reporting from the first study drug dose through the Week 24 follow-up visit. All adverse events were collected. This module reports all-cause mortality, serious adverse events, and other adverse events meeting the prespecified reporting threshold.
General disorders DIARRHOEA	1.4% 1/69 • Number of events 1 • From first study drug dose through the Week 24 follow-up visit (approximately 24 weeks). Adverse events were assessed by clinical evaluation, laboratory testing, and systematic adverse event reporting from the first study drug dose through the Week 24 follow-up visit. All adverse events were collected. This module reports all-cause mortality, serious adverse events, and other adverse events meeting the prespecified reporting threshold.
General disorders BRONCHIAL HYPERREACTIVITY	2.9% 2/69 • Number of events 2 • From first study drug dose through the Week 24 follow-up visit (approximately 24 weeks). Adverse events were assessed by clinical evaluation, laboratory testing, and systematic adverse event reporting from the first study drug dose through the Week 24 follow-up visit. All adverse events were collected. This module reports all-cause mortality, serious adverse events, and other adverse events meeting the prespecified reporting threshold.
Eye disorders CONJUNCTIVITIS BACTERIAL	1.4% 1/69 • Number of events 1 • From first study drug dose through the Week 24 follow-up visit (approximately 24 weeks). Adverse events were assessed by clinical evaluation, laboratory testing, and systematic adverse event reporting from the first study drug dose through the Week 24 follow-up visit. All adverse events were collected. This module reports all-cause mortality, serious adverse events, and other adverse events meeting the prespecified reporting threshold.
General disorders CONSTIPATION	5.8% 4/69 • Number of events 4 • From first study drug dose through the Week 24 follow-up visit (approximately 24 weeks). Adverse events were assessed by clinical evaluation, laboratory testing, and systematic adverse event reporting from the first study drug dose through the Week 24 follow-up visit. All adverse events were collected. This module reports all-cause mortality, serious adverse events, and other adverse events meeting the prespecified reporting threshold.
Skin and subcutaneous tissue disorders ACARODERMATITIS	2.9% 2/69 • Number of events 2 • From first study drug dose through the Week 24 follow-up visit (approximately 24 weeks). Adverse events were assessed by clinical evaluation, laboratory testing, and systematic adverse event reporting from the first study drug dose through the Week 24 follow-up visit. All adverse events were collected. This module reports all-cause mortality, serious adverse events, and other adverse events meeting the prespecified reporting threshold.
General disorders ARTHRITIS REACTIVE	1.4% 1/69 • Number of events 1 • From first study drug dose through the Week 24 follow-up visit (approximately 24 weeks). Adverse events were assessed by clinical evaluation, laboratory testing, and systematic adverse event reporting from the first study drug dose through the Week 24 follow-up visit. All adverse events were collected. This module reports all-cause mortality, serious adverse events, and other adverse events meeting the prespecified reporting threshold.
General disorders BODY TINEA	4.3% 3/69 • Number of events 3 • From first study drug dose through the Week 24 follow-up visit (approximately 24 weeks). Adverse events were assessed by clinical evaluation, laboratory testing, and systematic adverse event reporting from the first study drug dose through the Week 24 follow-up visit. All adverse events were collected. This module reports all-cause mortality, serious adverse events, and other adverse events meeting the prespecified reporting threshold.
General disorders PHARYNGITIS	2.9% 2/69 • Number of events 2 • From first study drug dose through the Week 24 follow-up visit (approximately 24 weeks). Adverse events were assessed by clinical evaluation, laboratory testing, and systematic adverse event reporting from the first study drug dose through the Week 24 follow-up visit. All adverse events were collected. This module reports all-cause mortality, serious adverse events, and other adverse events meeting the prespecified reporting threshold.
General disorders PHARYNGOTONSILLITIS	1.4% 1/69 • Number of events 1 • From first study drug dose through the Week 24 follow-up visit (approximately 24 weeks). Adverse events were assessed by clinical evaluation, laboratory testing, and systematic adverse event reporting from the first study drug dose through the Week 24 follow-up visit. All adverse events were collected. This module reports all-cause mortality, serious adverse events, and other adverse events meeting the prespecified reporting threshold.
Musculoskeletal and connective tissue disorders RADIUS FRACTURE	1.4% 1/69 • Number of events 1 • From first study drug dose through the Week 24 follow-up visit (approximately 24 weeks). Adverse events were assessed by clinical evaluation, laboratory testing, and systematic adverse event reporting from the first study drug dose through the Week 24 follow-up visit. All adverse events were collected. This module reports all-cause mortality, serious adverse events, and other adverse events meeting the prespecified reporting threshold.
General disorders ORAL CANDIDIASIS	1.4% 1/69 • Number of events 1 • From first study drug dose through the Week 24 follow-up visit (approximately 24 weeks). Adverse events were assessed by clinical evaluation, laboratory testing, and systematic adverse event reporting from the first study drug dose through the Week 24 follow-up visit. All adverse events were collected. This module reports all-cause mortality, serious adverse events, and other adverse events meeting the prespecified reporting threshold.
General disorders HYPERKALAEMIA	8.7% 6/69 • Number of events 6 • From first study drug dose through the Week 24 follow-up visit (approximately 24 weeks). Adverse events were assessed by clinical evaluation, laboratory testing, and systematic adverse event reporting from the first study drug dose through the Week 24 follow-up visit. All adverse events were collected. This module reports all-cause mortality, serious adverse events, and other adverse events meeting the prespecified reporting threshold.
General disorders HYPONATRAEMIA	1.4% 1/69 • Number of events 1 • From first study drug dose through the Week 24 follow-up visit (approximately 24 weeks). Adverse events were assessed by clinical evaluation, laboratory testing, and systematic adverse event reporting from the first study drug dose through the Week 24 follow-up visit. All adverse events were collected. This module reports all-cause mortality, serious adverse events, and other adverse events meeting the prespecified reporting threshold.
General disorders IMPETIGO	2.9% 2/69 • Number of events 2 • From first study drug dose through the Week 24 follow-up visit (approximately 24 weeks). Adverse events were assessed by clinical evaluation, laboratory testing, and systematic adverse event reporting from the first study drug dose through the Week 24 follow-up visit. All adverse events were collected. This module reports all-cause mortality, serious adverse events, and other adverse events meeting the prespecified reporting threshold.
General disorders GASTROENTERITIS	8.7% 6/69 • Number of events 6 • From first study drug dose through the Week 24 follow-up visit (approximately 24 weeks). Adverse events were assessed by clinical evaluation, laboratory testing, and systematic adverse event reporting from the first study drug dose through the Week 24 follow-up visit. All adverse events were collected. This module reports all-cause mortality, serious adverse events, and other adverse events meeting the prespecified reporting threshold.
General disorders HELMINTHIC INFECTION	1.4% 1/69 • Number of events 1 • From first study drug dose through the Week 24 follow-up visit (approximately 24 weeks). Adverse events were assessed by clinical evaluation, laboratory testing, and systematic adverse event reporting from the first study drug dose through the Week 24 follow-up visit. All adverse events were collected. This module reports all-cause mortality, serious adverse events, and other adverse events meeting the prespecified reporting threshold.
General disorders HERPES VIRUS INFECTION	1.4% 1/69 • Number of events 1 • From first study drug dose through the Week 24 follow-up visit (approximately 24 weeks). Adverse events were assessed by clinical evaluation, laboratory testing, and systematic adverse event reporting from the first study drug dose through the Week 24 follow-up visit. All adverse events were collected. This module reports all-cause mortality, serious adverse events, and other adverse events meeting the prespecified reporting threshold.
Blood and lymphatic system disorders EOSINOPHILIA	4.3% 3/69 • Number of events 3 • From first study drug dose through the Week 24 follow-up visit (approximately 24 weeks). Adverse events were assessed by clinical evaluation, laboratory testing, and systematic adverse event reporting from the first study drug dose through the Week 24 follow-up visit. All adverse events were collected. This module reports all-cause mortality, serious adverse events, and other adverse events meeting the prespecified reporting threshold.
General disorders FEBRILE CONVULSION	1.4% 1/69 • Number of events 1 • From first study drug dose through the Week 24 follow-up visit (approximately 24 weeks). Adverse events were assessed by clinical evaluation, laboratory testing, and systematic adverse event reporting from the first study drug dose through the Week 24 follow-up visit. All adverse events were collected. This module reports all-cause mortality, serious adverse events, and other adverse events meeting the prespecified reporting threshold.
Blood and lymphatic system disorders Neutropenia	7.2% 5/69 • Number of events 5 • From first study drug dose through the Week 24 follow-up visit (approximately 24 weeks). Adverse events were assessed by clinical evaluation, laboratory testing, and systematic adverse event reporting from the first study drug dose through the Week 24 follow-up visit. All adverse events were collected. This module reports all-cause mortality, serious adverse events, and other adverse events meeting the prespecified reporting threshold.
Respiratory, thoracic and mediastinal disorders RESPIRATORY TRACT INFLAMMATION	1.4% 1/69 • Number of events 1 • From first study drug dose through the Week 24 follow-up visit (approximately 24 weeks). Adverse events were assessed by clinical evaluation, laboratory testing, and systematic adverse event reporting from the first study drug dose through the Week 24 follow-up visit. All adverse events were collected. This module reports all-cause mortality, serious adverse events, and other adverse events meeting the prespecified reporting threshold.
Respiratory, thoracic and mediastinal disorders RESPIRATORY TRACT INFECTION	20.3% 14/69 • Number of events 14 • From first study drug dose through the Week 24 follow-up visit (approximately 24 weeks). Adverse events were assessed by clinical evaluation, laboratory testing, and systematic adverse event reporting from the first study drug dose through the Week 24 follow-up visit. All adverse events were collected. This module reports all-cause mortality, serious adverse events, and other adverse events meeting the prespecified reporting threshold.
Renal and urinary disorders URINARY TRACT INFECTION	4.3% 3/69 • Number of events 3 • From first study drug dose through the Week 24 follow-up visit (approximately 24 weeks). Adverse events were assessed by clinical evaluation, laboratory testing, and systematic adverse event reporting from the first study drug dose through the Week 24 follow-up visit. All adverse events were collected. This module reports all-cause mortality, serious adverse events, and other adverse events meeting the prespecified reporting threshold.
General disorders TOOTH EXTRACTION	2.9% 2/69 • Number of events 2 • From first study drug dose through the Week 24 follow-up visit (approximately 24 weeks). Adverse events were assessed by clinical evaluation, laboratory testing, and systematic adverse event reporting from the first study drug dose through the Week 24 follow-up visit. All adverse events were collected. This module reports all-cause mortality, serious adverse events, and other adverse events meeting the prespecified reporting threshold.
Ear and labyrinth disorders OTITIS MEDIA	4.3% 3/69 • Number of events 3 • From first study drug dose through the Week 24 follow-up visit (approximately 24 weeks). Adverse events were assessed by clinical evaluation, laboratory testing, and systematic adverse event reporting from the first study drug dose through the Week 24 follow-up visit. All adverse events were collected. This module reports all-cause mortality, serious adverse events, and other adverse events meeting the prespecified reporting threshold.
Blood and lymphatic system disorders ANEMIA	14.5% 10/69 • Number of events 10 • From first study drug dose through the Week 24 follow-up visit (approximately 24 weeks). Adverse events were assessed by clinical evaluation, laboratory testing, and systematic adverse event reporting from the first study drug dose through the Week 24 follow-up visit. All adverse events were collected. This module reports all-cause mortality, serious adverse events, and other adverse events meeting the prespecified reporting threshold.
General disorders URTICARIA PAPULAR	1.4% 1/69 • Number of events 1 • From first study drug dose through the Week 24 follow-up visit (approximately 24 weeks). Adverse events were assessed by clinical evaluation, laboratory testing, and systematic adverse event reporting from the first study drug dose through the Week 24 follow-up visit. All adverse events were collected. This module reports all-cause mortality, serious adverse events, and other adverse events meeting the prespecified reporting threshold.
Infections and infestations TONSILLITIS	1.4% 1/69 • Number of events 1 • From first study drug dose through the Week 24 follow-up visit (approximately 24 weeks). Adverse events were assessed by clinical evaluation, laboratory testing, and systematic adverse event reporting from the first study drug dose through the Week 24 follow-up visit. All adverse events were collected. This module reports all-cause mortality, serious adverse events, and other adverse events meeting the prespecified reporting threshold.
Immune system disorders ALLERGIC RHINITIS	5.8% 4/69 • Number of events 4 • From first study drug dose through the Week 24 follow-up visit (approximately 24 weeks). Adverse events were assessed by clinical evaluation, laboratory testing, and systematic adverse event reporting from the first study drug dose through the Week 24 follow-up visit. All adverse events were collected. This module reports all-cause mortality, serious adverse events, and other adverse events meeting the prespecified reporting threshold.
General disorders TEETHING	1.4% 1/69 • Number of events 1 • From first study drug dose through the Week 24 follow-up visit (approximately 24 weeks). Adverse events were assessed by clinical evaluation, laboratory testing, and systematic adverse event reporting from the first study drug dose through the Week 24 follow-up visit. All adverse events were collected. This module reports all-cause mortality, serious adverse events, and other adverse events meeting the prespecified reporting threshold.
General disorders TINEA CAPITIS	1.4% 1/69 • Number of events 1 • From first study drug dose through the Week 24 follow-up visit (approximately 24 weeks). Adverse events were assessed by clinical evaluation, laboratory testing, and systematic adverse event reporting from the first study drug dose through the Week 24 follow-up visit. All adverse events were collected. This module reports all-cause mortality, serious adverse events, and other adverse events meeting the prespecified reporting threshold.

Additional Information

Anneke C. Hesseling, Principal Investigator

Stellenbosch University

Phone: +27 21 938 9000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place