Assessment of the Safety, Tolerability, and Effectiveness of Rifapentine Given Daily for LTBI

NCT03474029 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: CDC-NCHSTP-7024
• Study Type: interventional
• Target: 3,400
• Locations: 8 countries
• Sites: 21

Brief Summary

This study is conducted to compare the safety and effectiveness of a novel short 6-week regimen of daily rifapentine (6wP, experimental arm) with a comparator arm of 12-16 weeks of rifamycin-based treatment (standard of care, control arm) of latent M. tuberculosis infection (LTBI). This trial is conducted among persons who are at increased risk of progression to tuberculosis (TB) and require treatment of LTBI. The study will be conducted in low, medium and high TB incidence settings that have treatment of LTBI as their standard of care and offer 12-16 week rifamycin-based therapy as standard of care. The hypothesis of this study is that the safety and effectiveness of the experimental treatment (6wP arm) is non-inferior to a comparator arm of 12-16 weeks of rifamycin-based treatment of LTBI (control arm). Participants are enrolled and randomly assigned to one of the two study arms: experimental 6wP or control. The comparator (control) arm's treatment regimens include 12 weeks of once-weekly isoniazid (INH) and rifapentine (3HP), 12 weeks of daily INH and rifampin (3HR), and 16 weeks of daily rifampin (4R). A total of 560 participants per arm (1,120 total) for the evaluation of safety and 1,700 participants per arm (3,400 total) for the evaluation of effectiveness will be enrolled, given treatment as per randomization assignment, and followed for 24 months from the date of enrollment. After completion of data collection, statistical analyses will be conducted to compare proportions of drug discontinuation due to adverse drug reaction (ADR) and proportions of newly diagnosed tuberculosis between 6wP and control arm.

Conditions

Latent Tuberculosis

Keywords

latent tuberculosis; rifapentine

Outcome Measures

Primary Outcomes (2)

• Treatment discontinuation due to adverse drug reaction

  1\. Safety: Drug discontinuation due to adverse drug reaction (ADR) associated with 6wP and the rifamycin-based comparator arm (3HP, 3HR, or 4R). • Attribution of an adverse event (AE) to study drugs will be initially determined by the local site investigator, reviewed by an independent, blinded adjudication panel and with final attribution determined by the sponsor.

  from the date of enrollment to the date of scheduled completion of assigned treatment

• Culture-confirmed tuberculosis (TB) in participants 18 years old and older and culture-confirmed or clinical TB in participants less then 18 years old.

  2\. Effectiveness: Culture-confirmed TB in participants \> 18 years old and culture-confirmed or clinical TB in participants \< 18 years old. * Diagnosis of culture-confirmed TB will be performed using liquid and/or solid media. * An independent, blinded adjudication panel will review all TB events.

  within 24 months from the date of enrollment

Secondary Outcomes (17)

• Proportion who complete assigned treatment

  from date of enrollment until the maximum accepted time for treatment completion as follows: 9 weeks for 6wP treatment, 16 weeks for 3HP, 16 weeks for 3HP, and 21 weeks for 4R

• Proportion of Participants Who Complete Assigned Study Treatment

  from date of enrollment until the maximum accepted time for treatment completion as follows: 9 weeks for 6wP treatment, 16 weeks for 3HP, 16 weeks for 3HP, and 21 weeks for 4R

• Proportion with any grade 3, 4, or 5 (i.e., death) adverse event associated with study drug

  within 6 months from the date of enrollment

• Proportion of Participants Who Die From Any Cause

  within 24 months from the date of enrollment

• Proportion of Participants With Hepatotoxicity or Non-Hepatotoxic Systemic Drug Reactions

  within 6 months from the date of enrollment

Other Outcomes (9)

• Proportion of Participants Who Discontinue Study Treatment Due to Adverse Drug Reactions by Treatment Arm

  from date of enrollment until the maximum accepted time for treatment completion as follows: 9 weeks for 6wP treatment, 16 weeks for 3HP, 16 weeks for 3HP, and 21 weeks for 4R

• Proportion of Participants Who Discontinue Study Treatment for Any Reason by Treatment Regimen

  from date of enrollment until the maximum accepted time for treatment completion as follows: 9 weeks for 6wP treatment, 16 weeks for 3HP, 16 weeks for 3HP, and 21 weeks for 4R

• Proportion of Participants Who Develop Tuberculosis (TB) by Treatment Regimen

  within 24 months from the date of enrollment

Study Arms (2)

6 weeks of daily rifapentine (6wP)

EXPERIMENTAL

Rifapentine daily for 6 weeks: 600 mg of Rifapentine (RPT) given once daily for 6 weeks

Drug: Rifapentine daily for 6 weeks

12-16 week rifamycin-based regimen

ACTIVE COMPARATOR

A 12-16 week rifamycin-based regimen available at the participant's site: "Rifapentine and Isoniazid weekly for 12 weeks" (3HP) or "Rifampin and Isoniazid daily for 12 weeks" (3HR) or "Rifampin daily for 16 weeks" (4R)

Drug: Rifapentine and Isoniazid weekly for 12 weeks; Drug: Rifampin and Isoniazid daily for 12 weeks; Drug: Rifampin daily for 16 weeks

Interventions

Rifapentine daily for 6 weeks DRUG

600 mg of Rifapentine (RPT) given once daily (o.d., omni die) for 6 weeks (6wP).

Also known as: priftin

6 weeks of daily rifapentine (6wP)

Rifapentine and Isoniazid weekly for 12 weeks DRUG

Rifapentine (RPT) 900 mg and isoniazid (INH) 900 mg given once-weekly for 12 weeks (3HP).\* \*Dose adjustments based on patient's weight will be made according to ATS/CDC/IDSA guidelines. RPT 900 mg once-weekly for persons weighing \> 50 kg. For persons weighing \< 50 kg, the following doses will be given: weight \> 25-32 kg - RPT 600 mg; weight \> 32-50 kg - RPT 750 mg; + INH 15 mg/kg (round up to nearest 50 or 100 mg; 900 mg max).

12-16 week rifamycin-based regimen

Rifampin and Isoniazid daily for 12 weeks DRUG

Rifampin (RIF) 600 mg and Isoniazid (INH) 300 mg given once-daily for 12 weeks (3HR)\*. \*Dose adjustments based on patient's weight will be made according to ATS/CDC/IDSA guidelines. RIF 600 mg daily for persons weighing \> 50 kg. For persons weighing \< 50 kg, give 10 mg/kg daily; round up to nearest 50 or 100 mg; + INH 5 mg/kg daily (rounded up to nearest 50 or 100 mg; 300 mg max).

12-16 week rifamycin-based regimen

Rifampin daily for 16 weeks DRUG

Rifampin (RIF) 600 mg given once-daily for 16 weeks (4R).\* \*Dose adjustments based on patient's weight will be made according to ATS/CDC/IDSA guidelines. RIF 600 mg daily for persons weighing \> 50 kg. For persons weighing \< 50 kg, 10 mg/kg daily; round up to nearest 50 or 100 mg.

12-16 week rifamycin-based regimen

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may not qualify if:

• Household and other close contacts (\> 4 hours of exposure in a one-week period) within 2 years prior to enrollment, of persons with bacteriologically confirmed TB.
• o Acceptable testing approaches for bacteriologic confirmation are 1) culture with rifamycin DST; or, 2) nucleic acid amplification tests (NAATs) that detect M. tuberculosis and detect mutations associated with rifamycin resistance. Additional details on bacteriologic confirmation, including accepted NAATs, will be included in the MOOP.
• Recent M. tuberculosis infection, defined as converting from a documented negative to positive TST or IGRA within 2 years prior to enrollment. Persons without known close contact to someone with active pulmonary TB who have a conversion by IGRA may require additional evaluation to rule out a false conversion. Additional guidance and definitions of conversion are in the MOOP.
• HIV co-infection (with CD4+ T-lymphocyte count \> 100 cells/mm3)
• ≥ 2 cm2 of pulmonary parenchymal fibrosis on chest X-ray and no prior history of treatment for TB or LTBI.
• Recent (within 3 years prior to enrollment) immigration to the United States or other country with low to moderate TB incidence, with abnormal chest X-ray, and no evidence of active TB.
• Recent (within 3 years prior to enrollment) immigration to the United States or other country with low to moderate TB incidence, from a country with an estimated incidence rate of TB \> 150 per 100,000 (see Appendix D) and either a positive IGRA or a TST ≥15 mm (TST \> 15 mm only applicable for those with recent immigration as their only risk factor for progression to TB).
• Recent (within 3 years prior to enrollment) immigration and seeking refugee/asylum status (see MOOP for additional details) to the United States or other country with low to moderate incidence from a country with an estimated incidence rate of TB \> 75 per 100,000 (see Appendix E) and either a positive IGRA or a TST ≥15 mm (TST \> 15 mm only applicable for those with recent immigration as their only risk factor for progression to TB).
• Individuals with an increased risk of TB due to medical conditions such as end-stage renal disease.
• Individuals currently using immunosuppressive medications such as chronic steroids.
• Individuals with planned use of TNF-α inhibitors.
• Individuals with planned solid organ or hematologic transplantation
• Willing to provide signed informed consent, or parental permission and participant assent.
• Pregnant women in their second or third trimester (≥14 weeks gestation).
• Stage 1: Include only those who agree to participate in the semi-intensive PK component.

Sponsors & Collaborators

• Centers for Disease Control and Prevention: lead

Study Sites (21)

Denver Health and Hospital Authority

Denver, Colorado, 80204, United States

RECRUITING

George Washington University

Washington D.C., District of Columbia, 20001, United States

RECRUITING

Washington DC VA Medical Center

Washington D.C., District of Columbia, 20001, United States

RECRUITING

New York Harbor Healthcare System

Manhattan, New York, 10001, United States

RECRUITING

New York City Bureau of TB Control

New York, New York, 11201, United States

RECRUITING

San Antonio VA

San Antonio, Texas, 78201, United States

ACTIVE NOT RECRUITING

Seattle King County Health Department

Seattle, Washington, 98101, United States

RECRUITING

Liverpool Hospital

Sydney, Australia

RECRUITING

Paramatta Chest

Sydney, Australia

RECRUITING

Royal Prince Alfred Hospital

Sydney, Australia

RECRUITING

National Referral University Hospital for Pneumo-physiology

Cotonou, Benin

ACTIVE NOT RECRUITING

Calgary TB Clinic

Calgary, Alberta, T1Y 6H6, Canada

RECRUITING

Edmonton TB Clinic

Edmonton, Alberta, Canada

RECRUITING

British Columbia Centre for Disease Control

Vancouver, British Columbia, Canada

RECRUITING

Toronto Western Hospital

Toronto, Ontario, M5P 1N5, Canada

RECRUITING

McGill University Health Centre

Montreal, Quebec, H3A 0G4, Canada

RECRUITING

Les Centres Gheskio (INLR) CRS

Port-au-Prince, Haiti

RECRUITING

Desmond Tutu TB Center

Stellenbosch, South Africa

NOT YET RECRUITING

Joint Clinical Research Centre/ Makerere Univ Med Sch

Kampala, Uganda

RECRUITING

Ho Chin Minh City-District 6 TB Unit

Ho Chi Minh City, Vietnam

RECRUITING

Ho Chin Minh City-Phoi Viet Resportory Centre

Ho Chi Minh City, Vietnam

RECRUITING

Related Links

• Tuberculosis Trials Consortium (TBTC)

MeSH Terms

Conditions

Latent Tuberculosis

Interventions

rifapentine; Rifampin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Timothy Sterling, MD

  Vanderbilt University Medical Center

  STUDY CHAIR

• Robert Belknap, MD

  Denver Public Health (USA)

  STUDY CHAIR

• Amber Robinson, PhD

  Centers for Disease Control and Prevention

  STUDY DIRECTOR

• Rosanna M Boyd, PhD

  Centers for Disease Control (USA)

  STUDY DIRECTOR

• Dick Menzies, MD

  McGill University

  STUDY CHAIR

Central Study Contacts

Amber B Robinson, PhD

CONTACT

1-800-CDC-INFO; nkj5@cdc.gov

TBTC Research Administrator

CONTACT

+1 (800)-232-4636; tbtcresearchadmin@cdc.gov

Study Design

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

Study Record Dates

• First Submitted: March 8, 2018
• First Posted: March 22, 2018
• Study Start: August 1, 2019
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2029
• Last Updated: May 6, 2026

Record last verified: 2026-05

Locations

ZA (1); CA (5); AU (3); US (7); BE (1); VN (2); UG (1); HA (1)