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

• Status: Active, not recruiting
• Trial end date: 2023-12-01
• Target enrollment: 0
• Participant gender: All

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 the United States, the United Kingdom, and other countries with low to moderate TB incidence (< 100 TB cases per 100,000 population) 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.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Centers for Disease Control and Prevention
• Collaborator: British Medical Research Council
• Treatments: Isoniazid; Rifampin; Rifamycin SV; Rifamycins; Rifapentine

Criteria

Inclusion Criteria:

• Males or non-pregnant, non-breastfeeding females > 12 years old. Women of child-bearing potential who are not surgically sterilized must agree to practice an adequate method of contraception (barrier method or non-hormonal intrauterine device) or abstain from heterosexual intercourse during study drug treatment.

• Persons with LTBI who do not have evidence of TB disease and are at increased risk of progression to TB. M. tuberculosis infection may be demonstrated by either a positive tuberculin skin test (TST) or a positive interferon gamma release assay (IGRA; e.g., QuantiFERON or T.SPOT.TB). Persons with LTBI at increased risk of progression to TB are those with one of the following:

1. Household and other close contacts (> 4 hours of exposure in a one week period) within 2 years prior to enrollment, of persons with culture-confirmed TB A positive nucleic acid amplification test (NAAT)/GeneXpert in the source case may be used for enrollment prior to culture confirmation

2. 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.

3. HIV co-infection.

4. ≥ 2 cm2 of pulmonary parenchymal fibrosis on chest X-ray and no prior history of treatment for TB or LTBI.

5. Recent (within 2 years prior to enrollment) immigration to the United States, United Kingdom, or other country with low to moderate TB incidence, with abnormal chest X-ray, and no evidence of active TB.

6. Recent (within 2 years prior to enrollment) immigration to the United States, United Kingdom, 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).

7. An increased risk of TB due to medical conditions such as end-stage renal disease, or due to use of immunosuppressive medications such as chronic steroids or TNF-alpha inhibitors.

• HIV-infected persons who are close contacts of a TB case, regardless of TST or IGRA result.

• Willing to provide signed informed consent, or parental permission and participant assent.

Exclusion Criteria:

• Current confirmed culture-positive or clinical TB.

• Suspected current TB. Includes cases in which active TB cannot be eliminated as a possibility (by the site investigator)

• TB resistant to any rifamycin in the source case

• A history of treatment for > 7 consecutive days with a rifamycin or > 30 consecutive days with INH within 2 years prior to enrollment.

• A documented history of completing an adequate course of treatment for TB disease or LTBI in a person who is HIV-seronegative.

• History of allergy or intolerance to rifamycins.

• Serum alanine aminotransferase (ALT; SGPT) or serum aspartate aminotransferase (AST; SGOT) > 5x upper limit of normal among persons in whom baseline ALT or AST is determined+.

• HIV-seropositive and on antiretroviral therapy that cannot be given with rifampin or rifapentine due to drug-drug interactions.

• Receiving concomitant medications that are known to be contraindicated with any study drug.

• Females who are currently pregnant, breastfeeding, or intend to become pregnant within 120 days of enrollment.

• Weight < 25 kg.