Bedaquiline Roll-out Evidence in Contacts and People Living With HIV to Prevent TB

NCT06568484 | Recruiting Phase 2 DMC

• 2 other identifiers: IRB004434187200AA22CA00005
• Study Type: interventional
• Target: 2,530
• Locations: 3 countries
• Sites: 6

Brief Summary

A seamless, staged Phase II/III, open-label, multicenter, non-inferiority trial, to compare the efficacy and safety of 4 weeks of bedaquiline (BDQ) versus a a standard regimen for preventing regimen for preventing confirmed or probable tuberculosis disease (TBD) during 72 weeks of follow-up among people living with HIV (PLHIV) and high-risk Close Contacts (CC) of adults with Drug Susceptible (DS) or Rifampin Resistant (RR) TB.

Conditions

Tuberculosis, Latent

Keywords

Bedaquiline

Outcome Measures

Primary Outcomes (6)

• Safety DS-TB CCs and PLHIV (Stage 1): Proportion of participants who permanently discontinue the randomized study drug due to a treatment-related adverse event by 18 weeks

  Estimate of the safety of 1BDQ and 3HP among adult, adolescent, and child CCs of DS-TB Index Patients at high risk of developing TBD, as well as adult and adolescent PLHIV in high TB-burden settings

  18 weeks

• Safety for RR-TB CCs (Stage 1): Proportion of participants who permanently discontinue the randomized study drug due to a treatment-related adverse event by 36 weeks

  Estimate of the safety of 1BDQ and 6 months of levofloxacin (6L) among adult, adolescent, and child CCs of RR-TB Index Patients at high risk of developing TBD

  36 weeks

• Treatment Completion - PLHIV & CCs of DS-TB (Stage 1): Proportion of participants completing assigned treatment within window prescribed in protocol

  Estimate on-time treatment completion of 1BDQ \& 3HP in adult, adolescent, \& child CCs of DS-TB Index Patients at high risk of developing TBD, \& adult and adolescent PLHIV in high TB-burden countries

  18 weeks

• Treatment Completion - CCs of RR-TB (Stage 1): Proportion of participants completing assigned treatment within window prescribed in protocol

  Estimate on-time treatment completion of 1BDQ and 6 months of levofloxacin (6L) among adult, adolescent, and child CCs of RR-TB Index Patients at high risk of developing TBD

  36 weeks

• Primary Efficacy Endpoint (Stage 2): Number of enrolled participants (PLHIV, contacts of DS-TB or RR-TB) diagnosed with bacteriologically confirmed or probable / (if adult), and confirmed or unconfirmed (if child) TB disease

  Number (per person-years) of participants diagnosed with confirmed or probable (if adult) and unconfirmed or confirmed (if child) TB disease, compared between the comparator arm and investigational (BDQ) arm and expressed as the averted events ratio (AER)

  Up to 72 weeks post-treatment initiation

• Primary Safety Endpoint (Stage 2): Cumulative number of enrolled participants (PLHIV, contacts of DS-TB or RR-TB) who permanently discontinue the assigned study regimen due to an adverse drug reaction

  Proportion of individuals who permanently discontinue assigned study regimen due to a treatment-related adverse event, compared between the comparator arm and investigational (BDQ) arm.

  Varies by treatment regimen (1 month, 3 months, or 6 months)

Secondary Outcomes (11)

• Stage 1: Proportion of participants who permanently discontinue the randomized study drug due to a treatment-related adverse event by 18 weeks

  18 weeks

• Stage 1: Proportion of participants who permanently discontinue the randomized study drug due to a treatment-related adverse event by 36 weeks

  36 weeks

• Stage 1: Proportion of participants completing assigned treatment within window prescribed in protocol

  Dependent on treatment assignment (1 month, 3 months, or 6 months)

• Stage 1: Proportion of individuals who experience a grade 3 or higher AE, compared between the comparator arm and investigational (1BDQ) arm at 18 weeks

  18 weeks

• Stage 1: Proportion of participants completing assigned treatment within window prescribed in protocol

  Dependent upon treatment assignment (1 month, 3 months, or 6 months)

Study Arms (3)

Bedaquiline

EXPERIMENTAL

4 weeks of daily bedaquiline

Drug: Bedaquiline

3HP

ACTIVE COMPARATOR

3 months of weekly isoniazid (H) and rifapentine (P)

Combination Product: Isoniazid, rifapentine

Levofloxacin

ACTIVE COMPARATOR

6 months of daily levofloxacin

Drug: Levofloxacin

Interventions

Bedaquiline DRUG

CCs (Close Contacts) of DS-TB Index Patients and PLHIV at high risk of developing TBD 1. Children 0 to \<5 years old who are HIV negative, regardless of latent tuberculosis infection (LTBI) result by TST (tuberculin skin test) or IGRA (interferon-gamma release assay) 2. Adults, pregnant people, adolescents, and children ≥5 years old who are HIV negative and LTBI positive (by IGRA) 3. Adults and adolescents ≥15 years of age who are living with HIV regardless of LTBI status, regardless of whether the participant is a CC CCs of RR-TB Index Patients at high risk of developing TBD 1. Children 0 to \<5 years old, regardless of HIV status or LTBI result (by TST or IGRA) 2. Adults, adolescents, and children ≥5 years old who are HIV negative and LTBI positive (by IGRA) 3. Adults, pregnant people, adolescents, and children ≥5 years old who are living with HIV regardless of LTBI status Bedaquiline based on weight and/or age at Enrollment daily for four weeks (28 doses)

Also known as: Sirturo

Bedaquiline

Isoniazid, rifapentine COMBINATION_PRODUCT

CCs of DS-TB Index Patients and PLHIV at high risk of developing TBD 1. Children 0 to \<5 years old who are HIV status negative, regardless of latent tuberculosis infection (LTBI) result (WHO-recommended skin test or interferon-gamma release assay \[IGRA\]) 2. Adults, adolescents, and children ≥5 years old who are HIV status negative and LTBI positive (by IGRA) 3. Adults and adolescents ≥15 years of age who are living with HIV regardless of LTBI status, regardless of whether they are a CC 3HP: 3 months of weekly isoniazid (H) and rifapentine (P) (12 doses)

Also known as: 3HP

3HP

Levofloxacin DRUG

CCs of RR-TB Index Patients at high risk of developing TBD 1. Children 0 to \<5 years old, regardless of HIV status or LTBI result (by TST or IGRA) 2. Adults, adolescents, and children ≥5 years old who are HIV status negative and LTBI positive (by IGRA) 3. Adults, pregnant people, adolescents, and children ≥5 years old who are living with HIV regardless of LTBI status Levofloxacin (LFX) based on weight at Enrollment daily for 6 months (182 doses)

Also known as: Levaquin

Levofloxacin

Eligibility Criteria

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

You may qualify if:

• For Index Patient
• Any age
• A diagnosis of bacteriologically proven pulmonary TB
• Initiated on treatment for pulmonary TB within the past 90 days
• Have at least one close contact that is likely to be eligible for the study
• For PLHIV Indication
• On a dolutegravir-based or other approved integrase inhibitor antiretroviral therapy (ART) regimen that does not interact with bedaquiline or rifapentine.
• If on a protease inhibitor-based ART regimen, a participant can be enrolled following a 5-day washout with switch to a dolutegravir-based regimen prior to enrollment. A 14-day washout is required for efavirenz-based ART regimen with switch to a dolutegravir-based regimen prior to enrollment
• If a participant is not currently on ART or is ART-naïve, the participant must have started a dolutegravir-based ART regimen prior to Enrollment.
• PLHIV who meet criteria for a TBD close contact should be enrolled under the close contact indication
• For Close Contact Indication (DS- or RR-TB Index Patient)
• Definition of Close Contact (either/or):
• o Lives or lived in the same dwelling unit or plot of land and shares or has shared the same housekeeping arrangements as the Index Patient for one or more nights ≤ 90 days prior to the Index Patient starting TB treatment
• o Has shared more than four hours of indoor airspace with the Index Patient during any one-week period ≤ 90 days prior to the Index Patient starting TB treatment. This may include indoor airspace within or outside the home.
• Close contacts must be in one of the following high-risk groups:

You may not qualify if:

• A. Unwilling or unable to provide informed consent
• B. Weight ≤ 3 kg
• C. A current diagnosis of confirmed or probable or possible pulmonary or extrapulmonary TB at time of enrollment or confirmed or unconfirmed TB for children.
• D. Previously completed treatment for TBD.
• E. Prior completion of TPT (including but not limited to 6 or 9H, 1HP, 3HP, 4R, 3HR, 6Lfx) \*
• \*NOTE: Completion of TBD treatment or TPT based on the opinion of the site investigator that a sufficient course of TPT was taken to constitute treatment completion
• F. Current enrollment into another therapeutic clinical trial (See Section 5.8).
• G. Any of the following medical conditions:
• Severe renal impairment (DAIDS Grade 4) or end-stage renal disease requiring hemodialysis or peritoneal dialysis
• Severe hepatic impairment (Child-Pugh C)
• Evidence of acute hepatitis, such as abdominal pain, jaundice, dark urine, and/or light stools within 90 days prior to enrollment
• Severe cardiac arrythmia requiring medication
• Peripheral neuropathy ≥ Grade 2 (DAIDS)
• Diagnosis of porphyria at any time prior to study enrollment
• Corrected QTcF (Fridericia's formula) of \>460 msec

Sponsors & Collaborators

• Johns Hopkins University: lead
• Elizabeth Glaser Pediatric AIDS Foundation: collaborator
• US Department of State: collaborator

Study Sites (6)

HNSEB (Hospital Nacional Sergio E. Bernales)

Lima, Peru

NOT YET RECRUITING

SES Policlinico

Lima, Peru

NOT YET RECRUITING

Kilimanjaro Clinical Research Institute

Moshi, Tanzania

RECRUITING

Joint Clinical Research Centre

Kampala, Uganda

RECRUITING

Makerere Lung Institute

Kampala, Uganda

NOT YET RECRUITING

MU-JHU Care Ltd.

Kampala, Uganda

RECRUITING

MeSH Terms

Conditions

Latent Tuberculosis

Interventions

bedaquiline; Isoniazid; rifapentine; Levofloxacin

Condition Hierarchy (Ancestors)

Tuberculosis; 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; Ofloxacin; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Eric Nuermberger, MD

  Johns Hopkins School of Medicine

  STUDY CHAIR

Central Study Contacts

Bonnie S. King, MHS

CONTACT

4106249189; bking6@jh.edu

Kate Boehner, RN, MSN

CONTACT

2012592222; kate.b@jhu.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: An independent Endpoint Review Committee (ERC), masked to study arm, will adjudicate the incident TB endpoints (both primary and secondary) and, if there are any deaths, determine the cause of death as TB-related or not TB-related.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A seamless, staged, Phase II/III, open-label, multicenter, noninferiority trial to compare the efficacy and safety of 4 weeks of oral bedaquiline (1BDQ) versus a standard regimen for preventing confirmed or probable tuberculosis disease (TBD) during 72 weeks of follow-up among people living with HIV (PLHIV) and high-risk Close Contacts (CC) of Index Patients with Drug-Susceptible (DS) or Rifampin-Resistant (RR) TB. CCs that are also household contacts will be cluster-randomized by household. The study will be divided into two stages, with a seamless transition between stages, meaning enrollment into Stage 2 will start while Stage 1 outcomes analyses are ongoing. All recruited patients will be followed up to 72 weeks post randomization.

Study Record Dates

• First Submitted: August 21, 2024
• First Posted: August 23, 2024
• Study Start: May 8, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: June 3, 2026

Record last verified: 2026-06

Data Sharing

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

Locations

UG (3); PE (2); TA (1)