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

NCT ID: NCT06568484

Last Updated: 2025-12-12

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 2530 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-02-28
• Study Completion Date: 2027-09-30

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.

Detailed Description

Treating adult, adolescent, child, and pregnant close contacts (CCs) of drug-sensitive tuberculosis (DS-TB) who are high-risk for developing tuberculosis disease (TBD) as well as adult and adolescent people living with HIV (PLHIV) in high-tuberculosis burden regions with bedaquiline (BDQ) will be noninferior in reducing the risk of developing TBD compared with a WHO-recommended rifamycin-containing short-course regimen for TB preventive therapy (TPT).

Treating adult, adolescent, child, and pregnant CCs of rifampin-resistant tuberculosis (RR-TB) who are high-risk for developing TBD with BDQ will be noninferior in reducing the risk of developing TBD compared with levofloxacin.

Conditions

Tuberculosis, Latent

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

Bedaquiline

4 weeks of daily bedaquiline

Group Type: EXPERIMENTAL

Bedaquiline

Intervention Type: 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)

3HP

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

Group Type: ACTIVE_COMPARATOR

Isoniazid, rifapentine

Intervention Type: 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)

Levofloxacin

6 months of daily levofloxacin

Group Type: ACTIVE_COMPARATOR

Levofloxacin

Intervention Type: 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)

Interventions

Bedaquiline

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)

Intervention Type: DRUG

Isoniazid, rifapentine

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)

Intervention Type: COMBINATION_PRODUCT

Levofloxacin

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)

Intervention Type: DRUG

Other Intervention Names

Sirturo; 3HP; Levaquin

Eligibility Criteria

Inclusion Criteria

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:

• All children 0 to <5 years old at the time of Enrollment, regardless of LTBI or HIV status
• Adults, adolescents, and children ≥5 years of age who are TBI test positive (either skin test positive* or IGRA-positive) and whose HIV status is negative, indeterminate, or unknown.
• Adults, adolescents, and children ≥5 years of age who have a documented HIV infection regardless of TBI test status.

A. Ability and willingness of participant (and/or parent/guardian) to provide informed consent (and assent, as applicable)

B. Documentation of HIV Status

For participants >=18 months of age known to be PLHIV:

• Certified copy of HIV clinic card or
• Certified copy of HIV testing that includes date, assay used and result

For participants <18 months of age who have never tested, or previous HIV test result was indeterminate, unknown, or negative more than three months prior to screening and/or result is not available:

• HIV-1 testing should be performed per Section 5.4.5 (HIV-1 Testing) during the study screen period.

For participants <18 months known to be CLHIV:

• Certified copies of HIV DNA and/or RNA testing that includes date, assay used, and result

For participants <18 months who have never tested, or previous HIV test result was indeterminate, unknown, or negative more than three months prior to screening and/or result is not available:

• HIV-1 testing should be performed per Section 5.4.5 (HIV-1 Testing) during the study screen period

C. Documentation of ART

• All PLHIV (for PLHIV indication and CC that are PLHIV) must be on a dolutegravir-based or other approved integrase inhibitor 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, they must have started a dolutegravir-based ART regimen prior to Enrollment.

D. Chest radiograph without evidence of active TBD, performed within 30 days prior to Enrollment

E. The following laboratory values obtained within 30 days prior to Enrollment.

• Alanine aminotransferase (ALT) ≤ 3 times the upper limit of normal
• Total bilirubin ≤ 2.5 times the upper limit of normal
• Alkaline phosphatase ≤ 3 times the upper limit of normal
• Creatinine clearance ≥ 29 ml/min
• Serum potassium at or above the lower limit of normal
• Serum magnesium at or above the lower limit of normal
• Serum calcium at or above the lower limit of normal
• Platelet count of ≥ 50,000 /mm3
• Absolute neutrophil count (ANC) ≥ 1,000/mm3

F. Pregnancy test (for study candidates of childbearing potential*)

• Negative serum or urine pregnancy test within 7 days prior to enrollment.

*NOTE: Participants of childbearing potential are defined as females who have reached menarche or who have not been post-menopausal for at least 24 consecutive months (i.e., who have had menses within the preceding 24 months) or have not undergone surgical sterilization (e.g., hysterectomy, bilateral oophorectomy, or bilateral tubal ligation).

Exclusion Criteria

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
• Unable to take oral medication
• Active drug or alcohol use or dependence that, in the site investigator's opinion, would interfere with adherence to study treatment.
• Serious illness requiring systemic treatment including parenteral therapy (e.g., antibiotics) and/or hospitalization within 30 days prior to Enrollment
• Prior exposure to bedaquiline or clofazimine
• Receipt of more than 7 cumulative days of isoniazid, a rifamycin, or a fluoroquinolone in the 90 days prior to enrollment
• Known bedaquiline resistance in Index Patient
• Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulation
• Currently taking another medication that is prohibited with study medicines which cannot be stopped (with or without replacement) or requires a washout period longer than 14 days (See Appendix 7)
• Known pregnancy or breastfeeding

• Known fluoroquinolone resistance in Index Patient
• Severe tendinopathy related to fluoroquinolones

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Elizabeth Glaser Pediatric AIDS Foundation

OTHER

Sponsor Role: collaborator

US Department of State

UNKNOWN

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Eric Nuermberger, MD

Role: STUDY_CHAIR

Johns Hopkins School of Medicine

Locations

HNSEB (Hospital Nacional Sergio E. Bernales)

Lima, , Peru

SES Policlinico

Lima, , Peru

Kilimanjaro Clinical Research Institute

Moshi, , Tanzania

Joint Clinical Research Centre

Kampala, , Uganda

Makerere Lung Institute

Kampala, , Uganda

MU-JHU Care Ltd.

Kampala, , Uganda

Countries

Peru; Tanzania; Uganda

Central Contacts

Bonnie S. King, MHS

Role: CONTACT

bking6@jh.edu

4106249189

Kate Boehner, RN, MSN

Role: CONTACT

kate.b@jhu.edu

2012592222

Facility Contacts

Program Manager Director

Role: primary

SESCRO@pih.org

Program Manager Director

Role: primary

SESCRO@pih.org

Director

Role: primary

blaymt@gmail.com

Deputy Director of Research

Role: primary

pamuge@jcrc.org.ug

Co-Investigator

Role: primary

jmukwaba@gmail.com

Site Leader

Role: primary

cnakabiito@mujhu.org

Other Identifiers

7200AA22CA00005

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

IRB00443418

Identifier Type: -

Identifier Source: org_study_id