Bedaquiline Enhanced Post ExpOsure Prophylaxis for Leprosy (Phase 2)

NCT05406479 | Completed Phase 2 Results DMC

• 1 other identifier: BE-PEOPLE Phase 2
• Study Type: interventional
• Target: 313
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate a combination of bedaquiline and rifampicin as post exposure prophylaxis (PEP) for leprosy in Comoros. It will be a follow-up to the PEOPLE trial on PEP with rifampicin, which is ending in 2022. This new trial will be called the 'Bedaquiline Enhanced Post ExpOsure Prophylaxis for Leprosy' or 'BE-PEOPLE' trial. There will be two main study arms, a comparator arm based on the current WHO recommendation of providing a single dose of rifampicin (10 mg/kg) to close contacts of leprosy patients and an intervention arm in which this regimen will be reinforced with bedaquiline, 400 or 800 mg depending on weight, to be repeated once after four weeks for household contacts. The main study will be preceded by a phase 2 safety study.

Conditions

Leprosy

Outcome Measures

Primary Outcomes (2)

• Mean Difference in QTc Interval Between the Two Arms 24 Hours After Treatment Administration

  Mean difference in QTc interval between the two arms 24 hours after treatment administration. Difference (BE-PEP - SDR-PEP)

  24 hours after treatment administration

• Occurence of Any Predetermined Study Stopping Criteria, Which Will Trigger an Immediate Pause on Enrollment

  Occurence of any of the following predetermined study stopping criteria, which will trigger an immediate pause on enrollment: 1. Death of a participant considered related to study drug 2. One or more participants experience an Serious Adverse Event (SAE) or Grade 4 Adverse Event (AE) or a persistent (upon repeat testing) Grade 4 laboratory abnormality that is determined to be related to study drug 3. Three or more participants experience a Grade 3 or greater AE of the same type (as per medical judgement) that is determined to be related to study drug 4. Three or more participants experience a persistent (upon repeat testing) Grade 3 laboratory abnormality related to the same laboratory parameter and considered to be related to study drug 5. Two or more participants experience QTc \> 500 ms 6. One or more participants has Aspartate transaminase (AST) or Alanine transaminase (ALT) \> 8x Upper limit of normal (ULN), in absence of causative explanation

  Until day 30 after treatment administration

Study Arms (2)

BE-PEP (Bedaquiline Post-Exposure Prophylaxis)

EXPERIMENTAL

Eligible participants will receive one dose of Bedaquiline plus Rifampicin

Drug: BE-PEP (Bedaquiline); Drug: BE-PEP (Rifampicine)

SDR-PEP (Single-Dose Rifampicin Post-Exposure Prophylaxis)

ACTIVE COMPARATOR

Eligible participants will receive one dose of Rifampicin (WHO recommendation)

Drug: SDR-PEP

Interventions

BE-PEP (Bedaquiline) DRUG

Single dose of Bedaquiline

BE-PEP (Bedaquiline Post-Exposure Prophylaxis)

SDR-PEP DRUG

Single dose of Rifampicin

SDR-PEP (Single-Dose Rifampicin Post-Exposure Prophylaxis)

BE-PEP (Rifampicine) DRUG

Single dose of Rifampicin

BE-PEP (Bedaquiline Post-Exposure Prophylaxis)

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Being a permanent resident of the study village, in good state of health
• Able and willing to provide informed consent
• Age 5 years or above and weight of 20 kg or above

You may not qualify if:

• Signs of active leprosy
• Signs of active pulmonary tuberculosis (cough ≥2 weeks duration)
• Signs of active extra-pulmonary tuberculosis (bluish-red nodules that cover the lymph nodes, bones or joints, or cervical glands with discharge)
• History of liver- or kidney disease
• Allergy to rifampicin or bedaquiline
• Having received rifampicin or bedaquiline (if applicable) in the last 2-year period
• Not able to swallow bedaquiline 100 mg tablets
• Self-reported (suspected) pregnancy or breastfeeding
• Concurrent (within the last three week period before D0) use of medications not included in the safe list (for bedaquiline only)
• QT-prolongation of ≥450 msec in baseline ECG within the last week.
• Jaundice or self-reported liver function abnormalities or hepatitis
• Value of baseline ALT or AST \>3x ULN within the last week. In case only ALT is available, this would suffice for enrollment

Sponsors & Collaborators

• Institute of Tropical Medicine, Belgium: lead
• Damien Foundation: collaborator

Study Sites (1)

Fondation Damien

Gege, Ndzuwani, Comoros

Location

Related Publications (1)

• de Jong BC, Nourdine S, Bergeman AT, Salim Z, Grillone SH, Braet SM, Wirdane Abdou M, Snijders R, Ronse M, Hoof C, Tsoumanis A, Ortuno-Gutierrez N, der Werf CV, Piubello A, Mzembaba A, Assoumani Y, Hasker E. Safety of single-dose bedaquiline combined with rifampicin for leprosy post-exposure prophylaxis: A Phase 2 randomized non-inferiority trial in the Comoros Islands. PLoS Med. 2024 Oct 21;21(10):e1004453. doi: 10.1371/journal.pmed.1004453. eCollection 2024 Oct.

  PMID: 39432509 DERIVED

MeSH Terms

Conditions

Leprosy

Interventions

bedaquiline; Rifampin

Condition Hierarchy (Ancestors)

Mycobacterium Infections, Nontuberculous; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Carolien Hoof
• Organization: Insitute of Tropical Medicine

choof@itg.be

+32470102562

Study Officials

• Younoussa Assoumani

  Damien Foundation Comoros

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: May 20, 2022
• First Posted: June 6, 2022
• Study Start: July 14, 2022
• Primary Completion: January 26, 2023
• Study Completion: January 26, 2023
• Last Updated: August 28, 2024
• Results First Posted: August 28, 2024

Record last verified: 2024-08

Locations

CO (1)