Bedaquiline Enhanced Post ExpOsure Prophylaxis for Leprosy (Phase 2)

NCT ID: NCT05406479

Last Updated: 2024-08-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 313 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-07-14
• Study Completion Date: 2023-01-26

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.

Detailed Description

Given the fact that the investigators are going to provide to healthy people a drug that has not been used before for this indication and which has only been conditionally approved for use in multi-drug resistant tuberculosis, they have first foreseen a phase 2 study in which BE-PEP will be provided to a limited number of contacts and in which safety will be closely monitored and evaluated by an independent data and safety monitoring board (DSMB). This will be done in a small village that is part arm 1 of the PEOPLE trial in which 8 new cases have been diagnosed since 2019 but no PEP has been provided. The investigators will conduct door-to-door screening in this village in June 2022 and offer a single dose of BE-PEP to a random sample of 150 people screened aged 5 years and above not meeting the exclusion criteria (active tuberculosis (TB) or leprosy or previously treated leprosy, known liver function or cardiac abnormalities, not able to swallow 100 mg bedaquiline tablets). Participants will be followed up closely with active monitoring for adverse events, including measurement of the corrected QT interval and liver function before and after administration, as well as gastro-intestinal (nausea, vomiting), nervous system-related (headache, dizziness) and cutaneous reactions. The remainder of the population of this village aged two years and above will be offered single dose rifampicin as per WHO recommendations. In a randomly sampled subset of 150 individuals receiving rifampicin only, the same stringent monitoring with ECG and liver function tests also applied in those receiving BE-PEP will be performed.

Conditions

Leprosy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

BE-PEP (Bedaquiline Post-Exposure Prophylaxis)

Eligible participants will receive one dose of Bedaquiline plus Rifampicin

Group Type: EXPERIMENTAL

BE-PEP (Bedaquiline)

Intervention Type: DRUG

Single dose of Bedaquiline

BE-PEP (Rifampicine)

Intervention Type: DRUG

Single dose of Rifampicin

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

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

Group Type: ACTIVE_COMPARATOR

SDR-PEP

Intervention Type: DRUG

Single dose of Rifampicin

Interventions

BE-PEP (Bedaquiline)

Single dose of Bedaquiline

Intervention Type: DRUG

SDR-PEP

Single dose of Rifampicin

Intervention Type: DRUG

BE-PEP (Rifampicine)

Single dose of Rifampicin

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Being a permanent resident of the study village, in good state of health

2. Able and willing to provide informed consent

3. Age 5 years or above and weight of 20 kg or above

Exclusion Criteria

1. Signs of active leprosy

2. Signs of active pulmonary tuberculosis (cough ≥2 weeks duration)

3. Signs of active extra-pulmonary tuberculosis (bluish-red nodules that cover the lymph nodes, bones or joints, or cervical glands with discharge)

4. History of liver- or kidney disease

5. Allergy to rifampicin or bedaquiline

6. Having received rifampicin or bedaquiline (if applicable) in the last 2-year period

7. Not able to swallow bedaquiline 100 mg tablets

8. Self-reported (suspected) pregnancy or breastfeeding

9. Concurrent (within the last three week period before D0) use of medications not included in the safe list (for bedaquiline only)

10. QT-prolongation of ≥450 msec in baseline ECG within the last week.

11. Jaundice or self-reported liver function abnormalities or hepatitis

12. Value of baseline ALT or AST >3x ULN within the last week. In case only ALT is available, this would suffice for enrollment

• Minimum Eligible Age: 5 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Damien Foundation

OTHER

Sponsor Role: collaborator

Institute of Tropical Medicine, Belgium

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Younoussa Assoumani

Role: PRINCIPAL_INVESTIGATOR

Damien Foundation Comoros

Locations

Fondation Damien

Gege, Ndzuwani, Comoros

Countries

Comoros

References

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.

Reference Type: DERIVED

PMID: 39432509 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

BE-PEOPLE Phase 2

Identifier Type: -

Identifier Source: org_study_id