Clinical trial NCT05406479: Bedaquiline Enhanced Post ExpOsure Prophylaxis for Leprosy (Phase 2)
Official title: Bedaquiline Enhanced Post ExpOsure Prophylaxis for Leprosy: Phase 2 Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leprosy
Lead sponsor: Institute of Tropical Medicine, Belgium
Sponsor class: OTHER
Collaborators: name: Damien Foundation
First posted: 2022-06-06
Enrollment: 313
Sex: ALL
Minimum age (years): 5
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Mean Difference in QTc Interval Between the Two Arms 24 Hours After Treatment Administration
timeFrame: 24 hours after treatment administration
measure: Occurence of Any Predetermined Study Stopping Criteria, Which Will Trigger an Immediate Pause on Enrollment
timeFrame: Until day 30 after treatment administration
Secondary outcomes:
Other outcomes:
Locations:
city: Gege
country: Comoros
facility: Fondation Damien
state: Anjouan
Study officials:
affiliation: Damien Foundation Comoros
name: Younoussa Assoumani
role: PRINCIPAL_INVESTIGATOR
References: