## Protocol Section
### Identification Module
**NCT ID:** NCT05406479

**Acronym:** BE-PEOPLE P2

**Brief Title:** Bedaquiline Enhanced Post ExpOsure Prophylaxis for Leprosy (Phase 2)

**Official Title:** Bedaquiline Enhanced Post ExpOsure Prophylaxis for Leprosy: Phase 2 Study

#### Organization Study ID Info
**ID:** BE-PEOPLE Phase 2
#### Organization
**Class:** OTHER
**Full Name:** Institute of Tropical Medicine, Belgium
### Status Module
#### Completion Date
**Date:** 2023-01-26

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2023-06-12

**Type:** ACTUAL

**Last Update Submit Date:** 2023-06-07

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2023-01-26

**Type:** ACTUAL

#### Start Date
**Date:** 2022-07-14

**Type:** ACTUAL

**Status Verified Date:** 2023-06

#### Study First Post Date
**Date:** 2022-06-06
**Type:** ACTUAL
**Study First Submit Date:** 2022-05-20
**Study First Submit QC Date:** 2022-06-02
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** Damien Foundation

#### Lead Sponsor

**Class:** OTHER

**Name:** Institute of Tropical Medicine, Belgium

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** True

### Description Module

**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 Module

**Conditions:**

- Leprosy

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** PREVENTION

#### Enrollment Info

**Count:** 321

**Type:** ACTUAL

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Eligible participants will receive one dose of Bedaquiline plus Rifampicin

**Intervention Names:**

- Drug: BE-PEP (Bedaquiline)

- Drug: BE-PEP (Rifampicine)

**Label:** BE-PEP (Bedaquiline Post-Exposure Prophylaxis)

**Type:** EXPERIMENTAL

#### Arm Group 2

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

**Intervention Names:**

- Drug: SDR-PEP

**Label:** SDR-PEP (Single-Dose Rifampicin Post-Exposure Prophylaxis)

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- BE-PEP (Bedaquiline Post-Exposure Prophylaxis)

**Description:** Single dose of Bedaquiline

**Name:** BE-PEP (Bedaquiline)

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

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

**Description:** Single dose of Rifampicin

**Name:** SDR-PEP

**Type:** DRUG

#### Intervention 3

**Arm Group Labels:**

- BE-PEP (Bedaquiline Post-Exposure Prophylaxis)

**Description:** Single dose of Rifampicin

**Name:** BE-PEP (Rifampicine)

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Mean difference in QTc interval between the two arms 24 hours after treatment administration

**Measure:** Mean difference in QTc interval between the two arms 24 hours after treatment administration

**Time Frame:** 24 hours after treatment administration

**Description:** 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

**Measure:** Occurence of any predetermined study stopping criteria, which will trigger an immediate pause on enrollment

**Time Frame:** Until day 30 after treatment administration

#### Secondary Outcomes

**Description:** To determine the baseline frequency of ALT in the population.

**Measure:** Baseline frequency of ALT in the population

**Time Frame:** At baseline

**Description:** To determine baseline frequency of AST elevations in the population

**Measure:** Baseline frequency of AST elevations in the population

**Time Frame:** At baseline

**Description:** To determine baseline frequency of QTc prolongations in the population

**Measure:** Baseline frequency of QTc prolongations in the population

**Time Frame:** At baseline

**Description:** Post administration QTc prolongation

**Measure:** Post administration QTc prolongation

**Time Frame:** 24 hours after treatment administration

**Description:** Post administration ALT level

**Measure:** Post-administration ALT level

**Time Frame:** Day 14 after treatment administration

**Description:** Post-administration AST level

**Measure:** Post-administration AST level

**Time Frame:** Day 14 after treatment administration

**Description:** Frequency of potentially common adverse events such as gastro-intestinal (nausea, vomiting), nervous system-related (headache, dizziness) and cutaneous reactions

**Measure:** Frequency of potentially common adverse events such as gastro-intestinal (nausea, vomiting), nervous system-related (headache, dizziness) and cutaneous reactions

**Time Frame:** Until day 30 after treatment administration

**Description:** Occurrence of any (serious)AEs

**Measure:** Occurrence of any (serious)AEs

**Time Frame:** Until day 30 after treatment administration

### Eligibility Module

**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

**Healthy Volunteers:** True

**Minimum Age:** 5 Years

**Sex:** ALL

**Standard Ages:**

- CHILD

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Gege

**Country:** Comoros

**Facility:** Fondation Damien

**State:** Anjouan

#### Overall Officials

**Official 1:**

**Affiliation:** Damien Foundation Comoros

**Name:** Younoussa Assoumani

**Role:** PRINCIPAL_INVESTIGATOR

## Document Section

### Large Document Module

#### Large Docs

- Date: 2023-03-01

- Filename: Prot_000.pdf

- Has ICF: False

- Has Protocol: True

- Has SAP: False

- Label: Study Protocol

- Size: 1039718

- Type Abbrev: Prot

- Upload Date: 2023-06-07T08:11

## Annotation Section

### Unposted Annotation

#### Event: RELEASE

- Date: 2023-07-18

- Date Unknown: Unknown

#### Event: RESET

- Date: 2024-02-22

- Date Unknown: Unknown

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009165

- Term: Mycobacterium Infections, Nontuberculous

- ID: D000009164

- Term: Mycobacterium Infections

- ID: D000000193

- Term: Actinomycetales Infections

- ID: D000016908

- Term: Gram-Positive Bacterial Infections

- ID: D000001424

- Term: Bacterial Infections

- ID: D000001423

- Term: Bacterial Infections and Mycoses

- ID: D000007239

- Term: Infections

### Condition Browse Module - Browse Branches

- Abbrev: BC01

- Name: Infections

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M10930

- Name: Leprosy

- Relevance: HIGH

- As Found: Leprosy

- ID: M10283

- Name: Infections

- Relevance: LOW

- As Found: Unknown

- ID: M6368

- Name: Communicable Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12119

- Name: Mycobacterium Infections

- Relevance: LOW

- As Found: Unknown

- ID: M12120

- Name: Mycobacterium Infections, Nontuberculous

- Relevance: LOW

- As Found: Unknown

- ID: M4722

- Name: Bacterial Infections

- Relevance: LOW

- As Found: Unknown

- ID: M19252

- Name: Gram-Positive Bacterial Infections

- Relevance: LOW

- As Found: Unknown

- ID: M12136

- Name: Mycoses

- Relevance: LOW

- As Found: Unknown

- ID: M4721

- Name: Bacterial Infections and Mycoses

- Relevance: LOW

- As Found: Unknown

- ID: T2664

- Name: Hansen's Disease

- Relevance: HIGH

- As Found: Leprosy

### Condition Browse Module - Meshes

- ID: D000007918

- Term: Leprosy

### Intervention Browse Module - Ancestors

- ID: D000000995

- Term: Antitubercular Agents

- ID: D000000900

- Term: Anti-Bacterial Agents

- ID: D000000890

- Term: Anti-Infective Agents

### Intervention Browse Module - Browse Branches

- Abbrev: Infe

- Name: Anti-Infective Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M15118

- Name: Rifampin

- Relevance: LOW

- As Found: Unknown

- ID: M341494

- Name: Bedaquiline

- Relevance: HIGH

- As Found: 115

- ID: M4311

- Name: Antitubercular Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4222

- Name: Anti-Bacterial Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4214

- Name: Anti-Infective Agents

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: C000493870

- Term: Bedaquiline

### Misc Info Module

#### Submission Tracking

- Estimated Results First Submit Date: 2023-07-18

##### Submission Infos

- MCP Release N: Unknown

- Release Date: 2023-07-18

- Reset Date: 2024-02-22

- Unrelease Date: Unknown

- Unrelease Date Unknown: Unknown

- MCP Release N: Unknown

- Release Date: 2024-03-12

- Reset Date: Unknown

- Unrelease Date: Unknown

- Unrelease Date Unknown: Unknown

- Version Holder: 2024-05-24
