A Study to Evaluate the Efficacy and Safety of Bedaquiline (TMC207) in Participants With Multibacillary Leprosy

An Open-Label Study to Evaluate the Efficacy and Safety of TMC207 in Subjects With Multibacillary Leprosy

The purpose of this study is to assess the efficacy of an 8-week bedaquiline monotherapy regimen in participants with treatment-naive, multibacillary (MB) leprosy.

Study Overview

• Status: Completed
• Conditions: Leprosy, Multibacillary
• Intervention / Treatment: Drug: Bedaquiline 200 mg

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Bauru, Brazil, 17034-971
    • Instituto Lauro de Souza Lima
  • Manaus, Brazil, 69065-130
    • Fundacao Hospitalar de Dermatologia Tropical e Venereologia Alfredo da Matta - FUHAM

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant has: a) multibacillary (MB) leprosy, defined as 6 or more skin lesions or extensive confluent lesions or diffuse skin involvement, and is either borderline lepromatous or polar lepromatous, as determined using Ridley and Jopling classification system; and b) has a bacteriological index of >=4+ from the lesion biopsy obtained at screening, and a bacteriological index of >= 1+ from each of 4 slit skin smear assessments taken at screening
• Otherwise healthy on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening. If there are abnormalities, they must be consistent with the underlying illness in the study population. This determination must be recorded in the participant's source documents and initialed by the investigator
• Otherwise healthy on the basis of clinical laboratory tests performed at screening. If the results of the serum chemistry panel, including liver enzymes, other specific tests, blood coagulation, hematology, or urinalysis are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study. This determination must be recorded in the participant's source documents and initialed by the investigator
• a man must agree not to donate sperm throughout treatment with TMC207 and for 3 months after treatment is stopped
• Willing and able to adhere to the prohibitions, restrictions, and long-term follow up requirements specified in this protocol
• If a woman is of childbearing potential, must be practising a highly effective method of birth control (failure rate of <1% per year when used consistently and correctly) before entry, and must also agree to use a barrier contraceptive method (that is, male or female condom, diaphragm or cervical cap) plus spermicide. participant must also agree to continue to use a highly effective method of contraception plus a barrier method throughout treatment with TMC207 and until 6 months after treatment is stopped

Exclusion Criteria:

• Has experienced or is experiencing a lepra reaction requiring treatment with a prohibited therapy
• Has a contraindication limiting the implementation of a medically accepted MB leprosy regimen
• a) Has ever received pharmacotherapy for leprosy; b) has ever been treated with a drug that is a component of the primary World Health Organization (WHO) regimen for the treatment of MB leprosy (example, dapsone, rifampicin, clofazimine). Short-term (<=2 weeks) pharmacotherapy with any antibiotic that could be used as a second line treatment for leprosy (eg, of the macrolide, quinolone, or tetracycline class) is acceptable as long as the last administration occurred >=4 weeks before first dose of study drug (TMC207)
• Has a concomitant infection that requires an additional systemic antimicrobial agent
• Has tuberculosis (TB), as determined by medical history and chest x-ray
• Is a woman who is pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study or within 6 months after the last dose of study drug

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bedaquiline; Participants will receive bedaquiline 200 (milligram) mg (2*100 mg tablets) once daily for 2 weeks followed by 100 mg tablet three times a week (tiw) for 6 weeks with at least 48 hours between doses.	Drug: Bedaquiline 200 mg; Participants will receive bedaquiline 200 mg (2*100 mg tablets) once daily for 2 weeks followed by 100 mg tablet tiw for 6 weeks with at least 48 hours between doses.; Other Names: TMC207

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in the Odds of Mycobacterium leprae (M. leprae) Growth in Mouse Footpads Following 8 Weeks of Treatment with Bedaquiline	Change from baseline in the odds of M. leprae growth in mouse footpads will be evaluated. M. leprae bacilli will be inoculated in footpads of mice, according to the method of Shepard. M. leprae growth will be determined by technologists trained and experienced in mouse footpad procedures, at 1 year after infection (or at mouse death or humane endpoint, if it occurs greater than or equal to [>=] 6 months after footpad inoculation). The number of footpads with positive growth (>=10^5 M. leprae) will be counted and used to determine the odds of bacterial growth.	Baseline up to Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events (AEs)	An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	Up to 124 Weeks
Number of Participants with AEs by Severity	Severity of adverse events will be graded by using division of microbiology and infectious diseases (DMID) adult toxicity scale to estimate grade of severity. Severity scale ranges from Grade 1 (Mild) to Grade 4 (Life-threatening). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, and Grade 4= Life-threatening.	Up to 124 Weeks

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2018
• Primary Completion (Actual): January 13, 2023
• Study Completion (Actual): January 9, 2024

Study Registration Dates

• First Submitted: December 20, 2017
• First Submitted That Met QC Criteria: December 20, 2017
• First Posted (Actual): December 27, 2017

Study Record Updates

• Last Update Posted (Estimated): February 2, 2024
• Last Update Submitted That Met QC Criteria: February 1, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Leprosy; Leprosy, Multibacillary; Anti-Infective Agents; Anti-Bacterial Agents; Antitubercular Agents; Bedaquiline
• Other Study ID Numbers: CR108416; TMC207LEP2001 (Other Identifier: Janssen Research & Development, LLC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No