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

NCT03384641 | Completed Phase 2

• 2 other identifiers: CR108416TMC207LEP2001
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Leprosy, Multibacillary

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Number of Participants with Adverse Events (AEs)

  Up to 124 Weeks

• Number of Participants with AEs by Severity

  Up to 124 Weeks

Study Arms (1)

Bedaquiline

EXPERIMENTAL

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

Interventions

Bedaquiline 200 mg DRUG

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.

Also known as: TMC207

Bedaquiline

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (2)

Instituto Lauro de Souza Lima

Bauru, 17034-971, Brazil

Location

Fundacao Hospitalar de Dermatologia Tropical e Venereologia Alfredo da Matta - FUHAM

Manaus, 69065-130, Brazil

Location

Related Publications (1)

• Barreto J, Sammarco Rosa P, Adams L, Aguilar Z, Bakare N, Chaplan SR, Akli RD, Ernault E, Kulke S, Lounis N, Millington D, Palmer JA, Remmerie B, Wang M, Young S, Truman R, Rebello PFB. Bedaquiline Monotherapy for Multibacillary Leprosy. N Engl J Med. 2024 Dec 12;391(23):2212-2218. doi: 10.1056/NEJMoa2312928.

  PMID: 39665652 DERIVED

MeSH Terms

Conditions

Leprosy, Multibacillary

Interventions

bedaquiline

Condition Hierarchy (Ancestors)

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

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2017
• First Posted: December 27, 2017
• Study Start: September 26, 2018
• Primary Completion: January 13, 2023
• Study Completion: January 9, 2024
• Last Updated: February 2, 2024

Record last verified: 2024-02

Locations

BR (2)