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Telacebec (T) Treatment in Adults With Buruli Ulcer (BU).

Phase 2
Active, not recruiting
Conditions
Buruli Ulcer
Interventions
Registration Number
NCT06481163
Lead Sponsor
Barwon Health
Brief Summary

The goal of this interventional clinical trial is to determine if treatment with 4 weeks of telacebac (T) will completely heal lesions in participants with Buruli ulcer (BU) by 52 weeks after treatment initiation, without relapse and/or surgery. Males and females age 18 and older will be included.

* Participants will attend visits every week during treatment (4 weeks)

* Thereafter they will be followed every 2 weeks until week 24 followed by visits as weeks 30, 40 and 52.

* Dependent on site requirements, there may be follow up visits on site or remotely.

Detailed Description

This is an open label single arm (telacebec), multi-centre, clinical trial. Eligible participants with clinically diagnosed World Health Organization (WHO) category I lesions and category II lesions ≤10 cm cross-sectional diameter and category III lesions where multiple and all lesions are ≤10 cm cross-sectional diameter, confirmed by polymerase chain reaction (PCR) or culture for presence of Mycobacterium ulcerans infection, will receive telacebec 300 mg orally once daily for 28 days with food.

Participants who meet entry criteria and give consent will attend a baseline enrolment visit (Day 1), then visits every week for 4 weeks during treatment (weeks 1, 2, 3 and 4). Thereafter they will be followed up every 2 weeks until week 24, followed by visits at weeks 30, 40, and 52.

BU lesion management will be provided to all trial participants. In case of participant early withdrawal from the trial during or after the treatment period, participants will be treated per the investigational site and/or country BU treatment guidelines.

A Data Review Committee (DRC) will be established to review efficacy and safety data. Enrolment and enrolled participants will continue the study whilst the DRC reviews are ongoing.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
40
Inclusion Criteria
  • Clinical diagnosis of BU WHO categories, single or multiples:

    1. I
    2. II with a cross-sectional diameter < 10 cm
    3. III category III lesions where multiple and all are < 10 cm cross-sectional diameter
  • Positive PCR or culture for confirmation of presence of mycobacterium ulcerans (MU).

Major

Exclusion Criteria
  • Participants with the following known or suspected medical conditions:

    1. Any non BU related condition where participation in the study, as judged by the Investigator, could compromise the well-being of the participant or prevent, limit or confound protocol specified treatment and assessments.
    2. History or current ascites, jaundice, myasthenia gravis, clinically significant renal dysfunction [estimated glomerular filtration rate (eGFR) < 50 mls/min], uncontrolled diabetes mellitus [glycated heaemoglobin (HbA1C )> 10%], and severe immune compromise (e.g., immunosuppressive drugs after organ transplant)
    3. History of previous BU (except current infection)
  • Planned/expected to require curative intent excision surgery, defined as excision of lesion which may include surrounding macroscopically healthy tissue with the aim of helping to sterilize the wound rather than improve wound healing alone, for their BU during the entire study period. Simple removal of necrotic slough and skin grafting is considered normal wound care and allowed.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
300 mg Telacebec per dayTelacebecTelacebec will be administered orally with food or within 30 minutes after food once daily for 28 consecutive days.
Primary Outcome Measures
NameTimeMethod
Rate of complete lesion healing by 52 weeks from treatment initiation.52 weeks from treatment initiation

Ulcerated Lesions: Healing and re-epithelialisation of ulcerated area with stable scar formation. Non-ulcerated Lesions: resolution of induration of skin.

Complete healing rate will be summarized as percentage with corresponding Clopper-Pearson 95% confidence interval.

Secondary Outcome Measures
NameTimeMethod
Complete lesion healing rate at 52 weeks from treatment initiation.52 weeks from treatment initiation

Complete healing rate will be summarized as percentage with corresponding Clopper-Pearson 95% confidence interval.

Median time to healing52 weeks from treatment initiation

Kaplan-Meier methods will be applied to estimate median time to healing.

Recurrence rate within 52 weeks from treatment initiation52 weeks from treatment initiation

Complete lesion healing followed by a recurrent lesion at the same site or a new lesion appearing at a separate site, detected within 52 weeks of treatment initiation, that is culture positive and not judged to be due to a paradoxical response to telacebec treatment on clinical and/or histological findings.

Treatment failure rate within 52 weeks from treatment initiation52 weeks from treatment initiation

Lack of complete healing within the 52 weeks observation period; Recurrence, Use of alternative buruli ulcer (BU) treatment, BU curative intent surgery

Paradoxical response rate with 52 weeks from treatment initiation52 weeks from treatment initiation

An increase in lesion surface area by more than 20% compared with a previous measurement, after initial reduction in lesion size, or the development of a new lesion appearing at a separate site that does not show evidence of disease relapse on histopathology and/or mycobacterial culture examination.

Trial Locations

Locations (2)

Barwon Health

🇦🇺

Geelong, Victoria, Australia

Royal Melbourne Hospital

🇦🇺

Melbourne, Australia

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