Telacebec in Adults With Multibacillary Leprosy (TEBULA Leprosy Trial) (TEBULA LEPROSY)

Inclusion Criteria:

• Be an individual aged 18-60 years.
• Has been diagnosed with MB leprosy with a Bacillary Index (BI) of at least 2+ on a slit skin smear (SSS).
• Have no prior leprosy treatment (WHO MDT and/or dapsone monotherapy).
• Be able to give voluntary informed consent.
• Be able to complete the full study period and follow-up (with no planned migration and an accurate, known and accessible address).
• Be able to accept hospitalisation for at least three months (site-specific requirement).
• "Body weight < 85 kg at screening." (participants with weight >= 85 kg have an increased risk of severe transaminitis under telacebec)

Exclusion Criteria:

• Unable to give voluntary informed consent.
• Is a pregnant or breastfeeding woman.
• Presenting with reinfection or relapse after WHO MDT/dapsone monotherapy, or has received anti-mycobacterial drugs in the last 30 days.
• Presenting a leprosy reaction at diagnosis.
• Being currently involved or having been involved within the last 30 days in a clinical trial.
• Has any of the following medical conditions: a baseline QTcF of >450 ms or a clinically significant ECG abnormality or significant heart disease; HIV co-infection; HBV co-infection; history of or current pancreatitis; known or suspected cirrhosis of the liver; active clinical tuberculosis; any condition which, in the opinion of the investigator, may cause harm to the patient; known alcohol or drug addiction; known uncontrolled chronic disease such as diabetes (HbA1c >10%) or renal failure (GFR <50 ml/min); anaemia requiring transfusion.
• Known glucose-6-phosphate dehydrogenase (G6PD) deficiency, due to risk of dapsone-induced haemolytic anaemia (G6PD testing required at screening).
• Abnormal screening laboratory values, including: WBC <2.5 × 10⁹/L; Neutrophils <1.0 × 10⁹/L; Platelets <100 × 10⁹/L; AST or ALT >2 times the upper limit of the reference range; Albumin <30 mg/dL; Bilirubin >2 mg/dL (34 μmol/L); Calculated creatinine clearance (Cockcroft-Gault) <50 ml/min; Lipase ≥1.6 times the upper limit of the reference range.

Other eligibility consideration - Contraception

All women of reproductive potential must be tested for pregnancy at screening, and again before dosing at baseline (Day 0) and on Days 28, 42, 56, and 84 of the experimental treatment phase. Women with a positive pregnancy test after enrolment will have their treatment shifted to MDT if randomised to a telacebec-containing arm.

All women of reproductive potential must use two reliable and effective methods of contraception simultaneously while taking the study medication and up to two months after the last dose of telacebec. One highly effective form of contraception must be used (hormonal, IUD, prior tubal ligation, or partner's prior vasectomy) plus one additional effective method (male latex or synthetic condom, diaphragm or cervical cap). Male participants whose female partners are of reproductive age must also use contraception for up to 90 days after the last telacebec dose.