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

A Multicentre, Phase 2, Open-label, Randomised, Standard of Care-controlled and Dose-ranging Clinical Trial, Evaluating Safety and Efficacy of Telacebec in Adults With Multibacillary Leprosy (TEBULA Leprosy Trial)

The goal of this clinical trail is to evaluate whether short-course telacebec-based regimens can induce rapid and measurable reductions in M. leprae viability, potentially establishing the foundation for future shorter, safer, and simplified therapeutic strategies for MB leprosy.

Participants will be randomised into one of the four study arms (A, B, C and D). The arm A is non interventional. For arms B, C, and D, the three-month study drug treatment will be followed by 9 months of MDT, bringing the total treatment time to 12 months. This provision of MDT ensures that the participant has received the recommended standard treatment for leprosy and is primarily for ethics considerations.

Study Overview

• Status: Not yet recruiting
• Conditions: Leprosy, Multibacillary
• Intervention / Treatment: Drug: Telacebec 300 mg; Drug: Telacebec 600 mg; Drug: Telacebec + Rifampicine

Detailed Description

This is an open-label, randomised, controlled, multicentre phase II clinical trial conducted in Benin, Côte d'Ivoire and Ethiopia to evaluate the bactericidal efficacy of telacebec-based regimens in the treatment of multibacillary (MB) leprosy, with safety and tolerability as secondary objectives.

Participants who meet entry criteria and give consent will be randomised into four parallel groups: one control group (Group A) receiving standard WHO multidrug therapy (MDT); two investigational groups (Groups B and C) receiving telacebec monotherapy at two different dose levels; and one investigational group (Group D) receiving telacebec in combination with rifampicin. Upon completion of the assigned telacebec-based regimen, participants in Groups B, C, and D will subsequently receive standard WHO MDT.

Follow-up will be at least 12 months for all study arms; however, with the support of national programmes, patients may be followed for up to five years where possible.

Every fortnightly visit during the first three months (during which participants are taking study drugs) needs to be performed on the appointment day (±2 days). During post-IP treatment, once participants are on regular WHO MB-MDT, they are followed up on a monthly basis (-3/+2 days window). During the post-MDT period, they are followed up on a 3-monthly basis (±14 days window). The monthly dose of study medication must be taken as directly observed treatment (DOT) on the day of the visit. The Day 1 of the monthly WHO MB-MDT must also be taken as DOT.

The TEP is composed of clinicians experienced in the clinical management of leprosy, independent of the trial sites, and will provide assistance in reviewing the clinical response of participants included in the clinical trial. During the clinical follow-up, pictures of the lesions are taken systematically at every scheduled visit to document clinical evolution, identified with a code guaranteeing patient and treatment anonymity. After Day 84, pictures will be sent separately to each member of the TEP blinded to treatment allocation. The Technical Expert Panel (TEP) will give an independent assessment classifying each participant as showing clear improvement, moderate improvement, or no improvement.

At least three assessments from the TEP need to be collected for the decision. The decision will be taken by simple majority. If 4 out of 5 members provide an assessment and the decision is divided, a reserve list TEP member will be contacted.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Roch Christian JOHNSON, Medical Doctor, Phd, HDR; Phone Number: +229(01)96221132; Email: rochchristianjohnson@gmail.com
• Study Contact Backup: Name: Esai ANAGONOU, PhD; Phone Number: +229(01)96826567; Email: esaianagonou@yahoo.fr

Study Locations

• Benin
  • Pobé
    • Pobé, Pobé, Benin
      • Centre de Dépistage et de Traitement de la Lèpre et de l'Ulcère de Buruli (Raoul et Madeline Follereau) de Pobè
      • Contact: Esai ANAGONOU, PhD; Phone Number: +229(01)96826567; Email: esaianagonou@yahoo.fr
      • Contact: Oswald ATTOLOU, Master; Phone Number: +229(01)94401778; Email: oattolou@raoul-follereau.org
      • Principal Investigator: Akimath Olagnidé Pélagie HABIB, Master

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: (Group A) receiving standard WHO multidrug therapy (MDT); The World Health Organization recommends Multidrug Therapy (MDT) to cure leprosy. This standard treatment combines three medicines: (Rifampicin 300mg x 2) + (Clofazimin 100 mg x 3) + (Dapsone 50 mg) x 12 months
Experimental: Group B (Low dose); (Telacebec 100 mg x 3 once monthly x 3 months) followed by (Rifampicin 300mg x 2) + (Clofazimin 100 mg x 3) + (Dapsone 50 mg) x 12 months	Drug: Telacebec 300 mg; Telacebec 300 mg once monthly × 3 months
Experimental: Group C (Hight dose); (Telacebec 100 mg x 6 once monthly x 3 months) followed by (Rifampicin 300mg x 2) + (Clofazimin 100 mg x 3) + (Dapsone 50 mg) x 12 months	Drug: Telacebec 600 mg; Telacebec 600 mg once monthly × 3 months
Experimental: Group D (Combinaison); (Telacebec 100 mg x 3 + Rifampicin 300 mg x 2 once monthly x 3 months) followed by (Rifampicin 300mg x 2) + (Clofazimin 100 mg x 3) + (Dapsone 50 mg) x 12 months	Drug: Telacebec + Rifampicine; (Telacebec 300 mg + Rifampicine 600 mg) once monthly x 3 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in viable Mycobacterium leprae load in participants' skin lesions	Treatment response of leprosy infection in each participant, measured in skin biopsies taken from the same lesion at baseline and Day 84 using the Molecular Viability Assay (MVA): quantitative RT-PCR of esxA and hsp18 transcripts, standardised to 3,000 bacilli. Reported as change in log10 viability; a larger decrease indicates a greater bactericidal effect of treatment in the participant. Arms B, C and D are compared with standard WHO MB-MDT (Arm A)	Baseline (Day 0) and Day 84

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)	Clinical and laboratory adverse events, graded for severity and assessed for relationship to study drug, in participants receiving telacebec 300 mg, telacebec 600 mg, telacebec 300 mg + rifampicin 600 mg, or WHO MB-MDT	From first dose through Day 84 (end of study drug period)
Proportion of participants with clinical improvement of leprosy skin lesions	Assessed with standardised lesion-response criteria based on clinical examination and standardised photographs, classified as clear, moderate or no improvement. Classification validated by an independent external expert panel.	Day 84 and Month 12 (end of treatment)
Incidence and severity of leprosy reactions	Number of participants with Type 1 (reversal) reactions, defined by WHO criteria, and Type 2 reactions (erythema nodosum leprosum). ENL severity scored with the ENLIST ENL Severity Scale (EESS).	Baseline through Month 24 (end of follow-up)
Change in peripheral nerve sensory function	Semmes-Weinstein monofilament thresholds at standardised sites of the hands and feet.	Baseline, Day 84, Month 12, Month 24
Change in peripheral nerve motor function	Voluntary Muscle Testing (VMT) scores.	Baseline, Day 84, Month 12, Month 24
Number of participants with new nerve function impairment		Baseline through Month 24
Change in health-related quality of life (EQ-5D)		Baseline, Day 84, Month 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participant-reported global impression of change (PGI-C)		Day 84, Month 12
Proportion of participants with viable M. leprae in skin lesions	Skin biopsy material from a subset of participants (5 to 6 per group) are tested: Data reported per participant (presence of viable bacilli on day 84 compared to that participant's baseline sample).	Baseline and Day 84
Change from baseline in M. leprae rRNA synthesis (RS) ratio in participants' skin lesions	Marker of ongoing bacterial replication in each participant's lesion	Baseline and Day 84
Number of participants who discontinue or interrupt study treatment because of adverse events		Throught Day 84
Number of participants with treatment-emergent laboratory abnormalities	Haematology, biochemistry and liver function tests	Throught Day 84
Plasma concentration of telacebec in participants	Sparse pharmacokinetic sampling	Day 0 through Day 84

Collaborators and Investigators

• Sponsor: Fondation Raoul Follereau
• Collaborators: London School of Hygiene and Tropical Medicine; Institut National de la Santé Et de la Recherche Médicale, France; Global Alliance for TB Drug Development; Liverpool School of Tropical Medicine; Instituto de Salud Carlos III; Kwame Nkrumah University of Science and Technology; Armauer Hansen Research Institute, Ethiopia; Centre Pasteur du Cameroun; Ministère de la Santé - Bénin; Ministère de la Santé, de l'Hygiène Publique et de la Couverture Maladie Universelle, Côte d'Ivoire; Instituut voor Tropische Geneeskunde, Belgium; Université de Sorbonne, Paris, France; Board of Governors of the Colorado State University System (CSU)
• Investigators: Principal Investigator: Roch Christian JOHNSON, Medical Doctor, PhD, HDR, Centre Interfacultaire de Formation et de Recherche en Environnement pour le Développement Durable (CIFRED), University of Abomey-Calavi

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2029

Study Registration Dates

• First Submitted: September 21, 2026
• First Submitted That Met QC Criteria: October 30, 2026
• First Posted (Actual): November 5, 2026

Study Record Updates

• Last Update Posted (Actual): November 5, 2026
• Last Update Submitted That Met QC Criteria: October 30, 2026
• Last Verified: October 1, 2026

More Information

Terms related to this study

• Keywords: Africa; Leprosy; Tebula; Telacebec
• Additional Relevant MeSH Terms: Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Actinomycetales Infections; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Leprosy; Leprosy, Multibacillary; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Polycyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Rifamycins; Lactams, Macrocyclic; Macrocyclic Compounds; Rifampin; telacebec
• Other Study ID Numbers: TEB-LEP2025-01; 101190742 (Other Grant/Funding Number: European Union)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

The plan is not yet developed

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