Efficacy and Safety Study of Dovramilast in People With Leprosy Type 2 Reaction

Not Applicable

Not yet recruiting

• Conditions: Erythema Nodosum Leprosum
• Interventions: Drug: Dovramilast; Drug: Prednisolone; Drug: Thalidomide

• Registration Number: NCT07172659
• Lead Sponsor: Medicines Development for Global Health

Brief Summary

Dovramilast has not been approved for leprosy type 2 reaction (erythema nodosum leprosum, ENL) or any other disease anywhere in the world. In this study, an experimental drug called dovramilast is being tested to see how it compares to current treatments for leprosy type 2 reaction. Specifically, this study aims to assess the efficacy of 100mg or 150 mg dovramilast compared with standard treatments (also known as standard of care). This study also aims to assess the safety of two strengths in adults with leprosy type 2 reaction.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-07
• Study First Submitted: 2025-08-07
• Study First Submitted QC: 2025-09-07
• Last Update Submitted: 2025-09-07
• Study First Posted: 2025-09-15
• Last Update Posted: 2025-09-15
• Study Start: 2025-10-01
• Primary Completion: 2026-12
• Study Completion: 2027-10-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 45

Inclusion Criteria

1. Aged 18 years of age or older.

2. Provision of written informed consent.

3. Laboratory confirmed previous or current Mycobacterium leprae or Mycobacterium lepromatosis infection.

4. Leprosy type 2 reaction meeting the following criteria:

   • Either:

     i. Acute (first episode and no treatment initiated) or ii. Recurrent (at least one further episode occurring 28 days or more after withdrawal of leprosy type 2 reaction treatment).

   • Presence of at least 10 leprosy type 2 reaction tender papular and/or nodular skin lesions (not including scars).

   • An ENLIST score of at least 9.

5. If a woman of reproductive potential, agree to the use of two reliable contraceptive measures (at least one of which is a highly effective form of contraception) from Screening until at least 4 weeks after completion of treatment with dovramilast or standard of care. Refer to Special Considerations for additional information.

6. If male (including those who have had a successful vasectomy), agree to using a latex condom during any sexual contact with women of reproductive potential from Screening until at least 4 weeks after completion of treatment with dovramilast or standard of care.

Exclusion Criteria

1. Chronic leprosy type 2 reaction, defined as the reaction occurring for 24 weeks or more during which a subject has required treatment either continuously or where any treatment free period had been < 28 days.

2. Receipt of thalidomide, lenalidomide, pomalidomide, systemic corticosteroids, clofazimine (> 50 mg/day), apremilast or any other phosphodiesterase (PDE) 4 inhibitor, or immunosuppressive/immunomodulatory treatment within 28 days of Baseline.

3. Receipt of an investigational agent within 28 days of Baseline or 5 half-lives of the investigational agent (whichever is longer).

4. Leprosy type 2 reaction with orchitis, uveitis, iritis, or severe neuritis (Grade 3 or greater severe neuritis).

5. Current diagnosis of leprosy type 1 reaction or Lucio's phenomenon.

6. Current tuberculosis, malaria, cutaneous or visceral leishmaniasis or other serious bacterial, viral, or parasitic infection at Screening or Baseline.

7. Active systemic fungal infection requiring or undergoing treatment.

8. Other than leprosy type 2 reaction, any clinically significant (as determined by the Investigator) cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, immunologic disease, or other major disease that is currently uncontrolled.

9. Other than leprosy type 2 reaction, any other dermatological condition that could, in the opinion of the Investigator, interfere with the study assessments.

10. Chronic hepatitis B, chronic hepatitis C, or human immunodeficiency virus (HIV) positive.

11. Pregnant women or breastfeeding mothers.

12. Use (or planned use) of antimetabolites or alkylating agents, rifampin use more frequent than monthly, phenobarbital, carbamazepine, phenytoin, traditional or herbal preparations (including St. John's wort), foods (including grapefruit) known to affect activity of the cytochrome (CYP)3A4 enzyme or use (or planned use) of all strong CYP3A and P-gp inhibitors including ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin, ritonavir, cobicistat, diltiazem. Substrates of CYP3A4, CYP2C9, CYP2C19, and P-gp should be used with caution when concomitantly administered with dovramilast.

13. Known or suspected active substance abuse or a history of substance abuse within 6 months prior to Screening.

14. Prior history of suicide attempt at any time in the subject's lifetime prior to Screening or Randomization, or major psychiatric illness requiring hospitalization within the last 3 years.

15. Current diagnosis of depression, and/or history of suicide ideation

16. History of or presence of cardiac disease, including:

    • Clinically significant abnormal electrocardiogram
    • QTcF > 450 msec

17. Receipt of a vaccination within 7 days of Baseline.

18. Known or suspected hypersensitivity to: PDE4 inhibitors including dovramilast or apremilast; thalidomide; prednisolone, or; excipients used in the formulation of dovramilast, thalidomide or prednisolone.

19. Body Mass Index < 15 kg/m^2 or > 35 kg/m^2.

20. Unable to, or significant difficulty with, swallowing tablets/capsules.

21. Anemia requiring transfusion.

22. History of or current pancreatitis.

23. Known or suspected cirrhosis of the liver.

24. The following laboratory abnormalities:

    • White blood cells (WBC) < 2.5 x 10^9/ L.
    • Neutrophils (granulocytes) < 1.0 x 10^9/L.
    • Platelets < 80 x 10^9/L.
    • Aspartate aminotransferase or alanine aminotransferase > 2 times the upper limit of reference range.
    • Albumin < 30 mg/dL.
    • Bilirubin > 2 mg/dL
    • Calculated creatinine clearance (Cockcroft Gault) < 50 milliliter (mL)/minute.
    • Lipase ≥ 1.6 times the upper limit

25. Previous participation in this study

26. Unwilling, unlikely or unable to comply with all protocol specified assessments, including photographic assessments

27. Enrolled in another leprosy type 2 reaction treatment study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dovramilast 100 mg	Dovramilast	-
Dovramilast 150 mg	Dovramilast	-
Standard of care	Prednisolone	Prednisolone (or thalidomide US sites only)
Standard of care	Thalidomide	Prednisolone (or thalidomide US sites only)

Primary Outcome Measures

Name	Time	Method
The proportion of dovramilast (100 mg or 150 mg) recipients achieving a 75% improvement in leprosy type 2 reaction skin lesions at week 12	12 weeks	The proportion of subjects achieving a reduction of leprosy type 2 reaction skin lesion count of at least 75% from Baseline at Week 12 without the need for rescue.; Rescue is defined as: 1. A change from dovramilast at any dose to standard of care or dose maintenance beyond taper time points defined in standard of care treatment guidelines (and specified in this protocol), or; 2. Standard of care dose increase, switching to or adding another leprosy type 2 reaction treatment
Incidence and severity of adverse events	12 weeks	The incidence and severity of adverse events, changes in vital signs and blood dyscrasias

Secondary Outcome Measures

Name	Time	Method
Changes in neuropathy from Baseline grade	12 weeks
Exposure metrics of dovramilast	48 weeks	Tmax.
Resolution of fever to ≤ Grade 1	12 weeks	Proportion of subjects with resolution of fever to ≤ Grade 1 among the subgroup of subjects with fever present at Baseline at Grade 2 or greater.
Skin lesion count changes	12 weeks	Proportion of subjects achieving a reduction of leprosy type 2 reaction skin lesion count from Baseline of 50%, 90% and 100% without Rescue at Week 12.
Change from Baseline ENLIST (Erythema Nodosum Leprosum International Study ) severity scale score	At each post Baseline time point
Change from Baseline of each of the following parameters when present at Baseline at Grade 2 or greater	from baseline to Week 12	* Leprosy type 2 reaction lesions with respect to: number, inflammation, and extent; * Neuritis; * Pain: * Fever; * Peripheral edema with respect to location and severity; * Inflammation of joints and/or digits; * Lymphadenopathy
Time to resolution	12 weeks	For each individual leprosy type 2 reaction when present at least Grade 1 at Baseline
Proportion of subjects requiring Rescue medication and time to initiation of Rescue medication	12 weeks
Total amount of treatment for leprosy type 2 reaction administered	12 weeks
Recurrences	48 weeks	Recurrence is defined as new signs and symptoms consistent with leprosy type 2 reaction. The number of Recurrence episodes requiring treatment.
Exposure metrics of the dovramilast metabolite M15	48 weeks	Area under the curve (AUC)

Trial Locations

Locations (6)

University of Southern California; 🇺🇸 Los Angeles, California, United States

Harborview Medical Center, University of Washington; 🇺🇸 Seattle, Washington, United States

Centre de Dépistage de Traitement de la Lèpre et de l'Ulcère de Burulli; 🇧🇯 Abomey-Calavi, Benin

Chr de Divo; Divo, Côte d’Ivoire

Universitas Gadjah Mada; 🇮🇩 Yogyakarta, Indonesia

Philippine General Hospital, University of the Philippines, Manila; 🇵🇭 Manila, Philippines