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

NCT07172659 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: MDGH-DOV-2001
• Study Type: interventional
• Target: 45
• Locations: 5 countries
• Sites: 6

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.

Conditions

Erythema Nodosum Leprosum

Keywords

Leprosy type 2 reaction; dovramilast

Outcome Measures

Primary Outcomes (2)

• The proportion of dovramilast (100 mg or 150 mg) recipients achieving a 75% improvement in leprosy type 2 reaction skin lesions at week 12

  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

  12 weeks

• Incidence and severity of adverse events

  The incidence and severity of adverse events, changes in vital signs and blood dyscrasias

  12 weeks

Secondary Outcomes (16)

• Resolution of fever to ≤ Grade 1

  12 weeks

• Skin lesion count changes

  12 weeks

• 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

• Changes in neuropathy from Baseline grade

  12 weeks

Other Outcomes (2)

• Quantification of immunological markers in whole blood samples by central laboratory, blinded to patient identification, treatment arm, and study visit

  48 weeks

• Quantification of immunological markers in skin biopsies by central laboratory, blinded to patient identification, treatment arm, and study visit

  48 weeks

Study Arms (3)

Dovramilast 100 mg

EXPERIMENTAL

Drug: Dovramilast

Dovramilast 150 mg

EXPERIMENTAL

Drug: Dovramilast

Standard of care

ACTIVE COMPARATOR

Prednisolone (or thalidomide US sites only)

Drug: Prednisolone; Drug: Thalidomide

Interventions

Dovramilast DRUG

Dovramilast

Dovramilast 100 mg; Dovramilast 150 mg

Prednisolone DRUG

Standard of care

Standard of care

Thalidomide DRUG

Standard of care (US only)

Standard of care

Eligibility Criteria

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

You may qualify if:

• Aged 18 years of age or older.
• Provision of written informed consent.
• Laboratory confirmed previous or current Mycobacterium leprae or Mycobacterium lepromatosis infection.
• 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.
• 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.
• 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.

You may not qualify if:

• 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.
• 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.
• Receipt of an investigational agent within 28 days of Baseline or 5 half-lives of the investigational agent (whichever is longer).
• Leprosy type 2 reaction with orchitis, uveitis, iritis, or severe neuritis (Grade 3 or greater severe neuritis).
• Current diagnosis of leprosy type 1 reaction or Lucio's phenomenon.
• Current tuberculosis, malaria, cutaneous or visceral leishmaniasis or other serious bacterial, viral, or parasitic infection at Screening or Baseline.
• Active systemic fungal infection requiring or undergoing treatment.
• 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.
• Other than leprosy type 2 reaction, any other dermatological condition that could, in the opinion of the Investigator, interfere with the study assessments.
• Chronic hepatitis B, chronic hepatitis C, or human immunodeficiency virus (HIV) positive.
• Pregnant women or breastfeeding mothers.
• 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.
• Known or suspected active substance abuse or a history of substance abuse within 6 months prior to Screening.
• 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.
• Current diagnosis of depression, and/or history of suicide ideation

Sponsors & Collaborators

• Medicines Development for Global Health: lead

Study Sites (6)

University of Southern California

Los Angeles, California, 90007, United States

Location

Harborview Medical Center, University of Washington

Seattle, Washington, 98104, United States

Location

Centre de Dépistage de Traitement de la Lèpre et de l'Ulcère de Burulli

Abomey-Calavi, Benin

Location

Chr de Divo

Divo, Côte d’Ivoire

Location

Universitas Gadjah Mada

Yogyakarta, Indonesia

Location

Philippine General Hospital, University of the Philippines, Manila

Manila, Philippines

Location

MeSH Terms

Interventions

Prednisolone; Thalidomide

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2025
• First Posted: September 15, 2025
• Study Start: January 1, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: December 23, 2025

Record last verified: 2025-12

Locations

PH (1); CÔ (1); ID (1); US (2); BE (1)