JMIR Publications

ABSTRACT

Background:

Erythema Nodosum Leprosum (ENL) is an immunological complication affecting up to 10% of borderline lepromatous and 50% of lepromatous leprosy cases with high bacterial index (BI, 3-6+). Current treatments often require prolonged therapy over years and cause significant long-term side effects, highlighting the need for new therapies. Therefore, it is imperative to identify new therapies for ENL. Phosphodiesterase 4 (PDE4) inhibitors are a class of compounds that mediate immune homeostasis and have the potential to treat ENL with fewer side effects. Dovramilast (formerly CC-11050) is an anti-inflammatory PDE4 inhibitor, and to date, has been shown to be well tolerated in phase 1 human studies. This is the first phase 2 study of dovramilast in ENL.

Objective:

The main aim of this trial is to evaluate the safety and efficacy of dovramilast in treating new and recurrent ENL.

Methods:

A Phase 2, open-label trial was designed to evaluate the safety and efficacy of dovramilast treatment of new or recurrent ENL in two steps: 1) 28 days of treatment for 10 males to ensure safety; and 2) initial 12 week treatment with the option to retreat if further ENL episodes occur (up to 48 weeks of treatment) for up to 40 males or females as required on a case-by-case basis. Demographic, clinical, and laboratory data will be collected, along with the ENL International Study Group (ENLIST) ENL Severity Scale (EESS), Brief Pain Inventory (BPI), and Douleur Neuropathique 4 (DN4) questionnaire for the identification of neuropathic pain. Patients will be followed for 12 months for ENL recurrence after cessation of the study drug.

Results:

Step 1 of this trial was completed in 2020 and the enrollment for step 2 is going on. Recruitment procedures for step 2 were started in September 2024 with the first participant enrolled on September 18, 2024. All data are anticipated to be collected by June 2027, and the results of the trial are expected to be published by December 2027.

Conclusions:

This trial combines a promising new drug with detailed observations of cohorts or ENL subjects to enhance the understanding of ENL treatment response. It will assess key data on ENL severity, monitoring, treatment duration, and outcomes. If proven both safe and efficacious, dovramilast could globally transform the management and outcomes of severe leprosy reactions. Clinical Trial: Clinicaltrials.gov NCT03807362; https://clinicaltrials.gov/study/NCT03807362