Dovramilast for Erythema Nodosum Leprosum in Patients With Leprosy in Nepal: Protocol for a Phase 2 Open-Label Pilot Study

Background: Erythema nodosum leprosum (ENL) is an immunological complication affecting up to 10% of borderline lepromatous and 50% of lepromatous leprosy cases with a high bacterial index (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 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 phosphodiesterase 4 inhibitor; to date, it has been shown to be well tolerated in phase 1 human studies. This is the first phase 2 study of dovramilast in ENL. Objective: This phase 2 pilot study aims to assess the safety and tolerability of dovramilast and to explore preliminary clinical responses in patients with new or recurrent ENL. Methods: This study was designed in two steps: (1) 28 days of treatment for 10 males to ensure safety and (2) an initial 12-week treatment course, with the option to retreat if further ENL episodes occur (up to 48 wk 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 longitudinally, along with the ENL International Study Group ENL Severity Scale, Brief Pain Inventory, and Douleur Neuropathique 4 questionnaire for the identification of neuropathic pain. Patients will be followed for 12 months for ENL recurrence after cessation of the study drug. Safety will be evaluated through adverse event reporting and laboratory monitoring, while efficacy will be assessed using descriptive and trend-based analyses of changes in ENL severity, pain, and clinical outcomes over time. Results: The initial safety evaluation (step 1) of this phase 2 pilot study was completed and reviewed by an independent Data Safety Monitoring Board, which did not identify safety concerns that would preclude continuation of the study. Based on the step 1 results, the study proceeded to step 2, which evaluates longer-term administration of dovramilast in male and female participants. As of April 2026, a total of 15 participants have been recruited. All study data are anticipated to be collected by September 2027, with publication of the main trial results expected by December 2027. Conclusions: This phase 2 pilot study is designed to generate preliminary data on the safety, tolerability, and potential clinical signals of dovramilast in patients with new or recurrent ENL. Findings from this exploratory trial will inform the feasibility, outcome measures, and design of future adequately powered randomized controlled studies and do not directly support changes to current clinical practice at this stage.