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.
Aged 18 years of age or older.
Provision of written informed consent.
Laboratory confirmed previous or current Mycobacterium leprae or Mycobacterium lepromatosis infection.
Presence of at least 10 leprosy type 2 reaction tender papular and/or nodular skin lesions (not including scars).
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).
Parallel
Dovramilast
DrugDovramilast
Prednisolone
DrugStandard of care
Thalidomide
DrugStandard of care (US only)
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
Incidence and severity of adverse events
The incidence and severity of adverse events, changes in vital signs and blood dyscrasias
Resolution of fever to ≤ Grade 1
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
• Change from Baseline in skin lesion count up to and including Week 12.
Change from Baseline ENLIST (Erythema Nodosum Leprosum International Study ) severity scale score
Change from Baseline of each of the following parameters when present at Baseline at Grade 2 or greater
* 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
Quantification of immunological markers in whole blood samples by central laboratory, blinded to patient identification, treatment arm, and study visit
Concentration of inflammatory cytokines
Quantification of immunological markers in skin biopsies by central laboratory, blinded to patient identification, treatment arm, and study visit
Leukocyte infiltration of skin lesions by histology
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