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

Exclusion Criteria37

• 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
• History of or presence of cardiac disease, including:
• Clinically significant abnormal electrocardiogram
• QTcF > 450 msec
• Receipt of a vaccination within 7 days of Baseline.
• Known or suspected hypersensitivity to: PDE4 inhibitors including dovramilast or apremilast; thalidomide; prednisolone, or; excipients used in the formulation of dovramilast, thalidomide or prednisolone.
• Body Mass Index < 15 kg/m\^2 or > 35 kg/m\^2.
• Unable to, or significant difficulty with, swallowing tablets/capsules.
• Anemia requiring transfusion.
• History of or current pancreatitis.
• Known or suspected cirrhosis of the liver.
• 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
• Previous participation in this study
• Unwilling, unlikely or unable to comply with all protocol specified assessments, including photographic assessments
• Enrolled in another leprosy type 2 reaction treatment study