ACTH as A Re-emerging theRapy for Uveitis (The ACTHAR Study)

Uveitis is a term used to describe a group of inflammatory disorders involving the uveal tract (iris, ciliary body and choroid). It is amongst the most common causes in the list of preventable cause of blindness in the developed world. H.P. Acthar Gel is a highly purified sterile preparation of the adrenocorticotropic hormone (ACTH) gelatin to provide a prolonged release after intramuscular or subcutaneous (SC) injection. ACTH is part of a group of molecules called melanocortins (MC) (ACTH, α, β, γ-MSH) that are produced, in human bodies, by breakdown of a common larger precursor called proopiomelanocortin (POMC). A very well-known anti-inflammatory mechanism of action of ACTH is the production glucocorticoids by stimulating the adrenal glands. ACTH has also been shown to bind with all five melanocortin receptors (MCRs). MCRs have a variety of roles including cortisol production and regulation of immune modulation by ACTH. ACTHAR is an open-label, multi-center, randomized, phase II study to evaluate the effect of two dose regimens of repeated SC injections of ACTH gel in patients with active non-infectious intermediate, posterior, or pan-uveitis followed over a period of 12 months. ACTHAR study will be conducted at up to 7 clinical sites in USA. The study will be coordinated by the Ocular Imaging Research and Reading Center (OIRRC), which will serve as the coordinating and reading center for the ACTHAR Study. The primary endpoint of the study will be at month 6, with an active, as-needed treatment extension phase from month 6 to month 12. Thirty-six (36) patients with non-infectious intermediate, posterior, or pan-uveitis will be enrolled and randomized (1:1) to one of the two treatment arms: 1. Mandatory twice a week (Mondays and Thursdays) treatment with SC ACTH gel 80 U/day starting at BL until month 6. Starting at month 6, the treatment will be administered on as needed basis, based on the retreatment criteria. 2. Mandatory thrice a week (Mondays, Wednesdays, and Fridays) treatment with SC ACTH gel 80 U/day starting at BL until month 6. Starting at month 6, the treatment will be administered on as needed basis, based on the retreatment criteria. Starting at month 6, retreatment will be offered to study subjects who have demonstrated any level of response during the first 6 months and who meet any of these Retreatment Criteria listed below. Patients receiving retreatment will receive the dose that was assigned to them at randomization.