Phase 3 Trial of Zilucoplan Enrolling Adults with Generalized MG
Ra Pharmaceuticals is enrolling adults with generalized myasthenia gravis (gMG) in RAISE, its global and pivotal Phase 3 trial evaluating the safety and efficacy of zilucoplan, the Muscular Dystrophy Association (MDA) has announced.
The company started preparing to launch the RAISE (NCT04115293) study in early 2019, and began patient dosing later that year. Recruitment is now underway at multiple sites in the U.S., Canada, France, Germany, Italy, Japan, Norway, Spain, and the U.K.
Additional information on trial contacts and recruiting sites can be found here.
Formerly known as RA101495, zilucoplan is an artificial peptide (or small protein) that binds to a protein called complement 5 (C5), blocking its activity and preventing the overactivation of the complement system. This system, which comprises a set of more than 50 blood proteins that form part of the body’s immune defenses, is thought to be involved in the formation of harmful auto-reactive antibodies in myasthenia gravis (MG).
The therapy has been granted orphan drug status by the U.S. Food and Drug Administration to treat MG. It is being developed by Ra Pharma, now part of UCB BioSciences, to treat people with gMG, immune-mediated necrotizing myopathy (IMNM), and other rare complement system disorders currently lacking treatment options.
RAISE is a randomized, double-blind, placebo-controlled Phase 3 trial, assessing the efficacy, safety, and tolerability of zilucoplan when self-administered at home at a daily dose of 0.3 mg/kg by a subcutaneous (under the skin) injection for 12 weeks, compared with a placebo injection.
The study plans to enroll 130 adults with gMG, ages 18–75, who tested positive for the presence of self-reactive antibodies directed against the acetylcholine receptor (AChR), and whose MG treatments — immunosuppressive therapies and corticosteroids — did not change in the month leading up to enrollment. Eligible patients are also expected to not require changes to these therapies during the study.
Seven clinic examination visits are required of people participating in RAISE. Following two initial assessments during screening and at the study’s start, all will be re-evaluated after trial weeks one, two, four, eight, and 12.
The study’s main goal is to assess the therapy’s ability to improve participants’ engagement in daily life activities, a measure of the disease’s severity. This will be assessed at the close of the 12-week treatment period, using the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale.
The secondary objective looks at zilucoplan’s ability to ameliorate patients’ muscle strength by measuring changes in the quantitative MG (QMG) score — a test of a patient’s level of muscle weakness — at the trial’s start and its end.
Patients who complete this main trial will be invited to enroll in an open-label long-term extension study, called RAISE-XT, to continue or start treatment with zilucoplan. Those not entering the extension study will be re-evaluated in a 40-day follow-up visit.
RAISE’s launch followed the completion of a Phase 2 trial (NCT03315130), in which gMG patients were randomly assigned to receive one of two daily doses of zilucoplan — 0.1 or 0.3 mg/kg — or a placebo, administered under the skin for 12 weeks.
Study findings showed that when given at the highest dose (0.3 mg/kg), zilucoplan significantly lowered both QMG and MG-ADL scores relative to the beginning of the study and compared with placebo.
The therapy was also found to be safe and well-tolerated, with only mild side effects reported and considered unrelated to zilucoplan. No serious side effects were reported.