Ra Pharmaceuticals is preparing to launch a Phase 3 clinical trial to assess the therapeutic potential of zilucoplan for the treatment of patients with generalized myasthenia gravis (gMG). This comes after the company’s completion of End-of-Phase 2 interactions with the U.S. Food and Drug Administration (FDA).
The 12-week study — a single, pivotal, randomized, double-blind, placebo-controlled Phase 3 trial expected to start in the second half of 2019 — will test the efficacy of self-administered zilucoplan at a daily dose of 0.3 mg/kg by subcutaneous (under the skin) injection. It’s expected to enroll approximately 130 patients with gMG.
The study’s primary goal will be to determine the degree of change in the patients’ scores on the myasthenia gravis activities of daily living (MG-ADL) scale from the beginning of the trial until week 12. The MG-ADL will be used to measure the therapy’s ability to improve participants’ engagement in daily activities.
Once the trial is completed, Ra Pharma is planning to offer patients the option to participate in an open-label, long-term extension of the study.
Zilucoplan (formerly known as RA101495) is an artificial peptide that binds to complement 5 (C5), inhibiting its activity and preventing the overactivation of the complement system — a set of more than 50 blood proteins that form part of the body’s immune defenses — which is thought to be involved in the formation of harmful autoantibodies in MG.
Based on the feedback received from the FDA, Ra Pharma decided to prioritize its clinical study of zilucoplan for patients with gMG. In the future, the company is planning to expand zilucoplan’s use for other complement system disorders currently lacking treatment options, such as paroxysmal nocturnal hemoglobinuria (PNH).
“We’re delighted by the feedback we received from the FDA regarding our Phase 3 clinical trial design for zilucoplan in gMG, which is a major step forward in our efforts to expand patient access to convenient complement inhibition in this disease. We look forward to working closely with regulators as we advance zilucoplan through Phase 3 clinical development in gMG, with initiation planned for the second half of this year,” Doug Treco, PhD, president and CEO of Ra Pharma, said in a press release.
“With a Phase 3 design that includes a 12-week trial duration and a primary efficacy endpoint that zilucoplan previously met in our completed Phase 2 study, we are well-positioned to rapidly advance this registrational program. We plan to focus our resources on accelerating this program as we aim to build a leading complement-focused neurology franchise,” Treco added.
The successful completion of the company’s previous Phase 2 clinical (NCT03315130) trial of zilucoplan opened the door to the interactions with the FDA. The trial assessed the safety and efficacy of daily doses of zilucoplan (0.1 mg/kg or 0.3 mg/kg) for the treatment of patients with gMG, compared with a placebo, for a period of 12 weeks.
The study’s findings showed that patients treated with the highest dose of zilucoplan attained a significant reduction of 6.0 points in the quantitative MG (QMG) score and of 3.4 points in the MG-ADL score since the beginning of the trial, compared with those treated with a placebo, who had a reduction of 2.8 points in their QMG score and of 2.3 points in their MG-ADL score. The QMG is a test that measures the degree of muscle weakness.
Unlike 20% of the patients in the placebo group, none of the patients treated with the highest dose of zilucoplan required rescue therapy (with intravenous antibodies or plasma exchange).
Zilucoplan was generally safe and well-tolerated by the patients, which was consistent with findings from previous studies. The majority of adverse events (AEs) reported during the trial were considered mild and not directly associated with zilucoplan. No serious AEs linked to treatment with zilucoplan were reported.