BACKGROUND: Inflammation is a key feature underlying the pathogenesis of numerous neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). In ALS, the complement system has been implicated in neuropathology and disease progression. Pegcetacoplan is a subcutaneously administered complement C3 inhibitor that is being investigated for hematology, nephrology, and neurology indications. The current clinical study (NCT04579666) is investigating whether attenuating C3 activity can improve survival and function in people with sporadic ALS.
OBJECTIVE: Determine the efficacy and safety of pegcetacoplan compared to placebo among people with ALS in a global, multicenter, randomized, double-blind, placebo-controlled, phase 2 study.
METHODS: 249 patients with sporadic ALS (diagnosed as definite, probable, or laboratory-supported probable as defined by the revised EI Escorial criteria), ≥18 years old, and with an ALS Functional Rating Scale-Revised (ALSFRS-R) score ≥30, slow vital capacity (SVC) ≥60% of the predicted value at screening, and symptom onset within 72 weeks prior to screening have been enrolled. Patients have been randomized 2:1 to receive subcutaneous pegcetacoplan (1080 mg) or placebo twice weekly for 52 weeks. The primary efficacy endpoint is the difference in the Combined Assessment of Function and Survival (CAFS) ranked score at 52 weeks after treatment initiation. Secondary endpoints include functional efficacy (ALSFRS-R, percent-predicted SVC, muscle strength, quality of life, and caregiver burden), which will be analyzed from baseline to Week 52. Additionally, safety and the number of participants with positive responses (yes) to the Columbia Suicide Severity Rating Scale (C-SSRS) will be assessed for up to 104 weeks. Following the placebo-controlled period, patients have the option to receive pegcetacoplan in an open-label period for an additional 52 weeks.
RESULTS: This ongoing study is no longer recruiting and results are expected in the summer of 2023.
CONCLUSIONS: Study results will determine the role of complement C3 inhibition in patients with ALS.