A Study to Evaluate, Safety, Tolerability, and PK of AP-101 in Participants With ALS

This Phase 2a, multicenter, randomized, double-blind, placebo-controlled study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamic markers of AP-101 in adults with sporadic ALS or SOD1-associated ALS. A total of 73 participants were randomized within each ALS cohort in a 2:1 ratio to receive AP-101 or placebo during a 24-week double-blind treatment period. Participants assigned to AP-101 received a 500 mg intravenous loading dose on Day 1, a 2500 mg intravenous dose on Day 2, and 2500 mg intravenously every 3 weeks beginning on Day 22 through Week 24. Participants assigned to placebo received matching intravenous infusions on the same schedule. Stable use of locally approved ALS treatments was permitted. Participants who completed the double-blind period could enter an optional 24-week open-label extension in which all participants received AP-101. To maintain the integrity of the double-blind period, the initial dose in the open-label extension remained blinded. Participants were followed for safety and pharmacokinetic assessments for up to 16 weeks after their final study dose. The primary assessments evaluated adverse events, serious adverse events, immunogenicity, vital signs, clinical laboratory assessments, physical and neurological examinations, electrocardiograms, and changes in weight. Secondary assessments included serum pharmacokinetics, AP-101 concentrations in cerebrospinal fluid, and the neurofilament biomarkers phosphorylated neurofilament heavy chain (pNfH) and neurofilament light chain (NfL). Exploratory assessments included the ALS Functional Rating Scale-Revised, slow vital capacity, muscle strength, King's staging, survival and ventilation outcomes, quality of life, and cerebrospinal fluid total and misfolded SOD1.