Study endpoints
weakness, Neuro-QoL Fatigue, fatigue
NEUROLOGIC DISORDERS, ADVERSE EVENTS, DOUBLE VISION, ADVERSE EVENT, EYELID DROOP
Efficacy was evaluated using the following validated measures: the MG-ADL score [The MG-ADL scale is an 8-item survey of patient-reported MG symptom severity with a total score range of 0–24. The QMG is a 13-item clinician assessment of strength with a total score range of 0–39. The MG-QOL15r is a 15-item questionnaire on health-related quality of life with a total score range of 0–30. The Neuro-QoL Fatigue subscale evaluates the effect of fatigue on the quality of life of patients with neurologic disorders. The long form of the subscale used in this study comprises 19 patient-reported items with a total score range of 19–95. For each of the four measures, a reduction in scores indicates an improvement.MG-ADL and QMG were assessed at screening, baseline, and Weeks 1, 2, 4, 10, 12, 18, and 26 of the RCP, and at Weeks 28, 30, 36, 38, 44, 52, and 60 during the OLE. MG-QOL15r and Neuro-QoL Fatigue subscale scores were assessed at baseline and Weeks 4, 12, 18, and 26 of the RCP, and at Weeks 30, 38, 44, 52, and 60 during the OLE. At each assessment, the order of endpoints assessed was MG-ADL, QMG, MG-QOL15r, and Neuro-QoL Fatigue. Administration of the MG-ADL questionnaire and QMG and MG-QOL15r assessments was performed by trained clinical evaluators; preferably the same person evaluated each patient throughout the study. Assessment of QMG was performed at approximately the same time of day at each scheduled visit if possible. Patients who were receiving a cholinesterase inhibitor during the RCP or OLE were required to refrain from taking it for at least 10 h before each scheduled assessment.Study endpoints were change from RCP or OLE baseline in MG-ADL, QMG, MG-QOL15r, and Neuro-QoL Fatigue scores. The primary endpoint was change in MG-ADL score at Week 60. In addition, a responder analysis of MG-ADL and QMG scores was performed, with a clinical response defined as an improvement from baseline of ≥ 3 points for MG-ADL or ≥ 5 points for QMG. Occurrence of clinical deterioration and the use of rescue therapy by patients experiencing clinical deterioration were also assessed. Clinical deterioration was defined as: an MG crisis (weakness severe enough to necessitate intubation or to delay extubation following surgery); significant symptomatic worsening (worsening to a score of 3, or a 2-point worsening from baseline, on any of the individual MG-ADL items other than double vision or eyelid droop, which in the investigator’s assessment was associated with significant symptomatic worsening); or use of rescue therapy for health in jeopardy (administration of rescue therapy to a patient whose health, in the opinion of the investigator, would be in jeopardy if rescue therapy were not given).Efficacy data were analyzed as follows: change from RCP baseline at Week 60 was assessed for all endpoints in both study groups (ravulizumab–ravulizumab and placebo–ravulizumab); change from OLE baseline to OLE Week 2 (MG-ADL and QMG scores), OLE Week 4 (MG-QOL15r and Neuro-QoL Fatigue scores), and OLE Week 34 (all endpoints) was assessed for the placebo–ravulizumab group only. The analysis from the RCP baseline allowed assessment of endpoints throughout the entire study, while the analysis from the OLE baseline allowed assessment of the immediate and longer-term impact of switching to ravulizumab in the placebo–ravulizumab group.Changes in corticosteroid use during the OLE were also assessed. The safety and tolerability of ravulizumab were evaluated based on the incidence of adverse events, clinical laboratory and vital sign findings, and electrocardiogram abnormalities throughout the study (RCP and OLE periods). The potential relationship between each adverse event and the study agent was evaluated by the principal investigators, who were trained in causality assessment. Serious adverse events were also reviewed by the sponsor.