An Efficacy and Safety Study of Ravulizumab in Adult Participants With NMOSD

An On-trial Relapse was defined as a new onset of neurologic symptoms or worsening of existing neurologic symptoms with an objective change (clinical sign) on neurologic examination that persisted for more than 24 hours as confirmed by the treating physician. An adjudicated On-trial Relapse was defined by the protocol and positively adjudicated by the independent relapse adjudication committee.

Time frame: Baseline up to 2.25 years (end of the Primary Treatment Period)

Population: The full analysis set (FAS) included all participants who had received at least 1 dose of study drug (ravulizumab or placebo).

The adjudicated On-trial ARR was computed as the total number of relapses divided by the total number of participant years in the study period. A central independent committee was used to adjudicate all On-trial Relapses as determined by the treating physician. Results reported as adjusted adjudicated On-trial ARR based on a Poisson regression centered on the mean historical ARR in the 24 months prior to screening.

Time frame: Baseline up to 2.25 years (end of the Primary Treatment Period)

Population: The FAS included all participants who had received at least 1 dose of study drug (ravulizumab or placebo).

The EQ-5D is a generic, standardized, self-administered instrument that provides a simple, descriptive profile and a single index value for health status. It consists of 2 parts; the EQ-5D descriptive system and the EQ-5D visual analogue scale (VAS). The EQ-5D VAS is an overall health state scale where the participant selects a number between 0 to 100 to describe the condition of their health, with 100 being 'The best health state you can imagine' and 0 being 'The worst health state you can imagine'. An increase in score indicates improvement.

Time frame: Baseline, up to 2.25 years (end of the Primary Treatment Period)

Population: The FAS included all participants who had received at least 1 dose of study drug (ravulizumab or placebo).

The EQ-5D is a generic, standardized, self-administered instrument that provides a simple, descriptive profile and a single index value for health status. It consists of 2 parts; the EQ-5D descriptive system and the EQ-5D visual analogue scale (VAS). The EQ-5D descriptive system includes 5 dimensions; mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension measured on 3 levels: no problem (level 1), some problems (level 2), extreme problems (level 3). The digits for 5 dimensions can be combined in a 5-digit number describing the respondent's health state. The 5 dimensional 3-level systems was converted into single index utility score that ranges from less than 0 to 1, with higher scores representing a better health status.

Time frame: Baseline, up to 2.25 years (end of the Primary Treatment Period)

Population: The FAS included all participants who had received at least 1 dose of study drug (ravulizumab or placebo).

Time frame: Baseline, Week 26 (Predose and EOI)

Population: The PK/PD analysis set included participants who received at least 1 dose of study drug and who had at least 1 evaluable PK or PD result. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. 'Number analyzed' = participants evaluable at specified timepoint.

Time frame: Baseline, Weeks 26, 50, 82, and 106

Population: The safety set included all participants who received at least 1 dose of study drug (ravulizumab or placebo). Here, 'Number analyzed' = participants evaluable at specified timepoint.

The HAI is a rating scale developed to assess mobility by evaluating the time and degree of assistance required to walk 25 feet. The scale ranges from 0 to 9, with 0 being the best score (asymptomatic; fully ambulatory with no assistance) and 9 being the worst (restricted to wheelchair; unable to transfer self independently). Clinically important change is conditional on the baseline value: worsening if the baseline HAI is 0 and at least 2 points increase or if the baseline HAI is \>0 and at least 1 point increase; improvement if the baseline value is at least 2 and at least 1 point decrease; and stable if baseline is 0 or 1 and a 0- or 1-point increase or decrease or baseline is at least 2 and not change.

Time frame: Baseline up to 2.25 years (end of the Primary Treatment Period)

Population: The FAS included all participants who had received at least 1 dose of study drug (ravulizumab or placebo).

Disease-related disability was measured by the EDSS. The EDSS is an ordinal clinical rating scale that ranges from 0 (normal neurologic examination) to 10 (death) in half-point increments. Clinically important worsening was defined as an increase in EDSS score conditional on the baseline value: If the baseline EDSS was 0 and at least 2-point increase; if the baseline is 1 to 5, and at least 1-point increase; if the baseline is \> 5 and at least 0.5 increase.

Time frame: Baseline up to 2.25 years (end of the Primary Treatment Period)

Population: The FAS included all participants who had received at least 1 dose of study drug (ravulizumab or placebo).

An AE was as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An SAE was an AE that met at least 1 of the following criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization for the AE, persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug), important medical event or reaction. TEAEs were AEs with a start date on or after the date of the first dose of study drug. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.

Time frame: Baseline up to 2.25 years (end of the Primary Treatment Period)

Population: The safety set included all participants who received at least 1 dose of study drug (ravulizumab or placebo).

Time frame: Predose and end of infusion (EOI) at Week 26

Population: Pharmacokinetics/pharmacodynamics (PK/PD) analysis set included participants who received at least 1 dose of study drug and who had at least 1 evaluable PK or PD result. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. 'Number analyzed' = participants evaluable at specified timepoint.