Safety and Efficacy of Daratumumab in Patients With Anti-Aquaporin 4 Antibody Positive Neuromyelitis Optica Spectrum Disorders

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 relapse adjudication committee.

The adjudicated On-trial ARR was computed as the total number of relapses divided by the total number of patient 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 adjusted for randomization strata and historical ARR in 24 months prior to Screening.

Disease-related disability was measured by the EDSS. The EDSS was an ordinal clinical rating scale that ranges from 0 (normal neurologic examination) to 10 (death) in half-point increments. A decrease in score indicates improvement.

Best corrected binocular visual acuity was measure with Early Treatment Diabetic Retinopathy Study (ETDRS) chart held at a distance of 2.52 meters.

Low-contrast visual acuity test was used to determine the number of letters that can be read on a standardized low-contrast retro-illuminated 2.5% Sloan letter chart held at a distance of 2.52 meters. Binocular score was the number of letters read correctly on the chart using both eyes simultaneously. The total score ranges from 0-70. Higher score indicates better vision.

Blood AQP4-IgG Concentration was measured by Cell-Based Assay (CBA).

Percentage of Blood ASCs was measured by flow cytometry.

Percentage of Blood NFL was measured with Simoa (Single-molecule array).

Percentage of Blood GFAP was measured with Simoa (Single-molecule array).

Disease-related disability was measured by the mRS score. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered from a neurological disability. The scale ranges from 0 (no disability) to 6 (death) in whole-point increments. A decrease in score indicates improvement.

The HAI was used to evaluate gait and assess the time and effort used by the participant to walk 25 feet (8 meters). 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 wheel chair; unable to transfer self independently). A decrease in score indicates improvement.

The EuroQoL EQ-5D was a generic, standardized, self-administered instrument that provides a simple, descriptive profile and a single index value for health status. Assessments were made using the EQ-5D Visual Analogue Scale, which captures the self-rating of current health status using a visual "thermometer" with the endpoints of 100 (best imaginable health state) at the top and zero (worst imaginable health state) at the bottom. An increase in score indicates improvement.

The EuroQoL EQ-5D was a generic, standardized, self-administered instrument that provides a simple, descriptive profile and a single index value for health status. Index scores range from less than 0 to 1, with higher scores representing a better health status.

The T25W was an assessment of walking ability. The time (in seconds) that the participant took to walk 25 feet was measured. Speed is calculated as 1/Timed 25-Foot Walk where time is measured in seconds. A positive change from baseline indicates an improvement.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.

A SAE was any AE that resulted in death, life threatening, inpatient hospitalization or prolongation of existing hospitalization