A Safety and Efficacy Extension Study of ONO-4641 (MSC2430913A) in Patients With Relapsing-Remitting Multiple Sclerosis

Number of Subjects With Clinically Significant Abnormal Vital Signs

时间窗: Baseline up to Week 255

Vital signs included oral temperature, pulse, respiration rate and blood pressure (BP) (taken after 5 minutes in the sitting position). The abnormalities in vital signs were decided as clinically significant or not based on the clinical judgment of the investigator.

Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)

时间窗: Baseline, Week 40, 52, 76, 100, 124, 148, early termination, Week 152, 200, early termination 2, Week 255

FEV1 was defined as the maximal volume of air exhaled in the 1st second of a forced expiration from a position of full inspiration. FEV1 was obtained from spirometry, performed before study treatment administration. Early termination visit was recorded when the subject was early terminated from the study during the first 2.5 year period, while early termination 2 visit was recorded when the subject early terminated from the study during the additional 2 year period with delay shall be defined.

Change From Baseline in Forced Vital Capacity (FVC)

时间窗: Baseline, Week 40, 52, 76, 100, 124, 148, early termination, Week 152, 200, early termination 2, Week 255

FVC (% of predicted value) was the volume of air which was forcibly exhaled from the lungs after taking the deepest breath possible. Early termination visit was recorded when the subject was early terminated from the study during the first 2.5 year period, while early termination 2 visit was recorded when the subject early terminated from the study during the additional 2 year period with delay shall be defined.

Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO)

时间窗: Baseline, Week 40, 52, early termination, Week 152, 200, 255

DLCO was one of the most clinically valuable tests of lung function. The DLCO measure the ability of the lungs to transfer gas from inhaled air to the red blood cells in pulmonary capillaries. Early termination visit was recorded when the subject was early terminated from the study during the first 2.5 year period, while early termination 2 visit was recorded when the subject was early terminated from the study during the additional 2 year period with delay. The values for the DLCO "% of predicted" was defined as the mean value of 2 test results that were within a 10% variability of each other.

Number of Subjects With Clinically Significant Abnormal Electrocardiogram (ECG) Measures

时间窗: Baseline up to Week 255

The 12-lead ECG was recorded after the subject was in supine position for 5 minutes. ECGs were acquired on digital cardiographs. Abnormal findings were analyzed as clinically significant or not clinically significant as per the discretion of the study investigator.

Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination

时间窗: Baseline up to Week 255

Subjects underwent comprehensive ophthalmic examination (COE) including best corrected visual acuity (Snellen), manifest refractions, pupil examination, ocular motility, nystagmus, confrontation visual fields, Ishihara color plates, Amsler grid, and tonometry as well as a biomicroscopy slit lamp examination of the conjunctiva, cornea, anterior chamber, iris and lens; and a fundoscopic examination (with dilation) of the vitreous, optic nerve, retinal vessels, macula, and peripheral retina. Optical Coherence Tomography (OCT): Thicknesses of the macular retina and retinal nerve fiber layer at the optic nerve head in each eye was assessed by OCT using the fast macular thickness map scan and the fast retinal nerve fiber layer (RNFL) scan features, respectively. The abnormalities of the ophthalmologic examination was judged to be clinically significant or not as per the investigators discretion. The ophthalmologic examination was performed for both right eye (RE) and left eye (LE).

Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination

时间窗: Baseline up to end of the treatment, assessed up to Week 255

A whole body examination, paying particular attention to identify precancerous or cancerous lesions was done by a dermatologist and based on the clinical judgment of the dermatologist the abnormalities were categorized as clinically significant or clinically not significant. Early termination visit was recorded when the subject was early terminated from the study during the first 2.5 year period, while early termination 2 visit was recorded when the subject early terminated from the study during the additional 2 year period with delay shall be defined.

Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation

时间窗: From the first dose of study drug administration up to 35 days after the last dose of study drug administration, assessed up to 5 years

An Adverse Event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. A Serious Adverse Event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs were defined as the AEs that occur between first dose of study drug administration and 35 days after the last dose of study drug administration that were absent before treatment or that worsened relative to pretreatment state.