Long-Term Assessment of Remyelinating Therapy

A full field visual evoked potential (FF-VEP) is an evoked potential caused by a visual stimulus, such as an alternating checkerboard pattern on a computer screen. Responses are recorded from electrodes that are placed on the back of the head and are observed as a reading on an electroencephalogram (EEG). These responses usually originate from the occipital cortex, the area of the brain involved in receiving and interpreting visual signals.

Time frame: Baseline (RENEW Study [NCT01721161]), Day 1 (NCT02657915)

Population: Per protocol (PP) population: defined as participants from ITT population who completed the study, did not miss more than 1 dose of BIIB033 (Opicinumab) or placebo, and did not receive MS modifying therapies in RENEW Study (NCT01721161). The statistical analysis plan specified that efficacy analyses performed in PP were considered primary analyses.

Change in disease activity from baseline with brain magnetic resonance imaging (MRI) was calculated and reported. MRI analysis included number of consensus GD-enhanced lesions as a measure of disease activity.

Time frame: Baseline (RENEW Study [NCT01721161]), Day 1 (NCT02657915)

Population: The PP population was defined as participants from the ITT population who completed the study, did not miss more than one dose of BIIB033 (Opicinumab) or placebo, and did not receive MS modifying therapies in RENEW Study (NCT01721161).

Change in disease activity from baseline with brain magnetic MRI was calculated and reported. MRI analysis included volume of T2 lesions as disease activity.

Time frame: Baseline (RENEW Study [NCT01721161]), Day 1 (NCT02657915)

Population: The PP population was defined as participants from the ITT population who completed the study, did not miss more than one dose of BIIB033 (Opicinumab) or placebo, and did not receive MS modifying therapies in RENEW Study (NCT01721161).

The diagnosis of clinically definite multiple sclerosis (CDMS) was made on the basis of clinical criteria and requires that a patient experience at least 2 neurologic events consistent with demyelination, separated both in time and in location in the central nervous system.

Time frame: RENEW Study (NCT01721161) to Day 1 (NCT02657915)

Population: The PP population was defined as participants from the ITT population who completed the study, did not miss more than one dose of BIIB033 (Opicinumab) or placebo, and did not receive MS modifying therapies in RENEW Study (NCT01721161).

The EDSS score is based on neurological testing and an examination of functional systems (FS), which are areas of the central nervous system which control bodily functions. These functional systems are: pyramidal (ability to walk), Cerebellar (coordination), brain stem (speech and swallowing), sensory (touch and pain), bowel and bladder functions, visual, mental and Other (includes any other neurological findings due to MS). An overall score ranging from 0 (normal) to 10 (disability) was calculated. Higher scores indicate greater disability.

Time frame: Day 1 (NCT02657915)

Population: The PP population was defined as participants from the ITT population who completed the study, did not miss more than one dose of BIIB033 (Opicinumab) or placebo, and did not receive MS modifying therapies in RENEW Study (NCT01721161).

MSFC has 3 component- timed 25-foot walk (T25FW), 9-hole peg test (9HPT) \[dominant and nondominant hands\] and (3-second) paced auditory serial addition Test (PASAT). The MSFC Z-score is calculated by creating Z-scores for each component of the MSFC and averaging them to create an overall composite score. MSFC Z-score = (Z25-foot-walk + Z9HPT + ZPASAT-3)/3, where Zj refers to Z-scores of component j. A Z-score represented the number of standard deviations participant's test result was higher (Z \>0) or lower (Z \<0) than the average test result (Z = 0) from the reference population. Higher scores indicate better outcomes.

Time frame: Day 1 (NCT02657915)

Population: The PP population was defined as participants from the ITT population who completed the study, did not miss more than one dose of BIIB033 (Opicinumab) or placebo, and did not receive MS modifying therapies in RENEW Study (NCT01721161).

SDMT is a screening test for cognitive impairment. Participants were given 90 seconds in which to pair specific numbers with given geometric figures using a key. Scores range from 0 to 110 (best). Originate from the occipital cortex, the area of the brain involved in receiving and interpreting visual signals.

Time frame: Day 1 (NCT02657915)

Population: The PP population was defined as participants from the ITT population who completed the study, did not miss more than one dose of BIIB033 (Opicinumab) or placebo, and did not receive MS modifying therapies in RENEW Study (NCT01721161).

The diagnosis of CDMS was made on the basis of clinical criteria and requires that a patient experience at least 2 neurologic events consistent with demyelination, separated both in time and in location in the central nervous system. Time to diagnosis of CDMS in Study NCT02657915 was the time from the diagnosis of acute optic neuritis (AON) to the date of confirmed MS. Measured in Days using the Median (50th percentile) for each arm.

Time frame: RENEW Study (NCT01721161) to Day 1 (NCT02657915)

Population: The PP population was defined as participants from the ITT population who completed the study, did not miss more than one dose of BIIB033 (Opicinumab) or placebo, and did not receive MS modifying therapies in RENEW Study (NCT01721161).