Long-Term Assessment of Remyelinating Therapy

Study Overview
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Brief Summary
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The primary objective of the study is to assess full-field visual evoked potential (FF-VEP) latency in subjects who were enrolled in Study NCT01721161 2 years (+ up to 12 months) after the last study visit. The secondary objective is to assess clinical progression and severity of central nervous system (CNS) demyelinating disease in subjects who were enrolled in Study NCT01721161 2 years (+ up to 12 months) after the last study visit. Intervention was administered in the previous study. The participants, investigator and outcome assessors remain blinded in this follow-up study.

Official Title
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A Multicenter, Follow-Up Study to Assess Long-Term Electrophysiologic and Clinical Outcomes in Subjects Previously Enrolled in Study 215ON201

Conditions
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Acute Optic Neuritis

Intervention / Treatment
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* Drug: Placebo
* Drug: BIIB033 100mg/Kg


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Must have participated in Study NCT01721161 and received at least 1 dose of BIIB033 or placebo, as per protocol, within 2 years (+ 4 months) from Day 1 of this study (2 years from Week 32 or projected Week 32 visit, if the subject did not complete all visits in Study NCT01721161). Key Exclusion Criteria: Not previously enrolled in Study NCT01721161 Subjects with recent kidney function, such as serum creatinine above upper limit of normal range, will not be allowed to receive administration of Gd but will otherwise be allowed to participate in the study, including magnetic resonance imaging (MRI) assessments not requiring the use of Gd. Female subjects must have had a recent pregnancy test and must not be breastfeeding prior to MRI assessments with Gd. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>This was a follow-up study, investigational product was administered in the previous study. Participants in the placebo arm have received at least 1 dose of placebo. | Drug: Placebo<br>* Administered as specified in the treatment arm.<br>* Other names: Sterile normal saline (0.9% sodium chloride for IV administration);|
| Experimental: BIIB033 100mg/Kg<br>This was a follow-up study, investigational product was administered in the previous study. Participants in the BIIB033 arm have received at least 1 dose of 100 mg/kg BIIB033. | Drug: BIIB033 100mg/Kg<br>* Administered as specified in the treatment arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FF-VEP Latency of the Affected Eye as Compared to the Baseline of the Fellow Eye at 2 Years (+ up to 12 Months) After the Last Study Visit Assessment (Week 32) in RENEW Study (NCT01721161) | 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. | Baseline (RENEW Study [NCT01721161]), Day 1 (NCT02657915) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants That Developed Clinically Definite Multiple Sclerosis (CDMS) After Enrollment 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. | RENEW Study (NCT01721161) to Day 1 (NCT02657915) | 
| Time to Diagnosis of CDMS | 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. | RENEW Study (NCT01721161) to Day 1 (NCT02657915) | 
| Severity of Central Nervous System (CNS) Demyelinating Disease as Assessed Using the Expanded Disability Status Scale (EDSS) | 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. | Day 1 (NCT02657915) | 
| Severity of CNS Demyelinating Disease as Assessed Using the Symbol- Digit Modalities Test (SDMT) | 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. | Day 1 (NCT02657915) | 
| Severity of CNS Demyelinating Disease as Assessed Using the Multiple Sclerosis Functional Composite (MSFC) Assessment | 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. | Day 1 (NCT02657915) | 
| Change in Number of Gadolinium (Gd)-Enhanced Lesions From Baseline in RENEW Study (NCT01721161) to Day 1 (NCT02657915) | 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. | Baseline (RENEW Study [NCT01721161]), Day 1 (NCT02657915) | 
| Change in Volume of T2 Lesions From Baseline in RENEW Study (NCT01721161) to Day 1 (NCT02657915) | Change in disease activity from baseline with brain magnetic MRI was calculated and reported. MRI analysis included volume of T2 lesions as disease activity. | Baseline (RENEW Study [NCT01721161]), Day 1 (NCT02657915) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AON, FF-VEP, mfVEP, Human anti-LINGO-1, BIIB033