BIIB033 In Acute Optic Neuritis (AON)

Study Overview
=================
Brief Summary
-----------------
The primary objective of the study is to evaluate the efficacy of BIIB033 in subjects with their first episode of unilateral acute optic neuritis (AON). The secondary objective of this study is to assess the safety, tolerability, and pharmacokinetics (PK) of BIIB033 in this study population.

Official Title
-----------------
A Randomized, Double-Blind, Parallel-Group, Placebo Controlled Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of BIIB033 in Subjects With First Episode of Acute Optic Neuritis

Conditions
-----------------
Acute Optic Neuritis

Intervention / Treatment
-----------------
* Biological: BIIB033 (anti-LINGO-1 mAb)
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Ability to provide written consent and any authorization required by law. Confirmed diagnosis of AON All male or female subjects of childbearing potential must practice effective contraception during the study and be willing and able to continue contraception for at least 6 months after their last dose of study treatment. Key Exclusion Criteria: Prior episode(s) of optic neuritis or loss of vision not due to AON. Subjects with an established diagnosis of multiple sclerosis are excluded except if newly diagnosed based on the current episode of AON and positive brain magnetic resonance imaging results consistent with the 2010 revisions to the McDonald's criteria. Previous history of a clinically significant disease. Females who have a positive pregnancy test result, or who are pregnant, breastfeeding, or planning to conceive during the study. History of human immunodeficiency virus (HIV), hepatitis C virus antibody, or hepatitis B virus. History or evidence of drug or alcohol abuse within 2 years prior to Screening. Current enrollment in any other study treatment or disease study within 3 months prior to Day 1/Baseline. NOTE: Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BIIB033<br>Participants will receive BIIB033 once every 4 weeks for 20 weeks (a total of 6 doses). | Biological: BIIB033 (anti-LINGO-1 mAb)<br>* 100 mg/kg via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses).<br>* Other names: Opicinumab;|
| Placebo Comparator: Placebo<br>Participants will receive Placebo via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses). | Drug: Placebo<br>* via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Full-field Visual Evoked Potential (FF-VEP) Latency at Week 24: Intent-to-treat (ITT) Population | Adjusted mean change in optic nerve conduction velocity (NCV) at Week 24 for the affected eye from the baseline of unaffected fellow eye as determined by FF-VEP. Adjusted for the baseline latency of fellow eye. | Baseline, Week 24 | 
| Change in FF-VEP Latency at Week 24: Per-protocol Population | Adjusted mean change in optic nerve conduction velocity (NCV) at Week 24 for the affected eye from the baseline of unaffected fellow eye as determined by FF-VEP. Adjusted for the baseline latency of fellow eye. | Baseline, Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change in Spectral-domain Optical Coherence Tomography (SD-OCT) Average Retinal Nerve Fiber Layer (RNFL) Thickness at Week 24: ITT Population | Adjusted mean percentage change in thickness of the RNFL at Week 24 for the affected eye from the baseline of unaffected fellow eye as determined by SD-OCT. Percentage change is calculated as (affected eye - baseline of fellow eye)/baseline of fellow eye*100. Adjusted for the baseline RNFL thickness. | Baseline, Week 24 | 
| Percentage Change in SD-OCT Average RNFL Thickness at Week 24: Per-protocol Population | Adjusted mean percentage change in thickness of the RNFL at Week 24 for the affected eye from the baseline of unaffected fellow eye as determined by SD-OCT. Percentage change is calculated as (affected eye - baseline of fellow eye)/baseline of fellow eye*100. Adjusted for the baseline RNFL thickness. | Baseline, Week 24 | 
| Change in SD-OCT Average Retinal Ganglion Cell Layer/Inner Plexiform Retinal Layer (RGCL/IPL) at Week 24: ITT Population | Adjusted mean change in thicknesses of the RGCL/IPL at Week 24 for the affected eye from the baseline of unaffected fellow eye as determined by segmentation of SD-OCT. Adjusted for the baseline RGCL/IPL thickness. | Baseline, Week 24 | 
| Change in SD-OCT Average RGCL/IPL at Week 24: Per-protocol Population | Adjusted mean change in thicknesses of the RGCL/IPL at Week 24 for the affected eye from the baseline of unaffected fellow eye as determined by segmentation of SD-OCT. Adjusted for the baseline RGCL/IPL thickness. | Baseline, Week 24 | 
| Change in Low-contrast Letter Acuity (LCLA) at Week 24: ITT Population | Adjusted mean change in LCLA at Week 24 from baseline as determined by 1.25% and 2.5% low contrast Sloan letter charts, adjusted for the baseline LCLA value. The fellow eye is the reference eye for the inter-eye asymmetry. The range for LCLA assessment is 0-60. | Baseline, Week 24 | 
| Change in LCLA at Week 24: Per-protocol Population | Adjusted mean change in LCLA at Week 24 from baseline as determined by 1.25% and 2.5% low contrast Sloan letter charts, adjusted for the baseline LCLA value. The fellow eye is the reference eye for the inter-eye asymmetry. The range for LCLA assessment is 0-60. | Baseline, Week 24 | 
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE was any untoward medical occurrence that did not necessarily have a causal relationship with this treatment. An SAE was any untoward medical occurrence that at any dose: resulted in death; in the view of the Investigators, placed the subject at immediate risk of death (a life-threatening event); however, this did not include an event that, had it occurred in a more severe form, might have caused death; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigators, could have jeopardized the subject or may have required intervention to prevent one of the other outcomes listed in the definition above. | 32 weeks | 
| Summary of BIIB033 Concentration | One pre-dose pharmacokinetic (PK) sample and 1 post-dose PK sample (approximately between 1 and 3 hours after the end of IV infusion) were collected for all participants on Day 1 and at Weeks 4 through 20 (every 4 weeks). Additionally, only 1 PK sample was collected at Week 24 and Week 32. (There was no dosing on Week 24 and Week 32, so only one blood sample for BIIB033 concentration was taken.) Samples collected at early termination visits were treated as predose samples for the next scheduled visit. | Up to 32 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Optic Neuritis