BIIB033 In Acute Optic Neuritis (AON)

Phase 2

Completed

Conditions: Acute Optic Neuritis

Interventions: Biological: BIIB033 (anti-LINGO-1 mAb)
Drug: Placebo

Registration Number: NCT01721161

Lead Sponsor: Biogen

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 82

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
BIIB033	BIIB033 (anti-LINGO-1 mAb)	Participants will receive BIIB033 once every 4 weeks for 20 weeks (a total of 6 doses).
Placebo	Placebo	Participants will receive Placebo via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses).

Primary Outcome Measures

Name	Time	Method
Change in Full-field Visual Evoked Potential (FF-VEP) Latency at Week 24: Intent-to-treat (ITT) Population	Baseline, Week 24	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.
Change in FF-VEP Latency at Week 24: Per-protocol Population	Baseline, Week 24	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.

Secondary Outcome Measures

Name	Time	Method
Change in SD-OCT Average RGCL/IPL at Week 24: Per-protocol Population	Baseline, Week 24	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.
Percentage Change in Spectral-domain Optical Coherence Tomography (SD-OCT) Average Retinal Nerve Fiber Layer (RNFL) Thickness at Week 24: ITT Population	Baseline, Week 24	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.
Change in LCLA at Week 24: Per-protocol Population	Baseline, Week 24	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.
Change in SD-OCT Average Retinal Ganglion Cell Layer/Inner Plexiform Retinal Layer (RGCL/IPL) at Week 24: ITT Population	Baseline, Week 24	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.
Change in Low-contrast Letter Acuity (LCLA) at Week 24: ITT Population	Baseline, Week 24	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.
Percentage Change in SD-OCT Average RNFL Thickness at Week 24: Per-protocol Population	Baseline, Week 24	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.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	32 weeks	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.
Summary of BIIB033 Concentration	Up to 32 weeks	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.