BIIB033 In Acute Optic Neuritis (AON)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Biogen
ClinicalTrials.gov Identifier:
NCT01721161
First received: October 25, 2012
Last updated: May 24, 2016
Last verified: May 2016
  Purpose
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.

Condition Intervention Phase
Acute Optic Neuritis
Biological: BIIB033 (anti-LINGO-1 mAb)
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Biogen:

Primary Outcome Measures:
  • Change in Full-field Visual Evoked Potential (FF-VEP) Latency at Week 24: Intent-to-treat (ITT) Population [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    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:
  • Percentage Change in Spectral-domain Optical Coherence Tomography (SD-OCT) Average Retinal Nerve Fiber Layer (RNFL) Thickness at Week 24: ITT Population [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    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.

  • Percentage Change in SD-OCT Average RNFL Thickness at Week 24: Per-protocol Population [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    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 SD-OCT Average Retinal Ganglion Cell Layer/Inner Plexiform Retinal Layer (RGCL/IPL) at Week 24: ITT Population [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    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 SD-OCT Average RGCL/IPL at Week 24: Per-protocol Population [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    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 LCLA at Week 24: Per-protocol Population [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: 32 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 32 weeks ] [ Designated as safety issue: No ]
    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.


Enrollment: 82
Study Start Date: December 2012
Study Completion Date: October 2014
Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BIIB033
Participants will receive BIIB033 once every 4 weeks for 20 weeks (a total of 6 doses).
Biological: BIIB033 (anti-LINGO-1 mAb)
100 mg/kg via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses).
Other Names:
  • anti-LINGO-1 monoclonal antibody (mAb)
  • Opicinumab
Placebo Comparator: Placebo
Participants will receive Placebo via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses).
Drug: Placebo
via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses)

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01721161

  Show 32 Study Locations
Sponsors and Collaborators
Biogen
Investigators
Study Director: Medical Director Biogen
  More Information

Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT01721161     History of Changes
Other Study ID Numbers: 215ON201 
Study First Received: October 25, 2012
Results First Received: May 24, 2016
Last Updated: May 24, 2016
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Spain: Spanish Agency for Medicines and Health Products
Australia: Department of Health and Ageing Therapeutic Goods Administration
Italy: The Italian Medicines Agency
Czech Republic: State Institute for Drug Control
Sweden: Medical Products Agency
Hungary: National Institute of Pharmacy
Canada: Health Canada
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Germany: Paul-Ehrlich-Institut

Keywords provided by Biogen:
Optic Neuritis

Additional relevant MeSH terms:
Neuritis
Optic Neuritis
Peripheral Nervous System Diseases
Neuromuscular Diseases
Nervous System Diseases
Optic Nerve Diseases
Cranial Nerve Diseases
Eye Diseases

ClinicalTrials.gov processed this record on August 29, 2016