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BIIB033 In Acute Optic Neuritis (AON)

Primary Purpose

Acute Optic Neuritis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
BIIB033 (anti-LINGO-1 mAb)
Placebo
Sponsored by
Biogen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Optic Neuritis focused on measuring Optic Neuritis

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

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Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

BIIB033

Placebo

Arm Description

Participants will receive BIIB033 once every 4 weeks for 20 weeks (a total of 6 doses).

Participants will receive Placebo via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses).

Outcomes

Primary Outcome Measures

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.
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.

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
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
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
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
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
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
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)
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
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.

Full Information

First Posted
October 25, 2012
Last Updated
May 24, 2016
Sponsor
Biogen
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1. Study Identification

Unique Protocol Identification Number
NCT01721161
Brief Title
BIIB033 In Acute Optic Neuritis (AON)
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2016
Overall Recruitment Status
Completed
Study Start Date
December 2012 (undefined)
Primary Completion Date
October 2014 (Actual)
Study Completion Date
October 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biogen

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Optic Neuritis
Keywords
Optic Neuritis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
82 (Actual)

8. Arms, Groups, and Interventions

Arm Title
BIIB033
Arm Type
Experimental
Arm Description
Participants will receive BIIB033 once every 4 weeks for 20 weeks (a total of 6 doses).
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will receive Placebo via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses).
Intervention Type
Biological
Intervention Name(s)
BIIB033 (anti-LINGO-1 mAb)
Other Intervention Name(s)
anti-LINGO-1 monoclonal antibody (mAb), Opicinumab
Intervention Description
100 mg/kg via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses).
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses)
Primary Outcome Measure Information:
Title
Change in Full-field Visual Evoked Potential (FF-VEP) Latency at Week 24: Intent-to-treat (ITT) Population
Description
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.
Time Frame
Baseline, Week 24
Title
Change in FF-VEP Latency at Week 24: Per-protocol Population
Description
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.
Time Frame
Baseline, Week 24
Secondary Outcome Measure Information:
Title
Percentage Change in Spectral-domain Optical Coherence Tomography (SD-OCT) Average Retinal Nerve Fiber Layer (RNFL) Thickness at Week 24: ITT Population
Description
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.
Time Frame
Baseline, Week 24
Title
Percentage Change in SD-OCT Average RNFL Thickness at Week 24: Per-protocol Population
Description
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.
Time Frame
Baseline, Week 24
Title
Change in SD-OCT Average Retinal Ganglion Cell Layer/Inner Plexiform Retinal Layer (RGCL/IPL) at Week 24: ITT Population
Description
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.
Time Frame
Baseline, Week 24
Title
Change in SD-OCT Average RGCL/IPL at Week 24: Per-protocol Population
Description
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.
Time Frame
Baseline, Week 24
Title
Change in Low-contrast Letter Acuity (LCLA) at Week 24: ITT Population
Description
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.
Time Frame
Baseline, Week 24
Title
Change in LCLA at Week 24: Per-protocol Population
Description
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.
Time Frame
Baseline, Week 24
Title
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
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.
Time Frame
32 weeks
Title
Summary of BIIB033 Concentration
Description
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.
Time Frame
Up to 32 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Biogen
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Parkville
Country
Australia
Facility Name
Research Site
City
Sidney
Country
Australia
Facility Name
Research Site
City
Brugge
Country
Belgium
Facility Name
Research Site
City
Brussels
Country
Belgium
Facility Name
Research Site
City
Ghent
Country
Belgium
Facility Name
Research Site
City
Limburg
Country
Belgium
Facility Name
Research Site
City
Halifax
Country
Canada
Facility Name
Research Site
City
Ottawa
Country
Canada
Facility Name
Research Site
City
Olomouc
Country
Czech Republic
Facility Name
Research Site
City
Prague
Country
Czech Republic
Facility Name
Research Site
City
Glostrup
Country
Denmark
Facility Name
Research Site
City
Bamberg
Country
Germany
Facility Name
Research Site
City
Berlin
Country
Germany
Facility Name
Research Site
City
Dresden
Country
Germany
Facility Name
Research Site
City
Dusseldorf
Country
Germany
Facility Name
Research Site
City
Tubingen
Country
Germany
Facility Name
Research Site
City
Budapest
Country
Hungary
Facility Name
Research Site
City
Fidenza
Country
Italy
Facility Name
Research Site
City
Firenze
Country
Italy
Facility Name
Research Site
City
Milano
Country
Italy
Facility Name
Research site
City
Roma
Country
Italy
Facility Name
Research Site
City
Barcelona
Country
Spain
Facility Name
Research Site
City
Cordoba
Country
Spain
Facility Name
Research Site
City
Palmar
Country
Spain
Facility Name
Research Site
City
Sevilla
Country
Spain
Facility Name
Research Site
City
Valencia
Country
Spain
Facility Name
Research Site
City
Lund
Country
Sweden
Facility Name
Research Site
City
Stockholm
Country
Sweden
Facility Name
Research Site
City
Birmingham
Country
United Kingdom
Facility Name
Research Site
City
Glasgow
Country
United Kingdom
Facility Name
Research Site
City
Leicester
Country
United Kingdom
Facility Name
Research Site
City
London
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
30267385
Citation
Klistorner A, Chai Y, Leocani L, Albrecht P, Aktas O, Butzkueven H, Ziemssen T, Ziemssen F, Frederiksen J, Xu L, Cadavid D; RENEW MF-VEP Investigators. Assessment of Opicinumab in Acute Optic Neuritis Using Multifocal Visual Evoked Potential. CNS Drugs. 2018 Dec;32(12):1159-1171. doi: 10.1007/s40263-018-0575-8.
Results Reference
derived
PubMed Identifier
30095536
Citation
Petrillo J, Balcer L, Galetta S, Chai Y, Xu L, Cadavid D. Initial Impairment and Recovery of Vision-Related Functioning in Participants With Acute Optic Neuritis From the RENEW Trial of Opicinumab. J Neuroophthalmol. 2019 Jun;39(2):153-160. doi: 10.1097/WNO.0000000000000697.
Results Reference
derived
PubMed Identifier
28229892
Citation
Cadavid D, Balcer L, Galetta S, Aktas O, Ziemssen T, Vanopdenbosch L, Frederiksen J, Skeen M, Jaffe GJ, Butzkueven H, Ziemssen F, Massacesi L, Chai Y, Xu L, Freeman S; RENEW Study Investigators. Safety and efficacy of opicinumab in acute optic neuritis (RENEW): a randomised, placebo-controlled, phase 2 trial. Lancet Neurol. 2017 Mar;16(3):189-199. doi: 10.1016/S1474-4422(16)30377-5. Epub 2017 Feb 15.
Results Reference
derived

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BIIB033 In Acute Optic Neuritis (AON)

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