Acute Optic NeuritisPhase 2NCT01721161

BIIB033 In Acute Optic Neuritis (AON)

A Phase 2 study testing BIIB033 (anti-LINGO-1 mAb) in people with Acute Optic Neuritis, run by Biogen at 32 sites in 11 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 55 years
Conditions the study is for: Acute Optic Neuritis
What is being tested?: BIIB033 (anti-LINGO-1 mAb)
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 82 participants
Where: 32 sitesin 11 countries
Study dates: Dec 2012to Oct 2014
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 55 years
All sexes
No healthy volunteers
Adult

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

32 sites in 11 countries.

Country

City, postcode or hospital

32 sites in 11 countries

Germany5 sites

Research Site
Bamberg
Research Site
Berlin
Research Site
Dresden
Research Site
Düsseldorf
Research Site
Tübingen

Other trials in Germany

Spain5 sites

Research Site
Barcelona
Research Site
Córdoba
Research Site
Palmar
Research Site
Seville
Research Site
Valencia

Other trials in Spain

Belgium4 sites

Research Site
Bruges
Research Site
Brussels
Research Site
Ghent
Research Site
Limbourg

Other trials in Belgium

Italy4 sites

Research Site
Fidenza
Research Site
Florence
Research Site
Milan
Research site
Roma

Other trials in Italy

United Kingdom4 sites

Research Site
Birmingham
Research Site
Glasgow
Research Site
Leicester
Research Site
London

Other trials in United Kingdom

Australia2 sites

Research Site
Parkville
Research Site
Sydney

Other trials in Australia

Canada2 sites

Research Site
Halifax
Research Site
Ottawa

Other trials in Canada

Czechia2 sites

Research Site
Olomouc
Research Site
Prague

Other trials in Czechia

Sweden2 sites

Research Site
Lund
Research Site
Stockholm

Other trials in Sweden

Denmark1 site

Research Site
Glostrup Municipality

Other trials in Denmark

Hungary1 site

Research Site
Budapest

Other trials in Hungary

About this study

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
Being tested: BIIB033 (anti-LINGO-1 mAb), Placebo
Keywords: Optic Neuritis
Medical subject headings: Optic Neuritis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BIIB033 (anti-LINGO-1 mAb)Biological
Also called anti-LINGO-1 monoclonal antibody (mAb), Opicinumab
100 mg/kg via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses).
PlaceboDrug
via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses)

Study groups in NCT01721161
Study group	Role	What they receive
BIIB033	Experimental	Participants will receive BIIB033 once every 4 weeks for 20 weeks (a total of 6 doses). Receives: Biological: BIIB033 (anti-LINGO-1 mAb)
Placebo	Placebo comparator	Participants will receive Placebo via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses). Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: Baseline, Week 24

Secondary outcomes (8)

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to 32 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Dec 2012Oct 2014

First posted5 Nov 2012 (estimated)
Study startDec 2012
Primary completionOct 2014
Study completionOct 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Acute Optic NeuritisStudies of the same condition, open and under way.
More trials run by BiogenThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 82 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01721161
Sponsor's protocol ID: 215ON201
Status last verified: May 2016
First submitted: 25 Oct 2012
Last updated: 30 Jun 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

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.
PubMed 30267385
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.
PubMed 30095536
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.
PubMed 28229892

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Acute Optic Neuritis trials

Study at a glance

From the registry record, last updated by the sponsor on 30 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01721161
Acronym / sponsor ID: 215ON201
Conditions: Acute Optic Neuritis
Keywords: Optic Neuritis
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 82 participants (actual)
Lead sponsor: BiogenIndustry (pharma, biotech, devices)
Study start: Dec 2012
Primary completion: Oct 2014 (actual)
Study completion: Oct 2014 (actual)
First posted: 5 Nov 2012 (estimated)
Results: Posted 30 Jun 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
BIIB033	Experimental	Biological: BIIB033 (anti-LINGO-1 mAb)Participants will receive BIIB033 once every 4 weeks for 20 weeks (a total of 6 doses).
Placebo	Placebo comparator	Drug: PlaceboParticipants will receive Placebo via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses).

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (3 listed)

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 (8 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
BIIB033 (anti-LINGO-1 mAb)Also: anti-LINGO-1 monoclonal antibody (mAb), Opicinumab100 mg/kg via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses).	Biological	BIIB033
Placebovia IV infusion once every 4 weeks for 20 weeks (a total of 6 doses)	Drug	Placebo

Primary outcome

Change in Full-field Visual Evoked Potential (FF-VEP) Latency at Week 24: Intent-to-treat (ITT) Population
Time frame: 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
Time frame: 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.

8 secondary outcomes

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
Percentage Change in SD-OCT Average RNFL Thickness at Week 24: Per-protocol Population
Time frame: Baseline, Week 24
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
Change in SD-OCT Average RGCL/IPL at Week 24: Per-protocol Population
Time frame: Baseline, Week 24
Change in Low-contrast Letter Acuity (LCLA) at Week 24: ITT Population
Time frame: Baseline, Week 24
Change in LCLA at Week 24: Per-protocol Population
Time frame: Baseline, Week 24
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: 32 weeks
Summary of BIIB033 Concentration
Time frame: Up to 32 weeks

Results and safety

Results posted to the registry on 30 Jun 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo	41	37
BIIB033	41	34

Primary outcome: Change in Full-field Visual Evoked Potential (FF-VEP) Latency at Week 24: Intent-to-treat (ITT) Population

Time frame: Baseline, Week 24. Mean (Standard Error). Unit: msec

Measure	Placebo n = 41	BIIB033 n = 41
Value	20.83 (2.53)	17.34 (2.53)

Placebo vs BIIB033: Difference: -3.48 (95% CI -10.61 to 3.65), p = 0.3337, ANCOVA

Population analysed: ITT population: all randomized subjects who received at least 1 dose of study treatment (BIIB033 or placebo). Last observation carried forward (LOCF) imputation was used if Week 24 data were missing.

Primary outcome: Change in FF-VEP Latency at Week 24: Per-protocol Population

Time frame: Baseline, Week 24. Mean (Standard Error). Unit: msec

Measure	Placebo n = 36	BIIB033 n = 33
Value	22.24 (2.61)	14.69 (2.72)

Placebo vs BIIB033: Difference: -7.55 (95% CI -15.12 to 0.01), p = 0.0504, ANCOVA

Population analysed: Per-protocol Population: participants from the ITT population who completed the study, did not miss more than 1 dose of BIIB033 or placebo, and did not receive multiple sclerosis (MS)-modifying therapies during the study period, which were prohibited per protocol. LOCF imputation was used if Week 24 data were missing.

8 secondary outcomes are reported in the full results.

Adverse events

Time frame: AEs were monitored from administration of first dose of study treatment through to Week 32 visit. SAEs were monitored from signing of the Informed Consent Form (ICF) through to Week 32 visit.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	2 of 41 (4.9%)	25 of 41 (61%)	Not reported
BIIB033 100 mg/kg	5 of 41 (12.2%)	27 of 41 (65.9%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Jun 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 30267385Klistorner 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.
Derived from this study: PubMed 30095536Petrillo 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.
Derived from this study: PubMed 28229892Cadavid 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.

Related trials for Acute Optic Neuritis

RecruitingPhase 2
Efgartigimod for the Treatment of Acute Optic Neuritis
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Biobank For MS And Other Demyelinating Diseases
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Biogen

32 sites in 11 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing BIIB033 (anti-LINGO-1 mAb) in people with Acute Optic Neuritis, run by Biogen at 32 sites in 11 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 32 sites in Germany, Spain, Belgium, Italy, United Kingdom and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Jun 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Full-field Visual Evoked Potential (FF-VEP) Latency at Week 24: Intent-to-treat (ITT) Population (time frame: Baseline, Week 24). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01721161, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jun 2016.