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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BIIB033 | Experimental | Participants will receive BIIB033 once every 4 weeks for 20 weeks (a total of 6 doses). |
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| Placebo | Placebo Comparator | Participants will receive Placebo via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BIIB033 (anti-LINGO-1 mAb) | Biological | 100 mg/kg via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses). |
|
| 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 |
| 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. |
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Key Inclusion Criteria:
Key Exclusion Criteria:
NOTE: Other protocol-defined inclusion/exclusion criteria may apply.
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Biogen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Parkville | Australia | ||||
| Research Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30267385 | Derived | 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. | |
| 30095536 | Derived |
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Placebo via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses) |
| FG001 | BIIB033 | BIIB033 100 mg/kg via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses) |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Placebo | Drug | via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses) |
|
| 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 |
| Sydney |
| Australia |
| Research Site | Bruges | Belgium |
| Research Site | Brussels | Belgium |
| Research Site | Ghent | Belgium |
| Research Site | Limbourg | Belgium |
| Research Site | Halifax | Canada |
| Research Site | Ottawa | Canada |
| Research Site | Olomouc | Czechia |
| Research Site | Prague | Czechia |
| Research Site | Glostrup Municipality | Denmark |
| Research Site | Bamberg | Germany |
| Research Site | Berlin | Germany |
| Research Site | Dresden | Germany |
| Research Site | Düsseldorf | Germany |
| Research Site | Tübingen | Germany |
| Research Site | Budapest | Hungary |
| Research Site | Fidenza | Italy |
| Research Site | Florence | Italy |
| Research Site | Milan | Italy |
| Research site | Roma | Italy |
| Research Site | Barcelona | Spain |
| Research Site | Córdoba | Spain |
| Research Site | Palmar | Spain |
| Research Site | Seville | Spain |
| Research Site | Valencia | Spain |
| Research Site | Lund | Sweden |
| Research Site | Stockholm | Sweden |
| Research Site | Birmingham | United Kingdom |
| Research Site | Glasgow | United Kingdom |
| Research Site | Leicester | United Kingdom |
| Research Site | London | United Kingdom |
| 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. |
| 28229892 | Derived | 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. |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Placebo via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses) |
| BG001 | BIIB033 | BIIB033 100 mg/kg via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses) |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Days from first AON symptom to first dose | First dose given, on average, 2 weeks after completion of high-dose (1 g daily for 3 to 5 days) IV methylprednisolone treatment. | Mean | Standard Deviation | days |
| ||||||||||||||
| Days from confirmed AON diagnosis to first dose | Mean | Standard Deviation | days |
| |||||||||||||||
| Affected eye | Number | participants |
| ||||||||||||||||
| Criteria for AON diagnosis | Number | participants |
| ||||||||||||||||
| AON signs and symptoms at screening or baseline | Symptoms were not uniformly tested in accordance with a predefined protocol. | Number | participants |
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| FF-VEP conduction block in the affected eye at baseline | FF-VEP=full-field visual evoked potentials | Number | participants |
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| FF-VEP latency in the fellow eye at baseline | Mean | Standard Deviation | ms |
| |||||||||||||||
| RGCL/IPL thickness in the affected eye at baseline | RGCL/IPL=retinal ganglion cell layer/inner plexiform retinal layer. n=38 in the placebo group and n=40 in the anti-LINGO-1 group, total n=78. | Mean | Standard Deviation | microns |
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| Brain Gd+ lesions before first dose | Gd+=gadolinium-enhancing. n=38 in each group, total n=76. | Mean | Standard Deviation | lesions |
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| Volume of brain T2 lesions before first dose | n=38 in each group, total n=76. | Mean | Standard Deviation | mL |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | 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. | Posted | Mean | Standard Error | msec | Baseline, Week 24 |
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| Secondary | 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. | ITT population: all randomized subjects who received at least 1 dose of study treatment (BIIB033 or placebo) and a valid RNFL assessment at Baseline. LOCF imputation was used if Week 24 data were missing. | Posted | Mean | Standard Error | percentage change | Baseline, Week 24 |
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| Secondary | 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. | 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 MS-modifying therapies during the study period, which were prohibited per protocol. LOCF imputation was used if Week 24 data were missing. | Posted | Mean | Standard Error | percentage change | Baseline, Week 24 |
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| Secondary | 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. | ITT population: all randomized subjects who received at least 1 dose of study treatment (BIIB033 or placebo) with a valid RGCL/IPL assessment at Baseline. LOCF imputation was used if Week 24 data were missing. | Posted | Mean | Standard Deviation | µm | Baseline, Week 24 |
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| Secondary | 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. | 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 MS-modifying therapies during the study period, which were prohibited per protocol. LOCF imputation was used if Week 24 data were missing. | Posted | Mean | Standard Deviation | µm | Baseline, Week 24 |
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| Secondary | 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. | ITT population: all randomized subjects who received at least 1 dose of study treatment (BIIB033 or placebo) with an LCLA assessment at Baseline. LOCF imputation was used if Week 24 data were missing. | Posted | Mean | Standard Deviation | letters on a chart | Baseline, Week 24 |
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| Secondary | 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. | 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 MS-modifying therapies during the study period, which were prohibited per protocol. LOCF imputation was used if Week 24 data were missing. | Posted | Mean | Standard Error | letters on a chart | Baseline, Week 24 |
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| Primary | 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. | 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. | Posted | Mean | Standard Error | msec | Baseline, Week 24 |
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| Secondary | 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. | Safety population: all participants who received at least 1 dose of study treatment. | Posted | Number | participants | 32 weeks |
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| Secondary | 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. | PK analysis population: all participants who received at least 1 dose of BIIB033 and had at least 1 serum concentration data on record. n=number of participants with a sample at given timepoint. | Posted | Median | Full Range | µg/mL | Up to 32 weeks |
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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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Placebo via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses) | 2 | 41 | 25 | 41 | ||
| EG001 | BIIB033 100 mg/kg | BIIB033 100 mg/kg via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses) | 5 | 41 | 27 | 41 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Liver disorder | Hepatobiliary disorders | MedDRA 17.0 | Systematic Assessment |
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| Hypersensitivity | Immune system disorders | MedDRA 17.0 | Systematic Assessment |
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| Viral pericarditis | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA 17.0 | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA 17.0 | Systematic Assessment |
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| Cytomegalovirus test positive | Investigations | MedDRA 17.0 | Systematic Assessment |
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| Multiple sclerosis | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
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| Multiple sclerosis relapse | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
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| Optic neuritis | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Colour blindness acquired | Eye disorders | MedDRA 17.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 17.0 | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Systematic Assessment |
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| Dysaesthesia | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
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| Multiple sclerosis | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
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| Paraesthesia | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
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| Uhthoff's phenomenon | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
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| Visual field defect | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
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Our agreement is subject to confidentiality but generally the PI can publish, for noncommercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Biogen Study Medical Director | Biogen | clinicaltrials@biogen.com |
| ID | Term |
|---|---|
| D009902 | Optic Neuritis |
| ID | Term |
|---|---|
| D009901 | Optic Nerve Diseases |
| D003389 | Cranial Nerve Diseases |
| D009422 | Nervous System Diseases |
| D005128 | Eye Diseases |
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| ID | Term |
|---|---|
| C000625770 | opicinumab |
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| Male |
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| Left eye |
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| Decreased color vision |
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| Relative afferent pupillary defect |
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| Visual field defect |
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| Ocular pain |
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| Not specified |
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| Color desaturation |
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| Uhthoff's symptom |
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| Swollen optic disc |
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| Relative afferent pupillary defect |
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| No FF-VEP conduction block |
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| Units | Counts |
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| Participants |
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