Using Optical Coherence Tomography (OCT) to Evaluate the Efficacy and Safety of PEGylated Interferon Beta-1a (BIIB017) in Patients With Relapsing Multiple Sclerosis

Study Overview
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Brief Summary
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This research sub-study is being completed as a part of the Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study to Evaluate the Efficacy and Safety of PEGylated Interferon Beta-1a (BIIB017) in Subjects with Relapsing Multiple Sclerosis (Protocol #: NA_00028117). This substudy is being done to understand the efficacy of BIIB017 by measuring the nerve fiber thickness in the eye.

Official Title
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Optical Coherence Tomography (OCT) in a Multicenter, Randomized,Double-Blind, Parallel-Group, Placebo-Controlled Study to Evaluate the Efficacy and Safety of PEGylated Interferon Beta-1a (BIIB017) in Subjects With Relapsing Multiple Sclerosis

Conditions
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Relapsing Remitting Multiple Sclerosis

Intervention / Treatment
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* Drug: BIIB017


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations. A participant in the ADVANCE study aged 18 to 55 years old, inclusive, at the time of informed consent Exclusion Criteria: As per the ADVANCE main study History of intraocular surgery, retinal disease, glaucoma, or diabetes Refractive errors of more than ±6.0 diopters Inability to tolerate OCT procedure

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo for 48 weeks, BIIB017 for 48 weeks<br>Placebo every 2 weeks for 48 weeks followed by 125 mcg BIIB017 SC every 2 or 4 weeks for 48 weeks. | Drug: BIIB017<br>* BIIB017 is supplied as a liquid in pre-filled syringes to deliver 0.5 mL of 0.25 mg/mL (125 mcg dose) of 20 kDa mPEG-O-2-methylpropionaldehyde-modified human IFN β-1a in 20 mM acetic acid/sodium acetate buffer pH 4.8, 150 mM arginine hydrochloride, and 0.005% Polysorbate 20.<br>* Other names: PEG IFN β-1a;|
| Experimental: BIIB017 every 2 weeks for 96 weeks<br>125 mcg BIIB017 SC every 2 weeks for 96 weeks. | Drug: BIIB017<br>* BIIB017 is supplied as a liquid in pre-filled syringes to deliver 0.5 mL of 0.25 mg/mL (125 mcg dose) of 20 kDa mPEG-O-2-methylpropionaldehyde-modified human IFN β-1a in 20 mM acetic acid/sodium acetate buffer pH 4.8, 150 mM arginine hydrochloride, and 0.005% Polysorbate 20.<br>* Other names: PEG IFN β-1a;|
| Experimental: BIIB017 every 4 weeks for 96 weeks<br>125 mcg BIIB017 SC every 4 weeks for 96 weeks. | Drug: BIIB017<br>* BIIB017 is supplied as a liquid in pre-filled syringes to deliver 0.5 mL of 0.25 mg/mL (125 mcg dose) of 20 kDa mPEG-O-2-methylpropionaldehyde-modified human IFN β-1a in 20 mM acetic acid/sodium acetate buffer pH 4.8, 150 mM arginine hydrochloride, and 0.005% Polysorbate 20.<br>* Other names: PEG IFN β-1a;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the proportion of patients with RNFL decrease of 5 microns or more from baseline to month 12 in the BIIB-17 vs. placebo arms. |  | 1 year | 
| To determine the proportion of patients with RNFL decrease of 5 microns or more from baseline to month 24 in the BIIB-17 vs. placebo arms. |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Analysis of proportion of patients with a decrease of >10 percent of baseline value in any RNFL quadrant from baseline to month 12 in the BIIB-17 vs. placebo arms. |  | baseline and 1 year | 
| Analysis of decrease between baseline scans and 3 month scan (to examine for pseudoatrophy) in this study population. |  | baseline and 3 months | 
| Analysis of decrease between 3 month scans (mean and/or quadrant) and follow up scans (12 months) in this study population. |  | 3 months and 1 year | 
| Analysis of macular volume decreases from baseline or 3 months to follow up scans at 12 months in this study population. |  | baseline and 1 year | 
| Analysis of retinal nuclear layer decreases from baseline or 3 months to follow up scan at 12 months in this study population. |  | baseline and 1 year | 
| Analysis of the above OCT parameters in patients with optic neuritis or history of optic neuritis. |  | 1 year | 
| Analysis of proportion of patients with a decrease of >10 percent of baseline value in any RNFL quadrant from baseline to month 24 in the BIIB-17 vs. placebo arms. |  | baseline and 2 years | 
| Analysis of decrease between 3 month scans (mean and/or quadrant) and follow up scans (24 months) in this study population. |  | 3 months and 2 years | 
| Analysis of macular volume decreases from baseline or 3 months to follow up scans at 24 months in this study population. |  | baseline and 2 years | 
| Analysis of retinal nuclear layer decreases from baseline or 3 months to follow up scan at 24 months in this study population. |  | baseline and 2 years | 
| Analysis of the above OCT parameters in patients with optic neuritis or history of optic neuritis. |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MS, multiple sclerosis, relapsing, injectable, subcutaneous, SC, PEGylated, interferon, PEG, OCT, Optical Coherence Tomography