Long-Term Safety and Efficacy Study of Peginterferon Beta-1a

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the long-term safety and tolerability of peginterferon beta-1a (BIIB017) in participants originally treated in Study 105MS301 (NCT00906399) who continue peginterferon beta-1a treatment. The secondary objective of this study is to describe long-term multiple sclerosis (MS) outcomes in participants originally treated in Study 105MS301 (NCT00906399) who continue peginterferon beta-1a treatment.

Official Title
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A Dose-Frequency Blinded, Multicenter, Extension Study to Determine the Long-Term Safety and Efficacy of PEGylated Interferon Beta-1a (BIIB017) in Subjects With Relapsing Multiple Sclerosis

Conditions
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Relapsing Multiple Sclerosis

Intervention / Treatment
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* Drug: peginterferon beta-1a


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Must have completed the study treatment and visit schedule through Week 96 in Study 105MS301 (NCT00906399). Key Exclusion Criteria: Subjects exceeding more than 6 weeks since completion of the Week 96 visit of Study 105MS301 (NCT00906399). Subjects with any clinically significant laboratory abnormalities, malignancies, cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, or other major disease Pregnant or nursing women. NOTE: Other protocol-defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: peginterferon beta-1a Q4W<br>125 µg peginterferon beta-1a administered by subcutaneous (SC) injection every 4 weeks (Q4W) for at least 2 years and up to 4 years. | Drug: peginterferon beta-1a<br>* Administered as specified in the treatment arm<br>* Other names: BIIB017;|
| Experimental: peginterferon beta-1a Q2W<br>125 μg peginterferon beta-1a administered by SC injection every 2 weeks (Q2W) for at least 2 years and up to 4 years. | Drug: peginterferon beta-1a<br>* Administered as specified in the treatment arm<br>* Other names: BIIB017;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Experiencing Adverse Events (AEs) Serious AEs, and Discontinuations Due to AEs | AE: any untoward medical occurrence that did not necessarily have a causal relationship with study treatment. SAE: any untoward medical occurrence that at any dose: resulted in death; in the view of the Investigator, placed the participant at immediate risk of death (a life threatening event); 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 Investigator, could have jeopardized the participant or may have required intervention to prevent one of the other outcomes listed in the definition above. Data collected after Amendment 3 took effect were excluded for participants enrolled into study 105MS302 on every 4 week dosing, but not excluded for participants enrolled on every 2 week dosing. | up to 4 years | 
| Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities | Data collected after Amendment 3 took effect were excluded for participants enrolled into study 105MS302 on every 4 week dosing, but not excluded for participants enrolled on every 2 week dosing. | up to 4 years | 
| Number of Participants With Shifts From Baseline: Liver Function Laboratory Values | Shift to low includes normal to low, high to low, and unknown to low. Shift to high includes normal to high, low to high, and unknown to high. For participants who switched to alternative MS medications, data after switch and 14 days after last dose of study treatment are excluded. Data collected after Amendment 3 took effect were excluded for participants enrolled into study 105MS302 on every 4 week dosing, but not excluded for participants enrolled on every 2 week dosing. ALT=alanine aminotransferase; AST=aspartate aminotransferase; GGT=gamma-glutamyl transferase. | Baseline (BIIB017 Treatment Baseline from Study 105MS301) up to 4 years | 
| Number of Participants With Shifts From Baseline: Kidney Function and Other Blood Chemistry | Shift to low includes normal to low, high to low, and unknown to low. Shift to high includes normal to high, low to high, and unknown to high. For participants who switched to alternative MS medications, data after switch and 14 days after last dose of study treatment are excluded. Data collected after Amendment 3 took effect were excluded for participants enrolled into study 105MS302 on every 4 week dosing, but not excluded for participants enrolled on every 2 week dosing. TSH=thyroid stimulating hormone. | Baseline (BIIB017 Treatment Baseline from Study 105MS301) up to 4 years | 
| Number of Participants With Shifts From Baseline: Urinalysis | Shift to low includes normal to low, high to low, and unknown to low. Shift to high/positive includes normal to high/positive, low to high/positive, negative to high/positive, and unknown to high/positive. For participants who switched to alternative MS medications, data after switch and 14 days after last dose of study treatment are excluded. Data collected after Amendment 3 took effect were excluded for participants enrolled into study 105MS302 on every 4 week dosing, but not excluded for participants enrolled on every 2 week dosing. Pos=positive; RBC=red blood cells; WBC=white blood cells. | Baseline (BIIB017 Treatment Baseline from Study 105MS301) up to 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized Relapse Rate (ARR) | Relapses are defined as new or recurrent neurologic symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings upon examination by the examining neurologist. The annualized relapse rate is calculated as the total number of relapses occurred during the period for all participants, divided by the total number of person-years followed in the period. | up to 4 years | 
| Percentage of Participants Who Relapsed | Relapses are defined as new or recurrent neurologic symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings upon examination by the examining neurologist. New or recurrent neurologic symptoms that occur less than 30 days following the onset of a relapse were considered part of the same relapse. Participants who did not experience a relapse prior to switching to alternative MS medications, withdrew from study, or Amendment 3 (A3) took effect were censored at the time of switch/withdrawal/A3 effective date. | Up to 4 years | 
| Number of New or Newly Enlarging T2 Hyperintense Lesions | The total number of new or newly enlarging T2 hyperintense lesions (from Study 105MS302 Baseline) as assessed by magnetic resonance imaging (MRI). Observed data after participants switched to alternative MS medications or after Amendment 3 took effect are excluded. | Week 48, Week 96 | 
| Number of New Active Lesions | The number of new active lesions as assessed by MRI. Observed data after participants switched to alternative MS medications or after Amendment 3 took effect are excluded. | Week 48, Week 96 | 
| Number of New T1 Hypointense Lesions | The total number of new T1 hypointense lesions as assessed by MRI. | Week 48, Week 96 | 
| Number of Gd-Enhancing Lesions | The number of Gd-enhancing lesions as assessed by MRI. Observed data after participants switched to alternative MS medications or after Amendment 3 took effect are excluded. | Baseline (start of 105MS302), Week 48, Week 96 | 
| Volume of T2 Hyperintense Lesions | The volume of T2 hyperintense lesions as assessed by MRI. Observed data after participants switched to alternative MS medications or after Amendment 3 took effect are excluded. | Baseline (start of 105MS302), Week 48, Week 96 | 
| Volume of T1 Hypointense Lesions | The volume of T1 hypointense lesions as assessed by MRI. Observed data after participants switched to alternative MS medications or after Amendment 3 took effect are excluded. | Baseline (start of 105MS302), Week 48, Week 96 | 
| Volume of Gd-Enhancing Lesions | The volume of Gd-enhancing lesions as assessed by MRI. Observed data after participants switched to alternative MS medications or after Amendment 3 took effect are excluded. | Baseline (start of 105MS302), Week 48, Week 96 | 
| Percentage Change of Whole Brain Volume | Percentage change of whole brain volume as assessed by MRI. Observed data after participants switched to alternative MS medications or after Amendment 3 took effect are excluded. | Baseline (start of 105MS302), Week 48, Week 96 | 
| Change From Baseline in Expanded Disability Status Scale (EDSS) | Change from Baseline in disability as measured by the Expanded Disability Status Scale (EDSS). The EDSS measures the disability status of people with multiple sclerosis on a scale that ranges from 0 to 10. The range of main categories include (0) = normal neurologic exam; to (5) = ambulatory without aid or rest for 200 meters; disability severe enough to impair full daily activities; to (10) = death due to MS. Data after participants switched to alternative MS medications or after Amendment 3 took effect are excluded. | Baseline (start of 105MS302), Weeks 12, 24, 48, 72, 96, 120, 144, 168 | 
| Time to Sustained Disability Progression | Estimated proportion of participants with progression and time to progression based on the Kaplan-Meier product limit method. Sustained disability progression is defined as: at least a 1.0 point increase on the EDSS from 105MS302 baseline EDSS ≥ 1.0 that is sustained for 24 weeks, or at least a 1.5 point increase on the EDSS from 105MS302 baseline EDSS = 0 that is sustained for 24 weeks. The EDSS measures the disability status of people with multiple sclerosis on a scale that ranges from 0 to 10. The range of main categories include (0) = normal neurologic exam; to (5) = ambulatory without aid or rest for 200 meters; disability severe enough to impair full daily activities; to (10) = death due to MS. Participants were censored at the time of withdrawal/switch/A3 effective date if they withdrew from study, switched to alternative MS medication, or Amendment 3 took effect without a progression. | Weeks 12, 24, 28, 72, 96, 120, 144, 168 | 
| Change From Baseline in Symbol Digit Modalities Test (SDMT) | SDMT is a screening test for cognitive impairment. Participants are given 90 seconds in which to pair specific numbers with given geometric figures using a key. Scores range from 0 (worst) to 110 (best). | Baseline (start of 105MS302), Weeks 24, 48, 72, 96, 120, 144, 168 | 
| Change From Baseline in Multiple Sclerosis Impact Scale (MSIS)-29 Physical Score | The 29-item MSIS-29 is a disease-specific participant-reported outcome measure that has been developed and validated to examine the physical and psychological impact of MS from a patient's perspective; it measures 20 physical items and 9 psychological items. Responses use a 5-point Likert scale ranging from 1 to 5. All questions are to be answered. The physical well being assessment portion of the MSIS-29 consists of 20 questions in which participants rate the impact of MS on their day-to-day life during the past two weeks from 1=no impact to 5=extreme impact for a total score of 20-100. A lower total score indicates less physically-related impact while a higher total score indicates greater physically-related impact on a participant's functioning. Observed data after participants switched to alternative MS medications or after Amendment 3 took effect are excluded. | Baseline (start of 105MS302), Weeks 24, 48, 72, 96, 120, 144, 168 | 
| Change From Baseline in 12-Item Short Form Health Survey (SF-12) Mental Component Score (MCS) | The SF-12 is a multipurpose short form survey with 12 questions, all selected from the SF-36 Health Survey. The questions were combined, scored, and weighted to create two scales that provide glimpses into mental and physical functioning and overall health-related-quality of life. MCS computed using the scores of 12 questions and range from 0 to 100, where a 0 score indicates the lowest level of health and 100 indicates the highest level of health. Observed data after participants switched to alternative MS medications or after Amendment 3 took effect are excluded. | Baseline (start of 105MS302), Weeks 24, 48, 72, 96, 120, 144, 168 | 
| Change From Baseline in SF-12 Physical Component Score (PCS) | The SF-12 is a multipurpose short form survey with 12 questions, all selected from the SF-36 Health Survey. The questions were combined, scored, and weighted to create two scales that provide glimpses into mental and physical functioning and overall health-related-quality of life. PCS was computed using the scores of 12 questions and range from 0 to 100, where a 0 score indicates the lowest level of health and 100 indicates the highest level of health. Observed data after participants switched to alternative MS medications or after Amendment 3 took effect are excluded. | Baseline (start of 105MS302), Weeks 24, 48, 72, 96, 120, 144, 168 | 
| Change From Baseline in Euro Quality of Life (EQ-5D) Index Score | The EQ-5D is a participant-answered questionnaire scoring 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Scores of 1, 2, or 3 are possible responses for each of 5 questions (1=no problems, 2=some problems, 3=severe problems). A scoring formula developed by the EuroQol Group is then used to assign utility values for each participant's Health State Profile. A summary index score (EQ-5D index score) is derived from the 5 questions by conversion with this scoring formula and a table of scores. EQ-5D Summary Index values ranged from -0.6 (worst health state) to 1.00 (perfect health state). Observed data after participants switched to alternative MS medications or after Amendment 3 took effect are excluded. | Baseline (start of 105MS302), Weeks 24, 48, 72, 96, 120, 144, 168 | 
| Change From Baseline in EQ-5D Visual Analogue Scale (VAS) | The EQ-5D VAS records the participant's self-rated health on a scale from 0-100 where 100 is the 'best imaginable health state' and 0 is the 'worst imaginable health state.' The scale was normalized to a scale of 0 to 1, with higher values indicating a better health state. Observed data after participants switched to alternative MS medications or after Amendment 3 took effect are excluded. | Baseline (start of 105MS302), Weeks 24, 48, 72, 96, 120, 144, 168 | 
| Number of Relapses Requiring IV Steroid Use | Observed data after participants switched to alternative MS medications or after Amendment 3 took effect are excluded. | up to 4 years | 
| Number of MS-Related Hospitalizations | Observed data after participants switched to alternative MS medications or after Amendment 3 took effect are excluded. | up to 4 years | 
| Summary of Participant-Reported Treatment Satisfaction: How Tolerable or Intolerable Do You Find the Medication? | Participants completed a Treatment Satisfaction Questionnaire composed of a range of 14 questions regarding the participant's perception of treatment satisfaction at the end of each year of treatment. For the question How tolerable or intolerable do you find the medication? answers were numerically rated from 1 (extremely intolerable) to 10 (extremely tolerable). Data after Amendment 3 took effect are excluded. | Year 1, Year 2, Year 3 | 
| Summary of Participant-Reported Treatment Satisfaction: How Convenient or Inconvenient Is It to Take Your Medication as Instructed? | Participants completed a Treatment Satisfaction Questionnaire composed of a range of 14 questions regarding the participant's perception of treatment satisfaction at the end of each year of treatment. For the question How convenient or inconvenient is it to take your medication as instructed? answers were numerically rated from 1 (extremely inconvenient) to 10 (extremely convenient). Data after Amendment 3 took effect are excluded. | Year 1, Year 2, Year 3 | 
| Summary of Participant-Reported Treatment Satisfaction: How Convenient or Inconvenient Is It to Take Your Medication Every 2 Weeks? | Participants completed a Treatment Satisfaction Questionnaire composed of a range of 14 questions regarding the participant's perception of treatment satisfaction at the end of each year of treatment. For the question How convenient or inconvenient is it to take your medication every 2 weeks? answers were numerically rated from 1 (extremely inconvenient) to 10 (extremely convenient). Data after Amendment 3 took effect are excluded. | Year 1, Year 2, Year 3 | 
| Summary of Participant-Reported Treatment Satisfaction: Overall, How Satisfied or Dissatisfied Are You With This Medication? | Participants completed a Treatment Satisfaction Questionnaire composed of a range of 14 questions regarding the participant's perception of treatment satisfaction at the end of each year of treatment. For the question Overall, how satisfied or dissatisfied are you with this medication? answers were numerically rated from 1 (extremely dissatisfied) to 10 (extremely satisfied). Data after Amendment 3 took effect are excluded. | Year 1, Year 2, Year 3 | 
| Summary of Participant-Reported Treatment Satisfaction: How Satisfied or Dissatisfied Are You With the Injection Frequency (Every 2 Weeks)? | Participants completed a Treatment Satisfaction Questionnaire composed of a range of 14 questions regarding the participant's perception of treatment satisfaction at the end of each year of treatment. For the question How satisfied or dissatisfied are you with the injection frequency (every 2 weeks)? answers were numerically rated from 1 (extremely dissatisfied) to 10 (extremely satisfied). Data after Amendment 3 took effect are excluded. | Year 1, Year 2, Year 3 | 
| Summary of Participant-Reported Treatment Satisfaction: How Likely Would You Be to Continue to Use This Medication? | Participants completed a Treatment Satisfaction Questionnaire composed of a range of 14 questions regarding the participant's perception of treatment satisfaction at the end of each year of treatment. For the question How likely would you be to continue to use this medication? answers were numerically rated from 1 (extremely unlikely) to 10 (extremely likely). Data after Amendment 3 took effect are excluded. | Year 1, Year 2, Year 3 | 
| Summary of Participant-Reported Treatment Satisfaction: This Medication Enables Me to Focus More on Myself and My Family Rather Than My MS. | Participants completed a Treatment Satisfaction Questionnaire composed of a range of 14 questions regarding the participant's perception of treatment satisfaction at the end of each year of treatment. For the statement This Medication Enables Me to Focus More on Myself and My Family Rather Than My MS, answers were numerically rated from 1 (strongly disagree) to 10 (strongly agree). Data after Amendment 3 took effect are excluded. | Year 1, Year 2, Year 3 | 
| Summary of Participant-Reported Treatment Satisfaction: This Medication Makes It Easy For Me to Carry Out My Daily Responsibilities. | Participants completed a Treatment Satisfaction Questionnaire composed of a range of 14 questions regarding the participant's perception of treatment satisfaction at the end of each year of treatment. For the statement This medication makes it easy for me to carry out my daily responsibilities (ie, going to work, doing household chores or caring for my family), answers were numerically rated from 1 (strongly disagree) to 10 (strongly agree). Data after Amendment 3 took effect are excluded. | Year 1, Year 2, Year 3 | 
| Summary of Participant-Reported Treatment Satisfaction: The Twice a Month Dosing Makes It More Convenient for Me to Travel/Vacation. | Participants completed a Treatment Satisfaction Questionnaire composed of a range of 14 questions regarding the participant's perception of treatment satisfaction at the end of each year of treatment. For the statement The twice a month dosing makes it more convenient for me to travel/vacation, answers were numerically rated from 1 (strongly disagree) to 10 (strongly agree). Data after Amendment 3 took effect are excluded. | Year 1, Year 2, Year 3 | 
| Summary of Participant-Reported Treatment Satisfaction: The Twice a Month Dosing Enables Me to Be More Spontaneous and Flexible. | Participants completed a Treatment Satisfaction Questionnaire composed of a range of 14 questions regarding the participant's perception of treatment satisfaction at the end of each year of treatment. For the statement The twice a month dosing enables me to be more spontaneous and flexible, answers were numerically rated from 1 (strongly disagree) to 10 (strongly agree). Data after Amendment 3 took effect are excluded. | Year 1, Year 2, Year 3 | 
| Summary of Participant-Reported Treatment Satisfaction: This Medication Improves My Self-Confidence and Self-Reliance. | Participants completed a Treatment Satisfaction Questionnaire composed of a range of 14 questions regarding the participant's perception of treatment satisfaction at the end of each year of treatment. For the statement This medication improves my self-confidence and self-reliance, answers were numerically rated from 1 (strongly disagree) to 10 (strongly agree). Data after Amendment 3 took effect are excluded. | Year 1, Year 2, Year 3 | 
| Summary of Participant-Reported Treatment Satisfaction: I Am Satisfied With the Dosing Frequency of This Medication. | Participants completed a Treatment Satisfaction Questionnaire composed of a range of 14 questions regarding the participant's perception of treatment satisfaction at the end of each year of treatment. For the statement I am satisfied with the dosing frequency (2 times per month) of this medication answers were numerically rated from 1 (strongly disagree) to 10 (strongly agree). Data after Amendment 3 took effect are excluded. | Year 1, Year 2, Year 3 | 
| Summary of Participant-Reported Treatment Satisfaction: Over the Past 4 Weeks, Did You Miss Any of Your Injections? | Participants completed a Treatment Satisfaction Questionnaire composed of a range of 14 questions regarding the participant's perception of treatment satisfaction at the end of each year of treatment. For the question Over the past 4 weeks, did you miss any of your injections? answer choices were given as none missed, miss 1 injection, or miss 2 injections. Data after Amendment 3 took effect are excluded. | Year 1, Year 2, Year 3 | 
| Summary of Participant-Reported Treatment Satisfaction: Main Reason for Missed Injections | Participants completed a Treatment Satisfaction Questionnaire composed of a range of 14 questions regarding the participant's perception of treatment satisfaction at the end of each year of treatment. For the question Main reason for missed injections? answer choices were given as medication side effects, injection pain, forget to take medication, tired of taking injections, don't think medication is working, or other. Data after Amendment 3 took effect are excluded. | Year 1, Year 2, Year 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Subcutaneous, Extension, Interferon, MS, PEGylated, Injectable, SC, PEG, peginterferon beta-1a, Relapsing