Characterize Flu-like Symptoms in Relapsing Multiple Sclerosis Patients Transitioning From Non-Pegylated Interferon Beta (IFN-β) Therapies to Peginterferon Beta-1a (BIIB017)

Study Overview
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Brief Summary
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The primary objective of this study is to determine the proportion of participants with relapsing multiple sclerosis who experience new and/or increased flu-like symptoms (FLS) after transitioning from nonpegylated IFN-β therapies to peginterferon beta-1a (BIIB017). Secondary objectives are: to determine the severity and frequency (measured by flu-like symptom score [FLS-S]) of FLS in these participants; to determine the duration (measured in number of hours) of FLS in these participants; to determine the effect of BIIB017 on other participant-reported outcomes, including treatment satisfaction (measured with the Treatment Satisfaction Questionnaire for Medication [TSQM]) and disability status (measured with the Patient Determined Disease Steps [PDDS]) over a 56-week period; to determine whether interferon-related FLS result in missed days of work/daily activities (e.g., absenteeism); to assess the use of additional medications (in addition to current medications used to treat FLS) to relieve BIIB017-related FLS; to determine the incidence of adverse events throughout the study period; to characterize the immunogenicity profiles of participants switching from prior IFN-β therapy to BIIB017.

Official Title
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An Open-Label, Two-Arm Randomized Study to Characterize Flu-Like Symptoms in Relapsing Multiple Sclerosis Patients Transitioning From Current Interferon Beta Therapies to BIIB017

Conditions
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Relapsing Multiple Sclerosis

Intervention / Treatment
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* Drug: BIIB017
* Drug: naproxen


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Must have a confirmed diagnosis of relapsing forms of multiple sclerosis (MS), as defined by McDonald criteria #1-4 [Polman 2005] Must have neurological findings consistent with an Expanded Disability Status Scale (EDSS) score of 0.0 - 5.0 Must be treated with IFN-β and must be receiving a stable dose of IFN-β for at least 4 months immediately prior to screening All male patients and female patients of childbearing potential must practice effective contraception during the study and be willing and able to continue contraception for 3 months after their last dose of study treatment. Key Exclusion Criteria: Primary progressive, secondary progressive, or progressive relapsing MS [Lublin and Reingold 1996]. These conditions require the presence of continuous clinical disease worsening over a period of at least 3 months. Patients with these conditions may also have superimposed relapse but are distinguished from patients with relapsing MS by the lack of clinically stable periods or clinical improvement History of severe allergic or anaphylactic reactions or known hypersensitivity to medication which might suggest potential for a reaction to IFN β-1a or polyethylene glycol History of malignant disease, including solid tumors and hematologic malignancies (with the exception of basal cell and squamous cell carcinomas of the skin that have been completely excised and are considered cured) History of seizure disorder or unexplained blackouts OR history of a seizure within 3 months prior to Baseline Known allergy to any component of the BIIB017 formulation An MS relapse that has occurred within the 50 days prior to Baseline (Day 1) and/or lack of stabilization from a previous relapse prior to Baseline. 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BIIB017 plus current FLS therapy<br>Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administer non-pegylated IFN therapy, participants receive BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus current FLS management regimen as determined by the clinician. | Drug: BIIB017<br> <br> * Other names: PEG IFN β-1a;|
| Experimental: BIIB017 plus naproxen<br>Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administer non-pegylated IFN therapy, participants receive BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently. | Drug: BIIB017<br> <br> * Other names: PEG IFN β-1a;Drug: naproxen<br> <br> * Other names: long-acting nonsteroidal anti-inflammatory drug;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Experiencing New or Increased FLS During the First 8 Weeks: Overall Population | The total Flu-like Symptoms Score (FLS-S) is the sum of all 4 symptom scores (muscle aches, chills, fatigue and fever), each rated from 0 (absent) to 3 (severe), with a range of 0-12 with 0 indicating no FLS and 12 indicating severe FLS. New or increased FLS is defined as an FLS overall score of 2 points or greater over Screening. Pre-dose data were not used; up to 48-hour data after dosing were used. Overall score was imputed as the average score after dose. | during the first 8 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From 4-Week Run-In Period at Each Visit for Treatment Satisfaction Questionnaire for Medication (TSQM), Effectiveness Scale Factor: Overall Population | The TSQM assessed participants' global satisfaction with treatment and captured information on treatment side effects, effectiveness, and convenience. Changes from the 4-week run-in period to each visit using transformed scores between 0 and 100 for effectiveness (with higher scores indicating greater satisfaction) are presented. 4WRI=4-week run-in. | 4-week run-in period, Weeks 4, 12, 24, 36, 48 (or Early Termination) | 
| Mean Change From 4-Week Run-In Period at Each Visit for TSQM, Side-Effects Scale Factor: Overall Population | The TSQM assessed participants' global satisfaction with treatment and captured information on treatment side effects, effectiveness, and convenience. Changes from the 4-week run-in period to each visit using transformed scores between 0 and 100 for side effects (with higher scores indicating greater satisfaction) are presented. 4WRI=4-week run-in. | 4-week run-in period, Weeks 4, 12, 24, 36, 48 (or Early Termination) | 
| Mean Change From 4-Week Run-In Period at Each Visit for TSQM, Convenience Scale Factor: Overall Population | The TSQM assessed participants' global satisfaction with treatment and captured information on treatment side effects, effectiveness, and convenience. Changes from the 4-week run-in period to each visit using transformed scores between 0 and 100 for convenience (with higher scores indicating greater satisfaction) are presented. 4WRI=4-week run-in. | 4-week run-in period, Weeks 4, 12, 24, 36, 48 (or Early Termination) | 
| Mean Change From 4-Week Run-In Period at Each Visit for TSQM, Global Satisfaction Scale Factor: Overall Population | The TSQM assessed participants' global satisfaction with treatment and captured information on treatment side effects, effectiveness, and convenience. Changes from the 4-week run-in period to each visit using transformed scores between 0 and 100 for global satisfaction (with higher scores indicating greater satisfaction) are presented. 4WRI=4-week run-in. | 4-week run-in period, Weeks 4, 12, 24, 36, 48 (or Early Termination) | 
| Mean Change From 4-Week Run-In Period at Week 4 for TSQM, Effectiveness Scale Factor: Between FLS Management Arms | The TSQM assessed participants' global satisfaction with treatment and captured information on treatment side effects, effectiveness, and convenience. Changes from the 4-week run-in period to Week 4 using transformed scores between 0 and 100 for effectiveness (with higher scores indicating greater satisfaction) are presented. This secondary endpoint was targeted for Week 4 only. 4WRI=4-week run-in. | 4-week run-in period, Week 4 | 
| Mean Change From 4-Week Run-In Period at Week 4 for TSQM, Side Effects Scale Factor: Between FLS Management Arms | The TSQM assessed participants' global satisfaction with treatment and captured information on treatment side effects, effectiveness, and convenience. Changes from the 4-week run-in period to Week 4 using transformed scores between 0 and 100 for side effects (with higher scores indicating greater satisfaction) are presented. This secondary endpoint was targeted for Week 4 only. 4WRI=4-week run-in. | 4-week run-in period, Week 4 | 
| Mean Change From 4-Week Run-In Period at Week 4 for TSQM, Convenience Scale Factor: Between FLS Management Arms | The TSQM assessed participants' global satisfaction with treatment and captured information on treatment side effects, effectiveness, and convenience. Changes from the 4-week run-in period to Week 4 using transformed scores between 0 and 100 for convenience (with higher scores indicating greater satisfaction) are presented. This secondary endpoint was targeted for Week 4 only. 4WRI=4-week run-in. | 4-week run-in period, Week 4 | 
| Mean Change From 4-Week Run-In Period at Week 4 for TSQM, Global Satisfaction Scale Factor: Between FLS Management Arms | The TSQM assessed participants' global satisfaction with treatment and captured information on treatment side effects, effectiveness, and convenience. Changes from the 4-week run-in period to Week 4 using transformed scores between 0 and 100 for global satisfaction (with higher scores indicating greater satisfaction) are presented. This secondary endpoint was targeted for Week 4 only. 4WRI=4-week run-in. | 4-week run-in period, Week 4 | 
| Mean Change From Screening at Each Visit in Absenteeism Questionnaire, Usual Work Days Per Week: Overall Population | Categorical questions in the Absenteeism Questionnaire asked participants to report the number of usual work days per week, the number of days missed in 2 weeks from multiple sclerosis (MS) symptoms, and the number of days missed in 2 weeks from MS treatment. This secondary endpoint was targeted to analyze the Overall Population only. 4WRI=4-week run-in. | Week -4 (screening), Week 12, Week 24, Week 36, Week 48, Early Termination | 
| Mean Change From Screening at Each Visit in Absenteeism Questionnaire, Days Missed in 2 Weeks From MS Symptoms: Overall Population | Categorical questions in the Absenteeism Questionnaire asked participants to report the number of usual work days per week, the number of days missed in 2 weeks from MS symptoms, and the number of days missed in 2 weeks from MS treatment. This secondary endpoint was targeted to analyze the Overall Population only. 4WRI=4-week run-in. | Week -4 (screening), Week 12, Week 24, Week 36, Week 48, Early Termination | 
| Mean Change From Screening at Each Visit in Absenteeism Questionnaire, Days Missed in 2 Weeks From MS Treatment: Overall Population | Categorical questions in the Absenteeism Questionnaire asked participants to report the number of usual work days per week, the number of days missed in 2 weeks from MS symptoms, and the number of days missed in 2 weeks from MS treatment. This secondary endpoint was targeted to analyze the Overall Population only. 4WRI=4-week run-in. | Week -4 (screening), Week 12, Week 24, Week 36, Week 48, Early Termination | 
| Change From Baseline Visit (Day 1) to Week 48 in Walking Disability Status as Measured by Patient Determined Disease Steps (PDDS): Overall Population | Subjects rated their perceived walking disability on a scale of 0 to 8 using the PDDS, with higher scores indicating more severe disability. This secondary endpoint was targeted to analyze the Overall Population only. | Day 1 (Baseline, pre-dose), Week 12, Week 48, Early Termination | 
| Summary of Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs | 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 Investigator, placed the subject 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 jeopardize the subject or could require intervention to prevent one of the other outcomes listed in the definition above. ISR=injection site reactions. | Day 1 to Week 52 | 
| Summary of Average Duration of FLS Within the Last 4 Weeks of the BIIB017 Treatment Period Compared With the Duration of FLS in the 4-Week Run-In Period | Average duration of FLS for the last 4 weeks (L4W) is defined as the mean duration of last 4 weeks. Duration of FLS for a treatment is defined as the sum of hours from the treatment to 48 hours with a FLS-S score > 0. The total FLS-S is the sum of all 4 symptom scores (muscle aches, chills, fatigue and fever), each rated from 0 (absent) to 3 (severe), with a range of 0-12 with 0 indicating no FLS and 12 indicating severe FLS. If a FLS is > 0 at an evaluation time, 6 hours were counted as the duration assuming the event started from previous evaluation time. 4WRI=4-week run-in. | Weeks -4 to -1 (Screening), Weeks 45-48 (last 4 weeks of study) | 
| Antibody Data in the Overall Population: IFN β-1a Antibody Screening | The number of participants who tested positive for IFN β-1a binding antibodies (BAbs). Value was coded as 'positive' if observed value > 0 or coded as 'negative' if observed value < 0. This secondary endpoint was targeted to analyze the Overall Population only. | Baseline (BL; Day 1), Week 12, Week 24, Week 36, Week 48 or early withdrawal (EW) | 
| Antibody Data in the Overall Population: IFN β-1a Anti-Pegylated (PEG) Antibody Testing | The number of participants who tested positive or negative for IFN β-1a anti-PEG antibodies. Value was coded as 'positive' if observed value > 0 or coded as 'negative' if observed value < 0. This secondary endpoint was targeted to analyze the Overall Population only. | Baseline (BL; Day 1), Week 12, Week 24, Week 36, Week 48 or early withdrawal (EW) | 
| Antibody Data in the Overall Population: IFN β-1a Neutralizing Antibodies (Nabs) Testing | The number of participants who tested positive for IFN β-1a Nabs. Value was coded as 'positive' if observed value > 0 or coded as 'negative' if observed value < 0. This secondary endpoint was targeted to analyze the Overall Population only. | Baseline (Day 1), Week 12, Week 24, Week 36, Week 48 or early withdrawal (EW) | 
| Percentage of Participants Experiencing New or Increased FLS During the First 8 Weeks: Between FLS Management Arms | The total FLS-S is the sum of all 4 symptom scores (muscle aches, chills, fatigue and fever), each rated from 0 (absent) to 3 (severe), with a range of 0-12 with 0 indicating no FLS and 12 indicating severe FLS. New or increased FLS is defined as an FLS overall score of 2 points or greater over Screening. Pre-dose data were not used; up to 48-hour data after dosing were used. Overall score was imputed as the average score after dose. | during the first 8 weeks of treatment | 
| Percentage of Participants With Any FLS in the 4-Week Run-In Period, During the First 8 Weeks of Treatment, and During 48 Weeks of Treatment | Any FLS is defined as an FLS-S total score > 0. The total FLS-S is the sum of all 4 symptom scores (muscle aches, chills, fatigue and fever), each rated from 0 (absent) to 3 (severe), with a range of 0-12 with 0 indicating no FLS and 12 indicating severe FLS. 4WRI=4-week run-in; F8W=first 8 weeks; 48W=48 weeks. | 4-week run-in period, first 8 weeks of treatment, 48 weeks of treatment | 
| Shift in Percentage of Participants With Any FLS From 4-Week Run-In Period to the First 8 Weeks | Any FLS is defined as an FLS-S total score > 0. The total FLS-S is the sum of all 4 symptom scores (muscle aches, chills, fatigue and fever), each rated from 0 (absent) to 3 (severe), with a range of 0-12 with 0 indicating no FLS and 12 indicating severe FLS. Pre-dose data not were used. Data up to 48-hours after dosing were used. Total score was imputed as the highest score after dose. 4WRI=4-week run-in period; F8W=first 8 weeks. | 4-week run-in period, first 8 weeks of treatment | 
| Shift in Percentage of Participants With Any FLS From 4-Week Run-In Period to 48 Weeks | Any FLS is defined as an FLS-S total score > 0. The total FLS-S is the sum of all 4 symptom scores (muscle aches, chills, fatigue and fever), each rated from 0 (absent) to 3 (severe), with a range of 0-12 with 0 indicating no FLS and 12 indicating severe FLS. Pre-dose data not were used. Data up to 48-hours after dosing were used. Total score was imputed as the highest score after dose. 4WRI=4-week run-in period; 48W=48 weeks. | 4-week run-in period, 48 weeks of treatment | 
| Summary of Severity of FLS (Per FLS-S) in the First 8 Weeks Compared to 4-Week Run-In Period Between Arms | The total FLS-S is the sum of all 4 symptom scores (muscle aches, chills, fatigue and fever), each rated from 0 (absent) to 3 (severe), with a range of 0-12 with 0 indicating no FLS and 12 indicating severe FLS. 4WRI=4-week run-in period; F8W=first 8 weeks. | 4-week run-in period, first 8 weeks of treatment | 
| Summary of Severity of FLS (Per FLS-S) in the 48 Weeks of Treatment Compared to 4-Week Run-In Period Between Arms | The total FLS-S is the sum of all 4 symptom scores (muscle aches, chills, fatigue and fever), each rated from 0 (absent) to 3 (severe), with a range of 0-12 with 0 indicating no FLS and 12 indicating severe FLS. 4WRI=4-week run-in period; 48W=48 weeks. | 4-week run-in period, 48 weeks of treatment | 
| Summary of Average Duration of FLS in the First 8 Weeks of Treatment | Duration of FLS for a treatment was defined as the sum of hours from the time of treatment to 48 hours with an FLS-S score > 0. The total FLS-S is the sum of all 4 symptom scores (muscle aches, chills, fatigue and fever), each rated from 0 (absent) to 3 (severe), with a range of 0-12 with 0 indicating no FLS and 12 indicating severe FLS. If an FLS is > 0 at an evaluation time, 6 hours were counted as the duration assuming the event started from previous evaluation time. Average duration of FLS for the first 8 weeks was defined as the mean duration from Weeks 0, 2, 4, 6, and 8. 4WRI=4-week run-in period; F8W=first 8 weeks. | 4-week run-in period, first 8 weeks of treatment | 
| Summary of Average Duration of FLS in the 48 Weeks of Treatment | Duration of FLS for a treatment was defined as the sum of hours from the time of treatment to 48 hours with a FLS-S score > 0. The total FLS-S is the sum of all 4 symptom scores (muscle aches, chills, fatigue and fever), each rated from 0 (absent) to 3 (severe), with a range of 0-12 with 0 indicating no FLS and 12 indicating severe FLS. If a FLS is > 0 at an evaluation time, 6 hours were counted as the duration assuming the event started from previous evaluation time. Average duration of FLS for the first 8 weeks was defined as the mean duration from Weeks 0, 2, 4, 6, and 8. 4WRI=4-week run-in period; 48W=48 weeks. | 4-week run-in period, 48 weeks of treatment | 
| Summary of FLS-Visual Analogue Scale (VAS) During the First 8 Weeks of Treatment Compared to 4-Week Run-In Period: Effectiveness of FLS Treatment | Participants reported the effectiveness of their FLS management regimen on a 100-mm VAS between not effective (0) and very effective (100). 4WRI=4-week run-in period; F8W=first 8 weeks. | 4-week run-in period, first 8 weeks of treatment | 
| Summary of FLS-VAS During the First 8 Weeks of Treatment Compared to 4-Week Run-In Period: Satisfaction With FLS Treatment | Participants reported their satisfaction with the effectiveness of their FLS management regimen on a 100-mm VAS between not satisfied (0) and very satisfied (100). 4WRI=4-week run-in period; F8W=first 8 weeks. | 4-week run-in period, first 8 weeks of treatment | 
| Summary of FLS-VAS During the 48 Weeks of Treatment Compared to 4-Week Run-In Period: Effectiveness of FLS Treatment | Participants reported the effectiveness of their FLS management regimen on a 100-mm VAS between not effective (0) and very effective (100). 4WRI=4-week run-in period; 48W=48 weeks. | 4-week run-in period, 48 weeks of treatment | 
| Summary of FLS-VAS During the 48 Weeks of Treatment Compared to 4-Week Run-In Period: Satisfaction With FLS Treatment | Participants reported their satisfaction with the effectiveness of their FLS management regimen on a 100-mm VAS between not satisfied (0) and very satisfied (100). 4WRI=4-week run-in period; 48W=48 weeks. | 4-week run-in period, 48 weeks of treatment | 
| Percentage of Participants Requiring Additional FLS Management Regimen to Relieve BIIB017-related FLS |  | during the first 8 weeks of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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flu-like symptoms