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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Biogen
ClinicalTrials.gov Identifier:
NCT01939002
First received: August 23, 2013
Last updated: November 30, 2016
Last verified: November 2016
  Purpose

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.


Condition Intervention Phase
Relapsing Multiple Sclerosis
Drug: BIIB017
Drug: naproxen
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Biogen:

Primary Outcome Measures:
  • Percentage of Participants Experiencing New or Increased FLS During the First 8 Weeks: Overall Population [ Time Frame: during the first 8 weeks of treatment ]
    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.


Secondary Outcome Measures:
  • Percentage of Participants Experiencing New or Increased FLS During the First 8 Weeks: Between FLS Management Arms [ Time Frame: during the first 8 weeks of treatment ]
    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.

  • 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 [ Time Frame: 4-week run-in period, first 8 weeks of treatment, 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.

  • Shift in Percentage of Participants With Any FLS From 4-Week Run-In Period to the First 8 Weeks [ Time Frame: 4-week run-in period, first 8 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. 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.

  • Shift in Percentage of Participants With Any FLS From 4-Week Run-In Period to 48 Weeks [ Time Frame: 4-week run-in period, 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. 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.

  • Summary of Severity of FLS (Per FLS-S) in the First 8 Weeks Compared to 4-Week Run-In Period Between Arms [ Time Frame: 4-week run-in period, first 8 weeks of treatment ]
    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.

  • Summary of Severity of FLS (Per FLS-S) in the 48 Weeks of Treatment Compared to 4-Week Run-In Period Between Arms [ Time Frame: 4-week run-in period, 48 weeks of treatment ]
    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.

  • Summary of Average Duration of FLS in the First 8 Weeks of Treatment [ Time Frame: 4-week run-in period, 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.

  • Summary of Average Duration of FLS in the 48 Weeks of Treatment [ Time Frame: 4-week run-in period, 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.

  • 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 [ Time Frame: 4-week run-in period, first 8 weeks of 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.

  • Summary of FLS-VAS During the First 8 Weeks of Treatment Compared to 4-Week Run-In Period: Satisfaction With FLS Treatment [ Time Frame: 4-week run-in period, first 8 weeks of 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.

  • Summary of FLS-VAS During the 48 Weeks of Treatment Compared to 4-Week Run-In Period: Effectiveness of FLS Treatment [ Time Frame: 4-week run-in period, 48 weeks of 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.

  • Summary of FLS-VAS During the 48 Weeks of Treatment Compared to 4-Week Run-In Period: Satisfaction With FLS Treatment [ Time Frame: 4-week run-in period, 48 weeks of 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.

  • Percentage of Participants Requiring Additional FLS Management Regimen to Relieve BIIB017-related FLS [ Time Frame: during the first 8 weeks of treatment ]
  • Mean Change From 4-Week Run-In Period at Each Visit for Treatment Satisfaction Questionnaire for Medication (TSQM), Effectiveness Scale Factor: Overall Population [ Time Frame: 4-week run-in period, Weeks 4, 12, 24, 36, 48 (or Early Termination) ]
    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.

  • Mean Change From 4-Week Run-In Period at Each Visit for TSQM, Side-Effects Scale Factor: Overall Population [ Time Frame: 4-week run-in period, Weeks 4, 12, 24, 36, 48 (or Early Termination) ]
    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.

  • Mean Change From 4-Week Run-In Period at Each Visit for TSQM, Convenience Scale Factor: Overall Population [ Time Frame: 4-week run-in period, Weeks 4, 12, 24, 36, 48 (or Early Termination) ]
    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.

  • Mean Change From 4-Week Run-In Period at Each Visit for TSQM, Global Satisfaction Scale Factor: Overall Population [ Time Frame: 4-week run-in period, Weeks 4, 12, 24, 36, 48 (or Early Termination) ]
    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.

  • Mean Change From 4-Week Run-In Period at Week 4 for TSQM, Effectiveness Scale Factor: Between FLS Management Arms [ Time Frame: 4-week run-in period, Week 4 ]
    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.

  • Mean Change From 4-Week Run-In Period at Week 4 for TSQM, Side Effects Scale Factor: Between FLS Management Arms [ Time Frame: 4-week run-in period, Week 4 ]
    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.

  • Mean Change From 4-Week Run-In Period at Week 4 for TSQM, Convenience Scale Factor: Between FLS Management Arms [ Time Frame: 4-week run-in period, Week 4 ]
    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.

  • Mean Change From 4-Week Run-In Period at Week 4 for TSQM, Global Satisfaction Scale Factor: Between FLS Management Arms [ Time Frame: 4-week run-in period, Week 4 ]
    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.

  • Mean Change From Screening at Each Visit in Absenteeism Questionnaire, Usual Work Days Per Week: Overall Population [ Time Frame: Week -4 (screening), Week 12, Week 24, Week 36, Week 48, Early Termination ]
    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.

  • Mean Change From Screening at Each Visit in Absenteeism Questionnaire, Days Missed in 2 Weeks From MS Symptoms: Overall Population [ Time Frame: Week -4 (screening), Week 12, Week 24, Week 36, Week 48, Early Termination ]
    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.

  • Mean Change From Screening at Each Visit in Absenteeism Questionnaire, Days Missed in 2 Weeks From MS Treatment: Overall Population [ Time Frame: Week -4 (screening), Week 12, Week 24, Week 36, Week 48, Early Termination ]
    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.

  • Change From Baseline Visit (Day 1) to Week 48 in Walking Disability Status as Measured by Patient Determined Disease Steps (PDDS): Overall Population [ Time Frame: Day 1 (Baseline, pre-dose), Week 12, Week 48, Early Termination ]
    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.

  • Summary of Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs [ Time Frame: Day 1 to Week 52 ]
    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.

  • 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 [ Time Frame: Weeks -4 to -1 (Screening), Weeks 45-48 (last 4 weeks of study) ]
    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.

  • Antibody Data in the Overall Population: IFN β-1a Antibody Screening [ Time Frame: Baseline (BL; Day 1), Week 12, Week 24, Week 36, Week 48 or early withdrawal (EW) ]
    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.

  • Antibody Data in the Overall Population: IFN β-1a Anti-Pegylated (PEG) Antibody Testing [ Time Frame: Baseline (BL; Day 1), Week 12, Week 24, Week 36, Week 48 or early withdrawal (EW) ]
    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.

  • Antibody Data in the Overall Population: IFN β-1a Neutralizing Antibodies (Nabs) Testing [ Time Frame: Baseline (Day 1), Week 12, Week 24, Week 36, Week 48 or early withdrawal (EW) ]
    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.


Enrollment: 251
Study Start Date: November 2013
Study Completion Date: November 2015
Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BIIB017 plus current FLS therapy
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
Other Names:
  • Plegridy
  • peginterferon beta-1a
  • PEGylated interferon beta-1a
  • PEG IFN β-1a
Experimental: BIIB017 plus naproxen
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
Other Names:
  • Plegridy
  • peginterferon beta-1a
  • PEGylated interferon beta-1a
  • PEG IFN β-1a
Drug: naproxen
Other Names:
  • naproxen sodium
  • Aleve
  • NSAID
  • long-acting nonsteroidal anti-inflammatory drug

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01939002

  Show 38 Study Locations
Sponsors and Collaborators
Biogen
Investigators
Study Director: Medical Director Biogen
  More Information

Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT01939002     History of Changes
Other Study ID Numbers: 105MS303
Study First Received: August 23, 2013
Results First Received: October 6, 2016
Last Updated: November 30, 2016

Keywords provided by Biogen:
flu-like symptoms

Additional relevant MeSH terms:
Sclerosis
Multiple Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Interferons
Interferon-beta
Interferon beta-1a
Naproxen
Anti-Inflammatory Agents, Non-Steroidal
Anti-Inflammatory Agents
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antirheumatic Agents
Gout Suppressants
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Adjuvants, Immunologic

ClinicalTrials.gov processed this record on May 25, 2017