Phase 3
N=201
Characterize Flu-like Symptoms in Relapsing Multiple Sclerosis Patients Transitioning From Non-Pegylated Interferon Beta (IFN-β) Therapies to Peginterferon Beta-1a (BIIB017)
Relapsing Multiple Sclerosis
Bottom Line
View on ClinicalTrials.gov: NCT01939002 ↗Enrolled (actual)
201
Serious AEs
5.0%
Results posted
Jan 2017
Primary outcome: Primary: Percentage of Participants Experiencing New or Increased FLS During the First 8 Weeks: Overall Population — 10.3 percentage of participants — p=<0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- BIIB017 (Drug); naproxen (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Biogen
- Primary completion
- Oct 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants Experiencing New or Increased FLS During the First 8 Weeks: Overall Population |
10.3 | <0.0001 sig |
| SECONDARY Percentage of Participants Experiencing New or Increased FLS During the First 8 Weeks: Between FLS Management Arms |
13; 7.4 | 0.2037 |
| SECONDARY 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 |
88; 91.5; 89.7; 91; 88.3; 89.7 | — |
| SECONDARY Shift in Percentage of Participants With Any FLS From 4-Week Run-In Period to the First 8 Weeks |
85.00; 82.98; 84.02; 3.00; 8.51; 5.67 | 1.00 |
| SECONDARY Shift in Percentage of Participants With Any FLS From 4-Week Run-In Period to 48 Weeks |
86.00; 87.23; 86.60; 2.00; 4.26; 3.09 | 0.0525 |
| SECONDARY Summary of Severity of FLS (Per FLS-S) in the First 8 Weeks Compared to 4-Week Run-In Period Between Arms |
1.198; 1.05; 1.126; 1.311; 1.036; 1.178 | 0.0945 |
| SECONDARY Summary of Severity of FLS (Per FLS-S) in the 48 Weeks of Treatment Compared to 4-Week Run-In Period Between Arms |
1.2; 1.05; 1.13; 1.28; 0.98; 1.14 | 0.3189 |
| SECONDARY Summary of Average Duration of FLS in the First 8 Weeks of Treatment |
16; 12.8; 13.75; 18; 18; 18 | 0.0009 sig |
| SECONDARY Summary of Average Duration of FLS in the 48 Weeks of Treatment |
16; 12.8; 13.75; 16.75; 16.96; 16.96 | 0.0019 sig |
| SECONDARY 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 |
64.5; 66.398; 65.422; 69.695; 74.253; 71.913 | 0.0105 sig |
| SECONDARY Summary of FLS-VAS During the First 8 Weeks of Treatment Compared to 4-Week Run-In Period: Satisfaction With FLS Treatment |
68.654; 72.778; 70.658; 71.153; 74.684; 72.871 | 0.1407 |
| SECONDARY Summary of FLS-VAS During the 48 Weeks of Treatment Compared to 4-Week Run-In Period: Effectiveness of FLS Treatment |
64.5; 66.398; 65.422; 70.547; 75.416; 72.918 | 0.0090 sig |
| SECONDARY Summary of FLS-VAS During the 48 Weeks of Treatment Compared to 4-Week Run-In Period: Satisfaction With FLS Treatment |
68.654; 72.778; 70.658; 72.192; 76.061; 74.076 | 0.0545 |
| SECONDARY Percentage of Participants Requiring Additional FLS Management Regimen to Relieve BIIB017-related FLS |
6.4; 15.3; 93.6; 84.7; 1.8; 11 | 0.0834 |
| SECONDARY Mean Change From 4-Week Run-In Period at Each Visit for Treatment Satisfaction Questionnaire for Medication (TSQM), Effectiveness Scale Factor: Overall Population |
73.871; -2.589; -1.274; 0.341; 1.864; 2.863 | 0.2123 |
| SECONDARY Mean Change From 4-Week Run-In Period at Each Visit for TSQM, Side-Effects Scale Factor: Overall Population |
85.17; 6.065; 5.109; 2.958; 3.37; 1.418 | 0.0001 sig |
| SECONDARY Mean Change From 4-Week Run-In Period at Each Visit for TSQM, Convenience Scale Factor: Overall Population |
66.665; 18.703; 18.12; 18.419; 18.704; 19.588 | <0.0001 sig |
| SECONDARY Mean Change From 4-Week Run-In Period at Each Visit for TSQM, Global Satisfaction Scale Factor: Overall Population |
75.985; 6.789; 7.354; 7.575; 9.179; 8.556 | <0.0001 sig |
| SECONDARY Mean Change From 4-Week Run-In Period at Week 4 for TSQM, Effectiveness Scale Factor: Between FLS Management Arms |
75.16; 72.5; 0.979; -6.356 | 0.7012 |
| SECONDARY Mean Change From 4-Week Run-In Period at Week 4 for TSQM, Side Effects Scale Factor: Between FLS Management Arms |
83.78; 86.649; 8.579; 3.411 | 0.0006 sig |
| SECONDARY Mean Change From 4-Week Run-In Period at Week 4 for TSQM, Convenience Scale Factor: Between FLS Management Arms |
65.94; 67.436; 19.768; 17.578 | <0.0001 sig |
| SECONDARY Mean Change From 4-Week Run-In Period at Week 4 for TSQM, Global Satisfaction Scale Factor: Between FLS Management Arms |
75.86; 76.117; 8.663; 4.811 | <0.0001 sig |
| SECONDARY Mean Change From Screening at Each Visit in Absenteeism Questionnaire, Usual Work Days Per Week: Overall Population |
4.691; -0.019; -0.081; -0.052; 0.032; 0.2 | 0.6569 |
| SECONDARY Mean Change From Screening at Each Visit in Absenteeism Questionnaire, Days Missed in 2 Weeks From MS Symptoms: Overall Population |
0.016; 0.057; 0.061; 0; 0.137; 0 | 0.2588 |
| SECONDARY Mean Change From Screening at Each Visit in Absenteeism Questionnaire, Days Missed in 2 Weeks From MS Treatment: Overall Population |
0.016; 0.019; 0.02; -0.021; 0.126; 0.2 | 0.4821 |
| SECONDARY Change From Baseline Visit (Day 1) to Week 48 in Walking Disability Status as Measured by Patient Determined Disease Steps (PDDS): Overall Population |
0.83; 0.029; 0.15; 0.346 | 0.6508 |
| SECONDARY Summary of Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs |
93; 90; 54; 60; 7; 12 | — |
| SECONDARY 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 |
16.067; 14.915; 15.497; 18.057; 15.892; 17 | 0.0049 sig |
| SECONDARY Antibody Data in the Overall Population: IFN β-1a Antibody Screening |
22; 177; 35; 178; 26; 157 | — |
| SECONDARY Antibody Data in the Overall Population: IFN β-1a Anti-Pegylated (PEG) Antibody Testing |
7; 194; 8; 196; 6; 176 | — |
| SECONDARY Antibody Data in the Overall Population: IFN β-1a Neutralizing Antibodies (Nabs) Testing |
14; 8; 17; 20; 15; 11 | — |
Summary
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.
Eligibility 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.
Data sourced from ClinicalTrials.gov (NCT01939002). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.