Efficacy and Safety of BIIB019 (Daclizumab High Yield Process) Versus Interferon β 1a in Participants With Relapsing-Remitting Multiple Sclerosis ((DECIDE))

Tracking Information
First Submitted Date ICMJE	January 26, 2010
First Posted Date ICMJE	February 8, 2010
Results First Submitted Date	May 31, 2016
Results First Posted Date	July 11, 2016
Last Update Posted Date	July 11, 2016
Study Start Date ICMJE	May 2010
Actual Primary Completion Date	March 2014 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: May 31, 2016)	Adjusted Annualized Relapse Rate (ARR) [ Time Frame: Up to 144 weeks ]; Relapses are defined as new or recurrent neurological 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. Only relapses confirmed by Independent Neurology Evaluation Committee (INEC) are included in this analysis. Adjusted ARR was estimated from a negative binomial regression model adjusted for the baseline relapse rate, history of prior IFN beta use, baseline Expanded Disability Status Scale score (EDSS; ≤ 2.5 vs > 2.5) and baseline age (≤ 35 vs > 35 years). Data after participants switched to alternative MS medications are excluded.
Original Primary Outcome Measures ICMJE; (submitted: February 5, 2010)	The primary study objective is to test the superiority of DAC HYP compared to IFN β-1a in preventing MS relapse in subjects with relapsing remitting MS (RRMS). [ Time Frame: Designated Visits from Baseline Visit and every 4 weeks thereafter for up to 144 weeks ]
Change History	Complete list of historical versions of study NCT01064401 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: May 31, 2016)	Adjusted Mean Number of New or Newly Enlarging T2 Hyperintense Lesions up to Week 96 [ Time Frame: up to 96 weeks ]The quantity of lesions is assessed by brain magnetic resonance imaging (MRI). The adjusted mean number is estimated from a negative binomial regression model, adjusted for baseline volume of T2 from a negative binomial regression model, adjusted for baseline volume of T2 hyperintense lesions, history of prior IFN beta use and baseline age (≤ 35 vs > 35 years). To account for the timing of the MRI measurement, the logarithmic transformation of the scan number of the MRI assessment is included in the model as the 'offset' parameter. Observed data after participants switched to alternative MS medications are excluded. Missing data are not imputed. Only observed new or newly enlarging T2 lesions at the last visit of the participant up to Week 96 visit are used in this analysis.; Proportion of Participants With Sustained Disability Progression at 144 Weeks [ Time Frame: Baseline through 144 weeks ]Sustained disability progression is defined as: at least a 1.0-point increase on the EDSS from Baseline EDSS ≥ 1.0 that is sustained for 12 weeks, or at least a 1.5-point increase on the EDSS from baseline EDSS = 0 that is sustained for 12 weeks. The EDSS measures the disability status of people with MS on a scale that ranges from 0 to 10, with higher scores indicating more disability. Estimated proportion of participants with progression is based on the Kaplan-Meier product limit method. Participants were censored at the time of withdrawal/switch if they withdrew from study or switched to alternative MS medication without a progression. Participants with a tentative progression at the End of Treatment Period Visit (or the last EDSS assessment prior to alternative MS start date) and no confirmation assessment were censored at their last EDSS assessment.; Proportion of Participants Relapse-free at Week 144 [ Time Frame: 144 weeks ]Relapses are defined as new or recurrent neurological 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. Only relapses confirmed by INEC are included in this analysis. Data after participants switched to alternative MS medications are excluded. The estimated proportion of subjects relapse-free at Week 144 is based on the Kaplan-Meier product limit method.; Percentage of Participants With a ≥ 7.5 Point Worsening From Baseline in the Multiple Sclerosis Impact Scale (MSIS-29) Physical Impact Score at 96 Weeks [ Time Frame: Baseline and 96 weeks ]The MSIS-29 is a 29-item disease-specific patient-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 physical and psychological items. Worsening in the MSIS-29 physical score is defined as an increase of ≥ 7.5 points in the MSIS-29 physical score at 96 weeks compared to baseline. If a participant was missing data for less than 10 of the 20 items that make up the physical score, then the mean of the non-missing items were used for the missing items. If a participant was missing 10 or more of the 20 items that make up the physical score, or missing the questionnaire entirely, or if the questionnaire was completed after the participant switched to alternative MS medication, a random effects model was used to estimate the MSIS-29 physical score.
Original Secondary Outcome Measures ICMJE; (submitted: February 5, 2010)	The secondary study objectives are to test the superiority of DAC HYP compared to IFN β-1a in slowing functional decline and disability progression and maintaining quality of life in this subject population. [ Time Frame: Designated Visits from Baseline Visit and every 4 weeks thereafter for up to 144 weeks ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Efficacy and Safety of BIIB019 (Daclizumab High Yield Process) Versus Interferon β 1a in Participants With Relapsing-Remitting Multiple Sclerosis
Official Title ICMJE	Multicenter, Double-blind, Randomized, Parallel-group, Monotherapy, Active-control Study to Determine the Efficacy and Safety of Daclizumab High Yield Process (DAC HYP) Versus Avonex® (Interferon β 1a) in Patients With Relapsing-Remitting Multiple Sclerosis
Brief Summary	The primary study objective is to test the superiority of Daclizumab High Yield Process (DAC HYP) compared to interferon β 1a (IFN β-1a) in preventing multiple sclerosis (MS) relapse in participants with relapsing remitting multiple sclerosis. The secondary study objectives are to test the superiority of DAC HYP compared to IFN β-1a in slowing functional decline and disability progression and maintaining quality of life in this participant population.
Detailed Description	Not Provided
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition ICMJE	Relapsing-Remitting Multiple Sclerosis
Intervention ICMJE	Biological: BIIB019 (Daclizumab High Yield Process) Daclizumab High Yield Process for subcutaneous injection Other Name: DAC HYP; Drug: Interferon beta-1a Placebo Placebo to interferon beta-1a intramuscular injection; Biological: Interferon beta-1a Interferon beta-1a for intramuscular injection Other Names: Avonex IFN β-1a; Drug: Daclizumab High Yield Process Placebo Placebo to Daclizumab High Yield Process subcutaneous injection
Study Arms	Experimental: Daclizumab High Yield Process 150 mg SC Daclizumab High Yield Process (DAC HYP) 150mg subcutaneous (SC) injection once every 4 weeks plus placebo to IFN β-1a intramuscular (IM) injection once weekly for 96 to 144 weeks Interventions: Biological: BIIB019 (Daclizumab High Yield Process) Drug: Interferon beta-1a Placebo; Active Comparator: IFN β-1a 30 µg IM Interferon beta-1a (IFN β-1a) 30 µg IM once weekly plus placebo to DAC HYP SC once every 4 weeks for 96 to 144 weeks Interventions: Biological: Interferon beta-1a Drug: Daclizumab High Yield Process Placebo
Publications *	Benedict RH, Cohan S, Lynch SG, Riester K, Wang P, Castro-Borrero W, Elkins J, Sabatella G. Improved cognitive outcomes in patients with relapsing-remitting multiple sclerosis treated with daclizumab beta: Results from the DECIDE study. Mult Scler. 2017 May 1:1352458517707345. doi: 10.1177/1352458517707345. [Epub ahead of print]; Liu Y, Vollmer T, Havrdova E, Riester K, Lee A, Phillips G, Wang P, Sabatella G. Impact of daclizumab versus interferon beta-1a on patient-reported outcomes in relapsing-remitting multiple sclerosis. Mult Scler Relat Disord. 2017 Jan;11:18-24. doi: 10.1016/j.msard.2016.11.005. Epub 2016 Nov 13.; Krueger JG, Kircik L, Hougeir F, Friedman A, You X, Lucas N, Greenberg SJ, Sweetser M, Castro-Borrero W, McCroskery P, Elkins J. Cutaneous Adverse Events in the Randomized, Double-Blind, Active-Comparator DECIDE Study of Daclizumab High-Yield Process Versus Intramuscular Interferon Beta-1a in Relapsing-Remitting Multiple Sclerosis. Adv Ther. 2016 Jul;33(7):1231-45. doi: 10.1007/s12325-016-0353-2. Epub 2016 Jun 1.; Kappos L, Wiendl H, Selmaj K, Arnold DL, Havrdova E, Boyko A, Kaufman M, Rose J, Greenberg S, Sweetser M, Riester K, O'Neill G, Elkins J. Daclizumab HYP versus Interferon Beta-1a in Relapsing Multiple Sclerosis. N Engl J Med. 2015 Oct 8;373(15):1418-28. doi: 10.1056/NEJMoa1501481.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: October 24, 2014)	1841
Original Estimated Enrollment ICMJE; (submitted: February 5, 2010)	1500
Actual Study Completion Date	July 2014
Actual Primary Completion Date	March 2014 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Key Inclusion Criteria: Must have a confirmed diagnosis of Relapsing Remitting Multiple Sclerosis (RRMS), and a cranial magnetic resonance imaging (MRI) demonstrating lesion(s) consistent with MS; Must have a baseline Expanded Disability Status Scale (EDSS) between 0.0 and 5.0, inclusive; Male subjects and female subjects of childbearing potential must be willing to practice effective contraception during the study and be willing and able to continue contraception for 4 months after their last dose of study treatment Key Exclusion Criteria: Known intolerance, contraindication to, or history of non-compliance with Avonex® 30 µg; History of treatment with Daclizumab High Yield Process (Dac HYP); History of malignancy; History of severe allergic or anaphylactic reactions; Known hypersensitivity to study drugs or their excipients; History of abnormal laboratory results indicative of any significant disease; History of human immunodeficiency virus (HIV) or other immunodeficient conditions; History of drug or alcohol abuse (as defined by the Investigator) within the 2 years prior to randomization; History of seizure disorder or unexplained blackouts OR history of a seizure within 6 months prior to Baseline; History of suicidal ideation or an episode of clinically severe depression (as determined by the Investigator) within 3 months prior to Day 1; An MS relapse that has occurred within the 50 days prior to randomization AND/OR the subject has not stabilized from a previous relapse prior to randomization; Known history of, or positive screening test result for hepatitis C virus or hepatitis B virus; Varicella or herpes zoster virus infection or any severe viral infection within 6 weeks before screening; Exposure to varicella zoster virus within 21 days before screening NOTE: Other protocol-defined Inclusion/Exclusion criteria may apply.
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 55 Years (Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Argentina, Australia, Brazil, Canada, Czech Republic, Denmark, Finland, France, Georgia, Germany, Greece, Hungary, India, Ireland, Israel, Italy, Mexico, Moldova, Republic of, Poland, Romania, Russian Federation, Serbia, Spain, Sweden, Switzerland, Ukraine, United Kingdom, United States
Removed Location Countries	Bulgaria, Egypt, Slovenia
Administrative Information
NCT Number ICMJE	NCT01064401
Other Study ID Numbers ICMJE	205MS301; 2009-012500-11
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Biogen
Study Sponsor ICMJE	Biogen
Collaborators ICMJE	AbbVie
Investigators ICMJE	Study Director: Medical Director Biogen
PRS Account	Biogen
Verification Date	May 2016
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP