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

• ClinicalTrials.gov Identifier: NCT01064401
• Recruitment Status: Completed
• First Posted: February 8, 2010
• Results First Posted: July 11, 2016
• Last Update Posted: July 11, 2016
• Sponsor: Biogen
• Collaborator: AbbVie
• Information provided by (Responsible Party): Biogen

Tracking Information

• First Submitted Date: January 26, 2010
• First Posted Date: 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: May 2010
• Actual Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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 ]

Current Secondary Outcome Measures (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 (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 Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy and Safety of BIIB019 (Daclizumab High Yield Process) Versus Interferon β 1a in Participants With Relapsing-Remitting Multiple Sclerosis
• Official Title: 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: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Relapsing-Remitting Multiple Sclerosis

Intervention

• 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 *

• Cohan S, Kappos L, Giovannoni G, Wiendl H, Selmaj K, Havrdova EK, Rose J, Greenberg S, Phillips G, Ma W, Wang P, Lima G, Sabatella G. Efficacy of daclizumab beta versus intramuscular interferon beta-1a on disability progression across patient demographic and disease activity subgroups in DECIDE. Mult Scler. 2018 Dec;24(14):1883-1891. doi: 10.1177/1352458517735190. Epub 2017 Oct 6.
• 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. 2018 May;24(6):795-804. doi: 10.1177/1352458517707345. Epub 2017 May 9.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 24, 2014): 1841
• Original Estimated Enrollment (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

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: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: 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: NCT01064401
• Other Study ID Numbers: 205MS301; 2009-012500-11
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Biogen
• Original Responsible Party: Biogen Idec (Medical Director), Biogen Idec
• Current Study Sponsor: Biogen
• Original Study Sponsor: Same as current
• Collaborators: AbbVie

Investigators

• Study Director: Medical Director; Biogen

• PRS Account: Biogen
• Verification Date: May 2016