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EXTEND: Long-Term Extension Study in Participants With Multiple Sclerosis Who Have Completed Study 205MS301 (NCT01064401) to Evaluate the Safety and Efficacy of BIIB019

Sponsor
Biogen (Industry)
Overall Status
Terminated
CT.gov ID
NCT01797965
Collaborator
AbbVie (Industry)
1,501
Enrollment
222
Locations
1
Arm
67.3
Actual Duration (Months)
6.8
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective of the study is to assess the safety and tolerability of long-term treatment with BIIB019 (Daclizumab High Yield Process; DAC HYP) monotherapy in participants with relapsing remitting multiple sclerosis (RRMS) who completed Study 205MS301 (NCT01064401), Study 205MS203 (NCT01051349) or Study 205MS302 (NCT01462318).

Secondary objectives of this study in this study population are as follows:

To describe MS-related outcomes, including MS relapse, disability progression, MS lesion formation, and participant-reported impact of MS, following long-term treatment with DAC HYP To assess the long-term immunogenicity of DAC HYP administered by prefilled syringe (PFS) To assess the safety, tolerability, and efficacy of switching to DAC HYP in participants previously on long-term treatment with interferon β-1a (Avonex) in Study 205MS301(NCT01064401).

Condition or Disease Intervention/Treatment Phase
  • Drug: BIIB019 (Daclizumab)
 Phase 3

Detailed Description

Enrollment will include up to 1600 Participants, this includes approximately 1200 Participants who completed Study 205MS301 (NCT01064401). Additionally, approximately 400 Participants from the other BIIB019 extension studies 205MS203 (NCT01051349) and 205MS302 (NCT01462318) will be eligible to enter Study 205MS303 at Week 144 of Study 205MS303 [Study 205MS301 (NCT01064401), study 205MS203 (NCT01051349) and study 205MS302 (NCT01462318) have been referred to as parent studies in the protocol]. All Participants will receive the same dose of DAC HYP as received in the parent studies; i.e., 150 mg by an SC injection every 4 weeks.

Study Design

Study Type:
Interventional
Actual Enrollment :
1501 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Multicenter, Open-Label, Extension Study to Evaluate the Long Term Safety and Efficacy of BIIB019, Daclizumab High Yield Process (DAC HYP), Monotherapy in Subjects With Multiple Sclerosis Who Have Completed Study 205MS301
Actual Study Start Date :
Feb 15, 2013
Actual Primary Completion Date :
Sep 24, 2018
Actual Study Completion Date :
Sep 24, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: BIIB019

BIIB019 150 mg subcutaneous (SC) every 4 weeks

Drug: BIIB019 (Daclizumab)
Participants will receive open-label treatment with BIIB019 150 mg subcutaneous injection every 4 weeks for up to 5 years.
Other Names:
  • Daclizumab High Yield Process
  • DAC HYP

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [First dose of study drug in Study 303 to within 180 days of last dose (up to approximately 5.5 years)]

      An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product; it does not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product. A SAE is any untoward medical occurrence or effect that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability / incapacity, is a congenital anomaly / birth defect or is medically important due to other reasons than the above mentioned criteria.

    Secondary Outcome Measures

    1. Annualized Relapse Rate (ARR) in the 205MS303 Treatment Period [Up to 4.6 years in the 303 study]

      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 Study Neurologist. The unadjusted ARR was calculated by tabulating the total number of relapses experienced in the group divided by the number of days up to the end of study, and the ratio then multiplied by 365.25. Relapses that occurred after participants received alternative multiple sclerosis (MS) medications were excluded from the analyses. ARR was adjusted for relapse rate, IFN beta use, Expanded Disability Status Scale (EDSS) (<=2.5 vs >2.5) and age (<=35 vs >35) prior to start of study treatment in 205MS301, calculated using the negative binomial model.

    2. ARR in the 205MS301-303 Combined Study Period and 205MS301 Treatment Period [Up to 5.6 years combining 303 with the initial Study 301; Up to 1 year in the 301 study]

      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 Study Neurologist. The unadjusted ARR was calculated by tabulating the total number of relapses experienced in the group divided by the number of days up to the end of study, and the ratio then multiplied by 365.25. Relapses that occurred after participants received alternative MS medications were excluded from the analyses. ARR was adjusted for relapse rate, IFN beta use, EDSS (<=2.5 vs >2.5) and age (<=35 vs >35) prior to start of study treatment in 301, calculated using the negative binomial model.

    3. Number of Participants With Relapse in the 205MS303 Treatment Period [Up to 4.6 years in the 303 study]

      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 Study Neurologist.

    4. Number of Participants With Relapse in the 205MS301-303 Combined Study Period [Up to 5.6 years combining 303 with the initial Study 301]

      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 Study Neurologist.

    5. Number of Participants With Sustained Disability Progression in the 205MS303 Treatment Period [Up to 4.6 years in Study 303]

      Sustained disability progression is defined as at least a 1.0-point increase on the Expanded Disability Status Scale (EDSS) from 303 baseline EDSS ≥1.0 that is sustained for 24 weeks, or at least a 1.5-point increase on the EDSS from 303 baseline EDSS of 0, that is sustained for 24 weeks. The EDSS measures the disability status of people with multiple sclerosis on a scale that ranges from 0 to 10. The range of main categories include (0) =normal neurologic exam; to (5) = ambulatory without aid or rest for 200 meters; disability severe enough to impair full daily activities; to (10) = death due to MS. Higher scores indicate more disability.

    6. Number of Participants With Sustained Disability Progression in the 205MS301-303 Combined Study Period [Up to 5.6 years combining 303 with the initial Study 301]

      Sustained disability progression is defined as at least a 1.0-point increase on the Expanded Disability Status Scale (EDSS) from 303 baseline EDSS ≥1.0 that is sustained for 24 weeks, or at least a 1.5-point increase on the EDSS from 303 baseline EDSS of 0, that is sustained for 24 weeks. The EDSS measures the disability status of people with multiple sclerosis on a scale that ranges from 0 to 10. The range of main categories include (0) =normal neurologic exam; to (5) = ambulatory without aid or rest for 200 meters; disability severe enough to impair full daily activities; to (10) = death due to MS. Higher scores indicate more disability.

    7. Number of Participants With New or Newly Enlarging T2 Hyperintense Lesions in the 205MS303 Treatment Period [Baseline 303, Weeks 48, 96, 144, 192, 240 in Study 303]

      T2 Hyperintense Lesions were assessed by magnetic resonance imaging (MRI) and were analyzed by a central MRI reader. The number of participants with New or Newly Enlarging T2 Hyperintense Lesions relative to the 303 Baseline in the 303 Treatment Period is reported.

    8. Number of Participants With New or Newly Enlarging T2 Hyperintense Lesions in the 205MS301 Treatment Period [Baseline 301, Weeks 24, 96, 144 in Study 301]

      T2 Hyperintense Lesions were assessed by MRI and were analyzed by a central MRI reader. The number of participants with New or Newly Enlarging T2 Hyperintense Lesions relative to the 301 Baseline in the 301 Treatment Period is reported.

    9. Number of Participants With Gadolinium-enhancing (Gd+) Lesions in the 205MS303 Treatment Period [301-303: Baseline 303, Weeks 48, 96, 144, 192, 240; 203-303 and 302-303: Week 96]

      Gd+ lesions were evaluated by MRI and were analyzed by a central MRI reader.

    10. Number of Participants With Gadolinium-enhancing (Gd+) Lesions in the 205MS301 Treatment Period [Baseline 301, Weeks 24, 96 and 144]

      Gd+ lesions were evaluated by MRI and were analyzed by a central MRI reader.

    11. Number of Participants With New T1 Hypointense Lesions in the 205MS303 Treatment Period [Baseline 303, Weeks 48, 96, 144, 192, 240 in Study 303]

      T1 hypointense lesions were evaluated by MRI and were analyzed by a central MRI reader. The number of participants with New T1 Hyperintense Lesions relative to the 303 Baseline in the 303 Treatment Period is reported.

    12. Number of Participants With New T1 Hypointense Lesions in the 205MS301 Treatment Period [Baseline 301, Weeks 24, 96, 144 in Study 301]

      T1 hypointense lesions were evaluated by MRI and were analyzed by a central MRI reader. The number of participants with New T1 Hyperintense Lesions relative to the 301 Baseline in the 301 Treatment Period is reported .

    13. Percent Change in Brain Volume From the 205MS303 Baseline [Baseline 303, Weeks 48, 96, 144, 192, 240 in Study 303]

      To assess brain atrophy, total brain volume was measured by MRI and was analyzed by a central MRI reader. A negative percent change from baseline indicates improvement.

    14. Percent Change in Brain Volume From 205MS301 Baseline [Baseline 301, Weeks 48, 96, 144, 192, 240 in Study 303]

      To assess brain atrophy, total brain volume was measured by MRI and was analyzed by a central MRI reader. A negative percent change from baseline indicates improvement.

    15. Total Volume of T2 Hyperintense Lesions in the 205MS303 Treatment Period [Baseline 303, Weeks 48, 96, 144, 192, 240 in Study 303; 203-303 and 302-303: Week 96]

      Volume of T2 hyperintense Lesions was evaluated by MRI and was analyzed by a central MRI reader.

    16. Change From Baseline in the Multiple Sclerosis Functional Composite (MSFC) Score in the 205MS303 Treatment Period [Baseline 303, Weeks 12, 24 and 48 in Study 303]

      MSFC is a three-part, standardized, quantitative, assessment instrument consisting of (Timed 25-Foot Walk, Nine-Hole Peg Test (9HPT) and Paced Auditory Serial Addition Test (PASAT-3"). 2 timed 25-foot walk scores are averaged. 4 trials of the Peg Test (2 for each hand) are converted to the reciprocals and averaged. The number correct of the PASAT-3 is used. The composite Z-score is calculated by: Z(25-foot walk) + Z (HPT) + Z(PASAT)/3. A positive change from baseline indicates improvement.

    17. Change From 205MS301 Baseline in the MSFC Score in the 205MS301-303 Combined Study Period [Baseline 301, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 in the 301 study, Baseline 303, Weeks 12, 24, 48 in the 303 study]

      MSFC is a three-part, standardized, quantitative, assessment instrument consisting of (Timed 25-Foot Walk, Nine-Hole Peg Test (9HPT) and Paced Auditory Serial Addition Test (PASAT-3"). 2 timed 25-foot walk scores are averaged. 4 trials of the Peg Test (2 for each hand) are converted to the reciprocals and averaged. The number correct of the PASAT-3 is used. The composite Z-score is calculated by: Z(25-foot walk) + Z (HPT) + Z(PASAT)/3. A positive change from baseline indicates improvement.

    18. Change From Baseline in the Expanded Disability Status Scale (EDSS) Score in the 205MS303 Treatment Period [301-303: Baseline 303, Weeks 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 260; 203-303 and 302-303: Baseline 303, Weeks 12, 24, 48, 72, 96, 116 in Study 303]

      The EDSS measures the disability status of people with multiple sclerosis as assessed by the Study Neurologist based on 8 functional systems that ranges from 0=normal neurologic exam; to 5=ambulatory without aid or rest for 200 meters; disability severe enough to impair full daily activities; to 10=death due to MS. Higher scores indicate more disability. A negative change from Baseline indicates improvement.

    19. Number of Participants Who Are Free From Disease Activity in the 205MS303 Treatment Period [Up to 4.6 years in Study 303]

      Participants without clinical or radiological activity are defined as disease-free. Clinical activity includes assessment of relapses and of disease progression. Radiological activity includes assessments of Gd+ lesions and new or enlarging T2 lesions.

    20. Change From Baseline in the Multiple Sclerosis Impact Scale 29 (MSIS 29) Physical and Psychological Scores in the 205MS303 Treatment Period [Baseline 303, Weeks 12, 24, 48, 96, 120 and 144]

      The 29-item MSIS-29 is a disease specific participant-reported outcome measure that has been developed and validated to examine the physical (coordination and mobility) and psychological (mental) impact of MS from a participant's perspective; it measures 20 physical items and 9 psychological items. The results for each of the physical and psychological scores are transformed to a score of 0 to 100 (worse state of health). A negative change from Baseline indicates improvement.

    21. Change From Baseline in Quality of Life as Assessed by the European Quality of Life, 5 Dimensions (EQ 5D) Health Scores in the 205MS303 Treatment Period [301-303: Baseline 303, Weeks 12, 24, 48, 96, 120, 144, 192, 240; 203-303 and 302-303: Baseline 303, Weeks 48 and 96 in Study 303]

      The EQ-5D is a self-administered questionnaire consisting of 5 domains pertaining to specific health state profile : mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The participants recorded their level of current health for each domain where: 1=no problems, 2=some problem and 3=severe problems. The health score is derived from the individual scores for each of the 5 domains transformed to a score of 0=worst health state to 1=perfect health state. A positive change from Baseline indicates improvement.

    22. Change From Baseline in Quality of Life as Assessed by the European Quality of Life, Visual Analog Scale (EQ VAS) in the 205MS303 Treatment Period [301-303: Baseline 303, Weeks 12, 24, 48, 96, 120, 44, 192, 240; 203-303 and 302-303: Baseline 303, Weeks 48 and 96 in Study 303]

      The participant rated their current heath state using the EQ VAS 20-centimeter horizontal line from 0 (worst imaginable health state) to 100 (best imaginable health state). A positive change from baseline indicates improvement.

    23. Direct Health Resource Utilization (HRU): Number of Unscheduled Site Visits in the 205MS303 Treatment Period [301-303: Baseline 303, Weeks 24, 48, 96, 144, 192, 240; 203-303 and 302-303: Baseline 303, Weeks 48, 96 in 303]

      Heath resource utilization was assessed by the number of hospitalizations, emergency room visits, and unscheduled neurologist visits for MS-related and non-MS-related visits.

    24. Direct Health Resource Utilization (HRU): Number of Unscheduled Site Visits in the 205MS301 Treatment Period [Baseline 301, Weeks 24, 48, 72, 96, 120 and 144 in 301]

      Heath resource utilization was assessed by the number of hospitalizations, emergency room visits, and unscheduled neurologist visits for MS-related and non-MS-related visits.

    25. Treatment Satisfaction as Assessed by the Participant in the 205MS303 Treatment Period [Baseline 303, Weeks 12, 24, 48, 72, 96, 120 in Study 303]

      Participants answered the question: "How satisfied or dissatisfied are you with the ability of the medication to prevent or treat the condition?" using the following scale: Dissatisfied (Extremely dissatisfied, Very dissatisfied, Dissatisfied) or Satisfied (Somewhat satisfied, Satisfied, Very Satisfied and Extremely satisfied). The number of participants in the Dissatisfied and Satisfied categories is reported.

    26. Health Related Productivity Questionnaire (HRPQ): Scheduled Work Hours in the 205MS303 Treatment Period [301-303: Baseline 303, Weeks 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240; 203-303 and 302-303: Baseline 303, Weeks 24, 48, 72, 96 in Study 303]

      The HRPQ was used by the participant to assess the impact of MS or its treatments on employment. The participant recorded their scheduled work hours. Data is reported by part time or full time employment.

    27. HRPQ: Number of Participants Where MS or Its Treatments Resulted in Missed Work in the 205MS303 Treatment Period [301-303: Baseline 303, Weeks 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240; 203-303 and 302-303: Baseline 303, Weeks 24, 48, 72, 96 in Study 303]

      The HRPQ was used by the participant to assess the impact of MS or its treatments on employment. The participant recorded whether their MS or its treatments caused them to miss work. Data is reported by part time or full time employment.

    28. HRPQ: Hours of Work Missed Due to MS or Its Treatment in the 205MS303 Treatment Period [301-303: Baseline 303, Weeks 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240; 203-303 and 302-303: Baseline 303, Weeks 24, 48, 72, 96 in Study 303]

      The HRPQ was used by the participant to assess the impact of MS or its treatments on employment. The participant recorded the hours they missed work due to MS or its treatments. Data is reported by part time or full time employment.

    29. HRPQ: Percent Impact on Employment in the 205MS303 Treatment Period [301-303: Baseline 303, Weeks 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240; 203-303 and 302-303: Baseline 303, Weeks 24, 48, 72, 96 in Study 303]

      The HRPQ was used by the participant to assess the impact of MS or its treatments on employment. The participants assessed the percent impact of MS and its treatments on their work output using a VAS where 0= MS or its treatments had no impact on how much I accomplished to 100=MS or its treatments kept me from accomplishing anything. Data is reported for part time or full time employment.

    30. HRPQ: Hours of Household Chores Planned to Perform in the 205MS303 Treatment Period [301-303: Baseline 303, Weeks 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240; 203-303 and 302-303: Baseline 303, Weeks 24, 48, 72, 96 in Study 303]

      The HRPQ was used by the participant to assess the impact of MS or its treatments on performing household chores. The participant recorded their planned hours for household chores.

    31. HRPQ: Number of Participants Where MS or Its Treatments Kept the Participant From Completing Chores in the 205MS303 Treatment Period [301-303: Baseline 303, Weeks 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240; 203-303 and 302-303: Baseline 303, Weeks 24, 48, 72, 96 in Study 303]

      The HRPQ was used by the participant to assess the impact of MS or its treatments on performing household chores. The participant recorded whether MS or its treatments kept them from completing household chores.

    32. HRPQ: Hours Not Performing Household Chores Due to MS or Its Treatment in 205MS303 Treatment Period [301-303: Baseline 303, Weeks 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240; 203-303 and 302-303: Baseline 303, Weeks 24, 48, 72, 96 in Study 303]

      The HRPQ was used by the participant to assess the impact of MS or its treatments on performing household chores. The participant recorded the hours where they were not able to perform household chores due to MS or its treatments.

    33. HRPQ: Percent Impact on Performing Household Chores in the 205MS303 Treatment Period [301-303: Baseline 303, Weeks 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240; 203-303 and 302-303: Baseline 303, Weeks 24, 48, 72, 96 in Study 303]

      The HRPQ was used by the participant to assess the impact of MS or its treatments on performing household chores. The participant assessed the percent impact of MS and its treatments on how much they accomplished using a VAS where 0= MS or its treatments had no impact on how much I accomplished to 100=MS or its treatments kept me from accomplishing anything.

    34. Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Assessments in the 205MS303 Treatment Period [Up to 4.6 years in 303]

      Clinical Laboratory assessments included tests of hematology, blood chemistry, renal function, and thyroid function. The investigator determined if the results were clinically significant.

    35. Local Tolerability as Assessed by Participant-reported Injection Site Pain VAS [After the first and fourth injections in 303, approximately Week 0 and Week 12]

      The VAS is a 10 cm-long horizontal line labeled with 2 extremes of pain at either end: 0 =no pain on the left and 100=very painful on the right. The participant rates their perceived pain of each injection by placing a vertical mark on the line to indicate the level of pain.

    36. Number of Participants in Local Tolerability Clinician Injection Site Assessment Categories [After the first and fourth injections in 303, approximately Week 0 and Week 12]

      The investigator assessed the injection site after the first dose and before the fourth dose for the presence of erythema (None, Mild, Moderate, Severe), pigmentation (None, Hypo, Hyper), Induration (None, Mild, Moderate, Severe), Tenderness (None, Mild, Moderate, Severe) and Temperature (Normal, Warm, Hot). The number of participants in each grade is reported.

    37. Number of Participants With Anti-BIIB019 Binding Antibodies (ADAbs) in the 205MS303 Treatment Period [Up to 4.6 years in the 303 Treatment Period]

      Blood samples were collected for ADAbs and were analyzed using a laboratory test. The number of participants ADAb positive at any post-baseline timepoint is reported.

    38. Number of Participants With Anti-BIIB019 Neutralizing Antibodies (Nabs) in the 205MS303 Treatment Period [Up to 4.6 years in the 303 Treatment Period]

      Blood samples were collected for NAbs and were analyzed using a laboratory test. The number of participants NAb positive at any post-baseline timepoint is reported.

    39. Change From 205MS303 Baseline in the Symbol Digit Modalities Test (SDMT) Score in the 205MS303 Treatment Period [Baseline 303, Weeks 144, 168, 192, 240 in 303]

      SDMT is a screening test for cognitive impairment. Participants are given 90 seconds in which to pair specific numbers with given geometric figures using a key. Scores range from 0 to 110 (best). A positive change from baseline indicates improvement.

    40. Change From 205MS301 Baseline in the SDMT Score in the 205MS301-303 Combined Study Period [Baseline 301, Weeks 24, 48, 72, 96, 120, 144 in 301; Weeks 144, 168, 192, 216, 240 in 303]

      SDMT is a screening test for cognitive impairment. Participants are given 90 seconds in which to pair specific numbers with given geometric figures using a key. Scores range from 0 to 110 (best). A positive change from baseline indicates improvement.

    41. Change From Baseline in 3-Second Paced Auditory Serial Addition Test (PASAT 3) Score in the 205MS303 Treatment Period [Baseline 303, Weeks 12, 24, 48, 120, 144, 168, 192, 216, 240 in 303]

      The PASAT 3 assesses auditory information processing speed. A random series of numbers from 1 to 9, inclusive, are presented and the participant is instructed to consecutively add pairs of numbers so that each number is added to the one that immediately preceded it. In the 3- second PASAT, numbers are presented at a rate of 1 every 3 seconds. The total possible score is the number of correct responses from 0 to 60 (best). A positive change from baseline indicates improvement.

    42. Change From Baseline in 3-Second Paced Auditory Serial Addition Test (PASAT 3) Score in the 205MS301-303 Combined Study Period [Baseline 301, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 in the 301 study, Baseline 303, Weeks 12, 24, 48, 120, 144,168, 192, 216, 240 in 303 study]

      The PASAT 3 assesses auditory information processing speed. A random series of numbers from 1 to 9, inclusive, are presented and the participant is instructed to consecutively add pairs of numbers so that each number is added to the one that immediately preceded it. In the 3- second PASAT, numbers are presented at a rate of 1 every 3 seconds. The total possible score is the number of correct responses from 0 to 60 (best). A positive change from baseline indicates improvement.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Key Inclusion Criteria:

    • Must be a subject currently participating in Study 205MS301 (NCT01064401), or subject currently participating in Study 205MS203 (NCT01051349) or Study 205MS302 (NCT01462318) who has completed End of Study Visit (Week 96 or later).

    • Women of childbearing potential must 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:

    • Any subject who permanently discontinued study treatment in Study 205MS301 (NCT01064401), Study 205MS203 (NCT01051349) or Study 205MS302 (NCT01462318) prior to the end of the study treatment period, or had an Early Termination visit in Study 205MS301, Study 205MS203 (NCT01051349) or Study 205MS302 (NCT01462318).

    • Any significant change in the subject's medical history that would preclude administration of BIIB019, including laboratory tests or a current clinically significant condition that, in the opinion of the Investigator, would have excluded the subject's participation in Study 205MS301 (NCT01064401), Study 205MS203 (NCT01051349) or Study 205MS302 (NCT01462318).

    The Investigator must re review the subject's medical fitness for participation and consider any factors that would preclude treatment in this Study 205MS303.

    NOTE: Other protocol-defined inclusion/exclusion criteria may apply.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Phoenix Arizona United States 85013
    2 Research Site Phoenix Arizona United States 85050
    3 Research Site Tucson Arizona United States 85704
    4 Research Site Little Rock Arkansas United States 72205
    5 Research Site La Jolla California United States 92037
    6 Research Site Aurora Colorado United States 80045
    7 Research Site Centennial Colorado United States 80112
    8 Research Site Naples Florida United States 34102
    9 Research Site Pompano Beach Florida United States 33060
    10 Research Site Atlanta Georgia United States 30327
    11 Research Site Fort Wayne Indiana United States 46804
    12 Research Site Indianapolis Indiana United States 46202
    13 Research Site Kansas City Kansas United States 66160
    14 Research Site Lexington Kentucky United States 40503
    15 Research Site Wellesley Massachusetts United States 02481
    16 Research Site Worcester Massachusetts United States 01605
    17 Research Site Farmington Hills Michigan United States 48334
    18 Research Site Lebanon New Hampshire United States 03756
    19 Research Site Albuquerque New Mexico United States 87131
    20 Research Site Buffalo New York United States 14203
    21 Research Site Latham New York United States 12110
    22 Research Site New York New York United States 10016
    23 Research Site New York New York United States 10065
    24 Research Site Rochester New York United States 14642
    25 Research Site Charlotte North Carolina United States 28207
    26 Research Site Raleigh North Carolina United States 27607
    27 Research Site Winston-Salem North Carolina United States 27103
    28 Research Site Dayton Ohio United States 45408
    29 Research Site Medford Oregon United States 97504
    30 Research Site Portland Oregon United States 97225
    31 Research Site Allentown Pennsylvania United States 18103
    32 Research Site Pittsburgh Pennsylvania United States 15213
    33 Research Site Cordova Tennessee United States 38018
    34 Research Site Franklin Tennessee United States 37064
    35 Research Site Knoxville Tennessee United States 37922
    36 Research Site Round Rock Texas United States 78681
    37 Research Site Henrico Virginia United States 23226
    38 Research Site Tacoma Washington United States 98405
    39 Research Site Milwaukee Wisconsin United States 53215
    40 Research Site Ciudad Autónoma de Buenos Aires Buenos Aires Argentina C1015ABR
    41 Research Site Ciudad Autónoma de Buenos Aires Buenos Aires Argentina C1061ABD
    42 Research Site Godoy Cruz Mendoza Argentina M5501
    43 Research Site Rosario Santa Fe Argentina S2000BZL
    44 Research Site Auchenflower Queensland Australia 4066
    45 Research Site Heidelberg Victoria Australia 3084
    46 Research Site Belo Horizonte Minas Gerais Brazil 30150-221
    47 Research Site Recife Pernambuco Brazil 52010-040
    48 Research Site Porto Alegre Rio Grande Do Sul Brazil 90035-001
    49 Research Site Campinas São Paulo Brazil 13083-888
    50 Research Site Ribeirão Preto São Paulo Brazil 14049-900
    51 Research Site Rio de Janeiro Brazil 20270-004
    52 Research Site Rio De Janeiro Brazil 21941-590
    53 Research Site Vancouver British Columbia Canada V6T 2B5
    54 Research Site Saint Johns Newfoundland and Labrador Canada A1B 3V6
    55 Research Site London Ontario Canada N6A 5A5
    56 Research Site Ottawa Ontario Canada K1H 8L6
    57 Research Site Gatineau Quebec Canada J9J 0A5
    58 Research Site Greenfield Park Quebec Canada J4V 2J2
    59 Research Site Brno Jihomoravský Kraj Czechia 625 00
    60 Research Site Brno Jihomoravský Kraj Czechia 656 91
    61 Research Site Jihlava Kray Vysocina Czechia 586 33
    62 Research Site Ostrava Moravskoslezský Kraj Czechia 708 52
    63 Research Site Pardubice Pardubický Kraj Czechia 532 03
    64 Research Site Praha 10 Praha Czechia 100 34
    65 Research Site Praha 2 Praha Czechia 128 08
    66 Research Site Olomouc Severomoravsky Kraj Czechia 775 20
    67 Research Site Hradec Kralove Czechia 500 03
    68 Research Site Praha 5 Czechia 150 06
    69 Research Site Teplice Ústecký Kraj Czechia 415 29
    70 Research Site Copenhagen Denmark 2100
    71 Research Site Glostrup Denmark 2600
    72 Research Site Odense C Denmark 5000
    73 Research Site Strasbourg Bas-Rhin France 67091
    74 Research Site Marseille Bouches-du-Rhône France 13385
    75 Research Site Caen Calvados France 14033
    76 Research Site Bordeaux Gironde France 33076
    77 Research Site Toulouse Haute-Garonne France 31059
    78 Research Site Bobigny Ile-de-France France 93009
    79 Research Site Nancy Meurthe-et-Moselle France 54000
    80 Research Site Lille Nord France 59037
    81 Research Site Amiens Cedex 1 France 80054
    82 Research Site Paris France 75019
    83 Research Site Tbilisi Georgia 0179
    84 Research Site Bad Mergentheim Baden-Württemberg Germany 97980
    85 Research Site Freiburg Baden-Württemberg Germany 79106
    86 Research Site Bayreuth Bayern Germany 95445
    87 Research Site Erlangen Bayern Germany 91054
    88 Research Site München Bayern Germany 81675
    89 Research Site Marburg Hessen Germany 35043
    90 Research Site Rostock Mecklenburg-Vorpommern Germany 18147
    91 Research Site Dresden Sachsen Germany 01307
    92 Research Site Bamberg Germany 96052
    93 Research Site Athens Attiki Greece 11525
    94 Research Site Thessaloniki Macedonia Greece 57010
    95 Research Site Athens Greece 115 21
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    Sponsors and Collaborators

    • Biogen
    • AbbVie

    Investigators

    • Study Director: Medical Director, Biogen

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Biogen
    ClinicalTrials.gov Identifier:
    NCT01797965
    Other Study ID Numbers:
    • 205MS303
    • 2012-003176-39
    First Posted:
    Feb 25, 2013
    Last Update Posted:
    Dec 4, 2019
    Last Verified:
    Nov 1, 2019
    Additional relevant MeSH terms:
    Multiple Sclerosis
    Multiple Sclerosis, Relapsing-Remitting
    Sclerosis
    Daclizumab

    Study Results

    Participant Flow

    Recruitment Details Participants were enrolled in the study at 226 investigative sites in 28 countries (United States, Canada, Western European countries, Australia, Israel, Eastern European countries, Argentina, Brazil, India, and Mexico) from 15 February 2013 to 24 September 2018.
    Pre-assignment Detail Participants who completed studies: 205MS301 (NCT01064401), 205MS203 (NCT01051349), 205MS302 (NCT01462318) were eligible to enroll in this long-term extension study.
    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303) DAC HYP 150 mg (302) /DAC HYP 150 mg (303) DAC HYP 150 mg (203) /DAC HYP 150 mg (303)
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 93.7 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS302 (302) every 4 weeks for up to 24 weeks followed by a 20-week washout period then continued treatment for up to an additional 3 years. DAC HYP 150 mg SC injection every 4 weeks for up to 94. 1 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS203 (203) every 4 weeks for up to 288 weeks.
    Period Title: Overall Study
    STARTED 597 607 70 227
    COMPLETED 48 38 62 154
    NOT COMPLETED 549 569 8 73

    Baseline Characteristics

    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303) DAC HYP 150 mg (302) /DAC HYP 150 mg (303) DAC HYP 150 mg (203) /DAC HYP 150 mg (303) Total
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 93.7 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS302 (302) every 4 weeks for up to 24 weeks followed by a 20-week washout period then continued treatment for up to an additional 3 years. DAC HYP 150 mg SC injection every 4 weeks for up to 94. 1 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS203 (203) every 4 weeks for up to 288 weeks. Total of all reporting groups
    Overall Participants 597 606 70 227 1500
    Age, Customized (Count of Participants)
    Adults (18-64 years)
    597
    100%
    606
    100%
    70
    100%
    227
    100%
    1500
    100%
    Sex: Female, Male (Count of Participants)
    Female
    394
    66%
    400
    66%
    42
    60%
    130
    57.3%
    966
    64.4%
    Male
    203
    34%
    206
    34%
    28
    40%
    97
    42.7%
    534
    35.6%
    Race/Ethnicity, Customized (Count of Participants)
    White
    546
    91.5%
    559
    92.2%
    2
    2.9%
    223
    98.2%
    1330
    88.7%
    Black or African American
    5
    0.8%
    5
    0.8%
    3
    4.3%
    0
    0%
    13
    0.9%
    Asian
    11
    1.8%
    10
    1.7%
    0
    0%
    4
    1.8%
    25
    1.7%
    Other
    18
    3%
    14
    2.3%
    1
    1.4%
    0
    0%
    33
    2.2%
    Not Reported
    17
    2.8%
    18
    3%
    64
    91.4%
    0
    0%
    99
    6.6%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
    Description An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product; it does not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product. A SAE is any untoward medical occurrence or effect that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability / incapacity, is a congenital anomaly / birth defect or is medically important due to other reasons than the above mentioned criteria.
    Time Frame First dose of study drug in Study 303 to within 180 days of last dose (up to approximately 5.5 years)

    Outcome Measure Data

    Analysis Population Description
    Safety Population consisted of all participants who completed Study 301, 203 or 302 and had at least 1 dose of DAC HYP during Study 303.
    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303) DAC HYP 150 mg (203) /DAC HYP 150 mg (303) DAC HYP 150 mg (302) /DAC HYP 150 mg (303)
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 94.1 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS203 (203) every 4 weeks for up to 288 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 93.7 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS302 (302) every 4 weeks for up to 24 weeks followed by a 20-week washout period then continued treatment for up to an additional 3 years.
    Measure Participants 597 606 227 70
    Participants with AEs
    541
    90.6%
    560
    92.4%
    172
    245.7%
    53
    23.3%
    Participants with SAEs
    157
    26.3%
    190
    31.4%
    38
    54.3%
    15
    6.6%
    2. Secondary Outcome
    Title Annualized Relapse Rate (ARR) in the 205MS303 Treatment Period
    Description 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 Study Neurologist. The unadjusted ARR was calculated by tabulating the total number of relapses experienced in the group divided by the number of days up to the end of study, and the ratio then multiplied by 365.25. Relapses that occurred after participants received alternative multiple sclerosis (MS) medications were excluded from the analyses. ARR was adjusted for relapse rate, IFN beta use, Expanded Disability Status Scale (EDSS) (<=2.5 vs >2.5) and age (<=35 vs >35) prior to start of study treatment in 205MS301, calculated using the negative binomial model.
    Time Frame Up to 4.6 years in the 303 study

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) Population consisted of all participants who completed Study 301, 203 or 302 and received at least 1 dose of DAC HYP during Study 303.
    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303) DAC HYP 150 mg (203) /DAC HYP 150 mg (303) DAC HYP 150 mg (302) /DAC HYP 150 mg (303)
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 94.1 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS203 (203) every 4 weeks for up to 288 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 93.7 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS302 (302) every 4 weeks for up to 24 weeks followed by a 20-week washout period then continued treatment for up to an additional 3 years.
    Measure Participants 597 606 227 70
    Mean (95% Confidence Interval) [relapses per year]
    0.158
    0.163
    0.080
    0.167
    3. Secondary Outcome
    Title ARR in the 205MS301-303 Combined Study Period and 205MS301 Treatment Period
    Description 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 Study Neurologist. The unadjusted ARR was calculated by tabulating the total number of relapses experienced in the group divided by the number of days up to the end of study, and the ratio then multiplied by 365.25. Relapses that occurred after participants received alternative MS medications were excluded from the analyses. ARR was adjusted for relapse rate, IFN beta use, EDSS (<=2.5 vs >2.5) and age (<=35 vs >35) prior to start of study treatment in 301, calculated using the negative binomial model.
    Time Frame Up to 5.6 years combining 303 with the initial Study 301; Up to 1 year in the 301 study

    Outcome Measure Data

    Analysis Population Description
    301-303 ITT Population consisted of all participants who completed Study 301 and received at least 1 dose of DAC HYP during Study 303.
    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks.
    Measure Participants 597 606
    301-303 Combined Study Period
    0.247
    0.175
    301 Treatment Period
    0.317
    0.195
    4. Secondary Outcome
    Title Number of Participants With Relapse in the 205MS303 Treatment Period
    Description 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 Study Neurologist.
    Time Frame Up to 4.6 years in the 303 study

    Outcome Measure Data

    Analysis Population Description
    ITT Population consisted of all participants who completed Study 301, 203 or 302 and had at least 1 dose of DAC HYP during Study 303.
    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303) DAC HYP 150 mg (203) /DAC HYP 150 mg (303) DAC HYP 150 mg (302) /DAC HYP 150 mg (303)
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 94.1 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS203 (203) every 4 weeks for up to 288 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 93.7 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS302 (302) every 4 weeks for up to 24 weeks followed by a 20-week washout period then continued treatment for up to an additional 3 years.
    Measure Participants 597 606 227 70
    Count of Participants [Participants]
    184
    30.8%
    172
    28.4%
    35
    50%
    16
    7%
    5. Secondary Outcome
    Title Number of Participants With Relapse in the 205MS301-303 Combined Study Period
    Description 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 Study Neurologist.
    Time Frame Up to 5.6 years combining 303 with the initial Study 301

    Outcome Measure Data

    Analysis Population Description
    301-303 ITT Population consisted of all participants who completed Study 301 and had at least 1 dose of DAC HYP during Study 303.
    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks.
    Measure Participants 597 606
    Count of Participants [Participants]
    339
    56.8%
    261
    43.1%
    6. Secondary Outcome
    Title Number of Participants With Sustained Disability Progression in the 205MS303 Treatment Period
    Description Sustained disability progression is defined as at least a 1.0-point increase on the Expanded Disability Status Scale (EDSS) from 303 baseline EDSS ≥1.0 that is sustained for 24 weeks, or at least a 1.5-point increase on the EDSS from 303 baseline EDSS of 0, that is sustained for 24 weeks. The EDSS measures the disability status of people with multiple sclerosis on a scale that ranges from 0 to 10. The range of main categories include (0) =normal neurologic exam; to (5) = ambulatory without aid or rest for 200 meters; disability severe enough to impair full daily activities; to (10) = death due to MS. Higher scores indicate more disability.
    Time Frame Up to 4.6 years in Study 303

    Outcome Measure Data

    Analysis Population Description
    ITT Population consisted of all participants who completed Study 301, 203 or 302 and had at least 1 dose of DAC HYP during Study 303.
    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303) DAC HYP 150 mg (203) /DAC HYP 150 mg (303) DAC HYP 150 mg (302) /DAC HYP 150 mg (303)
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 94.1 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS203 (203) every 4 weeks for up to 288 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 93.7 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS302 (302) every 4 weeks for up to 24 weeks followed by a 20-week washout period then continued treatment for up to an additional 3 years.
    Measure Participants 597 606 227 70
    Count of Participants [Participants]
    95
    15.9%
    97
    16%
    8
    11.4%
    2
    0.9%
    7. Secondary Outcome
    Title Number of Participants With Sustained Disability Progression in the 205MS301-303 Combined Study Period
    Description Sustained disability progression is defined as at least a 1.0-point increase on the Expanded Disability Status Scale (EDSS) from 303 baseline EDSS ≥1.0 that is sustained for 24 weeks, or at least a 1.5-point increase on the EDSS from 303 baseline EDSS of 0, that is sustained for 24 weeks. The EDSS measures the disability status of people with multiple sclerosis on a scale that ranges from 0 to 10. The range of main categories include (0) =normal neurologic exam; to (5) = ambulatory without aid or rest for 200 meters; disability severe enough to impair full daily activities; to (10) = death due to MS. Higher scores indicate more disability.
    Time Frame Up to 5.6 years combining 303 with the initial Study 301

    Outcome Measure Data

    Analysis Population Description
    301-303 ITT Population consisted of all participants who completed Study 301 and had at least 1 dose of DAC HYP during Study 303.
    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks.
    Measure Participants 597 606
    Count of Participants [Participants]
    144
    24.1%
    130
    21.5%
    8. Secondary Outcome
    Title Number of Participants With New or Newly Enlarging T2 Hyperintense Lesions in the 205MS303 Treatment Period
    Description T2 Hyperintense Lesions were assessed by magnetic resonance imaging (MRI) and were analyzed by a central MRI reader. The number of participants with New or Newly Enlarging T2 Hyperintense Lesions relative to the 303 Baseline in the 303 Treatment Period is reported.
    Time Frame Baseline 303, Weeks 48, 96, 144, 192, 240 in Study 303

    Outcome Measure Data

    Analysis Population Description
    301-303 ITT population consisted of all participants who completed Study 301 and received at least 1 dose of DAC HYP during Study 303. No data was collected for participants from the 203 and 302 studies. Number analyzed is the number of participants with data available at the given timepoint.
    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks.
    Measure Participants 597 606
    Week 48
    270
    45.2%
    144
    23.8%
    Week 96
    213
    35.7%
    130
    21.5%
    Week 144
    223
    37.4%
    157
    25.9%
    Week 192
    173
    29%
    126
    20.8%
    Week 240
    20
    3.4%
    22
    3.6%
    9. Secondary Outcome
    Title Number of Participants With New or Newly Enlarging T2 Hyperintense Lesions in the 205MS301 Treatment Period
    Description T2 Hyperintense Lesions were assessed by MRI and were analyzed by a central MRI reader. The number of participants with New or Newly Enlarging T2 Hyperintense Lesions relative to the 301 Baseline in the 301 Treatment Period is reported.
    Time Frame Baseline 301, Weeks 24, 96, 144 in Study 301

    Outcome Measure Data

    Analysis Population Description
    301-303 ITT population consisted of all participants who completed Study 301 and received at least 1 dose of DAC HYP during Study 303. Number analyzed is the number of participants with data available at the given timepoint.
    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks.
    Measure Participants 597 606
    Week 24
    347
    58.1%
    314
    51.8%
    Week 96
    435
    72.9%
    368
    60.7%
    Week 144
    126
    21.1%
    113
    18.6%
    10. Secondary Outcome
    Title Number of Participants With Gadolinium-enhancing (Gd+) Lesions in the 205MS303 Treatment Period
    Description Gd+ lesions were evaluated by MRI and were analyzed by a central MRI reader.
    Time Frame 301-303: Baseline 303, Weeks 48, 96, 144, 192, 240; 203-303 and 302-303: Week 96

    Outcome Measure Data

    Analysis Population Description
    ITT Population consisted of all participants who completed Study 301, 203 or 302 and received at least one dose of DAY HYP in Study 303. Number analyzed is the number of participants with data available at the given timepoint.
    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303) DAC HYP 150 mg (203) /DAC HYP 150 mg (303) DAC HYP 150 mg (302) /DAC HYP 150 mg (303)
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 94.1 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS203 (203) every 4 weeks for up to 288 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 93.7 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS302 (302) every 4 weeks for up to 24 weeks followed by a 20-week washout period then continued treatment for up to an additional 3 years.
    Measure Participants 597 606 227 70
    Baseline 303
    180
    30.2%
    77
    12.7%
    Week 48
    89
    14.9%
    46
    7.6%
    Week 96
    43
    7.2%
    23
    3.8%
    8
    11.4%
    2
    0.9%
    Week 144
    43
    7.2%
    42
    6.9%
    Week 192
    25
    4.2%
    29
    4.8%
    Week 240
    1
    0.2%
    7
    1.2%
    11. Secondary Outcome
    Title Number of Participants With Gadolinium-enhancing (Gd+) Lesions in the 205MS301 Treatment Period
    Description Gd+ lesions were evaluated by MRI and were analyzed by a central MRI reader.
    Time Frame Baseline 301, Weeks 24, 96 and 144

    Outcome Measure Data

    Analysis Population Description
    301-303 ITT Population consisted of all participants who completed Study 301 and received at least one dose of DAY HYP in Study 303. Number analyzed is the number of participants with data available at the given timepoint.
    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks.
    Measure Participants 597 606
    Baseline 301
    263
    44.1%
    265
    43.7%
    Week 24
    153
    25.6%
    119
    19.6%
    Week 96
    172
    28.8%
    66
    10.9%
    Week 144
    49
    8.2%
    20
    3.3%
    12. Secondary Outcome
    Title Number of Participants With New T1 Hypointense Lesions in the 205MS303 Treatment Period
    Description T1 hypointense lesions were evaluated by MRI and were analyzed by a central MRI reader. The number of participants with New T1 Hyperintense Lesions relative to the 303 Baseline in the 303 Treatment Period is reported.
    Time Frame Baseline 303, Weeks 48, 96, 144, 192, 240 in Study 303

    Outcome Measure Data

    Analysis Population Description
    301-303 ITT Population consisted of all participants who completed Study 303 and received at least one dose of DAC HYP in Study 303. Number analyzed is the number of participants with data available at the given timepoint. No data was collected from participants from the 203 and 302 studies.
    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks.
    Measure Participants 597 606
    Week 48
    200
    33.5%
    96
    15.8%
    Week 96
    168
    28.1%
    91
    15%
    Week 144
    184
    30.8%
    116
    19.1%
    Week 192
    152
    25.5%
    94
    15.5%
    Week 240
    16
    2.7%
    18
    3%
    13. Secondary Outcome
    Title Number of Participants With New T1 Hypointense Lesions in the 205MS301 Treatment Period
    Description T1 hypointense lesions were evaluated by MRI and were analyzed by a central MRI reader. The number of participants with New T1 Hyperintense Lesions relative to the 301 Baseline in the 301 Treatment Period is reported .
    Time Frame Baseline 301, Weeks 24, 96, 144 in Study 301

    Outcome Measure Data

    Analysis Population Description
    301-303 ITT Population consisted of all participants who completed Study 303 and received at least one dose of DAC HYP in Study 303. Number analyzed is the number of participants with data available at the given timepoint.
    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks.
    Measure Participants 597 606
    Week 24
    276
    46.2%
    244
    40.3%
    Week 96
    375
    62.8%
    300
    49.5%
    Week 144
    111
    18.6%
    87
    14.4%
    14. Secondary Outcome
    Title Percent Change in Brain Volume From the 205MS303 Baseline
    Description To assess brain atrophy, total brain volume was measured by MRI and was analyzed by a central MRI reader. A negative percent change from baseline indicates improvement.
    Time Frame Baseline 303, Weeks 48, 96, 144, 192, 240 in Study 303

    Outcome Measure Data

    Analysis Population Description
    301-303 ITT Population consisted of all participants who completed Study 303 and received at least one dose of DAC HYP in Study 303. Number analyzed is the number of participants with data available at the given timepoint. No data was collected for participants from the 203 and 302 studies.
    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks.
    Measure Participants 597 606
    Week 48
    -0.451
    (0.5917)
    -0.355
    (0.5100)
    Week 96
    -0.713
    (0.7288)
    -0.549
    (0.6126)
    Week 144
    -1.050
    (0.8566)
    -0.801
    (0.7145)
    Week 192
    -1.225
    (1.0139)
    -0.967
    (0.8772)
    Week 240
    -1.261
    (1.0382)
    -0.852
    (0.9890)
    15. Secondary Outcome
    Title Percent Change in Brain Volume From 205MS301 Baseline
    Description To assess brain atrophy, total brain volume was measured by MRI and was analyzed by a central MRI reader. A negative percent change from baseline indicates improvement.
    Time Frame Baseline 301, Weeks 48, 96, 144, 192, 240 in Study 303

    Outcome Measure Data

    Analysis Population Description
    301-303 ITT Population consisted of all participants who completed Study 303 and received at least one dose of DAC HYP in Study 303. Number analyzed is the number of participants with data available at the given timepoint.
    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks.
    Measure Participants 597 606
    Week 48
    -1.535
    (1.1975)
    -1.409
    (1.1538)
    Week 96
    -1.871
    (1.3720)
    -1.595
    (1.0736)
    Week 144
    -2.165
    (1.4596)
    -1.812
    (1.2044)
    Week 192
    -2.403
    (1.6088)
    -1.970
    (1.3439)
    Week 240
    -2.415
    (1.6005)
    -1.922
    (1.2258)
    16. Secondary Outcome
    Title Total Volume of T2 Hyperintense Lesions in the 205MS303 Treatment Period
    Description Volume of T2 hyperintense Lesions was evaluated by MRI and was analyzed by a central MRI reader.
    Time Frame Baseline 303, Weeks 48, 96, 144, 192, 240 in Study 303; 203-303 and 302-303: Week 96

    Outcome Measure Data

    Analysis Population Description
    ITT Population included all participants who completed Study 301, 203 or 302 and received at least 1 dose of DAC HYP in Study 303. Number Analyzed is the number of participants with data available at the given timepoint.
    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303) DAC HYP 150 mg (203) /DAC HYP 150 mg (303) DAC HYP 150 mg (302) /DAC HYP 150 mg (303)
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 94.1 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS203 (203) every 4 weeks for up to 288 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 93.7 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS302 (302) every 4 weeks for up to 24 weeks followed by a 20-week washout period then continued treatment for up to an additional 3 years.
    Measure Participants 597 606 227 70
    Baseline 303
    10357.54
    (11977.864)
    9323.33
    (10777.863)
    Week 48
    10738.32
    (12358.857)
    9524.23
    (10822.502)
    Week 96
    11498.94
    (12769.813)
    10018.09
    (11432.768)
    16116.01
    (16791.388)
    12627.51
    (14777.178)
    Week 144
    11242.79
    (12838.060)
    10265.04
    (11324.227)
    Week 192
    12453.96
    (13643.373)
    10662.66
    (11815.075)
    Week 240
    9368.05
    (12428.209)
    9230.78
    (11395.493)
    17. Secondary Outcome
    Title Change From Baseline in the Multiple Sclerosis Functional Composite (MSFC) Score in the 205MS303 Treatment Period
    Description MSFC is a three-part, standardized, quantitative, assessment instrument consisting of (Timed 25-Foot Walk, Nine-Hole Peg Test (9HPT) and Paced Auditory Serial Addition Test (PASAT-3"). 2 timed 25-foot walk scores are averaged. 4 trials of the Peg Test (2 for each hand) are converted to the reciprocals and averaged. The number correct of the PASAT-3 is used. The composite Z-score is calculated by: Z(25-foot walk) + Z (HPT) + Z(PASAT)/3. A positive change from baseline indicates improvement.
    Time Frame Baseline 303, Weeks 12, 24 and 48 in Study 303

    Outcome Measure Data

    Analysis Population Description
    301-303 ITT Population consisted of all participants who completed Study 301 and received at least one dose of DAC HYP in Study 303. Number analyzed is the number of participants with data available at the given timepoint. No data was collected from participants from the 203 and 302 studies.
    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks.
    Measure Participants 597 606
    Baseline 303
    0.24958
    0.30019
    Change to Week 12
    0.00010
    -0.01021
    Change to Week 24
    -0.00599
    -0.00010
    Change to Week 48
    -0.01026
    -0.01897
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change to Week 12
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.5937
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline Z-score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change to Week 24
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.6233
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline Z-score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change to Week 48
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1884
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline Z-score, baseline age (<=35 vs >35) and history of prior IFN beta.
    18. Secondary Outcome
    Title Change From 205MS301 Baseline in the MSFC Score in the 205MS301-303 Combined Study Period
    Description MSFC is a three-part, standardized, quantitative, assessment instrument consisting of (Timed 25-Foot Walk, Nine-Hole Peg Test (9HPT) and Paced Auditory Serial Addition Test (PASAT-3"). 2 timed 25-foot walk scores are averaged. 4 trials of the Peg Test (2 for each hand) are converted to the reciprocals and averaged. The number correct of the PASAT-3 is used. The composite Z-score is calculated by: Z(25-foot walk) + Z (HPT) + Z(PASAT)/3. A positive change from baseline indicates improvement.
    Time Frame Baseline 301, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 in the 301 study, Baseline 303, Weeks 12, 24, 48 in the 303 study

    Outcome Measure Data

    Analysis Population Description
    301-303 ITT Population consisted of all participants who completed Study 301 and received at least one dose of DAC HYP in Study 303. Number analyzed: Number of participants with data available at given timepoint.
    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks.
    Measure Participants 597 606
    Baseline 301
    0.14629
    0.14298
    Change from Baseline 301 to Week 12 for 301
    -0.00133
    0.02593
    Change from Baseline 301 to Week 24 for 301
    0.02377
    0.04728
    Change from Baseline 301 to Week 36 for 301
    0.04764
    0.05771
    Change from Baseline 301 to Week 48 for 301
    0.06491
    0.07793
    Change from Baseline 301 to Week 60 for 301
    0.06893
    0.08973
    Change from Baseline 301 to Week 72 for 301
    0.08645
    0.08690
    Change from Baseline 301 to Week 84 for 301
    0.05704
    0.10283
    Change from Baseline 301 to Week 96 for 301
    0.06731
    0.11283
    Change from Baseline 301 to Week 108 for 301
    0.08020
    0.09868
    Change from Baseline 301 to Week 120 for 301
    0.08406
    0.10367
    Change from Baseline 301 to Week 132 for 301
    0.07712
    0.08682
    Change from Baseline 301 to Week 144 for 301
    0.09674
    0.12943
    Change from Baseline 301 to Week 156 for 301
    -0.0272
    Change from Baseline 301 to Baseline 303
    0.06638
    0.11003
    Change from Baseline 301 to Week 12 for 303
    0.06449
    0.09616
    Change from Baseline 301 to Week 24 for 303
    0.07140
    0.12955
    Change from Baseline 301 to Week 48 for 303
    0.05533
    0.09332
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change from Baseline 301 to Week 12 for 301
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0204
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline Z-score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change from Baseline 301 to Week 24 for 301
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0805
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline Z-score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change from Baseline 301 to Week 36 for 301
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2535
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline Z-score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change from Baseline 301 to Week 48 for 301
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.4738
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline Z-score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change from Baseline 301 to Week 60 for 301
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2302
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline Z-score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change from Baseline 301 to Week 72 for 301
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.8522
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline Z-score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change from Baseline 301 to Week 84 for 301
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0431
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline Z-score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change from Baseline 301 to Week 96 for 301
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0339
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline Z-score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change from Baseline 301 to Week 108 for 301
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3195
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline Z-score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change from Baseline 301 to Week 120 for 301
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2119
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline Z-score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change from Baseline 301 to Week 132 for 301
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3619
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline Z-score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change from Baseline 301 to Week 144 for 301
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0170
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline Z-score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change from Baseline 301 to Baseline 303
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0170
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline Z-score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change from Baseline 301 to Week 12 for 303
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0849
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline Z-score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change from Baseline 301 to Week 24 for 303
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0057
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline Z-score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change from Baseline 301 to Week 48 for 303
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3960
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline Z-score, baseline age (<=35 vs >35) and history of prior IFN beta.
    19. Secondary Outcome
    Title Change From Baseline in the Expanded Disability Status Scale (EDSS) Score in the 205MS303 Treatment Period
    Description The EDSS measures the disability status of people with multiple sclerosis as assessed by the Study Neurologist based on 8 functional systems that ranges from 0=normal neurologic exam; to 5=ambulatory without aid or rest for 200 meters; disability severe enough to impair full daily activities; to 10=death due to MS. Higher scores indicate more disability. A negative change from Baseline indicates improvement.
    Time Frame 301-303: Baseline 303, Weeks 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 260; 203-303 and 302-303: Baseline 303, Weeks 12, 24, 48, 72, 96, 116 in Study 303

    Outcome Measure Data

    Analysis Population Description
    ITT Population consisted of all participants who completed Study 301, 203 or 302 and received at least one dose of DAC HYP in Study 303. Number analyzed is the number of participants with data available at the given timepoint.
    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303) DAC HYP 150 mg (203) /DAC HYP 150 mg (303) DAC HYP 150 mg (302) /DAC HYP 150 mg (303)
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 94.1 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS203 (203) every 4 weeks for up to 288 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 93.7 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS302 (302) every 4 weeks for up to 24 weeks followed by a 20-week washout period then continued treatment for up to an additional 3 years.
    Measure Participants 597 606 227 70
    Baseline 303
    2.50
    (1.468)
    2.44
    (1.409)
    2.86
    (1.500)
    2.56
    (1.395)
    Change at Week 12
    0.04
    (0.464)
    0.02
    (0.467)
    0.14
    (0.244)
    0.00
    (0.000)
    Change at Week 24
    0.06
    (0.570)
    0.03
    (0.480)
    0.02
    (0.237)
    -0.06
    (0.325)
    Change at Week 48
    0.09
    (0.614)
    0.06
    (0.495)
    0.00
    (0.349)
    -0.05
    (0.455)
    Change at Week 72
    0.11
    (0.670)
    0.10
    (0.548)
    0.04
    (0.378)
    0.00
    (0.542)
    Change at Week 96
    0.13
    (0.729)
    0.13
    (0.602)
    0.04
    (0.400)
    0.01
    (0.486)
    Change at Week 116
    0.05
    (0.353)
    0.11
    (0.572)
    Change at Week 120
    0.17
    (0.768)
    0.11
    (0.578)
    Change at Week 144
    0.16
    (0.742)
    0.17
    (0.701)
    Change at Week 168
    0.22
    (0.798)
    0.19
    (0.765)
    Change at Week 192
    0.22
    (0.756)
    0.22
    (0.777)
    Change at Week 216
    0.22
    (0.775)
    0.22
    (0.762)
    Change at Week 240
    0.19
    (0.789)
    0.26
    (0.829)
    Change at Week 260
    0.53
    (1.007)
    -0.17
    (0.718)
    20. Secondary Outcome
    Title Number of Participants Who Are Free From Disease Activity in the 205MS303 Treatment Period
    Description Participants without clinical or radiological activity are defined as disease-free. Clinical activity includes assessment of relapses and of disease progression. Radiological activity includes assessments of Gd+ lesions and new or enlarging T2 lesions.
    Time Frame Up to 4.6 years in Study 303

    Outcome Measure Data

    Analysis Population Description
    301-303 ITT Population consisted of all participants who completed Study 301 and received at least 1 dose of DAC HYP during Study 303. No data was collected for participants from the 203 and 302 studies.
    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks.
    Measure Participants 597 606
    Count of Participants [Participants]
    9
    1.5%
    7
    1.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.8417
    Comments
    Method Regression, Logistic
    Comments Adjusted for the baseline relapse rate, history of prior IFN beta use (yes/no), baseline EDSS (<=2.5 vs >2.5) and baseline age (<=35 vs >35).
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 0.902
    Confidence Interval (2-Sided) 95%
    0.329 to 2.473
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    21. Secondary Outcome
    Title Change From Baseline in the Multiple Sclerosis Impact Scale 29 (MSIS 29) Physical and Psychological Scores in the 205MS303 Treatment Period
    Description The 29-item MSIS-29 is a disease specific participant-reported outcome measure that has been developed and validated to examine the physical (coordination and mobility) and psychological (mental) impact of MS from a participant's perspective; it measures 20 physical items and 9 psychological items. The results for each of the physical and psychological scores are transformed to a score of 0 to 100 (worse state of health). A negative change from Baseline indicates improvement.
    Time Frame Baseline 303, Weeks 12, 24, 48, 96, 120 and 144

    Outcome Measure Data

    Analysis Population Description
    301-303 ITT Population consisted of all participants who completed Study 301 and received at least 1 dose of DAC HYP during Study 303. Number analyzed is the number of participants with data available at the given timepoint. No data was collected for participants from the 203 and 302 studies.
    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks.
    Measure Participants 597 606
    Physical Scores: Baseline 303
    20.61
    (20.134)
    19.19
    (19.390)
    Physical Scores: Change to Week 12
    0.22
    (11.114)
    -0.28
    (9.217)
    Physical Scores: Change to Week 24
    -0.46
    (10.313)
    -0.88
    (9.147)
    Physical Scores: Change to Week 48
    0.12
    (11.178)
    0.13
    (9.779)
    Physical Scores: Change to Week 96
    2.23
    (12.713)
    0.48
    (10.617)
    Physical Scores: Change to Week 120
    0.51
    (9.062)
    1.44
    (10.504)
    Physical Scores: Change to Week 144
    -1.25
    (0)
    -5.00
    (0)
    Psychological Scores: Baseline 303
    23.46
    (21.310)
    22.37
    (20.816)
    Psychological Scores: Change to Week 12
    -1.06
    (12.501)
    -0.34
    (11.226)
    Psychological Scores: Change to Week 24
    -1.14
    (14.154)
    -1.69
    (11.576)
    Psychological Scores: Change to Week 48
    -0.46
    (14.865)
    0.10
    (13.648)
    Psychological Scores: Change to Week 96
    -0.16
    (13.923)
    -0.89
    (14.411)
    Psychological Scores: Change to Week 120
    -2.26
    (10.105)
    0.00
    (8.642)
    Psychological Scores: Change to Week 144
    8.33
    (0)
    -13.89
    (0)
    22. Secondary Outcome
    Title Change From Baseline in Quality of Life as Assessed by the European Quality of Life, 5 Dimensions (EQ 5D) Health Scores in the 205MS303 Treatment Period
    Description The EQ-5D is a self-administered questionnaire consisting of 5 domains pertaining to specific health state profile : mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The participants recorded their level of current health for each domain where: 1=no problems, 2=some problem and 3=severe problems. The health score is derived from the individual scores for each of the 5 domains transformed to a score of 0=worst health state to 1=perfect health state. A positive change from Baseline indicates improvement.
    Time Frame 301-303: Baseline 303, Weeks 12, 24, 48, 96, 120, 144, 192, 240; 203-303 and 302-303: Baseline 303, Weeks 48 and 96 in Study 303

    Outcome Measure Data

    Analysis Population Description
    ITT Population consisted of all participants who completed Study 301, 203 or 302 and received at least one dose of DAC HYP in Study 303. Number analyzed is the number of participants with data available at the given timepoint.
    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303) DAC HYP 150 mg (203) /DAC HYP 150 mg (303) DAC HYP 150 mg (302) /DAC HYP 150 mg (303)
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 94.1 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS203 (203) every 4 weeks for up to 288 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 93.7 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS302 (302) every 4 weeks for up to 24 weeks followed by a 20-week washout period then continued treatment for up to an additional 3 years.
    Measure Participants 597 606 227 70
    Baseline 303
    0.77
    (0.233)
    0.79
    (0.201)
    0.71
    (0.242)
    0.77
    (0.213)
    Change to Week 12
    0.01
    (0.168)
    -0.01
    (0.137)
    Change to Week 24
    0.01
    (0.171)
    0.00
    (0.144)
    Change to Week 48
    -0.01
    (0.185)
    -0.01
    (0.152)
    0.00
    (0.164)
    0.00
    (0.174)
    Change to Week 96
    0.00
    (0.168)
    -0.02
    (0.170)
    -0.01
    (0.162)
    0.00
    (0.184)
    Change to Week 120
    0.01
    (0.166)
    -0.01
    (0.175)
    Change to Week 144
    0.01
    (0.187)
    -0.02
    (0.172)
    Change to Week 192
    0.00
    (0.187)
    -0.03
    (0.174)
    Change to Week 240
    -0.01
    (0.154)
    -0.06
    (0.187)
    23. Secondary Outcome
    Title Change From Baseline in Quality of Life as Assessed by the European Quality of Life, Visual Analog Scale (EQ VAS) in the 205MS303 Treatment Period
    Description The participant rated their current heath state using the EQ VAS 20-centimeter horizontal line from 0 (worst imaginable health state) to 100 (best imaginable health state). A positive change from baseline indicates improvement.
    Time Frame 301-303: Baseline 303, Weeks 12, 24, 48, 96, 120, 44, 192, 240; 203-303 and 302-303: Baseline 303, Weeks 48 and 96 in Study 303

    Outcome Measure Data

    Analysis Population Description
    ITT Population consisted of all participants who completed Study 301, 203 or 302 and received at least one dose of DAC HYP in Study 303. Number analyzed is the number of participants with data available at the given timepoint.
    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303) DAC HYP 150 mg (203) /DAC HYP 150 mg (303) DAC HYP 150 mg (302) /DAC HYP 150 mg (303)
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 94.1 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS203 (203) every 4 weeks for up to 288 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 93.7 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS302 (302) every 4 weeks for up to 24 weeks followed by a 20-week washout period then continued treatment for up to an additional 3 years.
    Measure Participants 597 606 227 70
    Baseline 303
    76.19
    (19.534)
    77.74
    (19.144)
    72.13
    (21.154)
    76.97
    (19.225)
    Change at Week 12
    1.42
    (12.753)
    0.25
    (12.358)
    Change at Week 24
    1.20
    (12.135)
    0.74
    (11.400)
    Change at Week 48
    0.66
    (12.966)
    -0.35
    (13.543)
    -1.50
    (13.604)
    -0.64
    (13.440)
    Change at Week 96
    -0.54
    (14.963)
    0.56
    (12.054)
    0.45
    (11.724)
    -0.95
    (11.222)
    Change at Week 120
    0.80
    (13.406)
    1.52
    (13.492)
    Change at Week 144
    0.36
    (14.263)
    1.64
    (13.648)
    Change at Week 192
    0.45
    (15.058)
    0.66
    (14.921)
    Change at Week 240
    -0.64
    (11.318)
    -1.53
    (13.082)
    24. Secondary Outcome
    Title Direct Health Resource Utilization (HRU): Number of Unscheduled Site Visits in the 205MS303 Treatment Period
    Description Heath resource utilization was assessed by the number of hospitalizations, emergency room visits, and unscheduled neurologist visits for MS-related and non-MS-related visits.
    Time Frame 301-303: Baseline 303, Weeks 24, 48, 96, 144, 192, 240; 203-303 and 302-303: Baseline 303, Weeks 48, 96 in 303

    Outcome Measure Data

    Analysis Population Description
    ITT Population consisted of all participants who completed Study 301, 203 or 302 and received at least one dose of DAC HYP in Study 303. Number analyzed is the number of participants with data available at the given timepoint.
    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303) DAC HYP 150 mg (203) /DAC HYP 150 mg (303) DAC HYP 150 mg (302) /DAC HYP 150 mg (303)
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 94.1 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS203 (203) every 4 weeks for up to 288 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 93.7 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS302 (302) every 4 weeks for up to 24 weeks followed by a 20-week washout period then continued treatment for up to an additional 3 years.
    Measure Participants 597 606 227 70
    MS-related Site Visits: Baseline 303
    141
    102
    27
    11
    MS-related Site Visits: Week 24
    80
    48
    MS-related Site Visits: Week 48
    100
    70
    15
    6
    MS-related Site Visits: Week 96
    46
    71
    20
    3
    MS-related Site Visits: Week 144
    37
    36
    MS-related Site Visits: Week 192
    26
    26
    MS-related Site Visits: Week 240
    6
    16
    Non-MS related Site Visits: Baseline 303
    90
    97
    15
    2
    Non-MS related Site Visits: Week 24
    81
    56
    Non-MS related Site Visits: Week 48
    111
    41
    16
    5
    Non-MS related Site Visits: Week 96
    90
    93
    23
    10
    Non-MS related Site Visits: Week 144
    52
    42
    Non-MS related Site Visits: Week 192
    42
    39
    Non-MS related Site Visits: Week 240
    10
    12
    25. Secondary Outcome
    Title Direct Health Resource Utilization (HRU): Number of Unscheduled Site Visits in the 205MS301 Treatment Period
    Description Heath resource utilization was assessed by the number of hospitalizations, emergency room visits, and unscheduled neurologist visits for MS-related and non-MS-related visits.
    Time Frame Baseline 301, Weeks 24, 48, 72, 96, 120 and 144 in 301

    Outcome Measure Data

    Analysis Population Description
    301-303 ITT Population consisted of all participants who completed Study 301 and received at least one dose of DAC HYP in Study 303. Number analyzed is the number of participants with data available at the given timepoint.
    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks.
    Measure Participants 597 606
    MS-related Site Visits: Baseline 301
    277
    349
    MS-related Site Visits: Week 24
    76
    78
    MS-related Site Visits: Week 48
    77
    49
    MS-related Site Visits: Week 72
    60
    49
    MS-related Site Visits: Week 96
    88
    53
    MS-related Site Visits: Week 120
    55
    18
    MS-related Site Visits: Week 144
    13
    24
    Non MS-related Site Visits: Baseline 301
    93
    93
    Non MS-related Site Visits: Week 24
    50
    45
    Non MS-related Site Visits: Week 48
    65
    51
    Non MS-related Site Visits: Week 72
    54
    69
    Non MS-related Site Visits: Week 96
    44
    52
    Non MS-related Site Visits: Week 120
    43
    41
    Non MS-related Site Visits: Week 144
    24
    32
    26. Secondary Outcome
    Title Treatment Satisfaction as Assessed by the Participant in the 205MS303 Treatment Period
    Description Participants answered the question: "How satisfied or dissatisfied are you with the ability of the medication to prevent or treat the condition?" using the following scale: Dissatisfied (Extremely dissatisfied, Very dissatisfied, Dissatisfied) or Satisfied (Somewhat satisfied, Satisfied, Very Satisfied and Extremely satisfied). The number of participants in the Dissatisfied and Satisfied categories is reported.
    Time Frame Baseline 303, Weeks 12, 24, 48, 72, 96, 120 in Study 303

    Outcome Measure Data

    Analysis Population Description
    301-303 ITT Population consisted of all participants who completed Study 301 and received at least 1 dose of DAC HYP during Study 303. Number analyzed is the number of participants with data available at the given timepoint. No data was collected for participants from the 203 and 302 studies.
    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks.
    Measure Participants 597 606
    Dissatisfied: Baseline 303
    49
    8.2%
    31
    5.1%
    Dissatisfied: Week 12
    46
    7.7%
    41
    6.8%
    Dissatisfied: Week 24
    44
    7.4%
    27
    4.5%
    Dissatisfied: Week 48
    32
    5.4%
    35
    5.8%
    Dissatisfied: Week 72
    27
    4.5%
    22
    3.6%
    Dissatisfied: Week 96
    19
    3.2%
    9
    1.5%
    Dissatisfied: Week 120
    2
    0.3%
    1
    0.2%
    Satisfied: Baseline 303
    529
    88.6%
    561
    92.6%
    Satisfied: Week 12
    540
    90.5%
    543
    89.6%
    Satisfied: Week 24
    525
    87.9%
    532
    87.8%
    Satisfied: Week 48
    498
    83.4%
    472
    77.9%
    Satisfied: Week 72
    476
    79.7%
    450
    74.3%
    Satisfied: Week 96
    133
    22.3%
    136
    22.4%
    Satisfied: Week 120
    25
    4.2%
    23
    3.8%
    27. Secondary Outcome
    Title Health Related Productivity Questionnaire (HRPQ): Scheduled Work Hours in the 205MS303 Treatment Period
    Description The HRPQ was used by the participant to assess the impact of MS or its treatments on employment. The participant recorded their scheduled work hours. Data is reported by part time or full time employment.
    Time Frame 301-303: Baseline 303, Weeks 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240; 203-303 and 302-303: Baseline 303, Weeks 24, 48, 72, 96 in Study 303

    Outcome Measure Data

    Analysis Population Description
    ITT Population consisted of all participants who completed Study 301, 203 or 302 and received at least one dose of DAC HYP in Study 303. Number analyzed is the number of participants with data available at the given timepoint.
    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303) DAC HYP 150 mg (203) /DAC HYP 150 mg (303) DAC HYP 150 mg (302) /DAC HYP 150 mg (303)
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 94.1 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS203 (203) every 4 weeks for up to 288 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 93.7 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS302 (302) every 4 weeks for up to 24 weeks followed by a 20-week washout period then continued treatment for up to an additional 3 years.
    Measure Participants 597 606 227 70
    Part Time: Baseline 303
    20.4
    (10.60)
    19.5
    (11.45)
    23.6
    (9.46)
    20.2
    (6.06)
    Part Time: Week 12
    21.4
    (10.30)
    22.4
    (13.62)
    Part Time: Week 24
    21.2
    (12.80)
    20.6
    (13.47)
    23.5
    (9.37)
    24.5
    (5.22)
    Part Time: Week 48
    22.3
    (11.12)
    21.9
    (11.28)
    22.7
    (11.23)
    27.7
    (13.79)
    Part Time: Week 72
    21.6
    (12.44)
    23.0
    (11.64)
    22.8
    (11.60)
    25.2
    (6.08)
    Part Time: Week 96
    25.7
    (17.40)
    19.9
    (11.79)
    24.8
    (10.13)
    23.5
    (7.98)
    Part Time: Week 120
    27.0
    (16.13)
    20.8
    (13.15)
    Part Time: Week 144
    22.9
    (14.79)
    21.4
    (12.90)
    Part Time: Week 168
    21.0
    (12.06)
    20.3
    (11.93)
    Part Time: Week 192
    23.2
    (12.07)
    23.2
    (16.37)
    Part Time: Week 216
    24.9
    (13.18)
    25.3
    (11.79)
    Part Time: Week 240
    21.3
    (8.54)
    Full Time: Baseline 303
    36.8
    (14.23)
    37.4
    (12.71)
    39.3
    (12.23)
    40.1
    (10.44)
    Full Time: Week 12
    37.3
    (14.23)
    38.5
    (18.79)
    Full Time: Week 24
    35.0
    (15.43)
    36.4
    (17.43)
    37.2
    (14.19)
    42.0
    (7.34)
    Full Time: Week 48
    36.0
    (13.47)
    38.2
    (20.63)
    38.6
    (10.90)
    41.1
    (8.50)
    Full Time: Week 72
    36.9
    (12.90)
    38.5
    (12.21)
    38.4
    (9.91)
    42.0
    (5.24)
    Full Time: Week 96
    36.0
    (13.42)
    37.6
    (12.35)
    36.4
    (14.36)
    41.5
    (5.05)
    Full Time: Week 120
    37.7
    (11.04)
    39.2
    (22.80)
    Full Time: Week 144
    37.3
    (12.79)
    39.7
    (12.68)
    Full Time: Week 168
    37.3
    (12.35)
    39.4
    (10.36)
    Full Time: Week 192
    37.7
    (10.31)
    40.4
    (9.00)
    Full Time: Week 216
    37.7
    (12.44)
    38.8
    (11.68)
    Full Time: Week 240
    39.8
    (4.16)
    39.3
    (12.33)
    28. Secondary Outcome
    Title HRPQ: Number of Participants Where MS or Its Treatments Resulted in Missed Work in the 205MS303 Treatment Period
    Description The HRPQ was used by the participant to assess the impact of MS or its treatments on employment. The participant recorded whether their MS or its treatments caused them to miss work. Data is reported by part time or full time employment.
    Time Frame 301-303: Baseline 303, Weeks 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240; 203-303 and 302-303: Baseline 303, Weeks 24, 48, 72, 96 in Study 303

    Outcome Measure Data

    Analysis Population Description
    ITT Population consisted of all participants who completed Study 301, 203 or 302 and received at least one dose of DAC HYP in Study 303. Number analyzed is the number of participants with data available at the given timepoint.
    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303) DAC HYP 150 mg (203) /DAC HYP 150 mg (303) DAC HYP 150 mg (302) /DAC HYP 150 mg (303)
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 94.1 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS203 (203) every 4 weeks for up to 288 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 93.7 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS302 (302) every 4 weeks for up to 24 weeks followed by a 20-week washout period then continued treatment for up to an additional 3 years.
    Measure Participants 597 606 227 70
    Part Time: Baseline 303
    11
    1.8%
    7
    1.2%
    1
    1.4%
    1
    0.4%
    Part Time: Week 12
    10
    1.7%
    8
    1.3%
    Part Time: Week 24
    12
    2%
    7
    1.2%
    3
    4.3%
    2
    0.9%
    Part Time: Week 48
    9
    1.5%
    7
    1.2%
    2
    2.9%
    1
    0.4%
    Part Time: Week 72
    7
    1.2%
    4
    0.7%
    2
    2.9%
    2
    0.9%
    Part Time: Week 96
    6
    1%
    5
    0.8%
    2
    2.9%
    2
    0.9%
    Part Time: Week 120
    11
    1.8%
    6
    1%
    Part Time: Week 144
    4
    0.7%
    6
    1%
    Part Time: Week 168
    5
    0.8%
    6
    1%
    Part Time: Week 192
    5
    0.8%
    3
    0.5%
    Part Time: Week 216
    1
    0.2%
    4
    0.7%
    Part Time: Week 240
    1
    0.2%
    Full Time: Baseline 303
    28
    4.7%
    30
    5%
    11
    15.7%
    3
    1.3%
    Full Time: Week 12
    19
    3.2%
    26
    4.3%
    Full Time: Week 24
    11
    1.8%
    21
    3.5%
    8
    11.4%
    3
    1.3%
    Full Time: Week 48
    20
    3.4%
    24
    4%
    6
    8.6%
    3
    1.3%
    Full Time: Week 72
    13
    2.2%
    10
    1.7%
    6
    8.6%
    3
    1.3%
    Full Time: Week 96
    10
    1.7%
    16
    2.6%
    3
    4.3%
    1
    0.4%
    Full Time: Week 120
    8
    1.3%
    18
    3%
    Full Time: Week 144
    16
    2.7%
    16
    2.6%
    Full Time: Week 168
    10
    1.7%
    17
    2.8%
    Full Time: Week 192
    10
    1.7%
    13
    2.1%
    Full Time: Week 216
    6
    1%
    10
    1.7%
    Full Time: Week 240
    0
    0%
    2
    0.3%
    29. Secondary Outcome
    Title HRPQ: Hours of Work Missed Due to MS or Its Treatment in the 205MS303 Treatment Period
    Description The HRPQ was used by the participant to assess the impact of MS or its treatments on employment. The participant recorded the hours they missed work due to MS or its treatments. Data is reported by part time or full time employment.
    Time Frame 301-303: Baseline 303, Weeks 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240; 203-303 and 302-303: Baseline 303, Weeks 24, 48, 72, 96 in Study 303

    Outcome Measure Data

    Analysis Population Description
    ITT Population consisted of all participants who completed Study 301, 203 or 302 and received at least one dose of DAC HYP in Study 303. Number analyzed is the number of participants who missed work with data available at the given timepoint.
    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303) DAC HYP 150 mg (203) /DAC HYP 150 mg (303) DAC HYP 150 mg (302) /DAC HYP 150 mg (303)
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 94.1 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS203 (203) every 4 weeks for up to 288 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 93.7 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS302 (302) every 4 weeks for up to 24 weeks followed by a 20-week washout period then continued treatment for up to an additional 3 years.
    Measure Participants 597 606 227 70
    Part Time: Baseline 303
    8.5
    (5.82)
    5.6
    (4.93)
    12.0
    (0)
    20.0
    (0)
    Part Time: Week 12
    8.7
    (8.43)
    8.4
    (8.11)
    Part Time: Week 24
    15.2
    (19.31)
    10.1
    (3.63)
    8.3
    (6.51)
    3.0
    (1.41)
    Part Time: Week 48
    8.6
    (4.85)
    12.3
    (12.83)
    4.5
    (3.54)
    15.0
    (0)
    Part Time: Week 72
    7.5
    (7.01)
    10.1
    (13.05)
    16.0
    (19.80)
    7.0
    (4.24)
    Part Time: Week 96
    22.2
    (38.48)
    8.7
    (12.02)
    5.0
    (0.00)
    22.5
    (3.54)
    Part Time: Week 120
    9.5
    (5.92)
    7.3
    (8.21)
    Part Time: Week 144
    3.3
    (2.22)
    10.3
    (7.18)
    Part Time: Week 168
    7.3
    (7.90)
    5.3
    (5.16)
    Part Time: Week 192
    3.6
    (1.14)
    9.0
    (4.24)
    Part Time: Week 216
    3.0
    (0)
    16.4
    (15.71)
    Part Time: Week 240
    5.0
    (0)
    Full Time: Baseline 303
    11.0
    (11.42)
    15.0
    (13.58)
    8.8
    (11.39)
    8.0
    (0.00)
    Full Time: Week 12
    8.5
    (10.13)
    7.9
    (8.06)
    Full Time: Week 24
    11.2
    (13.80)
    12.4
    (13.31)
    14.1
    (16.27)
    7.3
    (1.15)
    Full Time: Week 48
    15.7
    (15.50)
    11.7
    (11.11)
    12.7
    (15.57)
    6.7
    (3.06)
    Full Time: Week 72
    13.8
    (11.51)
    7.6
    (6.00)
    15.0
    (17.54)
    8.7
    (3.06)
    Full Time: Week 96
    14.2
    (13.19)
    16.1
    (15.14)
    6.7
    (2.89)
    3.0
    Full Time: Week 120
    12.4
    (13.88)
    10.7
    (11.19)
    Full Time: Week 144
    16.0
    (14.32)
    13.1
    (15.44)
    Full Time: Week 168
    7.3
    (4.45)
    16.9
    (15.73)
    Full Time: Week 192
    15.9
    (11.94)
    10.0
    (11.53)
    Full Time: Week 216
    10.3
    (13.98)
    11.2
    (14.00)
    Full Time: Week 240
    14.5
    (4.95)
    30. Secondary Outcome
    Title HRPQ: Percent Impact on Employment in the 205MS303 Treatment Period
    Description The HRPQ was used by the participant to assess the impact of MS or its treatments on employment. The participants assessed the percent impact of MS and its treatments on their work output using a VAS where 0= MS or its treatments had no impact on how much I accomplished to 100=MS or its treatments kept me from accomplishing anything. Data is reported for part time or full time employment.
    Time Frame 301-303: Baseline 303, Weeks 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240; 203-303 and 302-303: Baseline 303, Weeks 24, 48, 72, 96 in Study 303

    Outcome Measure Data

    Analysis Population Description
    ITT Population consisted of all participants who completed Study 301, 203 or 302 and received at least one dose of DAC HYP in Study 303. Number analyzed is the number of participants with data available at the given timepoint.
    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303) DAC HYP 150 mg (203) /DAC HYP 150 mg (303) DAC HYP 150 mg (302) /DAC HYP 150 mg (303)
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 94.1 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS203 (203) every 4 weeks for up to 288 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 93.7 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS302 (302) every 4 weeks for up to 24 weeks followed by a 20-week washout period then continued treatment for up to an additional 3 years.
    Measure Participants 597 606 227 70
    Part Time: Baseline 303
    18.4
    (24.18)
    21.1
    (26.16)
    19.0
    (24.78)
    32.2
    (34.65)
    Part Time: Week 12
    18.8
    (24.06)
    16.0
    (22.87)
    Part Time: Week 24
    17.5
    (24.30)
    16.8
    (22.84)
    26.5
    (33.85)
    14.4
    (14.42)
    Part Time: Week 48
    16.0
    (23.54)
    14.0
    (23.03)
    18.8
    (25.03)
    19.1
    (24.17)
    Part Time: Week 72
    20.8
    (27.63)
    18.8
    (27.93)
    23.3
    (29.50)
    11.1
    (10.83)
    Part Time: Week 96
    18.4
    (24.01)
    16.8
    (23.90)
    19.1
    (23.80)
    22.3
    (33.41)
    Part Time: Week 120
    19.6
    (26.58)
    22.4
    (30.15)
    Part Time: Week 144
    17.4
    (23.16)
    15.3
    (24.07)
    Part Time: Week 168
    35.7
    (33.82)
    15.3
    (22.93)
    Part Time: Week 192
    30.9
    (33.29)
    21.4
    (25.03)
    Part Time: Week 216
    23.6
    (27.73)
    20.3
    (28.78)
    Part Time: Week 240
    7.5
    (15.00)
    Full Time: Baseline 303
    10.0
    (19.52)
    11.8
    (24.02)
    13.9
    (25.56)
    6.7
    (16.33)
    Full Time: Week 12
    8.0
    (17.72)
    10.3
    (21.17)
    Full Time: Week 24
    9.1
    (20.13)
    8.3
    (18.54)
    12.7
    (25.79)
    11.2
    (25.20)
    Full Time: Week 48
    8.2
    (19.37)
    9.6
    (21.75)
    12.2
    (23.87)
    9.9
    (24.25)
    Full Time: Week 72
    9.7
    (21.40)
    7.8
    (18.39)
    14.0
    (23.47)
    11.3
    (22.72)
    Full Time: Week 96
    7.3
    (18.29)
    8.4
    (18.59)
    11.1
    (23.76)
    10.2
    (24.63)
    Full Time: Week 120
    6.4
    (13.87)
    8.6
    (19.19)
    Full Time: Week 144
    8.2
    (18.36)
    7.8
    (17.91)
    Full Time: Week 168
    8.8
    (18.53)
    10.1
    (22.45)
    Full Time: Week 192
    9.0
    (19.23)
    7.5
    (17.59)
    Full Time: Week 216
    10.0
    (22.36)
    9.3
    (20.91)
    Full Time: Week 240
    13.1
    (23.33)
    7.5
    (18.01)
    31. Secondary Outcome
    Title HRPQ: Hours of Household Chores Planned to Perform in the 205MS303 Treatment Period
    Description The HRPQ was used by the participant to assess the impact of MS or its treatments on performing household chores. The participant recorded their planned hours for household chores.
    Time Frame 301-303: Baseline 303, Weeks 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240; 203-303 and 302-303: Baseline 303, Weeks 24, 48, 72, 96 in Study 303

    Outcome Measure Data

    Analysis Population Description
    ITT Population consisted of all participants who completed Study 301, 203 or 302 and received at least one dose of DAC HYP in Study 303. Number analyzed is the number of participants with data available at the given timepoint.
    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303) DAC HYP 150 mg (203) /DAC HYP 150 mg (303) DAC HYP 150 mg (302) /DAC HYP 150 mg (303)
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 94.1 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS203 (203) every 4 weeks for up to 288 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 93.7 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS302 (302) every 4 weeks for up to 24 weeks followed by a 20-week washout period then continued treatment for up to an additional 3 years.
    Measure Participants 597 606 227 70
    Baseline 303
    10.1
    (10.87)
    10.0
    (10.85)
    15.8
    (13.68)
    11.5
    (7.94)
    Week 12
    11.8
    (11.38)
    12.2
    (12.33)
    Week 24
    12.0
    (11.75)
    12.6
    (11.24)
    14.4
    (13.66)
    11.1
    (7.72)
    Week 48
    11.6
    (11.43)
    12.6
    (11.39)
    15.7
    (14.74)
    11.6
    (8.37)
    Week 72
    13.3
    (12.10)
    13.9
    (12.87)
    15.0
    (13.55)
    12.3
    (8.94)
    Week 96
    11.9
    (10.70)
    13.5
    (12.10)
    14.8
    (12.20)
    12.6
    (9.17)
    Week 120
    12.6
    (12.09)
    13.1
    (12.09)
    Week 144
    13.0
    (12.89)
    13.4
    (11.99)
    Week 168
    12.9
    (12.35)
    13.7
    (12.58)
    Week 192
    13.4
    (11.78)
    13.9
    (12.43)
    Week 216
    14.2
    (13.01)
    14.0
    (11.46)
    Week 240
    13.6
    (11.49)
    10.1
    (7.89)
    32. Secondary Outcome
    Title HRPQ: Number of Participants Where MS or Its Treatments Kept the Participant From Completing Chores in the 205MS303 Treatment Period
    Description The HRPQ was used by the participant to assess the impact of MS or its treatments on performing household chores. The participant recorded whether MS or its treatments kept them from completing household chores.
    Time Frame 301-303: Baseline 303, Weeks 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240; 203-303 and 302-303: Baseline 303, Weeks 24, 48, 72, 96 in Study 303

    Outcome Measure Data

    Analysis Population Description
    ITT Population consisted of all participants who completed Study 301, 203 or 302 and received at least one dose of DAC HYP in Study 303. Number analyzed is the number of participants with data available at the given timepoint.
    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303) DAC HYP 150 mg (203) /DAC HYP 150 mg (303) DAC HYP 150 mg (302) /DAC HYP 150 mg (303)
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 94.1 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS203 (203) every 4 weeks for up to 288 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 93.7 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS302 (302) every 4 weeks for up to 24 weeks followed by a 20-week washout period then continued treatment for up to an additional 3 years.
    Measure Participants 597 606 227 70
    Baseline 303
    112
    18.8%
    104
    17.2%
    58
    82.9%
    15
    6.6%
    Week 12
    110
    18.4%
    111
    18.3%
    Week 24
    125
    20.9%
    110
    18.2%
    68
    97.1%
    12
    5.3%
    Week 48
    113
    18.9%
    93
    15.3%
    66
    94.3%
    19
    8.4%
    Week 72
    111
    18.6%
    93
    15.3%
    58
    82.9%
    15
    6.6%
    Week 96
    94
    15.7%
    79
    13%
    53
    75.7%
    16
    7%
    Week 120
    93
    15.6%
    84
    13.9%
    Week 144
    91
    15.2%
    87
    14.4%
    Week 168
    82
    13.7%
    81
    13.4%
    Week 192
    71
    11.9%
    65
    10.7%
    Week 216
    65
    10.9%
    65
    10.7%
    Week 240
    2
    0.3%
    7
    1.2%
    33. Secondary Outcome
    Title HRPQ: Hours Not Performing Household Chores Due to MS or Its Treatment in 205MS303 Treatment Period
    Description The HRPQ was used by the participant to assess the impact of MS or its treatments on performing household chores. The participant recorded the hours where they were not able to perform household chores due to MS or its treatments.
    Time Frame 301-303: Baseline 303, Weeks 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240; 203-303 and 302-303: Baseline 303, Weeks 24, 48, 72, 96 in Study 303

    Outcome Measure Data

    Analysis Population Description
    ITT Population consisted of all participants who completed Study 301, 203 or 302 and received at least one dose of DAC HYP in Study 303. Number analyzed is the number of participants unable to complete chores with data available at the given timepoint.
    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303) DAC HYP 150 mg (203) /DAC HYP 150 mg (303) DAC HYP 150 mg (302) /DAC HYP 150 mg (303)
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 94.1 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS203 (203) every 4 weeks for up to 288 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 93.7 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS302 (302) every 4 weeks for up to 24 weeks followed by a 20-week washout period then continued treatment for up to an additional 3 years.
    Measure Participants 597 606 227 70
    Baseline 303
    6.4
    (7.82)
    5.1
    (5.08)
    5.4
    (6.25)
    5.2
    (4.06)
    Week 12
    7.0
    (9.35)
    5.9
    (7.63)
    Week 24
    6.3
    (7.56)
    5.2
    (4.59)
    5.7
    (7.75)
    5.0
    (3.57)
    Week 48
    7.3
    (11.41)
    4.7
    (3.53)
    7.9
    (9.19)
    4.7
    (4.21)
    Week 72
    7.2
    (7.16)
    6.6
    (10.32)
    6.8
    (8.03)
    5.8
    (4.46)
    Week 96
    5.2
    (3.93)
    5.1
    (4.67)
    8.1
    (9.35)
    3.8
    (3.81)
    Week 120
    6.0
    (8.23)
    5.9
    (11.13)
    Week 144
    5.7
    (4.95)
    6.3
    (6.10)
    Week 168
    5.8
    (5.19)
    5.5
    (5.16)
    Week 192
    6.9
    (9.01)
    5.7
    (5.96)
    Week 216
    6.9
    (7.09)
    7.3
    (10.97)
    Week 240
    5.5
    (6.36)
    9.8
    (13.04)
    34. Secondary Outcome
    Title HRPQ: Percent Impact on Performing Household Chores in the 205MS303 Treatment Period
    Description The HRPQ was used by the participant to assess the impact of MS or its treatments on performing household chores. The participant assessed the percent impact of MS and its treatments on how much they accomplished using a VAS where 0= MS or its treatments had no impact on how much I accomplished to 100=MS or its treatments kept me from accomplishing anything.
    Time Frame 301-303: Baseline 303, Weeks 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240; 203-303 and 302-303: Baseline 303, Weeks 24, 48, 72, 96 in Study 303

    Outcome Measure Data

    Analysis Population Description
    ITT Population consisted of all participants who completed Study 301, 203 or 302 and received at least one dose of DAC HYP in Study 303. Number analyzed is the number of participants with data available at the given timepoint.
    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303) DAC HYP 150 mg (203) /DAC HYP 150 mg (303) DAC HYP 150 mg (302) /DAC HYP 150 mg (303)
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 94.1 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS203 (203) every 4 weeks for up to 288 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 93.7 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS302 (302) every 4 weeks for up to 24 weeks followed by a 20-week washout period then continued treatment for up to an additional 3 years.
    Measure Participants 597 606 227 70
    Baseline 303
    16.0
    (23.16)
    17.5
    (25.31)
    25.3
    (29.42)
    18.9
    (24.41)
    Week 12
    16.7
    (24.40)
    17.5
    (25.38)
    Week 24
    17.0
    (25.23)
    16.7
    (24.71)
    25.5
    (28.81)
    24.8
    (30.25)
    Week 48
    16.9
    (25.48)
    17.1
    (26.23)
    23.8
    (28.52)
    21.0
    (27.62)
    Week 72
    19.9
    (26.83)
    17.8
    (26.13)
    25.4
    (27.88)
    19.6
    (23.37)
    Week 96
    16.4
    (25.39)
    17.7
    (26.18)
    23.8
    (29.07)
    21.4
    (27.23)
    Week 120
    17.4
    (25.10)
    16.9
    (25.00)
    Week 144
    16.5
    (24.40)
    17.4
    (25.25)
    Week 168
    19.1
    (26.03)
    18.2
    (26.37)
    Week 192
    18.5
    (26.55)
    17.3
    (25.07)
    Week 216
    18.8
    (26.11)
    18.3
    (26.18)
    Week 240
    9.6
    (14.95)
    16.0
    (26.06)
    35. Secondary Outcome
    Title Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Assessments in the 205MS303 Treatment Period
    Description Clinical Laboratory assessments included tests of hematology, blood chemistry, renal function, and thyroid function. The investigator determined if the results were clinically significant.
    Time Frame Up to 4.6 years in 303

    Outcome Measure Data

    Analysis Population Description
    Safety Population consisted of all participants who completed Study 301, 203 or 302 and received at least one dose of DAC HYP in Study 303.
    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303) DAC HYP 150 mg (203) /DAC HYP 150 mg (303) DAC HYP 150 mg (302) /DAC HYP 150 mg (303)
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 94.1 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS203 (203) every 4 weeks for up to 288 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 93.7 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS302 (302) every 4 weeks for up to 24 weeks followed by a 20-week washout period then continued treatment for up to an additional 3 years.
    Measure Participants 597 606 227 70
    Count of Participants [Participants]
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    36. Secondary Outcome
    Title Local Tolerability as Assessed by Participant-reported Injection Site Pain VAS
    Description The VAS is a 10 cm-long horizontal line labeled with 2 extremes of pain at either end: 0 =no pain on the left and 100=very painful on the right. The participant rates their perceived pain of each injection by placing a vertical mark on the line to indicate the level of pain.
    Time Frame After the first and fourth injections in 303, approximately Week 0 and Week 12

    Outcome Measure Data

    Analysis Population Description
    Safety Population consisted of all participants who completed Study 301,203 or 302 and received at least one dose of DAC HYP in Study 303. Local tolerability of the DAC HYP injection was assessed for all participants who received DAC HYP in Study 303 with data available at the given timepoint and is independent of the treatment previously received.
    Arm/Group Title DAC HYP 150 mg
    Arm/Group Description All participants who received DAC HYP 150 mg SC injection in study 205MS303.
    Measure Participants 1500
    First Injection, Post-dose
    1.7
    (2.46)
    Fourth Injection, Post-dose
    1.6
    (2.34)
    37. Secondary Outcome
    Title Number of Participants in Local Tolerability Clinician Injection Site Assessment Categories
    Description The investigator assessed the injection site after the first dose and before the fourth dose for the presence of erythema (None, Mild, Moderate, Severe), pigmentation (None, Hypo, Hyper), Induration (None, Mild, Moderate, Severe), Tenderness (None, Mild, Moderate, Severe) and Temperature (Normal, Warm, Hot). The number of participants in each grade is reported.
    Time Frame After the first and fourth injections in 303, approximately Week 0 and Week 12

    Outcome Measure Data

    Analysis Population Description
    Safety Population included all participants who completed Study 301, 203 or 302 and received at least one dose of DAC HYP in Study 303. Local tolerability of the DAC HYP injection was assessed for all participants who received DAC HYP in Study 303 with data available at the given timepoint and is independent of the treatment previously received.
    Arm/Group Title DAC HYP 150 mg
    Arm/Group Description All participants who received DAC HYP 150 mg SC injection in study 205MS303.
    Measure Participants 1500
    First Injection Post-dose, Erythema: None
    87
    14.6%
    First Injection Post-dose, Erythema: Mild
    8
    1.3%
    First Injection Post-dose, Erythema: Moderate
    2
    0.3%
    First Injection Post-dose, Erythema: Severe
    0
    0%
    Fourth Injection Pre-dose, Erythema: None
    87
    14.6%
    Fourth Injection Pre-dose, Erythema: Mild
    0
    0%
    Fourth Injection Pre-dose, Erythema: Moderate
    0
    0%
    Fourth Injection Pre-dose, Erythema: Severe
    0
    0%
    First Injection Post-dose, Pigmentation: None
    90
    15.1%
    First Injection Post-dose, Pigmentation: Hypo
    7
    1.2%
    First Injection Post-dose, Pigmentation: Hyper
    0
    0%
    Fourth Injection Pre-dose, Pigmentation: None
    87
    14.6%
    Fourth Injection Pre-dose, Pigmentation: Hypo
    0
    0%
    Fourth Injection Pre-dose, Pigmentation: Hyper
    0
    0%
    First Injection Post-dose, Induration: None
    89
    14.9%
    First Injection Post-dose, Induration: Mild
    4
    0.7%
    First Injection Post-dose, Induration: Moderate
    0
    0%
    First Injection Post-dose, Induration: Severe
    0
    0%
    Fourth Injection Pre-dose, Induration: None
    87
    14.6%
    Fourth Injection Pre-dose, Induration: Mild
    0
    0%
    Fourth Injection Pre-dose, Induration: Moderate
    0
    0%
    Fourth Injection Pre-dose, Induration: Severe
    0
    0%
    First Injection Post-dose, Tenderness: None
    94
    15.7%
    First Injection Post-dose, Tenderness: Mild
    3
    0.5%
    First Injection Post-dose, Tenderness: Moderate
    0
    0%
    First Injection Post-dose, Tenderness: Severe
    0
    0%
    Fourth Injection Pre-dose, Tenderness: None
    87
    14.6%
    Fourth Injection Pre-dose, Tenderness: Mild
    0
    0%
    Fourth Injection Pre-dose, Tenderness: Moderate
    0
    0%
    Fourth Injection Pre-dose, Tenderness: Severe
    0
    0%
    First Injection Post-dose,Temperature: Normal
    97
    16.2%
    First Injection Post-dose,Temperature: Warm
    0
    0%
    First Injection Post-dose,Temperature: Hot
    0
    0%
    Fourth Injection Pre-dose, Temperature: Normal
    87
    14.6%
    Fourth Injection Pre-dose, Temperature: Warm
    0
    0%
    Fourth Injection Pre-dose, Temperature: Hot
    0
    0%
    38. Secondary Outcome
    Title Number of Participants With Anti-BIIB019 Binding Antibodies (ADAbs) in the 205MS303 Treatment Period
    Description Blood samples were collected for ADAbs and were analyzed using a laboratory test. The number of participants ADAb positive at any post-baseline timepoint is reported.
    Time Frame Up to 4.6 years in the 303 Treatment Period

    Outcome Measure Data

    Analysis Population Description
    Safety Population consisted of all participants who completed Study 301, 203 or 302 and received at least one dose of DAC HYP in Study 303. Number of participants analyzed is the number of participants with evaluable data for this outcome measure.
    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303) DAC HYP 150 mg (203) /DAC HYP 150 mg (303) DAC HYP 150 mg (302) /DAC HYP 150 mg (303)
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 94.1 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS203 (203) every 4 weeks for up to 288 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 93.7 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS302 (302) every 4 weeks for up to 24 weeks followed by a 20-week washout period then continued treatment for up to an additional 3 years.
    Measure Participants 597 603 68 35
    Count of Participants [Participants]
    113
    18.9%
    48
    7.9%
    0
    0%
    0
    0%
    39. Secondary Outcome
    Title Number of Participants With Anti-BIIB019 Neutralizing Antibodies (Nabs) in the 205MS303 Treatment Period
    Description Blood samples were collected for NAbs and were analyzed using a laboratory test. The number of participants NAb positive at any post-baseline timepoint is reported.
    Time Frame Up to 4.6 years in the 303 Treatment Period

    Outcome Measure Data

    Analysis Population Description
    Safety Population consisted of all participants who completed Study 301, 203 or 302 and received at least one dose of DAC HYP in Study 303. Number of participants analyzed is the number of participants with evaluable data for this outcome measure.
    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303) DAC HYP 150 mg (203) /DAC HYP 150 mg (303) DAC HYP 150 mg (302) /DAC HYP 150 mg (303)
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 94.1 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS203 (203) every 4 weeks for up to 288 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 93.7 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS302 (302) every 4 weeks for up to 24 weeks followed by a 20-week washout period then continued treatment for up to an additional 3 years.
    Measure Participants 597 606 67 35
    Count of Participants [Participants]
    45
    7.5%
    21
    3.5%
    0
    0%
    0
    0%
    40. Secondary Outcome
    Title Change From 205MS303 Baseline in the Symbol Digit Modalities Test (SDMT) Score in the 205MS303 Treatment Period
    Description SDMT is a screening test for cognitive impairment. Participants are given 90 seconds in which to pair specific numbers with given geometric figures using a key. Scores range from 0 to 110 (best). A positive change from baseline indicates improvement.
    Time Frame Baseline 303, Weeks 144, 168, 192, 240 in 303

    Outcome Measure Data

    Analysis Population Description
    ITT Population: All participants who completed Study 301, 203 or 302 and received at least one dose of DAC HYP in Study 303. Number analyzed is the number of participants with data available at the given timepoint. No data is collected for participants from 203 and 302 studies.
    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks.
    Measure Participants 408 400
    Baseline 303
    52.0
    (15.13)
    52.4
    (16.08)
    Change at Week 144
    -3.0
    (11.38)
    -3.5
    (11.91)
    Change at Week 168
    -1.9
    (11.59)
    -3.7
    (13.10)
    Change at Week 192
    -2.5
    (12.02)
    -2.8
    (12.92)
    Change at Week 240
    2.0
    (10.78)
    -2.0
    (15.38)
    41. Secondary Outcome
    Title Change From 205MS301 Baseline in the SDMT Score in the 205MS301-303 Combined Study Period
    Description SDMT is a screening test for cognitive impairment. Participants are given 90 seconds in which to pair specific numbers with given geometric figures using a key. Scores range from 0 to 110 (best). A positive change from baseline indicates improvement.
    Time Frame Baseline 301, Weeks 24, 48, 72, 96, 120, 144 in 301; Weeks 144, 168, 192, 216, 240 in 303

    Outcome Measure Data

    Analysis Population Description
    301-303 ITT Population consisted of all participants who completed Study 301 and received at least one dose of DAC HYP in Study 303. Number analyzed is the number of participants with data available at the given timepoint.
    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks.
    Measure Participants 577 584
    Baseline 301
    47.8
    (16.18)
    48.4
    (16.32)
    Change from Baseline 301 at Week 24 for 301
    1.3
    (11.20)
    1.1
    (12.42)
    Change from Baseline 301 at Week 48 for 301
    2.7
    (12.31)
    2.2
    (12.01)
    Change from Baseline 301 at Week 72 for 301
    3.0
    (13.12)
    3.6
    (12.98)
    Change from Baseline 301 at Week 96 for 301
    3.0
    (13.04)
    4.1
    (13.09)
    Change from Baseline 301 at Week 120 for 301
    3.5
    (13.53)
    5.4
    (12.75)
    Change from Baseline 301 at Week 144 for 301
    3.2
    (13.38)
    6.6
    (13.15)
    Change from Baseline 301 at Week 144 for 303
    0.7
    (14.95)
    1.3
    (13.92)
    Change from Baseline 301 at Week 168 for 303
    2.0
    (14.78)
    1.6
    (14.86)
    Change from Baseline 301 at Week 192 for 303
    1.7
    (15.81)
    2.1
    (15.35)
    Change from Baseline 301 at Week 216 for 303
    4.7
    (15.91)
    4.5
    (14.59)
    Change from Baseline 301 at Week 240 for 303
    3.8
    (11.41)
    8.8
    (9.42)
    42. Secondary Outcome
    Title Change From Baseline in 3-Second Paced Auditory Serial Addition Test (PASAT 3) Score in the 205MS303 Treatment Period
    Description The PASAT 3 assesses auditory information processing speed. A random series of numbers from 1 to 9, inclusive, are presented and the participant is instructed to consecutively add pairs of numbers so that each number is added to the one that immediately preceded it. In the 3- second PASAT, numbers are presented at a rate of 1 every 3 seconds. The total possible score is the number of correct responses from 0 to 60 (best). A positive change from baseline indicates improvement.
    Time Frame Baseline 303, Weeks 12, 24, 48, 120, 144, 168, 192, 216, 240 in 303

    Outcome Measure Data

    Analysis Population Description
    301-303 ITT Population consisted of all participants who completed Study 301 and received at least 1 dose of DAC HYP during Study 303. Number analyzed is the number of participants with data available at the given timepoint. No data was collected for participants from the 203 and 302 studies.
    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks.
    Measure Participants 597 606
    Baseline 303
    54.0
    54.0
    Change to Week 12
    0.0
    0.0
    Change to Week 24
    0.0
    0.0
    Change to Week 48
    0.0
    0.0
    Change to Week 120
    -3.0
    -1.0
    Change to Week 144
    -1.0
    -1.0
    Change to Week 168
    0.0
    0.0
    Change to Week 192
    0.0
    0.0
    Change to Week 216
    0.0
    0.0
    Change to Week 240
    0.0
    -2.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change to Week 12
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3813
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline raw score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change to Week 24
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1679
    Comments
    Method ANOVA
    Comments Based on ranks and adjusted for the baseline raw score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change to Week 48
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.5634
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline raw score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change to Week 144
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.7003
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline raw score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change to Week 168
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.7812
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline raw score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change to Week 192
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3246
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline raw score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change to Week 216
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.6423
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline raw score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change to Week 240
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0288
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline raw score, baseline age (<=35 vs >35) and history of prior IFN beta.
    43. Secondary Outcome
    Title Change From Baseline in 3-Second Paced Auditory Serial Addition Test (PASAT 3) Score in the 205MS301-303 Combined Study Period
    Description The PASAT 3 assesses auditory information processing speed. A random series of numbers from 1 to 9, inclusive, are presented and the participant is instructed to consecutively add pairs of numbers so that each number is added to the one that immediately preceded it. In the 3- second PASAT, numbers are presented at a rate of 1 every 3 seconds. The total possible score is the number of correct responses from 0 to 60 (best). A positive change from baseline indicates improvement.
    Time Frame Baseline 301, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 in the 301 study, Baseline 303, Weeks 12, 24, 48, 120, 144,168, 192, 216, 240 in 303 study

    Outcome Measure Data

    Analysis Population Description
    301-303 ITT Population consisted of all participants who completed study 301 and had at least 1 dose of DAC HYP during study 303. Number analyzed is the number of participants with data available at the given timepoint.
    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks.
    Measure Participants 597 606
    Baseline 301
    50.0
    51.0
    Change from Baseline 301 to Week 12 for 301
    0.0
    1.0
    Change from Baseline 301 to Week 24 for 301
    0.5
    1.0
    Change from Baseline 301 to Week 36 for 301
    1.0
    1.0
    Change from Baseline 301 to Week 48 for 301
    1.0
    1.0
    Change from Baseline 301 to Week 60 for 301
    1.0
    2.0
    Change from Baseline 301 to Week 72 for 301
    2.0
    2.0
    Change from Baseline 301 to Week 84 for 301
    2.0
    2.0
    Change from Baseline 301 to Week 96 for 301
    2.0
    2.0
    Change from Baseline 301 to Week 108 for 301
    1.0
    2.0
    Change from Baseline 301 to Week 120 for 301
    2.0
    2.0
    Change from Baseline 301 to Week 132 for 301
    2.0
    2.0
    Change from Baseline 301 to Week 144 for 301
    2.0
    3.0
    Change from Baseline 301 to Week 156 for 301
    -4.0
    Change from Baseline 301 to Baseline 303
    2.0
    2.0
    Change from Baseline 301 to Week 12 for 303
    2.0
    2.0
    Change from Baseline 301 to Week 24 for 303
    2.0
    2.0
    Change from Baseline 301 to Week 48 for 303
    2.0
    2.0
    Change from Baseline 301 to Week 120 for 303
    15.0
    3.0
    Change from Baseline 301 to Week 144 for 303
    1.0
    2.0
    Change from Baseline 301 to Week 168 for 303
    2.0
    2.0
    Change from Baseline 301 to Week 192 for 303
    2.0
    2.0
    Change from Baseline 301 to Week 216 for 303
    2.0
    2.0
    Change from Baseline 301 to Week 240 for 303
    1.5
    0.5
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change from Baseline 301 to Week 12 for 301
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2567
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline raw score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change from Baseline 301 to Week 24 for 301
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.6152
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline raw score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change from Baseline 301 to Week 36 for 301
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2024
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline raw score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change from Baseline 301 to Week 48 for 301
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.9988
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline raw score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change from Baseline 301 to Week 60 for 301
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.7962
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline raw score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change from Baseline 301 to Week 72 for 301
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.8486
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline raw score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change from Baseline 301 to Week 84 for 301
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.4478
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline raw score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change from Baseline 301 to Week 96 for 301
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3250
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline raw score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change from Baseline 301 to Week 108 for 301
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1290
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline raw score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change from Baseline 301 to Week 120 for 301
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.7295
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline raw score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change from Baseline 301 to Week 132 for 301
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.8647
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline raw score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change from Baseline 301 to Week 144 for 301
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2183
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline raw score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change from Baseline 301 to Baseline 303
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3945
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline raw score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change from Baseline 301 to Week 12 for 303
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.5068
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline raw score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change from Baseline 301 to Week 24 for 303
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1669
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline raw score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change from Baseline 301 to Week 48 for 303
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.5038
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline raw score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change from Baseline 301 to Week 144 for 303
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.6001
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline raw score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change from Baseline 301 to Week 168 for 303
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.8617
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline raw score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change from Baseline 301 to Week 192 for 303
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2590
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline raw score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change from Baseline 301 to Week 216 for 303
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.5159
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline raw score, baseline age (<=35 vs >35) and history of prior IFN beta.
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection IFN β-1a 30 µg (301)/DAC HYP 150 mg (303), DAC HYP 150 mg (301) /DAC HYP 150 mg (303)
    Comments Change from Baseline 301 to Week 240 for 303
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.6123
    Comments
    Method ANCOVA
    Comments Based on ranks and adjusted for the baseline raw score, baseline age (<=35 vs >35) and history of prior IFN beta.

    Adverse Events

    Time Frame First dose of study drug in study 205MS303 to within 180 days of last dose (up to approximately 5.5 years)
    Adverse Event Reporting Description
    Arm/Group Title IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303) DAC HYP 150 mg (302) /DAC HYP 150 mg (303) DAC HYP 150 mg (203) /DAC HYP 150 mg (303)
    Arm/Group Description DAC HYP 150 mg SC injection every 4 weeks for up to 4.6 years in this long-term extension study 303; includes participants who previously received IFN β-1a 30 µg IM injection once weekly in study 301 every 4 weeks for up to 144 weeks. Daclizumab High Yield Process (DAC HYP)150 mg subcutaneous (SC) injection every 4 weeks for up to 4.6 years in this long-term extension study 205MS303 (303); includes participants who previously received DAC HYP 150 mg SC injection in Study 205MS301 (301) every 4 weeks for up to 144 weeks. DAC HYP 150 mg SC injection every 4 weeks for up to 93.7 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS302 (302) every 4 weeks for up to 24 weeks followed by a 20-week washout period then continued treatment for up to an additional 3 years. DAC HYP 150 mg SC injection every 4 weeks for up to 94. 1 weeks in this long-term extension study 303 (participants started at Week 144 of the study); includes participants who previously received DAC HYP 150 mg SC injection in study 205MS203 (203) every 4 weeks for up to 288 weeks.
    All Cause Mortality
    IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303) DAC HYP 150 mg (302) /DAC HYP 150 mg (303) DAC HYP 150 mg (203) /DAC HYP 150 mg (303)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/597 (0.3%) 4/606 (0.7%) 0/70 (0%) 0/227 (0%)
    Serious Adverse Events
    IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303) DAC HYP 150 mg (302) /DAC HYP 150 mg (303) DAC HYP 150 mg (203) /DAC HYP 150 mg (303)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 157/597 (26.3%) 190/606 (31.4%) 15/70 (21.4%) 38/227 (16.7%)
    Blood and lymphatic system disorders
    Agranulocytosis 1/597 (0.2%) 2/606 (0.3%) 0/70 (0%) 0/227 (0%)
    Anaemia 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Granulocytopenia 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Haemolytic anaemia 2/597 (0.3%) 2/606 (0.3%) 0/70 (0%) 0/227 (0%)
    Leukopenia 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Lymphadenitis 2/597 (0.3%) 3/606 (0.5%) 0/70 (0%) 0/227 (0%)
    Lymphadenopathy 4/597 (0.7%) 10/606 (1.7%) 1/70 (1.4%) 2/227 (0.9%)
    Lymphoid tissue hyperplasia 4/597 (0.7%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Lymphopenia 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Pancytopenia 0/597 (0%) 2/606 (0.3%) 1/70 (1.4%) 0/227 (0%)
    Pernicious anaemia 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Pseudolymphoma 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Thrombocytopenia 3/597 (0.5%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Cardiac disorders
    Angina pectoris 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Angina unstable 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Cardiac arrest 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Cardiac failure 0/597 (0%) 2/606 (0.3%) 0/70 (0%) 0/227 (0%)
    Cardiomyopathy 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Coronary artery stenosis 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Left ventricular hypertrophy 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Myocardial infarction 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 1/227 (0.4%)
    Ear and labyrinth disorders
    Acute vestibular syndrome 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Vertigo 1/597 (0.2%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Endocrine disorders
    Goitre 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Hyperparathyroidism primary 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Eye disorders
    Eye haemorrhage 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Iritis 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Retinal detachment 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Gastrointestinal disorders
    Abdominal pain 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Abdominal pain upper 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Anorectal disorder 0/597 (0%) 0/606 (0%) 1/70 (1.4%) 0/227 (0%)
    Coeliac disease 0/597 (0%) 2/606 (0.3%) 0/70 (0%) 0/227 (0%)
    Colitis 0/597 (0%) 2/606 (0.3%) 0/70 (0%) 0/227 (0%)
    Colitis ulcerative 2/597 (0.3%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Constipation 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Crohn's disease 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Diarrhoea 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Diverticulum 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Duodenal ulcer 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Enteritis 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Functional gastrointestinal disorder 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Gastric ulcer 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Gastritis 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Gastrointestinal disorder 0/597 (0%) 0/606 (0%) 1/70 (1.4%) 0/227 (0%)
    Gingivitis ulcerative 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Haemorrhoids 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Inflammatory bowel disease 0/597 (0%) 0/606 (0%) 0/70 (0%) 1/227 (0.4%)
    Inguinal hernia 2/597 (0.3%) 2/606 (0.3%) 0/70 (0%) 1/227 (0.4%)
    Intestinal ischaemia 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Large intestine perforation 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Pancreatitis 2/597 (0.3%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Pancreatitis acute 3/597 (0.5%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Peptic ulcer haemorrhage 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Stomatitis necrotising 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Tongue necrosis 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Umbilical hernia 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    General disorders
    Asthenia 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Device dislocation 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Inflammation 0/597 (0%) 1/606 (0.2%) 1/70 (1.4%) 0/227 (0%)
    Multi-organ disorder 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Multi-organ failure 1/597 (0.2%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Pain 0/597 (0%) 0/606 (0%) 0/70 (0%) 1/227 (0.4%)
    Pyrexia 3/597 (0.5%) 3/606 (0.5%) 0/70 (0%) 1/227 (0.4%)
    Hepatobiliary disorders
    Cholecystitis 2/597 (0.3%) 2/606 (0.3%) 0/70 (0%) 0/227 (0%)
    Cholecystitis acute 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Cholelithiasis 5/597 (0.8%) 2/606 (0.3%) 0/70 (0%) 0/227 (0%)
    Chronic hepatitis 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Drug-induced liver injury 4/597 (0.7%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Hepatic necrosis 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Hepatitis cholestatic 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Hepatitis toxic 1/597 (0.2%) 2/606 (0.3%) 0/70 (0%) 0/227 (0%)
    Jaundice 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Liver injury 0/597 (0%) 2/606 (0.3%) 0/70 (0%) 0/227 (0%)
    Immune system disorders
    Drug hypersensitivity 0/597 (0%) 0/606 (0%) 1/70 (1.4%) 0/227 (0%)
    Hypersensitivity 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Sarcoidosis 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Serum sickness 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Infections and infestations
    Anal abscess 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Appendicitis 1/597 (0.2%) 2/606 (0.3%) 0/70 (0%) 0/227 (0%)
    Atypical pneumonia 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Bartholin's abscess 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Brucellosis 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Chlamydial infection 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Chronic hepatitis c 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Chronic sinusitis 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Clostridium difficile colitis 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Clostridium difficile infection 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Cytomegalovirus infection 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Erysipelas 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Genitourinary tract infection 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Hepatitis e 1/597 (0.2%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Infection 0/597 (0%) 2/606 (0.3%) 0/70 (0%) 0/227 (0%)
    Intervertebral discitis 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Lobar pneumonia 1/597 (0.2%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Localised infection 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Lyme disease 0/597 (0%) 0/606 (0%) 1/70 (1.4%) 0/227 (0%)
    Meningitis aseptic 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Myelitis 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Parotitis 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Pneumonia 5/597 (0.8%) 8/606 (1.3%) 0/70 (0%) 1/227 (0.4%)
    Pneumonia cytomegaloviral 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Pulmonary tuberculosis 2/597 (0.3%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Pyelonephritis 1/597 (0.2%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Reiter's syndrome 0/597 (0%) 0/606 (0%) 0/70 (0%) 1/227 (0.4%)
    Respiratory tract infection 1/597 (0.2%) 2/606 (0.3%) 0/70 (0%) 0/227 (0%)
    Salmonellosis 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Sepsis 0/597 (0%) 2/606 (0.3%) 0/70 (0%) 0/227 (0%)
    Septic shock 2/597 (0.3%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Sinusitis 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Tonsillitis 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Upper respiratory tract infection 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Urinary tract infection 6/597 (1%) 3/606 (0.5%) 2/70 (2.9%) 0/227 (0%)
    Urosepsis 2/597 (0.3%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Vaginal infection 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Viral infection 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Injury, poisoning and procedural complications
    Accident 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Ankle fracture 0/597 (0%) 0/606 (0%) 0/70 (0%) 1/227 (0.4%)
    Clavicle fracture 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Concussion 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Contusion 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Fall 1/597 (0.2%) 7/606 (1.2%) 1/70 (1.4%) 2/227 (0.9%)
    Femur fracture 0/597 (0%) 2/606 (0.3%) 0/70 (0%) 0/227 (0%)
    Fibula fracture 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Foot fracture 0/597 (0%) 2/606 (0.3%) 0/70 (0%) 0/227 (0%)
    Hand fracture 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Intentional overdose 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Jaw fracture 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Joint injury 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 1/227 (0.4%)
    Ligament injury 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Ligament rupture 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Limb injury 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Lower limb fracture 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Meniscus injury 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Multiple fractures 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Radius fracture 0/597 (0%) 0/606 (0%) 0/70 (0%) 1/227 (0.4%)
    Road traffic accident 0/597 (0%) 2/606 (0.3%) 0/70 (0%) 0/227 (0%)
    Snake bite 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Subdural haematoma 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Tibia fracture 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Toxicity to various agents 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Traumatic intracranial haemorrhage 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Ulna fracture 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Wrist fracture 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Investigations
    Alanine aminotransferase increased 1/597 (0.2%) 2/606 (0.3%) 0/70 (0%) 0/227 (0%)
    Aspartate aminotransferase increased 1/597 (0.2%) 2/606 (0.3%) 0/70 (0%) 0/227 (0%)
    Blood bilirubin increased 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Diagnostic procedure 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Hepatic enzyme increased 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Liver function test abnormal 0/597 (0%) 0/606 (0%) 0/70 (0%) 1/227 (0.4%)
    Protein urine present 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Weight decreased 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 1/227 (0.4%)
    Metabolism and nutrition disorders
    Diabetes mellitus 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Diabetes mellitus inadequate control 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Hyperamylasaemia 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Hypokalaemia 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Type 1 diabetes mellitus 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Type 2 diabetes mellitus 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Musculoskeletal and connective tissue disorders
    Arthritis 0/597 (0%) 1/606 (0.2%) 1/70 (1.4%) 0/227 (0%)
    Back pain 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Fibromyalgia 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Foot deformity 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Haemarthrosis 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Intervertebral disc protrusion 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Juvenile idiopathic arthritis 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Ligament laxity 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Muscular weakness 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Osteochondrosis 0/597 (0%) 0/606 (0%) 0/70 (0%) 1/227 (0.4%)
    Psoriatic arthropathy 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 1/227 (0.4%)
    Rheumatoid arthritis 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Rotator cuff syndrome 1/597 (0.2%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Seronegative arthritis 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Spondylolisthesis 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Still's disease adult onset 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Synovitis 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Systemic sclerosis 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Tendonitis 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Tenosynovitis 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma of colon 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Anorectal human papilloma virus infection 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    B-cell lymphoma 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Benign neoplasm of thyroid gland 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Breast cancer 3/597 (0.5%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Endometrial cancer 0/597 (0%) 0/606 (0%) 0/70 (0%) 1/227 (0.4%)
    Fibroadenoma of breast 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 1/227 (0.4%)
    Invasive ductal breast carcinoma 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Meningioma 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Metaplastic breast carcinoma 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Ovarian cancer 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Ovarian fibroma 0/597 (0%) 0/606 (0%) 0/70 (0%) 1/227 (0.4%)
    Parathyroid tumour benign 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Testicular neoplasm 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Uterine leiomyoma 0/597 (0%) 4/606 (0.7%) 0/70 (0%) 0/227 (0%)
    Uterine leiomyosarcoma 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Nervous system disorders
    Brain compression 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Brain oedema 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Carpal tunnel syndrome 0/597 (0%) 1/606 (0.2%) 1/70 (1.4%) 0/227 (0%)
    Cerebellar syndrome 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Cerebral haemorrhage 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Cerebral venous thrombosis 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Cerebrovascular accident 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Convulsion 1/597 (0.2%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Encephalitis autoimmune 3/597 (0.5%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Epilepsy 2/597 (0.3%) 3/606 (0.5%) 0/70 (0%) 0/227 (0%)
    Guillain-barre syndrome 2/597 (0.3%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Headache 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Multiple sclerosis 3/597 (0.5%) 3/606 (0.5%) 0/70 (0%) 0/227 (0%)
    Multiple sclerosis relapse 61/597 (10.2%) 65/606 (10.7%) 3/70 (4.3%) 17/227 (7.5%)
    Muscle spasticity 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Myasthenia gravis 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Neurological symptom 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Optic neuritis 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Status epilepticus 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Syncope 1/597 (0.2%) 2/606 (0.3%) 0/70 (0%) 0/227 (0%)
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Blighted ovum 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Foetal growth restriction 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Premature delivery 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Psychiatric disorders
    Acute stress disorder 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Anxiety 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Bipolar i disorder 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Confusional state 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Depression 2/597 (0.3%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Personality disorder 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Psychotic disorder 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Somatoform disorder 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Suicidal ideation 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Suicide attempt 2/597 (0.3%) 3/606 (0.5%) 0/70 (0%) 0/227 (0%)
    Renal and urinary disorders
    Calculus ureteric 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Hypertonic bladder 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Nephrolithiasis 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Renal colic 0/597 (0%) 2/606 (0.3%) 0/70 (0%) 0/227 (0%)
    Renal cyst 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Renal failure 0/597 (0%) 0/606 (0%) 0/70 (0%) 1/227 (0.4%)
    Renal failure acute 1/597 (0.2%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Renal failure chronic 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Tubulointerstitial nephritis 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Urinary retention 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Urogenital fistula 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Vesicoureteric reflux 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Reproductive system and breast disorders
    Adnexal torsion 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Cervical dysplasia 2/597 (0.3%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Dysfunctional uterine bleeding 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Endometrial hyperplasia 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Endometriosis 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Metrorrhagia 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Ovarian adhesion 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Ovarian cyst 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Ovarian cyst ruptured 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Pelvic prolapse 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Uterine haemorrhage 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Uterine polyp 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Asthma 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Bronchial hyperreactivity 0/597 (0%) 0/606 (0%) 1/70 (1.4%) 0/227 (0%)
    Bronchitis chronic 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Choking 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Chronic obstructive pulmonary disease 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Interstitial lung disease 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Nasal polyps 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Pharyngeal necrosis 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Pneumonia aspiration 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Pneumothorax 1/597 (0.2%) 0/606 (0%) 1/70 (1.4%) 0/227 (0%)
    Pulmonary fibrosis 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Pulmonary sarcoidosis 0/597 (0%) 3/606 (0.5%) 0/70 (0%) 0/227 (0%)
    Respiratory failure 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Tracheal fistula 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Skin and subcutaneous tissue disorders
    Alopecia scarring 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Dermatitis atopic 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Dermatitis contact 3/597 (0.5%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Drug eruption 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Drug reaction with eosinophilia and systemic symptoms 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Eczema 2/597 (0.3%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Erythema 0/597 (0%) 0/606 (0%) 0/70 (0%) 1/227 (0.4%)
    Erythema multiforme 1/597 (0.2%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Erythema nodosum 1/597 (0.2%) 1/606 (0.2%) 1/70 (1.4%) 0/227 (0%)
    Henoch-schonlein purpura 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Hidradenitis 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Pemphigoid 1/597 (0.2%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Perivascular dermatitis 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Photosensitivity reaction 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Pityriasis rosea 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Psoriasis 3/597 (0.5%) 2/606 (0.3%) 0/70 (0%) 1/227 (0.4%)
    Rash 1/597 (0.2%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Rash generalised 0/597 (0%) 3/606 (0.5%) 0/70 (0%) 0/227 (0%)
    Rash maculo-papular 2/597 (0.3%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Rosacea 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Seborrhoeic dermatitis 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Stevens-johnson syndrome 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Toxic epidermal necrolysis 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Toxic skin eruption 1/597 (0.2%) 1/606 (0.2%) 0/70 (0%) 1/227 (0.4%)
    Surgical and medical procedures
    Abdominoplasty 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Female sterilisation 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Hospitalisation 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Immunosuppressant drug therapy 0/597 (0%) 0/606 (0%) 0/70 (0%) 1/227 (0.4%)
    Mastectomy 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Vascular disorders
    Granulomatosis with polyangiitis 0/597 (0%) 0/606 (0%) 1/70 (1.4%) 0/227 (0%)
    Hypertension 1/597 (0.2%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Kawasaki's disease 0/597 (0%) 1/606 (0.2%) 0/70 (0%) 0/227 (0%)
    Varicose vein 2/597 (0.3%) 0/606 (0%) 0/70 (0%) 0/227 (0%)
    Other (Not Including Serious) Adverse Events
    IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) DAC HYP 150 mg (301) /DAC HYP 150 mg (303) DAC HYP 150 mg (302) /DAC HYP 150 mg (303) DAC HYP 150 mg (203) /DAC HYP 150 mg (303)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 463/597 (77.6%) 476/606 (78.5%) 42/70 (60%) 116/227 (51.1%)
    Blood and lymphatic system disorders
    Lymphadenopathy 47/597 (7.9%) 71/606 (11.7%) 3/70 (4.3%) 7/227 (3.1%)
    Gastrointestinal disorders
    Diarrhoea 42/597 (7%) 35/606 (5.8%) 2/70 (2.9%) 10/227 (4.4%)
    Toothache 17/597 (2.8%) 14/606 (2.3%) 4/70 (5.7%) 3/227 (1.3%)
    General disorders
    Fatigue 40/597 (6.7%) 41/606 (6.8%) 3/70 (4.3%) 4/227 (1.8%)
    Pyrexia 45/597 (7.5%) 43/606 (7.1%) 3/70 (4.3%) 7/227 (3.1%)
    Infections and infestations
    Bronchitis 29/597 (4.9%) 36/606 (5.9%) 3/70 (4.3%) 1/227 (0.4%)
    Influenza 46/597 (7.7%) 35/606 (5.8%) 1/70 (1.4%) 4/227 (1.8%)
    Nasopharyngitis 121/597 (20.3%) 125/606 (20.6%) 6/70 (8.6%) 18/227 (7.9%)
    Oral herpes 42/597 (7%) 35/606 (5.8%) 3/70 (4.3%) 6/227 (2.6%)
    Pharyngitis 53/597 (8.9%) 47/606 (7.8%) 1/70 (1.4%) 9/227 (4%)
    Sinusitis 41/597 (6.9%) 26/606 (4.3%) 1/70 (1.4%) 4/227 (1.8%)
    Tonsillitis 34/597 (5.7%) 14/606 (2.3%) 4/70 (5.7%) 2/227 (0.9%)
    Upper respiratory tract infection 116/597 (19.4%) 114/606 (18.8%) 13/70 (18.6%) 26/227 (11.5%)
    Urinary tract infection 77/597 (12.9%) 58/606 (9.6%) 4/70 (5.7%) 10/227 (4.4%)
    Investigations
    Alanine aminotransferase increased 45/597 (7.5%) 48/606 (7.9%) 3/70 (4.3%) 16/227 (7%)
    Aspartate aminotransferase increased 40/597 (6.7%) 48/606 (7.9%) 2/70 (2.9%) 11/227 (4.8%)
    Liver function test abnormal 32/597 (5.4%) 30/606 (5%) 2/70 (2.9%) 6/227 (2.6%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 45/597 (7.5%) 38/606 (6.3%) 3/70 (4.3%) 7/227 (3.1%)
    Back pain 65/597 (10.9%) 51/606 (8.4%) 3/70 (4.3%) 10/227 (4.4%)
    Pain in extremity 34/597 (5.7%) 40/606 (6.6%) 2/70 (2.9%) 2/227 (0.9%)
    Nervous system disorders
    Headache 57/597 (9.5%) 56/606 (9.2%) 7/70 (10%) 16/227 (7%)
    Multiple sclerosis relapse 179/597 (30%) 169/606 (27.9%) 15/70 (21.4%) 36/227 (15.9%)
    Psychiatric disorders
    Depression 45/597 (7.5%) 38/606 (6.3%) 1/70 (1.4%) 1/227 (0.4%)
    Skin and subcutaneous tissue disorders
    Dermatitis 13/597 (2.2%) 16/606 (2.6%) 4/70 (5.7%) 4/227 (1.8%)
    Eczema 32/597 (5.4%) 46/606 (7.6%) 1/70 (1.4%) 5/227 (2.2%)
    Erythema 31/597 (5.2%) 27/606 (4.5%) 0/70 (0%) 1/227 (0.4%)
    Rash 39/597 (6.5%) 64/606 (10.6%) 0/70 (0%) 9/227 (4%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Our agreement is subject to confidentiality but generally the PI can publish, for noncommercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.

    Results Point of Contact

    Name/Title Biogen Study Medical Director
    Organization Biogen
    Phone 866-633-4636
    Email clinicaltrials@biogen.com
    Responsible Party:
    Biogen
    ClinicalTrials.gov Identifier:
    NCT01797965
    Other Study ID Numbers:
    • 205MS303
    • 2012-003176-39
    First Posted:
    Feb 25, 2013
    Last Update Posted:
    Dec 4, 2019
    Last Verified:
    Nov 1, 2019