A Phase 3 interventional study of BIIB019 (Daclizumab) in Relapsing-Remitting Multiple Sclerosis and Multiple Sclerosis, sponsored by Biogen. Terminated at 222 sites in 27 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-12-04.
Sponsored by Biogen · Phase 3, Interventional, and Treatment
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).
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.
3,460 studies on the registry are indexed under Multiple Sclerosis; 661 are open to participants now.
This study's enrollment of 1,501 is above the median of 50 across 2,342 interventional studies indexed under Multiple Sclerosis.
Browse Multiple Sclerosis studies →Biogen is the lead sponsor of 494 studies on the registry; 22 are open to participants now.
Of its 98 completed or terminated interventional studies of FDA-regulated products, 49 (50%) have results posted.
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Key Inclusion Criteria:
Key Exclusion Criteria:
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.
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.
Also known as: Daclizumab High Yield Process, DAC HYP
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
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)
Annualized Relapse Rate (ARR) in the 205MS303 Treatment Period
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
ARR in the 205MS301-303 Combined Study Period and 205MS301 Treatment Period
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
Number of Participants With Relapse in the 205MS303 Treatment Period
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
Number of Participants With Relapse in the 205MS301-303 Combined Study Period
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
Number of Participants With Sustained Disability Progression in the 205MS303 Treatment Period
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
Number of Participants With Sustained Disability Progression in the 205MS301-303 Combined Study Period
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
Number of Participants With New or Newly Enlarging T2 Hyperintense Lesions in the 205MS303 Treatment Period
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
Number of Participants With New or Newly Enlarging T2 Hyperintense Lesions in the 205MS301 Treatment Period
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
Number of Participants With Gadolinium-enhancing (Gd+) Lesions in the 205MS303 Treatment Period
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
Number of Participants With Gadolinium-enhancing (Gd+) Lesions in the 205MS301 Treatment Period
Gd+ lesions were evaluated by MRI and were analyzed by a central MRI reader.
Time frame: Baseline 301, Weeks 24, 96 and 144
Number of Participants With New T1 Hypointense Lesions in the 205MS303 Treatment Period
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
Number of Participants With New T1 Hypointense Lesions in the 205MS301 Treatment Period
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
Percent Change in Brain Volume From the 205MS303 Baseline
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
Percent Change in Brain Volume From 205MS301 Baseline
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
Total Volume of T2 Hyperintense Lesions in the 205MS303 Treatment Period
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
Change From Baseline in the Multiple Sclerosis Functional Composite (MSFC) Score in the 205MS303 Treatment Period
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
Change From 205MS301 Baseline in the MSFC Score in the 205MS301-303 Combined Study Period
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
Change From Baseline in the Expanded Disability Status Scale (EDSS) Score in the 205MS303 Treatment Period
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
Number of Participants Who Are Free From Disease Activity in the 205MS303 Treatment Period
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
Change From Baseline in the Multiple Sclerosis Impact Scale 29 (MSIS 29) Physical and Psychological Scores in the 205MS303 Treatment Period
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
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
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
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
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
Direct Health Resource Utilization (HRU): Number of Unscheduled Site Visits in the 205MS303 Treatment Period
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
Direct Health Resource Utilization (HRU): Number of Unscheduled Site Visits in the 205MS301 Treatment Period
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
Treatment Satisfaction as Assessed by the Participant in the 205MS303 Treatment Period
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
Health Related Productivity Questionnaire (HRPQ): Scheduled Work Hours in the 205MS303 Treatment Period
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
HRPQ: Number of Participants Where MS or Its Treatments Resulted in Missed Work in the 205MS303 Treatment Period
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
HRPQ: Hours of Work Missed Due to MS or Its Treatment in the 205MS303 Treatment Period
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
HRPQ: Percent Impact on Employment in the 205MS303 Treatment Period
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
HRPQ: Hours of Household Chores Planned to Perform in the 205MS303 Treatment Period
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
HRPQ: Number of Participants Where MS or Its Treatments Kept the Participant From Completing Chores in the 205MS303 Treatment Period
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
HRPQ: Hours Not Performing Household Chores Due to MS or Its Treatment in 205MS303 Treatment Period
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
HRPQ: Percent Impact on Performing Household Chores in the 205MS303 Treatment Period
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
Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Assessments in the 205MS303 Treatment Period
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
Local Tolerability as Assessed by Participant-reported Injection Site Pain VAS
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
Number of Participants in Local Tolerability Clinician Injection Site Assessment Categories
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
Number of Participants With Anti-BIIB019 Binding Antibodies (ADAbs) in the 205MS303 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.
Time frame: Up to 4.6 years in the 303 Treatment Period
Number of Participants With Anti-BIIB019 Neutralizing Antibodies (Nabs) in the 205MS303 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.
Time frame: Up to 4.6 years in the 303 Treatment Period
Change From 205MS303 Baseline in the Symbol Digit Modalities Test (SDMT) Score in the 205MS303 Treatment Period
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
Change From 205MS301 Baseline in the SDMT Score in the 205MS301-303 Combined Study Period
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
Change From Baseline in 3-Second Paced Auditory Serial Addition Test (PASAT 3) Score in the 205MS303 Treatment Period
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
Change From Baseline in 3-Second Paced Auditory Serial Addition Test (PASAT 3) Score in the 205MS301-303 Combined Study Period
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
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.
| Milestone | 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) |
|---|---|---|---|---|
| Started | 597 | 607 | 70 | 227 |
| Completed | 48 | 38 | 62 | 154 |
| Not completed | 549 | 569 | 8 | 73 |
| Withdrew: Adverse event | 104 | 129 | 4 | 21 |
| Withdrew: Lost to follow-up | 9 | 8 | 1 | 2 |
| Withdrew: Consent withdrawn | 130 | 117 | 3 | 35 |
| Withdrew: Investigator decision | 21 | 15 | 0 | 0 |
| Withdrew: Death | 2 | 4 | 0 | 0 |
| Withdrew: Disease progression, defined by protocol | 3 | 1 | 0 | 0 |
| Withdrew: Reason not specified | 280 | 295 | 0 | 15 |
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.
| Participants | 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) |
|---|---|---|---|---|
| Participants with AEs | 541 | 560 | 172 | 53 |
| Participants with SAEs | 157 | 190 | 38 | 15 |
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.
| relapses per year | 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) |
|---|---|---|---|---|
| Annualized Relapse Rate (ARR) in the 205MS303 Treatment Period | 0.158 (0.134 to 0.188) | 0.163 (0.138 to 0.193) | 0.080 (0.047 to 0.136) | 0.167 (0.097 to 0.288) |
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.
| relapses per year | IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) | DAC HYP 150 mg (301) /DAC HYP 150 mg (303) |
|---|---|---|
| 301-303 Combined Study Period | 0.247 (0.220 to 0.279) | 0.175 (0.154 to 0.199) |
| 301 Treatment Period | 0.317 (0.280 to 0.360) | 0.195 (0.169 to 0.225) |
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.
| Participants | 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) |
|---|---|---|---|---|
| Number of Participants With Relapse in the 205MS303 Treatment Period | 184 | 172 | 35 | 16 |
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.
| Participants | IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) | DAC HYP 150 mg (301) /DAC HYP 150 mg (303) |
|---|---|---|
| Number of Participants With Relapse in the 205MS301-303 Combined Study Period | 339 | 261 |
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.
| Participants | 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) |
|---|---|---|---|---|
| Number of Participants With Sustained Disability Progression in the 205MS303 Treatment Period | 95 | 97 | 8 | 2 |
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.
| Participants | IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) | DAC HYP 150 mg (301) /DAC HYP 150 mg (303) |
|---|---|---|
| Number of Participants With Sustained Disability Progression in the 205MS301-303 Combined Study Period | 144 | 130 |
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.
| Participants | IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) | DAC HYP 150 mg (301) /DAC HYP 150 mg (303) |
|---|---|---|
| Week 48 | 270 | 144 |
| Week 96 | 213 | 130 |
| Week 144 | 223 | 157 |
| Week 192 | 173 | 126 |
| Week 240 | 20 | 22 |
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.
| Participants | IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) | DAC HYP 150 mg (301) /DAC HYP 150 mg (303) |
|---|---|---|
| Week 24 | 347 | 314 |
| Week 96 | 435 | 368 |
| Week 144 | 126 | 113 |
Gd+ lesions were evaluated by MRI and were analyzed by a central MRI reader.
| Participants | 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) |
|---|---|---|---|---|
| Baseline 303 | 180 | 77 | — | — |
| Week 48 | 89 | 46 | — | — |
| Week 96 | 43 | 23 | 8 | 2 |
| Week 144 | 43 | 42 | — | — |
| Week 192 | 25 | 29 | — | — |
| Week 240 | 1 | 7 | — | — |
Gd+ lesions were evaluated by MRI and were analyzed by a central MRI reader.
| Participants | IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) | DAC HYP 150 mg (301) /DAC HYP 150 mg (303) |
|---|---|---|
| Baseline 301 | 263 | 265 |
| Week 24 | 153 | 119 |
| Week 96 | 172 | 66 |
| Week 144 | 49 | 20 |
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.
| Participants | IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) | DAC HYP 150 mg (301) /DAC HYP 150 mg (303) |
|---|---|---|
| Week 48 | 200 | 96 |
| Week 96 | 168 | 91 |
| Week 144 | 184 | 116 |
| Week 192 | 152 | 94 |
| Week 240 | 16 | 18 |
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 .
| Participants | IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) | DAC HYP 150 mg (301) /DAC HYP 150 mg (303) |
|---|---|---|
| Week 24 | 276 | 244 |
| Week 96 | 375 | 300 |
| Week 144 | 111 | 87 |
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.
| percent change | IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) | DAC HYP 150 mg (301) /DAC HYP 150 mg (303) |
|---|---|---|
| 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 |
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.
| percent change | IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) | DAC HYP 150 mg (301) /DAC HYP 150 mg (303) |
|---|---|---|
| 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 |
Volume of T2 hyperintense Lesions was evaluated by MRI and was analyzed by a central MRI reader.
| millimeters cubed (mm^3) | 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) |
|---|---|---|---|---|
| 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 | — | — |
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.
| z-score | IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) | DAC HYP 150 mg (301) /DAC HYP 150 mg (303) |
|---|---|---|
| Baseline 303 | 0.24958 (-5.5818 to 1.2110) | 0.30019 (-6.1660 to 1.5643) |
| Change to Week 12 | 0.00010 (-3.3934 to 1.6147) | -0.01021 (-4.5948 to 0.9577) |
| Change to Week 24 | -0.00599 (-2.7855 to 1.6913) | -0.00010 (-3.4062 to 1.3673) |
| Change to Week 48 | -0.01026 (-3.7220 to 1.7775) | -0.01897 (-3.5941 to 1.4111) |
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.
| z-score | IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) | DAC HYP 150 mg (301) /DAC HYP 150 mg (303) |
|---|---|---|
| Baseline 301 | 0.14629 (-6.4963 to 1.3731) | 0.14298 (-2.9163 to 1.3865) |
| Change from Baseline 301 to Week 12 for 301 | -0.00133 (-1.8674 to 6.4516) | 0.02593 (-1.7953 to 2.3905) |
| Change from Baseline 301 to Week 24 for 301 | 0.02377 (-1.9966 to 6.2712) | 0.04728 (-4.3661 to 2.1389) |
| Change from Baseline 301 to Week 36 for 301 | 0.04764 (-3.0131 to 6.2565) | 0.05771 (-11.0047 to 2.1389) |
| Change from Baseline 301 to Week 48 for 301 | 0.06491 (-1.6103 to 6.5816) | 0.07793 (-1.3713 to 2.1024) |
| Change from Baseline 301 to Week 60 for 301 | 0.06893 (-4.4756 to 6.6543) | 0.08973 (-1.3564 to 1.9165) |
| Change from Baseline 301 to Week 72 for 301 | 0.08645 (-3.7849 to 6.7127) | 0.08690 (-5.6579 to 2.0135) |
| Change from Baseline 301 to Week 84 for 301 | 0.05704 (-4.3418 to 6.6940) | 0.10283 (-5.4012 to 2.0493) |
| Change from Baseline 301 to Week 96 for 301 | 0.06731 (-4.1506 to 6.8296) | 0.11283 (-5.8373 to 2.2536) |
| Change from Baseline 301 to Week 108 for 301 | 0.08020 (-4.8814 to 6.8182) | 0.09868 (-5.0171 to 2.4199) |
| Change from Baseline 301 to Week 120 for 301 | 0.08406 (-4.4964 to 6.8441) | 0.10367 (-3.4544 to 1.2502) |
| Change from Baseline 301 to Week 132 for 301 | 0.07712 (-4.6292 to 3.6137) | 0.08682 (-3.9359 to 3.2500) |
| Change from Baseline 301 to Week 144 for 301 | 0.09674 (-2.1875 to 4.0089) | 0.12943 (-0.8767 to 1.2626) |
| Change from Baseline 301 to Week 156 for 301 | — | -0.0272 (-0.0272 to -0.0272) |
| Change from Baseline 301 to Baseline 303 | 0.06638 (-1.9364 to 6.8441) | 0.11003 (-5.0171 to 3.3811) |
| Change from Baseline 301 to Week 12 for 303 | 0.06449 (-2.8537 to 6.9351) | 0.09616 (-5.3094 to 3.3600) |
| Change from Baseline 301 to Week 24 for 303 | 0.07140 (-2.7241 to 6.7870) | 0.12955 (-5.0936 to 3.2141) |
| Change from Baseline 301 to Week 48 for 303 | 0.05533 (-2.8215 to 7.0425) | 0.09332 (-5.3475 to 3.3180) |
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.
| score on a scale | 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) |
|---|---|---|---|---|
| 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 | — | — |
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.
| Participants | IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) | DAC HYP 150 mg (301) /DAC HYP 150 mg (303) |
|---|---|---|
| Number of Participants Who Are Free From Disease Activity in the 205MS303 Treatment Period | 9 | 7 |
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.
| score on a scale | IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) | DAC HYP 150 mg (301) /DAC HYP 150 mg (303) |
|---|---|---|
| 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 |
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.
| score on a scale | 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) |
|---|---|---|---|---|
| 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 | — | — |
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.
| score on a scale | 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) |
|---|---|---|---|---|
| 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 | — | — |
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.
| site visits | 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) |
|---|---|---|---|---|
| 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 | — | — |
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.
| site visits | IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) | DAC HYP 150 mg (301) /DAC HYP 150 mg (303) |
|---|---|---|
| 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 |
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.
| Participants | IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) | DAC HYP 150 mg (301) /DAC HYP 150 mg (303) |
|---|---|---|
| Dissatisfied: Baseline 303 | 49 | 31 |
| Dissatisfied: Week 12 | 46 | 41 |
| Dissatisfied: Week 24 | 44 | 27 |
| Dissatisfied: Week 48 | 32 | 35 |
| Dissatisfied: Week 72 | 27 | 22 |
| Dissatisfied: Week 96 | 19 | 9 |
| Dissatisfied: Week 120 | 2 | 1 |
| Satisfied: Baseline 303 | 529 | 561 |
| Satisfied: Week 12 | 540 | 543 |
| Satisfied: Week 24 | 525 | 532 |
| Satisfied: Week 48 | 498 | 472 |
| Satisfied: Week 72 | 476 | 450 |
| Satisfied: Week 96 | 133 | 136 |
| Satisfied: Week 120 | 25 | 23 |
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.
| hours | 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) |
|---|---|---|---|---|
| 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 | — | — |
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.
| Participants | 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) |
|---|---|---|---|---|
| Part Time: Baseline 303 | 11 | 7 | 1 | 1 |
| Part Time: Week 12 | 10 | 8 | — | — |
| Part Time: Week 24 | 12 | 7 | 3 | 2 |
| Part Time: Week 48 | 9 | 7 | 2 | 1 |
| Part Time: Week 72 | 7 | 4 | 2 | 2 |
| Part Time: Week 96 | 6 | 5 | 2 | 2 |
| Part Time: Week 120 | 11 | 6 | — | — |
| Part Time: Week 144 | 4 | 6 | — | — |
| Part Time: Week 168 | 5 | 6 | — | — |
| Part Time: Week 192 | 5 | 3 | — | — |
| Part Time: Week 216 | 1 | 4 | — | — |
| Part Time: Week 240 | 1 | — | — | — |
| Full Time: Baseline 303 | 28 | 30 | 11 | 3 |
| Full Time: Week 12 | 19 | 26 | — | — |
| Full Time: Week 24 | 11 | 21 | 8 | 3 |
| Full Time: Week 48 | 20 | 24 | 6 | 3 |
| Full Time: Week 72 | 13 | 10 | 6 | 3 |
| Full Time: Week 96 | 10 | 16 | 3 | 1 |
| Full Time: Week 120 | 8 | 18 | — | — |
| Full Time: Week 144 | 16 | 16 | — | — |
| Full Time: Week 168 | 10 | 17 | — | — |
| Full Time: Week 192 | 10 | 13 | — | — |
| Full Time: Week 216 | 6 | 10 | — | — |
| Full Time: Week 240 | 0 | 2 | — | — |
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.
| hours | 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) |
|---|---|---|---|---|
| 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 | — | — |
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.
| percent impact | 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) |
|---|---|---|---|---|
| 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 | — | — |
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.
| hours | 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) |
|---|---|---|---|---|
| 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 | — | — |
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.
| Participants | 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) |
|---|---|---|---|---|
| Baseline 303 | 112 | 104 | 58 | 15 |
| Week 12 | 110 | 111 | — | — |
| Week 24 | 125 | 110 | 68 | 12 |
| Week 48 | 113 | 93 | 66 | 19 |
| Week 72 | 111 | 93 | 58 | 15 |
| Week 96 | 94 | 79 | 53 | 16 |
| Week 120 | 93 | 84 | — | — |
| Week 144 | 91 | 87 | — | — |
| Week 168 | 82 | 81 | — | — |
| Week 192 | 71 | 65 | — | — |
| Week 216 | 65 | 65 | — | — |
| Week 240 | 2 | 7 | — | — |
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.
| hours | 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) |
|---|---|---|---|---|
| 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 | — | — |
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.
| percent impact | 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) |
|---|---|---|---|---|
| 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 | — | — |
Clinical Laboratory assessments included tests of hematology, blood chemistry, renal function, and thyroid function. The investigator determined if the results were clinically significant.
| Participants | 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) |
|---|---|---|---|---|
| Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Assessments in the 205MS303 Treatment Period | 0 | 0 | 0 | 0 |
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.
| score on scale | DAC HYP 150 mg |
|---|---|
| First Injection, Post-dose | 1.7 ± 2.46 |
| Fourth Injection, Post-dose | 1.6 ± 2.34 |
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.
| Participants | DAC HYP 150 mg |
|---|---|
| First Injection Post-dose, Erythema: None | 87 |
| First Injection Post-dose, Erythema: Mild | 8 |
| First Injection Post-dose, Erythema: Moderate | 2 |
| First Injection Post-dose, Erythema: Severe | 0 |
| Fourth Injection Pre-dose, Erythema: None | 87 |
| Fourth Injection Pre-dose, Erythema: Mild | 0 |
| Fourth Injection Pre-dose, Erythema: Moderate | 0 |
| Fourth Injection Pre-dose, Erythema: Severe | 0 |
| First Injection Post-dose, Pigmentation: None | 90 |
| First Injection Post-dose, Pigmentation: Hypo | 7 |
| First Injection Post-dose, Pigmentation: Hyper | 0 |
| Fourth Injection Pre-dose, Pigmentation: None | 87 |
| Fourth Injection Pre-dose, Pigmentation: Hypo | 0 |
| Fourth Injection Pre-dose, Pigmentation: Hyper | 0 |
| First Injection Post-dose, Induration: None | 89 |
| First Injection Post-dose, Induration: Mild | 4 |
| First Injection Post-dose, Induration: Moderate | 0 |
| First Injection Post-dose, Induration: Severe | 0 |
| Fourth Injection Pre-dose, Induration: None | 87 |
| Fourth Injection Pre-dose, Induration: Mild | 0 |
| Fourth Injection Pre-dose, Induration: Moderate | 0 |
| Fourth Injection Pre-dose, Induration: Severe | 0 |
| First Injection Post-dose, Tenderness: None | 94 |
| First Injection Post-dose, Tenderness: Mild | 3 |
| First Injection Post-dose, Tenderness: Moderate | 0 |
| First Injection Post-dose, Tenderness: Severe | 0 |
| Fourth Injection Pre-dose, Tenderness: None | 87 |
| Fourth Injection Pre-dose, Tenderness: Mild | 0 |
| Fourth Injection Pre-dose, Tenderness: Moderate | 0 |
| Fourth Injection Pre-dose, Tenderness: Severe | 0 |
| First Injection Post-dose,Temperature: Normal | 97 |
| First Injection Post-dose,Temperature: Warm | 0 |
| First Injection Post-dose,Temperature: Hot | 0 |
| Fourth Injection Pre-dose, Temperature: Normal | 87 |
| Fourth Injection Pre-dose, Temperature: Warm | 0 |
| Fourth Injection Pre-dose, Temperature: Hot | 0 |
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.
| Participants | 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) |
|---|---|---|---|---|
| Number of Participants With Anti-BIIB019 Binding Antibodies (ADAbs) in the 205MS303 Treatment Period | 113 | 48 | 0 | 0 |
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.
| Participants | 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) |
|---|---|---|---|---|
| Number of Participants With Anti-BIIB019 Neutralizing Antibodies (Nabs) in the 205MS303 Treatment Period | 45 | 21 | 0 | 0 |
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.
| score on a scale | IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) | DAC HYP 150 mg (301) /DAC HYP 150 mg (303) |
|---|---|---|
| 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 |
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.
| score on a scale | IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) | DAC HYP 150 mg (301) /DAC HYP 150 mg (303) |
|---|---|---|
| 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 |
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.
| score on a scale | IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) | DAC HYP 150 mg (301) /DAC HYP 150 mg (303) |
|---|---|---|
| Baseline 303 | 54.0 (0 to 60) | 54.0 (3 to 60) |
| Change to Week 12 | 0.0 (-40 to 19) | 0.0 (-23 to 25) |
| Change to Week 24 | 0.0 (-26 to 26) | 0.0 (-27 to 39) |
| Change to Week 48 | 0.0 (-41 to 21) | 0.0 (-21 to 41) |
| Change to Week 120 | -3.0 (-3 to -3) | -1.0 (-2 to 0) |
| Change to Week 144 | -1.0 (-34 to 23) | -1.0 (-31 to 35) |
| Change to Week 168 | 0.0 (-35 to 21) | 0.0 (-30 to 25) |
| Change to Week 192 | 0.0 (-33 to 26) | 0.0 (-42 to 40) |
| Change to Week 216 | 0.0 (-22 to 16) | 0.0 (-23 to 39) |
| Change to Week 240 | 0.0 (-8 to 12) | -2.0 (-9 to 6) |
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.
| score on a scale | IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) | DAC HYP 150 mg (301) /DAC HYP 150 mg (303) |
|---|---|---|
| Baseline 301 | 50.0 (0 to 60) | 51.0 (9 to 60) |
| Change from Baseline 301 to Week 12 for 301 | 0.0 (-58 to 40) | 1.0 (-59 to 25) |
| Change from Baseline 301 to Week 24 for 301 | 0.5 (-26 to 31) | 1.0 (-32 to 22) |
| Change from Baseline 301 to Week 36 for 301 | 1.0 (-29 to 30) | 1.0 (-37 to 28) |
| Change from Baseline 301 to Week 48 for 301 | 1.0 (-25 to 42) | 1.0 (-38 to 30) |
| Change from Baseline 301 to Week 60 for 301 | 1.0 (-46 to 40) | 2.0 (-34 to 37) |
| Change from Baseline 301 to Week 72 for 301 | 2.0 (-20 to 40) | 2.0 (-21 to 41) |
| Change from Baseline 301 to Week 84 for 301 | 2.0 (-31 to 39) | 2.0 (-41 to 29) |
| Change from Baseline 301 to Week 96 for 301 | 2.0 (-28 to 41) | 2.0 (-25 to 38) |
| Change from Baseline 301 to Week 108 for 301 | 1.0 (-27 to 43) | 2.0 (-25 to 40) |
| Change from Baseline 301 to Week 120 for 301 | 2.0 (-27 to 35) | 2.0 (-31 to 41) |
| Change from Baseline 301 to Week 132 for 301 | 2.0 (-30 to 35) | 2.0 (-19 to 38) |
| Change from Baseline 301 to Week 144 for 301 | 2.0 (-25 to 31) | 3.0 (-21 to 31) |
| Change from Baseline 301 to Week 156 for 301 | — | -4.0 (-4 to -4) |
| Change from Baseline 301 to Baseline 303 | 2.0 (-34 to 44) | 2.0 (-41 to 45) |
| Change from Baseline 301 to Week 12 for 303 | 2.0 (-38 to 43) | 2.0 (-26 to 41) |
| Change from Baseline 301 to Week 24 for 303 | 2.0 (-31 to 40) | 2.0 (-27 to 43) |
| Change from Baseline 301 to Week 48 for 303 | 2.0 (-47 to 44) | 2.0 (-24 to 41) |
| Change from Baseline 301 to Week 120 for 303 | 15.0 (15 to 15) | 3.0 (1 to 5) |
| Change from Baseline 301 to Week 144 for 303 | 1.0 (-32 to 37) | 2.0 (-24 to 38) |
| Change from Baseline 301 to Week 168 for 303 | 2.0 (-36 to 42) | 2.0 (-29 to 42) |
| Change from Baseline 301 to Week 192 for 303 | 2.0 (-40 to 42) | 2.0 (-21 to 42) |
| Change from Baseline 301 to Week 216 for 303 | 2.0 (-27 to 40) | 2.0 (-30 to 41) |
| Change from Baseline 301 to Week 240 for 303 | 1.5 (-10 to 26) | 0.5 (-11 to 23) |
Collected over First dose of study drug in study 205MS303 to within 180 days of last dose (up to approximately 5.5 years). Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| IFN β-1a 30 µg (301)/DAC HYP 150 mg (303) | 2/597 (0.3%) | 157/597 (26.3%) | 463/597 (77.6%) |
| DAC HYP 150 mg (301) /DAC HYP 150 mg (303) | 4/606 (0.7%) | 190/606 (31.4%) | 476/606 (78.5%) |
| DAC HYP 150 mg (302) /DAC HYP 150 mg (303) | 0/70 (0%) | 15/70 (21.4%) | 42/70 (60%) |
| DAC HYP 150 mg (203) /DAC HYP 150 mg (303) | 0/227 (0%) | 38/227 (16.7%) | 116/227 (51.1%) |
| Event | 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) |
|---|---|---|---|---|
| Multiple sclerosis relapseNervous system disorders | 61/597 | 65/606 | 3/70 | 17/227 |
| Urinary tract infectionInfections and infestations | 6/597 | 3/606 | 2/70 | 0/227 |
| LymphadenopathyBlood and lymphatic system disorders | 4/597 | 10/606 | 1/70 | 2/227 |
| PancytopeniaBlood and lymphatic system disorders | 0/597 | 2/606 | 1/70 | 0/227 |
| Anorectal disorderGastrointestinal disorders | 0/597 | 0/606 | 1/70 | 0/227 |
| Gastrointestinal disorderGastrointestinal disorders | 0/597 | 0/606 | 1/70 | 0/227 |
| InflammationGeneral disorders | 0/597 | 1/606 | 1/70 | 0/227 |
| Drug hypersensitivityImmune system disorders | 0/597 | 0/606 | 1/70 | 0/227 |
| Lyme diseaseInfections and infestations | 0/597 | 0/606 | 1/70 | 0/227 |
| FallInjury, poisoning and procedural complications | 1/597 | 7/606 | 1/70 | 2/227 |
| Event | 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) |
|---|---|---|---|---|
| Multiple sclerosis relapseNervous system disorders | 179/597 | 169/606 | 15/70 | 36/227 |
| NasopharyngitisInfections and infestations | 121/597 | 125/606 | 6/70 | 18/227 |
| Upper respiratory tract infectionInfections and infestations | 116/597 | 114/606 | 13/70 | 26/227 |
| Urinary tract infectionInfections and infestations | 77/597 | 58/606 | 4/70 | 10/227 |
| LymphadenopathyBlood and lymphatic system disorders | 47/597 | 71/606 | 3/70 | 7/227 |
| Back painMusculoskeletal and connective tissue disorders | 65/597 | 51/606 | 3/70 | 10/227 |
| RashSkin and subcutaneous tissue disorders | 39/597 | 64/606 | 0/70 | 9/227 |
| HeadacheNervous system disorders | 57/597 | 56/606 | 7/70 | 16/227 |
| PharyngitisInfections and infestations | 53/597 | 47/606 | 1/70 | 9/227 |
| Alanine aminotransferase increasedInvestigations | 45/597 | 48/606 | 3/70 | 16/227 |
Intent-to-treat (ITT) population included all participants who completed Study 301, 302 or 203 and received at least 1 dose of DAC HYP during Study 303.
| Age, Customized(Participants) | 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 |
|---|---|---|---|---|---|
| Adults (18-64 years) | 597 | 606 | 70 | 227 | 1500 |
| Sex: Female, Male(Participants) | 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 |
|---|---|---|---|---|---|
| Female | 394 | 400 | 42 | 130 | 966 |
| Male | 203 | 206 | 28 | 97 | 534 |
| Race/Ethnicity, Customized(Participants) | 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 |
|---|---|---|---|---|---|
| White | 546 | 559 | 2 | 223 | 1330 |
| Black or African American | 5 | 5 | 3 | 0 | 13 |
| Asian | 11 | 10 | 0 | 4 | 25 |
| Other | 18 | 14 | 1 | 0 | 33 |
| Not Reported | 17 | 18 | 64 | 0 | 99 |
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