Safety and Efficacy Extension Study of Daclizumab High Yield Process (DAC HYP) in Participants With Multiple Sclerosis Who Have Completed Study 205MS201 (NCT00390221) to Treat Relapsing-Remitting Multiple Sclerosis

Study Overview
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Brief Summary
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The primary objective of the study was to assess the safety and immunogenicity of extended treatment with DAC HYP. This evaluation included the following major components: An assessment of safety and immunogenicity of extended treatment with DAC HYP when administered to MS subjects who had completed 52 weeks of active therapy with DAC HYP in Study 201. An assessment of safety and immunogenicity during a 6-month washout period from DAC HYP. An assessment of safety and immunogenicity during reinitiation of therapy with DAC HYP after a 6-month washout period. An assessment of safety and immunogenicity of DAC HYP when administered to MS subjects who previously received placebo during Study 201. The secondary objective is to assess the durability of the effect of DAC HYP on multiple sclerosis (MS) disease activity as measured by brain magnetic resonance imaging (MRI) scans and clinical MS relapses.

Detailed Description
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This study, an extension to Study 205MS201 (NCT00390221), will evaluate the long-term safety, efficacy, and immunogenicity of DAC HYP in MS. In Study 205MS201, study treatment was scheduled to stop at the Week 52 visit. This extension study will provide for the initiation of active therapy with DAC HYP among participants who received placebo during Weeks 0 through 52 in 205MS201. In addition, participants who received active therapy with DAC HYP during Weeks 0 through 52 in Study 205MS201 will continue DAC HYP therapy or resume DAC HYP therapy after a 6-month washout period in this study.

Official Title
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A Double-Blind, Multicenter, Extension Study to Evaluate the Safety and Efficacy of DAC HYP in Subjects With Multiple Sclerosis Who Have Completed Treatment in Study 205MS201 (SELECT)

Conditions
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Relapsing-Remitting Multiple Sclerosis

Intervention / Treatment
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* Biological: BIIB019 (Daclizumab High Yield Process)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Participated in Study 205MS201 (NCT00390221) for at least 52 weeks and was compliant with the 205MS201 protocol in the opinion of the Investigator. Key Exclusion Criteria: Subjects with any significant change in their medical status from 205MS201 that would preclude administration of DAC HYP, as determined by the Investigator Any subject who has permanently discontinued study treatment in Study 205MS201 except subjects who were unblinded during evaluation of an adverse event (AE) and found to be on placebo Planned ongoing treatment with any approved or experimental treatment for MS except for the protocol-allowed use of concomitant interferon-beta NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: DAC HYP 150 mg<br>Participants who received placebo in 205MS201 receive DAC HYP 150 mg subcutaneous (SC) injection every 4 weeks for a total of 13 doses. | Biological: BIIB019 (Daclizumab High Yield Process)<br>* SC injection<br>* Other names: DAC HYP;|
| Experimental: Group 1: DAC HYP 300 mg<br>Participants who received placebo in 205MS201 receive DAC HYP 300 mg SC injection every 4 weeks for a total of 13 doses. | Biological: BIIB019 (Daclizumab High Yield Process)<br>* SC injection<br>* Other names: DAC HYP;|
| Experimental: Group 2: Washout then DAC HYP 150 mg<br>Participants who received DAC HYP 150 mg SC injection in 205MS201 undergo a washout period (placebo SC every 4 weeks for a total of 5 doses) and then receive DAC HYP 150 mg SC every 4 weeks for a total of 8 doses. | Biological: BIIB019 (Daclizumab High Yield Process)<br>* SC injection<br>* Other names: DAC HYP;Drug: Placebo<br>* Placebo SC injection<br>|
| Experimental: Group 2: DAC HYP 150 mg<br>Participants who received DAC HYP 150 mg SC injection in 205MS201 receive DAC HYP 150 mg SC every 4 weeks for a total of 13 doses. | Biological: BIIB019 (Daclizumab High Yield Process)<br>* SC injection<br>* Other names: DAC HYP;|
| Experimental: Group 3: Washout then DAC HYP 300 mg<br>Participants who received DAC HYP 300 mg SC in 205MS201 undergo a washout period (placebo SC every 4 weeks for a total of 5 doses) and then receive DAC HYP 300 mg SC every 4 weeks for a total of 8 doses. | Biological: BIIB019 (Daclizumab High Yield Process)<br>* SC injection<br>* Other names: DAC HYP;Drug: Placebo<br>* Placebo SC injection<br>|
| Experimental: Group 3: DAC HYP 300 mg<br>Participants who received DAC HYP 300 mg SC in 205MS201 receive DAC HYP 300 mg SC every 4 weeks for a total of 13 doses. | Biological: BIIB019 (Daclizumab High Yield Process)<br>* SC injection<br>* Other names: DAC HYP;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-emergent Adverse Events (AEs) | Treatment-emergent AE: any untoward medical occurrence after the first dose of study treatment that did not necessarily have a causal relationship with this treatment. Serious AE (SAE): any untoward medical occurrence that at any dose: resulted in death; in the view of the Investigator, placed the subject at immediate risk of death (a life-threatening event); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect. An SAE could also have been a medically significant event that, in the opinion of the Investigator, jeopardized the subject or required intervention to prevent one of the other outcomes listed in the definition above. | Up to 72 weeks | 
| Number of Participants With Abnormalities in Vital Signs | For participants who took DAC HYP during 205MS201 (NCT00390221) the baseline is defined as the baseline from 205MS201, and for participants who took placebo during 205MS201 the baseline is defined as the baseline from 205MS202 (NCT00870740). All post-baseline data are taken after first dose in 205MS202 only. SBP=systolic blood pressure; DBP=diastolic blood pressure; bpm=beats per minute; ↑ BL=increase from baseline; ↓ BL=decrease from baseline. | Up to Week 72 | 
| Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities | Hematology parameters evaluated include: white blood cells, lymphocytes, neutrophils, red blood cells (RBC), hemoglobin, and platelets. | Up to 72 Weeks | 
| Number of Participants With Abnormalities in Blood Chemistry Laboratory Data | For each abnormality a subject can be counted once. If a subject has more than one occurrence of the same abnormality the highest toxicity grade is counted. ALT=alanine aminotransferase; AST=aspartate aminotransferase; ALP=alkaline phosphatase; GGT=gamma-glutamyl transferase; TSH=thyroid stimulating hormone, ULN=upper limit of normal. | Up to 72 Weeks | 
| Number of Participants With Development of Anti-DAC Antibodies (ADAb) and Neutralizing Antibodies (NAb) Post-baseline | Number of participants positive and negative for ADAb and NAb, based on all post-baseline immunogenicity assessments during treatment period and follow-up. Participants are stratified differently in this Outcome Measure as per the pre-specified statistical analysis plan. | Up to 72 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Annualized Relapse Rate | 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 Independent Neurology Evaluation Committee (INEC). Relapse rate is calculated as: (Total number of relapses that occurred during the 205MS202 [NCT00870740] treatment phase divided by the total number of days followed in the treatment phase for 205MS202), multiplied by 365 days. Participants who received an alternative multiple sclerosis (MS) medication during 205MS201 (NCT00390221; Year 1) are not included in the summary of relapses and relapse rate for this study (Year 2). Participants are stratified differently in this Outcome Measure as per the pre-specified statistical analysis plan. | Up to 72 weeks | 
| Estimated Proportion of Participants With a Relapse | Relapses are defined as new or recurrent neurologic symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings upon examination by the INEC. Estimated using Kaplan-Meier analysis where time to first relapse is calculated from date of first dose in the study to date of first confirmed relapse. Participants who received an alternative MS medication before the first relapse were censored at the time of taking the alternative MS medication. | Up to 72 weeks | 
| Mean Number of New Gadolinium-enhancing Lesions | Evaluated by magnetic resonance imaging (MRI) by a central reader. Number of new Gd lesions since the previous scan (the previous scan for Week 20 was Week 52 of study 205MS201 [NCT00390221]). The number of Gd lesions may be imputed using last observation carried forward or using the mean value across all subjects within the treatment group. Baseline visits are not imputed. Participants are stratified differently in this Outcome Measure as per the pre-specified statistical analysis plan. | Week 20, Week 52 | 
| Mean Number of New or Newly-enlarging T2 Hyperintense Lesions | Lesions detected on T2-weighted sequences represent a range of histopathology related to MS, including edema, inflammation, demyelination, gliosis, and axon loss. Evaluated by MRI by a central reader. New or newly enlarging T2 lesions since baseline of study 205MS202 (NCT00870740). For post-baseline visits, the number of T2 lesions may be imputed using the mean value across all participants within the treatment group, if the participant has non-missing baseline data. Baseline visits are not imputed. Participants are stratified differently in this Outcome Measure as per the pre-specified statistical analysis plan. | Baseline, Week 20, Week 52 | 
| Mean Volume of New T1 Hypointense Lesions | T1-weighted scans detect areas of hypointensity that represent a greater degree of tissue destruction and axon loss than T2 hyperintense lesions and are more highly correlated with clinical disability measures and neurological deficit. Evaluated by MRI by a central reader. Baseline is volume of new T1 hypointense lesions since baseline in study 205MS201 (NCT00390221). Scans at Week 20 and Week 52 in 205MS202 are relative to baseline in 205MS202 (NCT00870740). For post-baseline visits, the total volume of T1 lesions may be imputed using the mean value across all subjects within the treatment group. Baseline visits are not imputed. | Baseline, Week 20, Week 52 | 
| Mean Percentage Change From Baseline in Total Lesion Volume of T2 Hyperintense Lesions | Lesions detected on T2-weighted sequences represent a range of histopathology related to MS, including edema, inflammation, demyelination, gliosis, and axon loss. Evaluated by MRI by a central reader. Baseline values = baseline for study 205MS202 (NCT00870740). For post-baseline visits, the total volume of T2 lesions may be imputed using the mean value across all subjects within the treatment group. Baseline visits are not imputed. | Baseline, Week 52 | 
| Mean Percentage Change From Baseline in Total Volume of Non-gadolinium (Gd)-Enhancing T1 Hypointense Lesions | T1-weighted scans detect areas of hypointensity that represent a greater degree of tissue destruction and axon loss than T2 hyperintense lesions and are more highly correlated with clinical disability measures and neurological deficit. Evaluated by MRI by a central reader. Baseline values = baseline for study 205MS202 (NCT00870740). For post-baseline visits, the total volume of T1 lesions may be imputed using the mean value across all participants within the treatment group. Baseline visits are not imputed. | Baseline, Week 52 | 
| Rate of Percentage Change From Baseline in Mean Total Brain Volume | Total brain volume was measured by MRI and analyzed by a central reader. Rate of percentage change from baseline calculated using an analysis of covariance adjusting for baseline normalized brain volume. Baseline values = baseline for study 205MS202 (NCT00870740). Missing values post-baseline were imputed using the average value across subjects in the treatment group. | Baseline, Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MS, Multiple Sclerosis