Safety and Efficacy Study of Daclizumab High Yield Process (DAC HYP) to Treat Relapsing-Remitting Multiple Sclerosis

Study Overview
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Brief Summary
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The primary objective of this study is to determine whether DAC HYP, when compared to placebo, is effective in reducing the rate of relapses between baseline and Week 52. The secondary objectives are to determine whether DAC HYP is effective in reducing the number of new gadolinium (Gd)-enhancing lesions, reducing the number of new or newly-enlarging T2 hyperintense lesions, reducing the proportion of participants with relapses, and improving quality of life.

Official Title
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Multicenter, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Determine the Safety and Efficacy of Daclizumab HYP (DAC HYP) as a Monotherapy Treatment in Subjects With Relapsing-Remitting Multiple Sclerosis

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: Multiple Sclerosis (MS) subjects who have a confirmed diagnosis of relapsing-remitting MS according to McDonald criteria #1-4 and a baseline Expanded Disability Status Scale (EDSS) between 0.0 and 5.0, inclusive, who meet either of the following 2 criteria: Have experienced at least 1 relapse within the 12 months prior to randomization, with a cranial magnetic resonance imaging (MRI) demonstrating lesion(s) consistent with MS , OR Show evidence of gadolinium-enhancing lesions of the brain on an MRI performed within the 6 weeks prior to randomization. Key Exclusion Criteria: Diagnosis of primary progressive, secondary progressive, or progressive relapsing MS History of malignancy History of severe allergic or anaphylactic reactions or known drug hypersensitivity History of abnormal laboratory results based on investigator judgment History of human immunodeficiency virus (HIV) or other immunodeficient conditions History of drug or alcohol abuse within the 2 years prior to randomization An MS relapse that has occurred within the 50 days prior to randomization AND/OR the subject has not stabilized from a previous relapse prior to randomization Positive screening for active infection with Hepatitis B virus or Hepatitis C virus Varicella or herpes zoster virus infection or any severe viral infection within 6 weeks before Screening Exposure to varicella zoster virus within 21 days before Screening. Abnormal blood tests at Screening: Hemoglobin ≤9.0 g/dL, Platelets ≤100 × 10^9/L, Lymphocytes ≤1.0 × 10^9/L, Neutrophils ≤1.5 × 10^9/L, alanine aminotransferase/serum glutamate pyruvate transaminase (ALT/SGPT), aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT), or gamma-glutamyl-transferase >2 times the upper limit of normal (ULN) and serum creatinine >ULN. 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 |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants will receive 3 subcutaneous (SC) injections of placebo every 4 weeks for up to 52 weeks. | Drug: Placebo<br>* Placebo SC injection<br>|
| Experimental: 150 mg DAC HYP<br>Participants will receive 3 SC injections every 4 weeks for up to 52 weeks. | Biological: BIIB019 (Daclizumab High Yield Process)<br>* SC injection<br>* Other names: Daclizumab HYP;|
| Experimental: 300 mg DAC HYP<br>Participants will receive 3 SC injections every 4 weeks for up to 52 weeks. | Biological: BIIB019 (Daclizumab High Yield Process)<br>* SC injection<br>* Other names: Daclizumab HYP;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Annualized Relapse Rate Between Baseline and Week 52 | 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 examining neurologist. The annualized relapse rate was calculated as the total number of relapses that occurred during the study divided by the total number of subject-years followed in the study. | Baseline through Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Mean Number of New Gadolinium (Gd)-Enhancing Lesions Between Week 8 and Week 24 | Gd-enhancing lesions are detected when Gd leaks into a perivascular space due to local breakdown of the blood-brain barrier, indicating the presence of active inflammation. For participants with missing data the last valid nonbaseline measurement was carried forward if the participant was missing only 1 or 2 consecutive postbaseline scans. Otherwise the mean based on treatment group and visit was used as the imputed value. Estimated from a negative binomial model adjusted for the baseline number of Gd-enhancing lesions. | Week 8 through Week 24 | 
| Adjusted Mean Number of New or Newly-enlarging T2 Hyperintense Lesions at Week 52 | Lesions detected on T2-weighted sequences represent a range of histopathology related to MS, including edema, inflammation, demyelination, gliosis, and axon loss. | Week 52 | 
| Proportion of Participants Who Relapsed at Week 52 | Estimated cumulative proportion of participants relapsed at Week 52, based on the Kaplan-Meier product limit method. Only relapses confirmed by the Independent Neurology Evaluation Committee were included in the analysis. | Week 52 | 
| Mean Change From Baseline in Multiple Sclerosis Impact Scale (MSIS)-29 Physical Impact Score at Week 52 | The 29-item Multiple Sclerosis Impact Scale (MSIS-29) is a disease specific patient-reported outcome measure that has been developed and validated to examine the physical and psychological impact of MS from a patient's perspective; it measures 20 physical items and 9 psychological items. Responses use a 5 point Likert scale range from 1 to 5. All questions are to be answered. The total score is the sum of points for all 29 questions, with a minimum score of 29, and a maximum score of 145. A lower total score indicates less physically-related impact while a higher total score indicates greater physically-related impact on a subject's functioning. | Baseline and Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MS, multiple sclerosis