Efficacy and Safety of Daclizumab in Participants With RRMS Switching From Natalizumab

Study Overview
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Brief Summary
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The primary objective of the study is to evaluate the effects of treatment with daclizumab on the proportion of participants relapse-free at 6 months in Relapsing-Remitting Multiple Sclerosis (RRMS) participants, who switched from treatment with natalizumab to daclizumab due to safety concerns. The secondary objectives of this study in this study population are to evaluate the effects of daclizumab on the following: 1) Multiple Sclerosis (MS) relapse activity including the annualized relapse rate (ARR) and the proportion of participants experiencing relapses requiring hospitalization and/or steroid treatment; 2) MS-related outcomes measured using magnetic resonance imaging (MRI); 3) Safety and tolerability in participants previously treated with natalizumab.

Official Title
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A Phase 3b, 12-month, Open-label, Multicenter Study to Evaluate the Efficacy and Safety of BIIB019, Daclizumab, in Subjects With Relapsing-Remitting Multiple Sclerosis (RRMS) Switching From Natalizumab (SUSTAIN)

Conditions
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Relapsing-Remitting Multiple Sclerosis (RRMS)

Intervention / Treatment
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* Drug: Daclizumab


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria Must have documented diagnosis of RRMS (McDonald 2010 Criteria) at screening [Polman 2011]. Must have been treated with natalizumab for at least the 12 months prior to screening and have not missed 2 or more consecutive scheduled doses. Must be naïve to daclizumab and other forms of daclizumab such as Zenapax® prior to enrollment. Must have a confirmed Expanded Disability Status Scale (EDSS) score of 0 to 5.5, inclusive, at screening. Female participants of childbearing potential must practice effective contraception from Day -1 and be willing and able to continue contraception for duration of the study. Key Exclusion Criteria Current participation in another investigational study. Diagnosis of primary progressive, secondary progressive, or progressive relapsing MS (as defined by Lublin and Reingold) [Lublin 2014]. Females breastfeeding, pregnant, or planning to become pregnant; or women who have a positive pregnancy test result during screening. History of drug or alcohol abuse (as defined by the Investigator) within 1 year prior to screening. History of severe hypersensitivity (e.g., anaphylaxis or anaphylactoid reactions) to the active ingredient or any of the excipients. History of severe opportunistic infections (including progressive multifocal leukoencephalopathy (PML)) or any clinically significant, cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic (other than MS), dermatologic, psychiatric, and renal, or other major disease, as determined by the Investigator. Discontinued natalizumab due to suspicion of PML. Known active malignancies (participants with cutaneous basal cell carcinoma that has been completely excised prior to study entry remain eligible). The participant is using another MS therapy concomitantly. Known history of human immunodeficiency virus (HIV). Positive test result for Hepatitis C virus (test for hepatitis C virus antibody [HCV Ab]) or hepatitis B virus (test for hepatitis B surface antigen [HBsAg] and/or hepatitis B core antibody [HBcAb]). The participant has been treated with immunosuppressive or immunomodulating treatments including mitoxantrone, azathioprine, methotrexate, cyclophosphamide, or mycophenolate mofetil. 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Daclizumab<br> | Drug: Daclizumab<br>* High yield formulation<br>* Other names: Zinbryta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Relapse-free at Month 6 | Relapses were defined as new or recurrent neurological symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings upon examination by the Examining Neurologist. The Kaplan-Meier estimate of the percentage of participants relapse-free at Month 6 is reported. | Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Relapse-free at Month 12 | Relapses were defined as new or recurrent neurological symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings upon examination by the Examining Neurologist. | Month 12 | 
| Percentage of Participants Experiencing Relapse Requiring Hospitalization and/or Steroid Treatment at Month 12 | Relapses were defined as new or recurrent neurological symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings upon examination by the Examining Neurologist. | Month 12 | 
| Annualized Relapse Rate (ARR) at Month 12 | Relapses were defined as new or recurrent neurological symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings upon examination by the Examining Neurologist. The 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 Month 12, and the ratio then multiplied by 365. | Month 12 | 
| Number of Participants With New Gadolinium-Enhanced (Gd+) and T1 Hypointense Lesions at Months 6 and 12 | New Gadolinium-Enhanced (Gd+) and T1 Hypointense Lesions were assessed using magnetic resonance imaging (MRI). | Months 6 and 12 | 
| Number of Participants With New and Newly Enlarged T2 Hypointense Lesions at Months 6 and 12 | New and newly enlarged T2 Hypointense Lesions were measured by MRI. | Months 6 and 12 | 
| Permanent Discontinuation Rate of Daclizumab at Month 12 | Permanent Discontinuation Rate was calculated as the ratio of number of participants who had permanently discontinued daclizumab prior to Month 12 over the total number of participants who received at least 1 dose of daclizumab in the study. | Month 12 | 
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE is any untoward medical occurrence that at any dose results in death or in the view of the Investigator, places the participant at immediate risk of death or requires inpatient hospitalization or prolongation of existing hospitalization or results in persistent or significant disability or results in a birth defect. | First dose of study drug to within 30 days of last dose (up to 11 months) | 
| Number of Participants With Clinically Relevant Shifts in Laboratory Assessments | Clinical Laboratory assessments were tests of Chemistry and Hematology. The investigator determined if any of the laboratory results were clinically relevant shifts from Baseline. | First dose of study drug to within 30 days of last dose (up to 11 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Sclerosis, Daclizumab, Tysabri-Switch