Safety and Efficacy Extension Study of Daclizumab High Yield Process (DAC HYP) (BIIB019) in Participants Who Have Completed Study 205MS202 (NCT00870740) to Treat Relapsing Remitting Multiple Sclerosis

Study Overview
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Brief Summary
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Primary Objective is to assess the safety of extended treatment with Daclizumab High Yield Process (DAC HYP, BIIB019) monotherapy in participants with relapsing remitting multiple sclerosis (RRMS). Secondary Objective is to assess the long-term immunogenicity of DAC HYP and to assess the durability of response to DAC HYP in preventing multiple sclerosis (MS) relapse, slowing disability progression, and reducing new MS lesion formation in this study population.

Detailed Description
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This study will provide participants who complete Study 205MS202 (NCT00870740) with the option to receive continued open-label Daclizumab High Yield Process (DAC HYP) monotherapy and to evaluate the long-term safety, efficacy, and immunogenicity of DAC HYP monotherapy in participants with relapsing remitting multiple sclerosis (RRMS). Approximately 60 to 100 participants will be enrolled into an optional open-label, 16-week autoinjector substudy at a selected subset of sites which will run concurrently during the main study, and will evaluate the systemic exposure and local tolerability of subcutaneous administration of DAC HYP by autoinjector. The 2013-2014 trivalent influenza vaccine will be offered to all eligible participants as an optional substudy to assess the effect of DAC-HYP treatment on the immune response to vaccination,

Official Title
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A Multicenter, Open-label, Extension Study to Evaluate the Long Term Safety and Efficacy of Daclizumab High Yield Process (DAC HYP) Monotherapy in Subjects With Multiple Sclerosis Who Have Completed Treatment in Study 205MS202 (SELECTION)

Conditions
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Relapsing-Remitting Multiple Sclerosis

Intervention / Treatment
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* Biological: BIIB019 (Daclizumab)
* Biological: trivalent seasonal influenza vaccine


Participation Criteria
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Eligibility Criteria
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Main Study Eligibility: Key Inclusion Criteria: Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations. Subjects who have completed 52 weeks in Study 205MS202 (NCT00870740) and were compliant with the 205MS202 protocol in the opinion of the Investigator. Women of childbearing potential must practice effective contraception during the study and be willing and able to continue contraception for 4 months after their last dose of study treatment. Key Exclusion Criteria: Subjects with any significant change in their medical status from the previous study that would prelude administration of Daclizumab High Yield Process (DAC HYP) as determined by the Investigator including laboratory tests or a current clinically significant condition that, in the opinion of the Investigator, would have excluded the subject's participation in the 205MS201 (NCT00390221) or 205MS202 (NCT00870740) studies. The Investigator must re-review the subject's medical fitness for participation and must consider any diseases that would preclude treatment. Any subject who has permanently discontinued study treatment in Study 205MS202 (NCT00870740) due to an adverse event. Current enrollment in any investigational drug study other than Study 205MS202 (NCT00870740). Ongoing treatment with any approved or experimental disease-modifying treatment for multiple sclerosis. For subjects currently taking valproic acid, carbamazepine, lamotrigine, or phenytoin: Subjects treated with any of these agents for fewer than 6 months prior to study entry are excluded from study participation unless they discontinue the agent(s) prior to study entry. Subjects treated with 2 or more of these agents for more than 6 months prior to study entry are excluded from study participation unless they reduce to ≤1 agent prior to study entry. Subjects who have had dose escalations of one of these agents within the 6 months prior to study entry are excluded from study participation unless they revert to a previous dose that had been used for at least 6 months prior to study entry or unless they discontinue the agent prior to study entry Subjects who are currently receiving treatment with isoniazid, propylthiouracil, or nimesulide at the time of study entry and are not able to discontinue the agent or change to an alternative medication allowed by the protocol. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: BIIB019<br>Participants received BIIB019, 150 mg subcutaneous injection every 4 weeks up to Week 288. | Biological: BIIB019 (Daclizumab)<br>* Administered as specified in the treatment arm.<br>* Other names: DAC HYP;Biological: trivalent seasonal influenza vaccine<br>* All participants who participate in the 2013-2014 influenza vaccine substudy will receive the vaccine at the study site<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuation Due to AEs, Withdrawals Due to AEs | An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. 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. | Baseline up to 24 weeks after last dose of treatment (Up to 300 weeks) | 
| Area Under the Concentration-Time Curve Over the Dosing Interval (AUC0-t) After Dose 4 for Daclizumab |  | Day 90 (Week 12) at predose and 8, 24, 72 and 120 hours post-dose and 7, 10, 14, 21 and 28 days post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With New or Newly Enlarging T2 Hyperintense Lesions Compared to Baseline | New or newly enlarging T2 hyperintense lesions evaluated by magnetic resonance imaging (MRI) and analyzed by a central reader. | From Baseline through 288 weeks | 
| Annual Change in Volume of New or Newly Enlarging T2 Hyperintense Lesions Compared to Baseline | New or newly enlarging T2 hyperintense lesions evaluated by MRI and analyzed by a central reader. | From Baseline through 288 weeks | 
| Number of Participants With Total Number of New Gadolinium-enhancing Lesions | New Gadolinium-enhancing lesions was evaluated by MRI and analyzed by a central reader. | From Baseline through 288 weeks | 
| Annual Change in Number of T1 Hypointense Lesions |  | From Baseline through 288 weeks | 
| Annual Change in Volume of New Gadolinium-Enhancing Lesions |  | From Baseline through 288 weeks | 
| Annual Change in Volume of T1 Hypointense Lesions | Volume of T1 hypointense lesions was evaluated by MRI and analyzed by a central reader. | From Baseline through 288 weeks | 
| Percent Change in Total Brain Volume | To assess brain atrophy, total brain volume was be measured by MRI and analyzed by a central reader. | From Baseline through 288 weeks | 
| Number of Participants With Antibodies to DAC HYP |  | Up to Week 288 | 
| Annualized Relapse Rate (ARR) | 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 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. Adjusted ARR was reported. | Week 288 | 
| Number of Participants With Sustained Disability Progression for 12 Weeks | Sustained disability progression defined by at least a 1.0-point increase on the Expanded Disability Status Scale (EDSS) from a baseline EDSS ≥1.0 that is sustained for 12 weeks, or at least a 1.5-point increase on the EDSS from a baseline EDSS <1.0 that is sustained for 12 weeks. The EDSS measures the disability status of people with multiple sclerosis on a scale that ranges from 0 to 10, with higher scores indicating more disability. | Week 48 up to Week 288 | 
| Number of Participants With Sustained Disability Progression for 24 Weeks | Sustained disability progression defined by at least a 1.0-point increase on the Expanded Disability Status Scale (EDSS) from a baseline EDSS ≥1.0 that is sustained for 24 weeks, or at least a 1.5-point increase on the EDSS from a baseline EDSS <1.0 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, with higher scores indicating more disability. | Week 48 up to Week 288 | 
| Observed Maximum Concentration (Cmax) After Dose 4 for Daclizumab |  | Day 90 (Week 12) at predose and 8, 24, 72 and 120 hours post-dose and 7, 10, 14, 21 and 28 days post-dose | 
| Time to Reach Maximum Concentration (Tmax) for Daclizumab After Dose 4 |  | Day 90 (Week 12) at predose and 8, 24, 72 and 120 hours post-dose and 7, 10, 14, 21 and 28 days post-dose | 
| Observed Minimum Concentration (Cmin) for Daclizumab After Dose 4 |  | Day 90 (Week 12) at predose and 8, 24, 72 and 120 hours post-dose and 7, 10, 14, 21 and 28 days post-dose | 
| Participant-Reported Pain Visual Analog Scale (VAS) Score | 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. | First injection (Day 1) and fourth injection (Day 90) 0 hour, 30 minutes, 60 minutes and 8 hours post-dose | 
| Summary of Injection Site Assessment Performed by Clinician | Injection site assessment was performed by clinician and are defined as erythema (redness) rated on a 4 point scale ranging from 0-3, where 0=none, 1=mild, 2=moderate and 3=severe; pigmentation changes (skin discoloration other than redness) rated on a 3 point scale from 0-2, where 0=none, 1=hypopigmentation and 2=hyperpigmentation; induration (swelling) rated on a 4 point scale ranging from 0-3, where 0=none, 1=mild, 2=moderate and 3=severe; tenderness to pressure rated on a 4 point scale ranging from 0-3, where 0=none, 1=mild, 2=moderate and 3=severe; and local temperature changes of injection sites rated on a 3 point scale where 0=normal, 1=warm and 1=hot. Only those score categories for which there was at least 1 participant are reported. Here, Injection=Inj, post-dose=PD | First injection (Day 1) and fourth injection (Day 90) 30 minutes; 8, 24, 72, and 120 hours; and 7, 10, and 14 days post-dose | 

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