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 (SELECTION)

July 19, 2016 updated by: Biogen

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)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

517

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Czech Republic
      • Brno, Czech Republic
        • Research Site
      • Hraddec Kralove, Czech Republic
        • Research Site
      • Olomouc, Czech Republic
        • Research Site
      • Plzen, Czech Republic
        • Research Site
      • Prague, Czech Republic
        • Research Site
      • Teplice, Czech Republic
        • Research Site
  • Germany
      • Bayreuth, Germany
        • Research Site
      • Erlangen, Germany
        • Research Site
      • Marburg, Germany
        • Research Site
      • Osnabruck, Germany
        • Research Site
      • Regensburg, Germany
        • Research Site
      • Rostock, Germany
        • Research Site
  • Hungary
      • Budapest, Hungary
        • Research Site
      • Debrecen, Hungary
        • Research Site
      • Esztergom, Hungary
        • Research Site
      • Gyor, Hungary
        • Research Site
      • Kecskemet, Hungary
        • Research Site
      • Miskolc, Hungary
        • Research Site
      • Nyiregyhaza, Hungary
        • Research Site
      • Siofok, Hungary
        • Research Site
      • Zalaegerszeg, Hungary
        • Research Site
  • India
      • Andra-Pradeash, India
        • Research Site
      • Bangalore, India
        • Research Site
      • Jaipur, India
        • Research Site
      • Kolkata, India
        • Research Site
      • Mumbai, India
        • Research Site
      • Visakhapatnam, India
        • Research Site
  • Poland
      • Bialystok, Poland
        • Research Site
      • Gdansk, Poland
        • Research Site
      • Katowice, Poland
        • Research Site
      • Krakow, Poland
        • Research Site
      • Lodz, Poland
        • Research Site
      • Lublin, Poland
        • Research Site
      • Warsaw, Poland
        • Research Site
      • Warszawa, Poland
        • Research Site
  • Russian Federation
      • Kazan, Russian Federation
        • Research Site
      • Krasnoyarsk, Russian Federation
        • Research Site
      • Moscow, Russian Federation
        • Research Site
      • Nizhny Novgorod, Russian Federation
        • Research Site
      • Novosibirsk, Russian Federation
        • Research Site
      • Omsk, Russian Federation
        • Research Site
      • Samara, Russian Federation
        • Research Site
      • Smolensk, Russian Federation
        • Research Site
      • St Petersburg, Russian Federation
        • Research Site
      • Ufa, Russian Federation
        • Research Site
      • Yaroskavl, Russian Federation
        • Research Site
  • Ukraine
      • Chernivtsi, Ukraine
        • Research Site
      • Dnipropetrovsk, Ukraine
        • Research Site
      • Donetsk, Ukraine
        • Research Site
      • Kharkiv, Ukraine
        • Research Site
      • Kiev, Ukraine
        • Research Site
      • Lviv, Ukraine
        • Research Site
      • Poltava, Ukraine
        • Research Site
      • Zaporizhzhya, Ukraine
        • Research Site
      • Zaporozhye, Ukraine
        • Research Site
  • United Kingdom
      • Devon, United Kingdom
        • Research Site
      • London, United Kingdom
        • Research Site
      • Nottingham, United Kingdom
        • Research Site
      • Sheffield, United Kingdom
        • Research Site
      • Stoke-on-Trent, United Kingdom
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group 1: DAC HYP 150 mg
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)
SC injection
Other Names:
  • DAC HYP
  • Daclizumab HYP
Experimental: Group 1: DAC HYP 300 mg
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)
SC injection
Other Names:
  • DAC HYP
  • Daclizumab HYP
Experimental: Group 2: Washout then DAC HYP 150 mg
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.
Drug: Placebo
Placebo SC injection
Biological: BIIB019 (Daclizumab High Yield Process)
SC injection
Other Names:
  • DAC HYP
  • Daclizumab HYP
Experimental: Group 2: DAC HYP 150 mg
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)
SC injection
Other Names:
  • DAC HYP
  • Daclizumab HYP
Experimental: Group 3: Washout then DAC HYP 300 mg
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.
Drug: Placebo
Placebo SC injection
Biological: BIIB019 (Daclizumab High Yield Process)
SC injection
Other Names:
  • DAC HYP
  • Daclizumab HYP
Experimental: Group 3: DAC HYP 300 mg
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)
SC injection
Other Names:
  • DAC HYP
  • Daclizumab HYP

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Treatment-emergent Adverse Events (AEs)
Time Frame: Up to 72 weeks
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
Time Frame: Up to Week 72
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
Time Frame: Up to 72 Weeks
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
Time Frame: Up to 72 Weeks
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
Time Frame: Up to 72 weeks
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
Time Frame: Up to 72 weeks
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
Time Frame: Up to 72 weeks
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
Time Frame: Week 20, Week 52
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
Time Frame: Baseline, Week 20, Week 52
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
Time Frame: Baseline, Week 20, Week 52
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
Time Frame: Baseline, Week 52
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
Time Frame: Baseline, Week 52
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
Time Frame: Baseline, Week 52
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Biogen

Collaborators

AbbVie

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2009

Primary Completion (Actual)

May 1, 2012

Study Completion (Actual)

October 1, 2012

Study Registration Dates

First Submitted

March 26, 2009

First Submitted That Met QC Criteria

March 26, 2009

First Posted (Estimate)

March 27, 2009

Study Record Updates

Last Update Posted (Estimate)

August 30, 2016

Last Update Submitted That Met QC Criteria

July 19, 2016

Last Verified

July 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 205-MS-202
  • EUDRA CT No.: 2008-005559-46

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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