search
Back to results

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

Primary Purpose

Relapsing-Remitting Multiple Sclerosis (RRMS)

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Daclizumab
Sponsored by
Biogen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Relapsing-Remitting Multiple Sclerosis (RRMS) focused on measuring Multiple Sclerosis, Daclizumab, Tysabri-Switch

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Daclizumab

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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).
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.
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.
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.
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.

Full Information

First Posted
August 24, 2016
Last Updated
September 25, 2019
Sponsor
Biogen
Collaborators
AbbVie
search

1. Study Identification

Unique Protocol Identification Number
NCT02881567
Brief Title
Efficacy and Safety of Daclizumab in Participants With RRMS Switching From Natalizumab
Acronym
SUSTAIN
Official Title
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)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2019
Overall Recruitment Status
Terminated
Why Stopped
Study terminated in line with Biogen decision to withdraw Zinbryta from the market and not to pursue further studies of daclizumab in MS.
Study Start Date
April 18, 2017 (Actual)
Primary Completion Date
September 12, 2018 (Actual)
Study Completion Date
September 12, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biogen
Collaborators
AbbVie

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsing-Remitting Multiple Sclerosis (RRMS)
Keywords
Multiple Sclerosis, Daclizumab, Tysabri-Switch

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
41 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Daclizumab
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Daclizumab
Other Intervention Name(s)
BIIB019, Zinbryta
Intervention Description
High yield formulation
Primary Outcome Measure Information:
Title
Percentage of Participants Relapse-free at Month 6
Description
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.
Time Frame
Month 6
Secondary Outcome Measure Information:
Title
Percentage of Participants Relapse-free at Month 12
Description
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.
Time Frame
Month 12
Title
Percentage of Participants Experiencing Relapse Requiring Hospitalization and/or Steroid Treatment at Month 12
Description
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.
Time Frame
Month 12
Title
Annualized Relapse Rate (ARR) at Month 12
Description
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.
Time Frame
Month 12
Title
Number of Participants With New Gadolinium-Enhanced (Gd+) and T1 Hypointense Lesions at Months 6 and 12
Description
New Gadolinium-Enhanced (Gd+) and T1 Hypointense Lesions were assessed using magnetic resonance imaging (MRI).
Time Frame
Months 6 and 12
Title
Number of Participants With New and Newly Enlarged T2 Hypointense Lesions at Months 6 and 12
Description
New and newly enlarged T2 Hypointense Lesions were measured by MRI.
Time Frame
Months 6 and 12
Title
Permanent Discontinuation Rate of Daclizumab at Month 12
Description
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.
Time Frame
Month 12
Title
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
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.
Time Frame
First dose of study drug to within 30 days of last dose (up to 11 months)
Title
Number of Participants With Clinically Relevant Shifts in Laboratory Assessments
Description
Clinical Laboratory assessments were tests of Chemistry and Hematology. The investigator determined if any of the laboratory results were clinically relevant shifts from Baseline.
Time Frame
First dose of study drug to within 30 days of last dose (up to 11 months)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Biogen
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Research Site
City
Des Moines
State/Province
Iowa
ZIP/Postal Code
50314
Country
United States
Facility Name
Research Site
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53501
Country
United States
Facility Name
Research Site
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2G3
Country
Canada
Facility Name
Research Site
City
Muenchen
State/Province
Bayern
ZIP/Postal Code
81675
Country
Germany
Facility Name
Research Site
City
Potsdam
State/Province
Brandenburg
ZIP/Postal Code
14471
Country
Germany
Facility Name
Research Site
City
Dresden
State/Province
Sachsen
ZIP/Postal Code
01307
Country
Germany
Facility Name
Research Site
City
Hamburg
ZIP/Postal Code
20249
Country
Germany
Facility Name
Research Site
City
Pozzilli
State/Province
Isernia
ZIP/Postal Code
86077
Country
Italy
Facility Name
Research Site
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
Research Site
City
Guaynabo
ZIP/Postal Code
00968
Country
Puerto Rico

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs