Clinical Trial Results:
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)
|
Summary
|
|
EudraCT number |
2016-002820-10 |
Trial protocol |
GB DE IT |
Global end of trial date |
12 Sep 2018
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
22 Sep 2019
|
First version publication date |
22 Sep 2019
|
Other versions |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
205MS305
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT02881567 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
Biogen
|
||
Sponsor organisation address |
250 Binney Street, Cambridge, United States, 02142
|
||
Public contact |
Biogen Study Medical Director, Biogen, clinicaltrials@biogen.com
|
||
Scientific contact |
Biogen Study Medical Director, Biogen, clinicaltrials@biogen.com
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
12 Sep 2018
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
12 Sep 2018
|
||
Was the trial ended prematurely? |
Yes
|
||
|
General information about the trial
|
|||
Main objective of the trial |
The primary objective of the study was to evaluate the effects of treatment with daclizumab on the proportion of subjects relapse-free at 6 months in RRMS subjects, who switched from treatment with natalizumab to daclizumab due to safety concerns. The secondary objectives of this study in this study population were 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 subjects experiencing relapses requiring hospitalization and/or steroid treatment 2) MS-related outcomes measured using magnetic resonance imaging (MRI) 3) Safety and tolerability in subjects previously treated with natalizumab.
|
||
Protection of trial subjects |
Written informed consent was obtained from each subject or subject’s legally authorised representative (e.g., parent or legal guardian), as applicable, prior to evaluations performed for eligibility. Subjects or the subject’s legally authorised representative were given adequate time to review the information in the informed consent/assent and were allowed to ask, and have answered, questions concerning all portions of the conduct of the study.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
18 Apr 2017
|
||
Long term follow-up planned |
Yes
|
||
Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
6 Months | ||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Canada: 1
|
||
Country: Number of subjects enrolled |
Germany: 10
|
||
Country: Number of subjects enrolled |
Italy: 17
|
||
Country: Number of subjects enrolled |
United States: 13
|
||
Worldwide total number of subjects |
41
|
||
EEA total number of subjects |
27
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
41
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
||
|
|||||||||||||||||||||
|
Recruitment
|
|||||||||||||||||||||
Recruitment details |
Subjects enrolled in the study at 11 investigative sites in Canada, Germany, Italy, and the United States from 05 April 2017 to 12 September 2018. | ||||||||||||||||||||
|
Pre-assignment
|
|||||||||||||||||||||
Screening details |
Subjects who discontinued treatment with natalizumab due to safety concerns were enrolled to receive daclizumab 150 milligrams (mg) per 1.0 millilitre (mL). | ||||||||||||||||||||
|
Period 1
|
|||||||||||||||||||||
Period 1 title |
Overall Study (overall period)
|
||||||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||||||
Allocation method |
Non-randomised - controlled
|
||||||||||||||||||||
Blinding used |
Not blinded | ||||||||||||||||||||
|
Arms
|
|||||||||||||||||||||
|
Arm title
|
Daclizumab | ||||||||||||||||||||
Arm description |
Subjects previously treated with natalizumab for at least 12 months and who discontinued treatment, received daclizumab 150 mg per 1.0 mL administered subcutaneously once a month for up to 11 months. | ||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||
Investigational medicinal product name |
Daclizumab
|
||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||
Other name |
Zinbryta
|
||||||||||||||||||||
Pharmaceutical forms |
Solution for injection
|
||||||||||||||||||||
Routes of administration |
Subcutaneous use
|
||||||||||||||||||||
Dosage and administration details |
Daclizumab was administered as 150 mg per 1.0 mL subcutaneously, once a month for up to 11 months.
|
||||||||||||||||||||
|
|||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Daclizumab
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects previously treated with natalizumab for at least 12 months and who discontinued treatment, received daclizumab 150 mg per 1.0 mL administered subcutaneously once a month for up to 11 months. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Daclizumab
|
||
Reporting group description |
Subjects previously treated with natalizumab for at least 12 months and who discontinued treatment, received daclizumab 150 mg per 1.0 mL administered subcutaneously once a month for up to 11 months. | ||
|
|||||||||
End point title |
Percentage of Subjects Relapse-free at Month 6 [1] | ||||||||
End point 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 subjects relapse-free at Month 6 is reported. FAS included all subjects enrolled in the study.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Month 6
|
||||||||
| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses are reported for this endpoint. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Percentage of Subjects Experiencing Relapse Requiring Hospitalization and/or Steroid Treatment at Month 12 | ||||||||
End point 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.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Month 12
|
||||||||
|
|||||||||
| Notes [2] - The study was terminated. No subjects reached the 12-month time point. |
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Percentage of Subjects Relapse-free at Month 12 | ||||||||
End point 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.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Month 12
|
||||||||
|
|||||||||
| Notes [3] - The study was terminated. No subjects reached the 12-month time point. |
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Annualised Relapse Rate (ARR) at Month 12 | ||||||||
End point 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.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Month 12
|
||||||||
|
|||||||||
| Notes [4] - The study was terminated. No subjects reached the 12-month time point. |
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||||
End point title |
Number of Subjects with New Gadolinium-Enhanced (Gd+) and T1 Hypointense Lesions at Months 6 and 12 | ||||||||||||||
End point description |
New Gadolinium-Enhanced (Gd+) and T1 Hypointense Lesions were assessed using magnetic resonance imaging (MRI). FAS included all subjects enrolled in the study. Number of Subjects Analyzed is the number of subjects with available assessment. 'n' signifies the number of subjects analysed at specified time point. '99999' for Month 6, T1 Hypointense Lesions indicates that no data was collected. '99999' for Month 12, Gd+ and Month 12, T1 Hypointense Lesions indicates that the study was terminated and no subjects reached the 12-month time point.
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
Months 6 and 12
|
||||||||||||||
|
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||||||
End point title |
Number of Subjects with New and Newly Enlarged T2 Hypointense Lesions at Months 6 and 12 | ||||||||||
End point description |
New and newly enlarged T2 Hypointense Lesions were measured by MRI. FAS included all subjects enrolled in the study. Number of Subjects Analyzed is the number of subjects with available assessment. 'n' signifies the number of subjects analysed at specified time point. '99999' indicates that the study was terminated and no subjects reached the 12-month time point.
|
||||||||||
End point type |
Secondary
|
||||||||||
End point timeframe |
Months 6 and 12
|
||||||||||
|
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||||
End point title |
Permanent Discontinuation Rate of Daclizumab at Month 12 | ||||||||
End point description |
Permanent Discontinuation Rate was calculated as the ratio of number of subjects who had permanently discontinued daclizumab prior to Month 12 over the total number of subjects who received at least 1 dose of daclizumab in the study.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Month 12
|
||||||||
|
|||||||||
| Notes [5] - The study was terminated. No subjects reached the 12-month time point |
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||
End point title |
Number of Subjects with Adverse Events (AEs) and Serious Adverse Events (SAEs) | ||||||||||
End point description |
An AE can be any unfavourable 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 subject at immediate risk of death or requires inpatient hospitalisation or prolongation of existing hospitalisation or results in persistent or significant disability or results in a birth defect. Safety Population included all enrolled subjects who received at least 1 dose of study drug.
|
||||||||||
End point type |
Secondary
|
||||||||||
End point timeframe |
The first dose of study drug to within 30 days of last dose (up to 11 months)
|
||||||||||
|
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||
End point title |
Number of Subjects with Clinically Relevant Shifts in Laboratory Assessments | ||||||
End point 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. Safety Population included all enrolled subjects who received at least 1 dose of study drug.
|
||||||
End point type |
Secondary
|
||||||
End point timeframe |
First dose of study drug to within 30 days of last dose (up to 11 months)
|
||||||
|
|||||||
| No statistical analyses for this end point | |||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
First dose of study drug to within 30 days of last dose (up to 11 months)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
21.1
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Daclizumab
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects previously treated with natalizumab for at least 12 months and who discontinued treatment received daclizumab 150 mg per 1.0 mL administered subcutaneously once a month for up to 11 months. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||
Substantial protocol amendments (globally) |
|||||||
| Were there any global substantial amendments to the protocol? No | |||||||
Interruptions (globally) |
|||||||
| Were there any global interruptions to the trial? Yes | |||||||
|
|||||||
Limitations and caveats |
|||||||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
| None reported | |||||||
