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Natalizumab as an Efficacy Switch in Participants With Relapsing Multiple Sclerosis After Failure on Other Therapies (ESCALATE)

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ClinicalTrials.gov Identifier: NCT02241785
Recruitment Status : Terminated (Business Decision)
First Posted : September 16, 2014
Results First Posted : June 5, 2017
Last Update Posted : June 5, 2017
Sponsor:
Information provided by (Responsible Party):
Biogen

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Relapsing Multiple Sclerosis
Intervention Drug: natalizumab
Enrollment 47
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Natalizumab
Hide Arm/Group Description natalizumab 300 mg intravenously (IV) every 4 weeks
Period Title: Overall Study
Started 47
Completed 0
Not Completed 47
Reason Not Completed
Sponsor Termination             43
Withdrawal by Subject             1
Lost to Follow-up             2
Adverse Event             1
Arm/Group Title Natalizumab
Hide Arm/Group Description natalizumab 300 mg IV every 4 weeks
Overall Number of Baseline Participants 47
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 47 participants
41.9  (10.43)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 47 participants
Female
34
  72.3%
Male
13
  27.7%
1.Primary Outcome
Title Proportion of Participants With No Evidence of Disease Activity (NEDA) From Reset Baseline (Week 8) to Week 56
Hide Description The proportion of participants with NEDA, defined as follows: no Expanded Disability Status Scale (EDSS) progression (12-week sustained); no relapses; no gadolinium enhancing (Gd+) lesions; no new or enlarging T2 hyperintense lesions over 48 weeks after resetting the Baseline at Week 8 to remove contribution of combined unique active (CUA) lesions that occurred prior to Week 8, when natalizumab was not yet active. The EDSS quantifies disability in 8 functional systems. The final EDSS score is an ordinal clinical rating scale ranging from 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments.
Time Frame Reset Baseline (Week 8) to Week 56
Hide Outcome Measure Data
Hide Analysis Population Description
The limited number of participants enrolled and the early termination of the study resulted in efficacy data not collected, and efficacy outcomes not analyzed, as per the pre-specified plan of analysis.
Arm/Group Title Natalizumab
Hide Arm/Group Description:
natalizumab 300 mg IV every 4 weeks
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
2.Secondary Outcome
Title Change in T1 Unenhancing Lesion Volume and T2 Lesion Volume From Baseline (Day -1) to Reset Baseline (Week 8)
Hide Description As measured by magnetic resonance imaging.
Time Frame Baseline (Day -1) to Reset Baseline (Week 8)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: participants who received at least 1 infusion of study treatment and had an assessment.
Arm/Group Title Natalizumab
Hide Arm/Group Description:
natalizumab 300 mg IV every 4 weeks
Overall Number of Participants Analyzed 43
Mean (Standard Deviation)
Unit of Measure: cc
Change in T1 Unenhancing Lesion Volume 0.11  (0.65)
Change in T2 Lesion Volume 0.01  (1.76)
3.Secondary Outcome
Title Proportion of Participants With NEDA From Week 8 (Reset Baseline) to Week 104
Hide Description Proportion of participants with NEDA from Week 8 (Reset Baseline) to Week 104 (with no 12-week confirmed EDSS progression determined at Week 116). NEDA was defined as follows: no EDSS progression (12-week sustained); no relapses; no Gd+ lesions; no new or enlarging T2 hyperintense lesions over 48 weeks after resetting the Baseline at Week 8 to remove contribution of CUA lesions that occurred prior to Week 8, when natalizumab was not yet active. The EDSS quantifies disability in 8 functional systems. The final EDSS score is an ordinal clinical rating scale ranging from 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments.
Time Frame from Week 8 (Reset Baseline) to Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
The limited number of participants enrolled and the early termination of the study resulted in efficacy data not collected, and efficacy outcomes not analyzed, as per the pre-specified plan of analysis.
Arm/Group Title Natalizumab
Hide Arm/Group Description:
natalizumab 300 mg IV every 4 weeks
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
4.Secondary Outcome
Title Pre- and Post-Natalizumab Infusion Annualized Relapse Rate (ARR) Comparison at Month 12
Hide Description An MS relapse was defined as the onset of new or recurrent neurological symptoms lasting at least 24 hours, accompanied by new objective abnormalities on a neurological examination, and not explained solely by non-MS processes such as fever, infection, severe stress, or drug toxicity. 95% confidence interval is based on a Poisson regression model.
Time Frame From 12 months prior to natalizumab infusion and 12 months post-natalizumab infusion
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: participants who received at least 1 infusion of study treatment and had an assessment.
Arm/Group Title Natalizumab
Hide Arm/Group Description:
natalizumab 300 mg IV every 4 weeks
Overall Number of Participants Analyzed 47
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: relapses per subject-year
12 months pre-natalizumab infusion
1.553
(1.306 to 1.847)
12 months post-natalizumab infusion
0.159
(0.076 to 0.331)
5.Secondary Outcome
Title Change in MSIS-29 Physical Impact Scores From Baseline (Day -1) to Reset Baseline (Week 8)
Hide Description The MSIS-29 is a brief self-administered MS-specific instrument measuring physical (20 items) and mental/psychological (9 items) impact of MS. The physical score is generated by summing individual items and then transforming to a scale with a range of 0 to 100, where high scores indicate worse health.
Time Frame Baseline (Day -1) to Reset Baseline (Week 8)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: participants who received at least 1 infusion of study treatment and had an assessment.
Arm/Group Title Natalizumab
Hide Arm/Group Description:
natalizumab 300 mg IV every 4 weeks
Overall Number of Participants Analyzed 45
Mean (Standard Deviation)
Unit of Measure: units on a scale
-2.53  (12.42)
Time Frame From Screening through end of study. Duration of study treatment was up to 13 months.
Adverse Event Reporting Description SAEs only were collected per protocol. Events were not coded by MedDRA.
 
Arm/Group Title Natalizumab
Hide Arm/Group Description natalizumab 300 mg IV every 4 weeks
All-Cause Mortality
Natalizumab
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Natalizumab
Affected / at Risk (%) # Events
Total   2/47 (4.26%)    
General disorders   
Non-cardiac chest pain   1/47 (2.13%)  1
Nervous system disorders   
Syncope   1/47 (2.13%)  1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Natalizumab
Affected / at Risk (%) # Events
Total   0/0    
As a result of early study termination and limited available data, no meaningful conclusions can be drawn.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Our agreement is subject to confidentiality but generally the PI can publish, for noncommercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Biogen Study Medical Director
Organization: Biogen
EMail: clinicaltrials@biogen.com
Layout table for additonal information
Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT02241785     History of Changes
Other Study ID Numbers: 101MS409
2013-005586-39 ( EudraCT Number )
First Submitted: September 12, 2014
First Posted: September 16, 2014
Results First Submitted: April 24, 2017
Results First Posted: June 5, 2017
Last Update Posted: June 5, 2017