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Exploratory Study of the Safety, Tolerability and Efficacy of Multiple Regimens of Natalizumab in Adult Participants With Relapsing Multiple Sclerosis (MS) (REFINE)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Biogen
ClinicalTrials.gov Identifier:
NCT01405820
First received: July 14, 2011
Last updated: August 3, 2015
Last verified: August 2015
Results First Received: June 29, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Relapsing-Remitting Multiple Sclerosis
Interventions: Drug: natalizumab IV
Drug: natalizumab SC
Drug: IV Placebo
Drug: SC Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Four of the 6 arms in the Randomized Treatment Period (the ‘every 12 weeks’ arms) were closed prematurely. Participants who completed randomized treatment, met rescue criteria, or were impacted by arm closure (and met rescue criteria) were eligible to enroll in the open-label treatment period.

Reporting Groups
  Description
Natalizumab 300 mg Intravenous (IV) Every 4 Weeks Natalizumab 300 mg IV every 4 weeks for 60 weeks. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.
Natalizumab 300 mg Subcutaneous (SC) Every 4 Weeks Natalizumab 300 mg SC every 4 weeks for 60 weeks. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.
Natalizumab 300 mg IV Every 12 Weeks Natalizumab 300 mg IV every 12 weeks for 60 weeks with matching IV placebo administered during the intervening 4-week periods. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.
Natalizumab 300 mg SC Every 12 Weeks Natalizumab 300 mg SC every 12 weeks for 60 weeks with matching SC placebo administered during the intervening 4-week periods. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.
Natalizumab 150 mg IV Every 12 Weeks Natalizumab 150 mg IV every 12 weeks for 60 weeks with matching IV placebo administered during the intervening 4-week periods. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.
Natalizumab 150 mg SC Every 12 Weeks Natalizumab 150 mg SC every 12 weeks for 60 weeks with matching SC placebo administered during the intervening 4-week periods. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.

Participant Flow for 2 periods

Period 1:   Randomized Treatment Period
    Natalizumab 300 mg Intravenous (IV) Every 4 Weeks   Natalizumab 300 mg Subcutaneous (SC) Every 4 Weeks   Natalizumab 300 mg IV Every 12 Weeks   Natalizumab 300 mg SC Every 12 Weeks   Natalizumab 150 mg IV Every 12 Weeks   Natalizumab 150 mg SC Every 12 Weeks
STARTED   54   45   52   54   47   38 
Safety Population   54   45   52   53 [1]   47   38 
COMPLETED   43   35   9   3   2   1 
NOT COMPLETED   11   10   43   51   45   37 
Adverse Event                3                3                3                0                2                1 
Withdrawal by Subject                6                2                2                2                0                0 
Not Specified                2                2                1                1                0                0 
Physician Decision                0                2                1                0                0                0 
Rescue                0                1                13                10                8                8 
Incorrect Study Treatment                0                0                3                0                2                0 
Treatment Arm Closed                0                0                20                36                33                28 
Death                0                0                0                1                0                0 
Withdrew Prior to Dosing                0                0                0                1                0                0 
[1] 1 participant did not receive any study medication.

Period 2:   Open-Label Treatment Period
    Natalizumab 300 mg Intravenous (IV) Every 4 Weeks   Natalizumab 300 mg Subcutaneous (SC) Every 4 Weeks   Natalizumab 300 mg IV Every 12 Weeks   Natalizumab 300 mg SC Every 12 Weeks   Natalizumab 150 mg IV Every 12 Weeks   Natalizumab 150 mg SC Every 12 Weeks
STARTED   44 [1]   35   42   42   42   32 
COMPLETED   40   33   39   37   40   30 
NOT COMPLETED   4   2   3   5   2   2 
Withdrawal by Subject                3                1                1                1                0                1 
Not Specified                1                1                1                1                1                1 
Physician Decision                0                0                1                2                1                0 
Adverse Event                0                0                0                1                0                0 
[1] 1 participant discontinued randomized period due to an adverse event but entered open-label period.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Randomized Period: Natalizumab 300 mg IV Every 4 Weeks Natalizumab 300 mg IV every 4 weeks for 60 weeks.
Randomized Period: Natalizumab 300 mg SC Every 4 Weeks Natalizumab 300 mg SC every 4 weeks for 60 weeks.
Randomized Period: Natalizumab 300 mg IV Every 12 Weeks Natalizumab 300 mg IV every 12 weeks for 60 weeks with matching IV placebo administered during the intervening 4-week periods.
Randomized Period: Natalizumab 300 mg SC Every 12 Weeks Natalizumab 300 mg SC every 12 weeks for 60 weeks with matching SC placebo administered during the intervening 4-week periods.
Randomized Period: Natalizumab 150 mg IV Every 12 Weeks Natalizumab 150 mg IV every 12 weeks for 60 weeks with matching IV placebo administered during the intervening 4-week periods.
Randomized Period: Natalizumab 150 mg SC Every 12 Weeks Natalizumab 150 mg SC every 12 weeks for 60 weeks with matching SC placebo administered during the intervening 4-week periods.
Total Total of all reporting groups

Baseline Measures
   Randomized Period: Natalizumab 300 mg IV Every 4 Weeks   Randomized Period: Natalizumab 300 mg SC Every 4 Weeks   Randomized Period: Natalizumab 300 mg IV Every 12 Weeks   Randomized Period: Natalizumab 300 mg SC Every 12 Weeks   Randomized Period: Natalizumab 150 mg IV Every 12 Weeks   Randomized Period: Natalizumab 150 mg SC Every 12 Weeks   Total 
Overall Participants Analyzed 
[Units: Participants]
 54   45   52   54   47   38   290 
Age 
[Units: Years]
Mean (Standard Deviation)
 38.4  (7.84)   36.3  (8.92)   38.7  (8.43)   38.7  (7.85)   38.7  (8.61)   36.0  (9.03)   37.9  (8.41) 
Age, Customized 
[Units: Participants]
             
18 to 19 years   0   1   0   0   0   0   1 
20 to 29 years   7   11   7   7   5   11   48 
30 to 39 years   22   15   21   24   21   14   117 
40 to 49 years   20   16   17   17   16   9   95 
50 to 56 years   5   2   7   6   5   4   29 
Gender 
[Units: Participants]
             
Female   39   29   37   41   34   24   204 
Male   15   16   15   13   13   14   86 


  Outcome Measures

1.  Primary:   Cumulative Number of Combined Unique Active Lesions   [ Time Frame: Up to Week 60 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
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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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Biogen Study Medical Director
Organization: Biogen
e-mail: clinicaltrials@biogen.com



Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT01405820     History of Changes
Other Study ID Numbers: 101MS206
2010-024000-10 ( EudraCT Number )
Study First Received: July 14, 2011
Results First Received: June 29, 2015
Last Updated: August 3, 2015
Health Authority: Italy: Ethics Committee
France: Institutional Ethical Committee
Spain: Comité Ético de Investigación Clínica
Belgium: Institutional Review Board
Germany: Ethics Commission