Evaluate Early Glatiramer Acetate Treatment in Delaying Conversion to Clinically Definite Multiple Sclerosis of Subjects Presenting With Clinically Isolated Syndrome (PreCISe)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Teva Pharmaceutical Industries
ClinicalTrials.gov Identifier:
NCT00666224
First received: April 22, 2008
Last updated: June 19, 2012
Last verified: June 2012
Results First Received: May 3, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Multiple Sclerosis
Interventions: Drug: Glatiramer Acetate (DB)
Drug: Placebo
Drug: Glatiramer Acetate (OL)

  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
A clinically isolated syndrome (CIS) is a first neurological episode, lasting at least 24 hours, caused by inflammation/demyelination in one or more sites in the central nervous system (CNS.) Subjects were enrolled within 90 days of the event and randomized up to 32 days following screening.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Six-hundred and nineteen (619) subjects were screened for this study; 138 subjects were screening failures, including one subject, randomized in error. This subject, who had a relapse between screening visit and baseline, never received any treatment, and is considered a screening failure.

Reporting Groups
  Description
Glatiramer Acetate Glatiramer acetate (GA) 20 mg once daily by subcutaneous injection during the double-blind period. Following a pre-planned interim analysis, the Data Monitoring Committee (DMC) recommended that the double blind period be closed and participants moved into the Open Label (OL) period. Participants in this treatment arm continued taking glatiramer acetate 20 mg once daily by subcutaneous injection during the open-label (OL) period.
Placebo (DB) to GA (OL) Placebo matching glatiramer acetate given once daily by subcutaneous injection during the double-blind period (DB). Following a pre-planned interim analysis, the Data Monitoring Committee (DMC) recommended that the double blind period be closed and participants moved into the Open Label (OL) period. Glatiramer acetate (GA) given 20 mg once daily by subcutaneous injection during the open-label period (OL).

Participant Flow for 2 periods

Period 1:   Double-Blind
    Glatiramer Acetate     Placebo (DB) to GA (OL)  
STARTED     243     238  
COMPLETED     198 [1]   211 [2]
NOT COMPLETED     45     27  
Adverse Event                 15                 5  
Lost to Follow-up                 2                 2  
Withdrawal by Subject                 18                 14  
Physician Decision                 0                 3  
Sponsor decision                 1                 0  
Pregnancy                 3                 2  
Noncompliance                 1                 0  
Death                 1                 0  
Undefined/Unknown                 4                 1  
[1] 78 completed 3 years treatment, 66 converted to CDMS, 54 switched to OL as per DMC
[2] 55 completed 3 years treatment, 109 converted to CDMS, 47 switched to OL as per DMC

Period 2:   Open-Label
    Glatiramer Acetate     Placebo (DB) to GA (OL)  
STARTED     198 [1]   211  
COMPLETED     163     126  
NOT COMPLETED     35     85  
Adverse Event                 8                 43  
Lost to Follow-up                 4                 5  
Withdrawal by Subject                 12                 25  
Physician Decision                 7                 5  
Pregnancy                 1                 5  
Noncompliance                 2                 1  
Undefined/Unknown                 1                 1  
[1] 454 participants took at least one dose of GA including 45 who didn't continue into the OL.



  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.
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Reporting Groups
  Description
Glatiramer Acetate (Double-blind Period) Glatiramer acetate 20 mg once daily by subcutaneous injection during the double-blind period.
Placebo (Double-blind Period) Placebo matching GA once daily by subcutaneous injection during the double-blind period.
Total Total of all reporting groups

Baseline Measures
    Glatiramer Acetate (Double-blind Period)     Placebo (Double-blind Period)     Total  
Number of Participants  
[units: participants]
  243     238     481  
Age  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     243     238     481  
>=65 years     0     0     0  
Age  
[units: years]
Mean ± Standard Deviation
  31.5  ± 6.9     30.8  ± 7.0     31.2  ± 6.9  
Gender  
[units: participants]
     
Female     159     163     322  
Male     84     75     159  
Race/Ethnicity, Customized  
[units: participants]
     
Asian / Oriental     2     1     3  
Black or African American     1     1     2  
Caucasian     233     229     462  
Hispanic     3     2     5  
Other (not specified)     4     5     9  
Region of Enrollment  
[units: participants]
     
Argentina     7     6     13  
Australia     7     6     13  
Austria     5     6     11  
Denmark     5     6     11  
Finland     10     10     20  
France     11     11     22  
Germany     32     31     63  
Hungary     16     15     31  
Italy     56     57     113  
New Zealand     4     3     7  
Norway     2     2     4  
Romania     28     30     58  
Spain     23     22     45  
Sweden     2     0     2  
United Kingdom     15     12     27  
United States     20     21     41  
Participants Who Used Corticosteroids for Initial Attack  
[units: participants]
     
Used corticosteroids     149     159     308  
Did not use corticosteroids     94     79     173  



  Outcome Measures
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1.  Primary:   Time to Clinically Definite Multiple Sclerosis (CDMS) Conversion   [ Time Frame: up to 3 years ]

2.  Primary:   Twenty-fifth Percentile (25%) Kaplan-Meier Estimates for Time From Randomization to Conversion to Clinically Definite Multiple Sclerosis (CDMS) During the Double-blind Period   [ Time Frame: up to 3 years ]

3.  Secondary:   Number of New T2 Brain Lesions Observed at the Last Observed Value (LOV) in the Double-blind Period   [ Time Frame: up to 3 years ]

4.  Secondary:   Change From Baseline to Last Observed Value (LOV) in T2 Brain Lesion Volume in the Double-blind Period   [ Time Frame: Day 0 (baseline), up to 3 years ]

5.  Secondary:   Percentage Change in Brain Volume From Baseline to the Last Observed Value (LOV) During the Double-blind Period Using the Structural Image Evaluation of Normalized Atrophy (SIENA) Technique   [ Time Frame: Day 0 (baseline), up to 3 years ]

6.  Secondary:   Percentage of Participants Who Converted to Clinically Definite Multiple Sclerosis (CDMS) During the Double-blind Period   [ Time Frame: up to 3 years ]


  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
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  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: Yossi Gilgun, PhD, Global Clinical Leader
Organization: Teva Pharmaceutical Industries, Ltd.
phone: 972-9-863-1491
e-mail: yossi.gilgun@teva.co.il


Publications of Results:

Responsible Party: Teva Pharmaceutical Industries
ClinicalTrials.gov Identifier: NCT00666224     History of Changes
Other Study ID Numbers: GA 9010
Study First Received: April 22, 2008
Results First Received: May 3, 2012
Last Updated: June 19, 2012
Health Authority: United States: Food and Drug Administration
European Union: European Medicines Agency