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;   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.
No text entered.

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 
Overall Participants Analyzed 
[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