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

Multiple Sclerosis Clinical Trial

— PreCISe  

Official title:

A Multinational, Multicenter, Randomized, Double-Blind, Placebo Controlled, Parallel Group Study to Evaluate the Effect of Early Glatiramer Acetate Treatment in Delaying the Conversion to Clinically Definite Multiple Sclerosis (CDMS) of Subjects Presenting With Clinically Isolated Syndrome (CIS)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00666224
• Other study ID #: GA 9010
• Status: Completed
• Phase: Phase 3
• First received: April 22, 2008
• Last updated: June 19, 2012
• Start date: January 2004
• Est. completion date: June 2010

Study information

• Verified date: June 2012
• Source: Teva Pharmaceutical Industries
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationEuropean Union: European Medicines Agency
• Study type: Interventional

Clinical Trial Summary

The primary objective is to assess the effect of treatment with glatiramer acetate (GA) compared to placebo on the time to conversion to CDMS, as determined by Poser criteria (the occurrence of the second clinical attack) during the double-blind period. The secondary objective is to assess, within the time frame of the up to 3-year double-blind, placebo-controlled study period, the effect of GA on clinical and Magnetic Resonance Imaging (MRI) parameters. The long-term objectives of the study (exploratory in nature) are to assess, within the time frame of 5 years, the neuroprotective effect of early versus delayed treatment with GA as reflected by clinical and MRI parameters measuring the accumulated irreversible brain tissue damage.

A pre-planned interim analysis was performed on all efficacy and safety data accumulated in the database up to October 14, 2007, i.e. when 81% of exposure to treatment in the double-blind, placebo-controlled period had been collected. Upon review of the interim analysis results, the Data Monitoring Committee (DMC) recommended that the double-blind portion of the study be stopped and that subjects be switched to the 2-year Open-label period, during which time they would have the option of receiving GA therapy. The sponsor (Teva) adopted the DMC recommendations and took the necessary action towards its implementation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 481
• Est. completion date: June 2010
• Est. primary completion date: October 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

1. The subject must have undergone a single clinical attack.

2. The subject must have a unifocal clinical presentation.

3. The subject should be enrolled within the period of 90 days after onset of a single unifocal clinical attack (index attack).

4. There must be 2 or more cerebral lesions highly suspicious of multiple sclerosis (MS) on the screening Magnetic Resonance Imaging (MRI), measuring 6mm or more in diameter.

5. Subjects must be between the ages of 18 and 45 years inclusive.

6. Subjects must not have taken corticosteroids within the 30 days prior to the MRI at the baseline visit.

7. Subjects may be male or female. Women of child-bearing potential must practice a medically acceptable method of birth control. Acceptable methods include oral contraceptive, contraceptive patch, long-acting injectable contraceptive, or double-barrier method (condom or intrauterine device with spermicide).

8. The subjects must be willing and able to give written informed consent, prior to entering the study.

Exclusion Criteria:

1. Multifocal clinical presentation.

2. Diseases other than MS responsible for the clinical/MRI presentation. The following laboratory tests must be part of the subject's medical history for differential diagnosis of clinically isolated syndrome (CIS): erythrocyte sedimentation rate (ESR), antinuclear antibody (ANA), complement (C3, C4) and anticardiolipin IgG - IgM. In the event that the results of these tests are inconclusive, the following additional tests may be requested by the Eligibility Evaluation Committee: syphilis screening, vitamin B12 and folic acid. In the case of spinal cord CIS presentation, a spinal cord MRI is required for confirmation of diagnosis in the medical history of the subject.

3. Use of experimental or investigational drugs, including IV immunoglobulin, and/or participation in an investigational drug study within 6 months prior to study entry.

4. Use of interferon agents within 6 months prior to the screening visit.

5. Chronic corticosteroid treatment (more than 30 consecutive days) in the 6 months prior to study entry.

6. Pregnancy or breast feeding.

7. Subjects who experience a relapse between the screening (month -1) and baseline (month 0) visits.

8. Life-threatening or other clinically significant disease.

9. A medical or psychiatric condition that affects the subject's ability to give informed consent, or to complete the study, or if the subject is considered by the treating neurologist/physician to be, for any other reason, an unsuitable candidate for this study.

10. A known history of sensitivity to mannitol.

11. A known history of sensitivity to gadolinium.

12. Inability to successfully undergo MRI scanning.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• Glatiramer Acetate (DB)
Double blind period (DB): glatiramer acetate (GA) by subcutaneous injection, 20mg, once daily, for up to 36 months or until conversion to clinically definite multiple sclerosis (CDMS).
• Placebo
Double blind period (DB): subcutaneous injection of placebo, once daily, for up to 36 months or until conversion to CDMS
• Glatiramer Acetate (OL)
Open label period (OL): glatiramer acetate (GA), 20 mg, subcutaneous injection, once daily, given for up to an additional 24 months.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Teva Pharmaceutical Industries

References & Publications (1)

Comi G, Martinelli V, Rodegher M, Moiola L, Bajenaru O, Carra A, Elovaara I, Fazekas F, Hartung HP, Hillert J, King J, Komoly S, Lubetzki C, Montalban X, Myhr KM, Ravnborg M, Rieckmann P, Wynn D, Young C, Filippi M; PreCISe study group. Effect of glatiram — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Clinically Definite Multiple Sclerosis (CDMS) Conversion	Data from interim analysis with database lock on October 14, 2007. The time from randomization to conversion to CDMS as determined by the occurrence of a second clinical attack during the double-blind period. Poser criteria are: Two relapses and clinical evidence of two separate lesions; clinical evidence of one lesion and paraclinical evidence of another separate lesion. The two relapses must involve different parts of Central Nervous System and must be separated by a period of at least one month. Lesions are determined by Magnetic Resonance Imaging (MRI).	up to 3 years	No
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	Data from interim analysis with database lock on October 14, 2007. Due to the number of participants in the glatiramer acetate group that converted to CDMS (see outcome #6), the 25th percentile was considered when running the Kaplan-Meier estimate for time to conversion to CDMS. Conversion to CDMS is determined by the occurrence of the second clinical attack.	up to 3 years	No
Secondary	Number of New T2 Brain Lesions Observed at the Last Observed Value (LOV) in the Double-blind Period	Data from interim analysis with database lock on October 14, 2007. T2 lesions are brain lesions that show on magnetic resonance imaging (MRI) and are associated with multiple sclerosis. This outcome measures the number of new lesions at the last observed value. Last Observed Value (LOV) is defined as the last post baseline measurement taken on study drug but no more than 30 days after study drug cessation.	up to 3 years	No
Secondary	Change From Baseline to Last Observed Value (LOV) in T2 Brain Lesion Volume in the Double-blind Period	Data from interim analysis with database lock on October 14, 2007. The difference in T2 brain lesion volume as observed in MRIs from baseline to the last observed value. Last Observed Value (LOV) is defined as the last post baseline measurement taken on study drug but no more than 30 days after study drug cessation.	Day 0 (baseline), up to 3 years	No
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	Data from interim analysis with database lock on October 14, 2007. Brain volume was measured annually by magnetic resonance imaging (MRI) during the Double-blind period. Brain atrophy was measured by comparing the change in brain volume from baseline to the Last Observed Value (LOV). LOV is defined as the last post baseline measurement taken on study drug but no more than 30 days after study drug cessation. SIENA is a fully automated method of analyzing longitudinal brain change.	Day 0 (baseline), up to 3 years	No
Secondary	Percentage of Participants Who Converted to Clinically Definite Multiple Sclerosis (CDMS) During the Double-blind Period	Data from interim analysis with database lock on October 14, 2007. Conversion to CDMS as determined by the occurrence of a second clinical attack during the double-blind period. Poser criteria are: Two relapses and clinical evidence of two separate lesions; clinical evidence of one lesion and paraclinical evidence of another separate lesion. The two relapses must involve different parts of Central Nervous System and must be separated by a period of at least one month. Lesions are determined by Magnetic Resonance Imaging (MRI).	up to 3 years	No