Clinical trial NCT00666224: Evaluate Early Glatiramer Acetate Treatment in Delaying Conversion to Clinically Definite Multiple Sclerosis of Subjects Presenting With Clinically Isolated Syndrome
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Sclerosis
Keywords: Clinically Definite Multiple Sclerosis
Clinically Isolated Syndrome
Multiple Sclerosis
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2008-04-24
Enrollment: 481
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Time to Clinically Definite Multiple Sclerosis (CDMS) Conversion
timeFrame: up to 3 years
measure: Twenty-fifth Percentile (25%) Kaplan-Meier Estimates for Time From Randomization to Conversion to Clinically Definite Multiple Sclerosis (CDMS) During the Double-blind Period
timeFrame: up to 3 years
Secondary outcomes:
measure: Number of New T2 Brain Lesions Observed at the Last Observed Value (LOV) in the Double-blind Period
timeFrame: up to 3 years
measure: Change From Baseline to Last Observed Value (LOV) in T2 Brain Lesion Volume in the Double-blind Period
timeFrame: Day 0 (baseline), up to 3 years
measure: 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
timeFrame: Day 0 (baseline), up to 3 years
measure: Percentage of Participants Who Converted to Clinically Definite Multiple Sclerosis (CDMS) During the Double-blind Period
timeFrame: up to 3 years
Other outcomes:
Locations:
Study officials:
References:
citation: 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 glatiramer acetate on conversion to clinically definite multiple sclerosis in patients with clinically isolated syndrome (PreCISe study): a randomised, double-blind, placebo-controlled trial. Lancet. 2009 Oct 31;374(9700):1503-11. doi: 10.1016/S0140-6736(09)61259-9. Epub 2009 Oct 6.