Evaluate Early Glatiramer Acetate Treatment in Delaying Conversion to Clinically Definite Multiple Sclerosis of Subjects Presenting With Clinically Isolated Syndrome
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Sclerosis
Intervention: Glatiramer Acetate (DB); Placebo; Glatiramer Acetate (OL)
Intervention description: 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).; Double blind period (DB): subcutaneous injection of placebo, once daily, for up to 36 months or until conversion to CDMS; Open label period (OL): glatiramer acetate (GA), 20 mg, subcutaneous injection, once daily, given for up to an additional 24 months.
Intervention MeSH terms: Glatiramer Acetate; (T,G)-A-L
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 481.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: No
Keywords: Clinically Definite Multiple Sclerosis; Clinically Isolated Syndrome; Multiple Sclerosis

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.