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
  Purpose

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.


Condition Intervention Phase
Multiple Sclerosis
Drug: Glatiramer Acetate (DB)
Drug: Placebo
Drug: Glatiramer Acetate (OL)
Phase 3

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
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)

Resource links provided by NLM:


Further study details as provided by Teva Pharmaceutical Industries:

Primary Outcome Measures:
  • Time to Clinically Definite Multiple Sclerosis (CDMS) Conversion [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]
    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).

  • 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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Number of New T2 Brain Lesions Observed at the Last Observed Value (LOV) in the Double-blind Period [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Who Converted to Clinically Definite Multiple Sclerosis (CDMS) During the Double-blind Period [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]
    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).


Enrollment: 481
Study Start Date: January 2004
Study Completion Date: June 2010
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Glatiramer acetate
Glatiramer acetate 20 mg once daily by subcutaneous injection is administered in both the double-blind and open label periods.
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).
Other Name: Copaxone®
Drug: Glatiramer Acetate (OL)
Open label period (OL): glatiramer acetate (GA), 20 mg, subcutaneous injection, once daily, given for up to an additional 24 months.
Other Name: Copaxone®
Placebo Comparator: Placebo (DB) to GA (OL)
Placebo matching glatiramer acetate once daily by subcutaneous injection during the double-blind period (DB). Glatiramer acetate (GA) 20 mg once daily by subcutaneous injection during the open-label period (OL).
Drug: Placebo
Double blind period (DB): subcutaneous injection of placebo, once daily, for up to 36 months or until conversion to CDMS
Drug: Glatiramer Acetate (OL)
Open label period (OL): glatiramer acetate (GA), 20 mg, subcutaneous injection, once daily, given for up to an additional 24 months.
Other Name: Copaxone®

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

Publications:
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

Keywords provided by Teva Pharmaceutical Industries:
Clinically Definite Multiple Sclerosis
Clinically Isolated Syndrome
Multiple Sclerosis

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Syndrome
Autoimmune Diseases
Autoimmune Diseases of the Nervous System
Demyelinating Autoimmune Diseases, CNS
Demyelinating Diseases
Disease
Immune System Diseases
Nervous System Diseases
Pathologic Processes
Copolymer 1
Adjuvants, Immunologic
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 29, 2014