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

NCT00666224 | Completed Phase 3 Results DMC

• 1 other identifier: GA 9010
• Study Type: interventional
• Target: 481
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Multiple Sclerosis

Keywords

Clinically Definite Multiple Sclerosis; Clinically Isolated Syndrome; Multiple Sclerosis

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Secondary Outcomes (4)

• Number of New T2 Brain Lesions Observed at the Last Observed Value (LOV) in the Double-blind Period

  up to 3 years

• Change From Baseline to Last Observed Value (LOV) in T2 Brain Lesion Volume in the Double-blind Period

  Day 0 (baseline), up to 3 years

• 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

  Day 0 (baseline), up to 3 years

• Percentage of Participants Who Converted to Clinically Definite Multiple Sclerosis (CDMS) During the Double-blind Period

  up to 3 years

Study Arms (2)

Glatiramer acetate

EXPERIMENTAL

Glatiramer acetate 20 mg once daily by subcutaneous injection is administered in both the double-blind and open label periods.

Drug: Glatiramer Acetate (DB); Drug: Glatiramer Acetate (OL)

Placebo (DB) to GA (OL)

PLACEBO COMPARATOR

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; Drug: Glatiramer Acetate (OL)

Interventions

Glatiramer Acetate (DB) DRUG

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).

Also known as: Copaxone®

Glatiramer acetate

Placebo DRUG

Double blind period (DB): subcutaneous injection of placebo, once daily, for up to 36 months or until conversion to CDMS

Placebo (DB) to GA (OL)

Glatiramer Acetate (OL) DRUG

Open label period (OL): glatiramer acetate (GA), 20 mg, subcutaneous injection, once daily, given for up to an additional 24 months.

Also known as: Copaxone®

Glatiramer acetate; Placebo (DB) to GA (OL)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• The subject must have undergone a single clinical attack.
• The subject must have a unifocal clinical presentation.
• The subject should be enrolled within the period of 90 days after onset of a single unifocal clinical attack (index attack).
• 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.
• Subjects must be between the ages of 18 and 45 years inclusive.
• Subjects must not have taken corticosteroids within the 30 days prior to the MRI at the baseline visit.
• 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).
• The subjects must be willing and able to give written informed consent, prior to entering the study.

You may not qualify if:

• Multifocal clinical presentation.
• 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.
• Use of experimental or investigational drugs, including IV immunoglobulin, and/or participation in an investigational drug study within 6 months prior to study entry.
• Use of interferon agents within 6 months prior to the screening visit.
• Chronic corticosteroid treatment (more than 30 consecutive days) in the 6 months prior to study entry.
• Pregnancy or breast feeding.
• Subjects who experience a relapse between the screening (month -1) and baseline (month 0) visits.
• Life-threatening or other clinically significant disease.
• 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.
• A known history of sensitivity to mannitol.
• A known history of sensitivity to gadolinium.
• Inability to successfully undergo MRI scanning.

Sponsors & Collaborators

• Teva Branded Pharmaceutical Products R&D, Inc.: lead

Related 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 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.

  PMID: 19815268 RESULT

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Glatiramer Acetate

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Yossi Gilgun, PhD, Global Clinical Leader
• Organization: Teva Pharmaceutical Industries, Ltd.

yossi.gilgun@teva.co.il

972-9-863-1491

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2008
• First Posted: April 24, 2008
• Study Start: January 1, 2004
• Primary Completion: October 1, 2007
• Study Completion: June 1, 2010
• Last Updated: June 25, 2012
• Results First Posted: June 13, 2012

Record last verified: 2012-06