Assessment Study of Steroid Effect in Relapsing Multiple Sclerosis Subjects Treated With Glatiramer Acetate

NCT ID: NCT00203047

Last Updated: 2014-01-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 414 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-01-31
• Study Completion Date: 2009-05-31

Brief Summary

This is a study evaluating the effect on brain volume of daily glatiramer acetate (GA) and add-on pulse steroids.

Detailed Description

One interim analysis was planned for possible early termination due to proven efficacy when 75% of the preplanned 500 (approx. 375 patients) recruited patients completed the entire study duration or early discontinued.

In addition to the stopping rule already given for proven efficacy, the sponsor was also interested in examining the data for futility (i.e., absence of the desired treatment effect) with the view to terminating the trial if an "insufficient" effect of the treatment is seen. The reasons why the need for futility arose were:

1. Recruitment difficulties

2. Increasing dropout rate

3. Budgetary constraints

The primary efficacy measure is defined as the percent change from baseline to termination (Month 36 or Early Termination) in normalized brain volume (Brain Atrophy) measured according to the SIENA (Structural Imaging Evaluation using Normalization of Atrophy) method. However, since not many patients had completed the entire study at the time of futility analysis, it was the sponsor's decision that the futility analysis be performed on patients with MRI scans at months 24 or 36 or at early termination visits - the latest available.

Based on the recalculation of study power (probability is unconditioned on the interim result and provide the real power of the study if designed anew), conditional power (based on the interim results) and risk assessment of a false negative, the Data Monitoring Committee agreed that the study should be terminated early.

Conditions

Relapsing Remitting Multiple Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

GA + Placebo

Glatiramer acetate (GA) 10mg as a subcutaneous injection daily, plus a placebo to mimic prednisone given daily.

Group Type: ACTIVE_COMPARATOR

Glatiramer Acetate

Intervention Type: DRUG

20mg glatiramer acetate (GA) administered by daily subcutaneous injections

Placebo

Intervention Type: DRUG

Placebo for prednisone given daily

GA + Prednisone

Glatiramer acetate (GA) 20mg daily as a subcutaneous injection, plus 1250 mg of prednisone daily.

Group Type: EXPERIMENTAL

Glatiramer Acetate

Intervention Type: DRUG

20mg glatiramer acetate (GA) administered by daily subcutaneous injections

Prednisone

Intervention Type: DRUG

Prednisone 1250 mg taken daily

Interventions

Glatiramer Acetate

20mg glatiramer acetate (GA) administered by daily subcutaneous injections

Intervention Type: DRUG

Placebo

Placebo for prednisone given daily

Intervention Type: DRUG

Prednisone

Prednisone 1250 mg taken daily

Intervention Type: DRUG

Other Intervention Names

Copaxone; corticosteroid

Eligibility Criteria

Inclusion Criteria

1. Clinically definite multiple sclerosis (CDMS) according to Poser (Ann. Neurol. 1983) or McDonald (Ann. Neurol. 2001)

2. Subjects eligible for GA treatment based on the investigator's clinical assessment and according to the current indication.

3. Subjects must have a relapsing remitting disease course.

4. Subjects must have had at least 1 documented relapse within the last year prior to study entry.

5. Subjects may be male or female. Women of childbearing potential must practice an acceptable method of birth control. Acceptable methods include oral contraceptive, contraceptive patch, long-acting injectable contraceptive, double-barrier method (condom or intrauterine device [IUD] with spermicide), or partner's vasectomy.

6. Subjects must be between the ages of 18 and 55 years inclusive.

7. Subjects must be ambulatory, with a Kurtzke Expanded Disability Status Scale (EDSS) score between 0 and 5.0 inclusive.

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

Exclusion Criteria

1. Long-term glatiramer acetate users who have been on therapy within 6 months of the baseline magnetic resonance imaging (MRI). New glatiramer acetate users who have initiated therapy for more than 6 weeks prior to the baseline MRI.

2. Previous use of cladribine.

3. Previous use of mitoxantrone.

4. Use of digitalis at study entry.

5. Previous use of immunosuppressive agents (such as azathioprine, cyclophosphamide or mycophenolate mofetil) in the last 6 months prior to screening.

6. Use of experimental or investigational drugs, including intravenous (IV) immunoglobulin within 6 months prior to screening.

7. Use of interferon agents within 1 month prior to the baseline MRI.

8. Use of corticosteroids (IV, intramuscular [IM] and/or by mouth [PO]) within 30 days prior to the baseline MRI.

9. Chronic corticosteroid (IV, IM and/or PO) treatment (more than 30 consecutive days) in the 6 months prior to the screening visit.

10. Subjects with diabetes.

11. Previous total body irradiation or total lymphoid irradiation.

12. Pregnancy or breast feeding.

13. Significant medical or psychiatric condition that affects the subject's ability to give informed consent, or to complete the study, or any condition which the investigator feels may interfere with participation in the study (e.g. alcohol or drug abuse).

14. Other diseases that can cause brain atrophy (ex. neurodegenerative disorder, cerebrovascular disease, history of alcohol abuse).

15. Bone density less than -2.5 standard deviations (SD) (osteoporosis).

16. A known history of sensitivity to mannitol.

17. Contraindication to, or known history of, sensitivity or severe reaction to steroids.

18. A known history of sensitivity to gadolinium.

19. Inability to successfully undergo MRI scanning.

20. Previous use of natalizumab.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Teva Branded Pharmaceutical Products R&D, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jean-Louis Stril, MD

Role: STUDY_CHAIR

Teva Neuroscience Canada

References

Milo R, Panitch H. Combination therapy in multiple sclerosis. J Neuroimmunol. 2011 Feb;231(1-2):23-31. doi: 10.1016/j.jneuroim.2010.10.021. Epub 2010 Dec 15.

Reference Type: RESULT

PMID: 21111490 (View on PubMed)

Other Identifiers

TNC GA MS 2004_01

Identifier Type: -

Identifier Source: org_study_id