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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00203047
Recruitment Status : Terminated (Slow enrollment decreased sample size; No unexpected safety issues.)
First Posted : September 20, 2005
Results First Posted : January 6, 2014
Last Update Posted : January 6, 2014
Sponsor:
Information provided by (Responsible Party):
Teva Branded Pharmaceutical Products R&D, Inc.

Tracking Information
First Submitted Date  ICMJE September 13, 2005
First Posted Date  ICMJE September 20, 2005
Results First Submitted Date  ICMJE August 29, 2013
Results First Posted Date  ICMJE January 6, 2014
Last Update Posted Date January 6, 2014
Study Start Date  ICMJE January 2005
Actual Primary Completion Date May 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 15, 2013)
Percent Change From Baseline to Termination in Normalized Brain Volume Measured According to the SIENA (Structural Imaging Evaluation Using Normalization of Atrophy) Method [ Time Frame: Day 0, latest scan at month 24, 36 or early termination visit ]
Results represent the database as of January 29, 2009. Brain volume was measured at baseline and at months 24, 36 and at early termination visits by magnetic resonance imaging (MRI). Brain atrophy was measured by comparing the change in brain volume from baseline to the latest scan at the three during study timeframes. SIENA is a fully automated method of analyzing longitudinal brain change. Adjusted (least square) mean values are presented.
Original Primary Outcome Measures  ICMJE
 (submitted: September 13, 2005)
The primary objective of this study is to evaluate the add-on treatment effect of oral steroids on brain volume changes as measured by the 3-year change from baseline in brain volume, in relapsing remitting multiple sclerosis subjects treated with GA.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 15, 2013)
  • Cumulative Number of Enhancing Lesions at Months 12, 24 and 36 [ Time Frame: Months 12, 24, and 36 ]
    Results represent the database as of January 29, 2009. Enhancing lesions are lesions that show inflammation on an MRI and are assumed to be new lesions. The sum of enhancing lesions observed in MRIs taken at months 12, 24 and 36 are offered.
  • Change From Baseline to Month 36 or Early Termination Visit in Volume of T2-Lesions [ Time Frame: Day 0, Month 36 or the early termination visit ]
    Results represent the database as of January 29, 2009. The difference in T2 brain lesion volume as observed in MRIs from baseline to Month 36 or the early termination visit. T2 lesions are hyperintense lesions meaning that they appear as bright spots on the MRI image. These tend to show the total number of lesions and disease burden.
  • Change From Baseline to Month 36 or Early Termination Visit in Volume of Hypointense Lesions [ Time Frame: Day 0, Month 36 or early termination visit ]
    Results represent the database as of January 29, 2009. The difference in hypointense brain lesion volume as observed in MRIs from baseline to Month 36 or the early termination visit. Hypointense lesions display as dark areas on the MRI image, and represent areas of permanent axonal damage.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Assessment Study of Steroid Effect in Relapsing Multiple Sclerosis Subjects Treated With Glatiramer Acetate
Official Title  ICMJE A Multi-Centered, Randomized, Double-Blind, Placebo Controlled Study Assessing the Add-on Effect of Oral Steroids in Relapsing Remitting Multiple Sclerosis Subjects Treated With Glatiramer Acetate (GA)
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Relapsing Remitting Multiple Sclerosis
Intervention  ICMJE
  • Drug: Glatiramer Acetate
    20mg glatiramer acetate (GA) administered by daily subcutaneous injections
    Other Name: Copaxone
  • Drug: Placebo
    Placebo for prednisone given daily
  • Drug: Prednisone
    Prednisone 1250 mg taken daily
    Other Name: corticosteroid
Study Arms  ICMJE
  • Active Comparator: GA + Placebo
    Glatiramer acetate (GA) 10mg as a subcutaneous injection daily, plus a placebo to mimic prednisone given daily.
    Interventions:
    • Drug: Glatiramer Acetate
    • Drug: Placebo
  • Experimental: GA + Prednisone
    Glatiramer acetate (GA) 20mg daily as a subcutaneous injection, plus 1250 mg of prednisone daily.
    Interventions:
    • Drug: Glatiramer Acetate
    • Drug: Prednisone
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: March 23, 2009)
414
Original Enrollment  ICMJE
 (submitted: September 13, 2005)
500
Actual Study Completion Date  ICMJE May 2009
Actual Primary Completion Date May 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries Canada,   United States
 
Administrative Information
NCT Number  ICMJE NCT00203047
Other Study ID Numbers  ICMJE TNC GA MS 2004_01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Teva Branded Pharmaceutical Products R&D, Inc.
Original Responsible Party Not Provided
Current Study Sponsor  ICMJE Teva Branded Pharmaceutical Products R&D, Inc.
Original Study Sponsor  ICMJE Teva Neuroscience, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Jean-Louis Stril, MD Teva Neuroscience Canada
PRS Account Teva Branded Pharmaceutical Products R&D, Inc.
Verification Date November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP