search
Back to results

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

Primary Purpose

Relapsing Remitting Multiple Sclerosis

Status
Terminated
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Glatiramer Acetate
Placebo
Prednisone
Sponsored by
Teva Branded Pharmaceutical Products R&D, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Relapsing Remitting Multiple Sclerosis focused on measuring Multiple Sclerosis, brain atrophy, Glatiramer Acetate, Copaxone, Steroids, Prednisone

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Clinically definite multiple sclerosis (CDMS) according to Poser (Ann. Neurol. 1983) or McDonald (Ann. Neurol. 2001) Subjects eligible for GA treatment based on the investigator's clinical assessment and according to the current indication. Subjects must have a relapsing remitting disease course. Subjects must have had at least 1 documented relapse within the last year prior to study entry. 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. Subjects must be between the ages of 18 and 55 years inclusive. Subjects must be ambulatory, with a Kurtzke Expanded Disability Status Scale (EDSS) score between 0 and 5.0 inclusive. Subjects must be willing and able to give written informed consent prior to entering the study. Exclusion Criteria: 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. Previous use of cladribine. Previous use of mitoxantrone. Use of digitalis at study entry. Previous use of immunosuppressive agents (such as azathioprine, cyclophosphamide or mycophenolate mofetil) in the last 6 months prior to screening. Use of experimental or investigational drugs, including intravenous (IV) immunoglobulin within 6 months prior to screening. Use of interferon agents within 1 month prior to the baseline MRI. Use of corticosteroids (IV, intramuscular [IM] and/or by mouth [PO]) within 30 days prior to the baseline MRI. Chronic corticosteroid (IV, IM and/or PO) treatment (more than 30 consecutive days) in the 6 months prior to the screening visit. Subjects with diabetes. Previous total body irradiation or total lymphoid irradiation. Pregnancy or breast feeding. 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). Other diseases that can cause brain atrophy (ex. neurodegenerative disorder, cerebrovascular disease, history of alcohol abuse). Bone density less than -2.5 standard deviations (SD) (osteoporosis). A known history of sensitivity to mannitol. Contraindication to, or known history of, sensitivity or severe reaction to steroids. A known history of sensitivity to gadolinium. Inability to successfully undergo MRI scanning. Previous use of natalizumab.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Experimental

    Arm Label

    GA + Placebo

    GA + Prednisone

    Arm Description

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

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

    Outcomes

    Primary Outcome Measures

    Percent Change From Baseline to Termination in Normalized Brain Volume Measured According to the SIENA (Structural Imaging Evaluation Using Normalization of Atrophy) Method
    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.

    Secondary Outcome Measures

    Cumulative Number of Enhancing Lesions at 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
    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
    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.

    Full Information

    First Posted
    September 13, 2005
    Last Updated
    November 15, 2013
    Sponsor
    Teva Branded Pharmaceutical Products R&D, Inc.
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT00203047
    Brief Title
    Assessment Study of Steroid Effect in Relapsing Multiple Sclerosis Subjects Treated With Glatiramer Acetate
    Acronym
    ASSERT
    Official Title
    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)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    November 2013
    Overall Recruitment Status
    Terminated
    Why Stopped
    Slow enrollment decreased sample size; No unexpected safety issues.
    Study Start Date
    January 2005 (undefined)
    Primary Completion Date
    May 2009 (Actual)
    Study Completion Date
    May 2009 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Teva Branded Pharmaceutical Products R&D, Inc.

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    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: Recruitment difficulties Increasing dropout rate 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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Relapsing Remitting Multiple Sclerosis
    Keywords
    Multiple Sclerosis, brain atrophy, Glatiramer Acetate, Copaxone, Steroids, Prednisone

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 4
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    414 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    GA + Placebo
    Arm Type
    Active Comparator
    Arm Description
    Glatiramer acetate (GA) 10mg as a subcutaneous injection daily, plus a placebo to mimic prednisone given daily.
    Arm Title
    GA + Prednisone
    Arm Type
    Experimental
    Arm Description
    Glatiramer acetate (GA) 20mg daily as a subcutaneous injection, plus 1250 mg of prednisone daily.
    Intervention Type
    Drug
    Intervention Name(s)
    Glatiramer Acetate
    Other Intervention Name(s)
    Copaxone
    Intervention Description
    20mg glatiramer acetate (GA) administered by daily subcutaneous injections
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    Placebo for prednisone given daily
    Intervention Type
    Drug
    Intervention Name(s)
    Prednisone
    Other Intervention Name(s)
    corticosteroid
    Intervention Description
    Prednisone 1250 mg taken daily
    Primary Outcome Measure Information:
    Title
    Percent Change From Baseline to Termination in Normalized Brain Volume Measured According to the SIENA (Structural Imaging Evaluation Using Normalization of Atrophy) Method
    Description
    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.
    Time Frame
    Day 0, latest scan at month 24, 36 or early termination visit
    Secondary Outcome Measure Information:
    Title
    Cumulative Number of Enhancing Lesions at Months 12, 24 and 36
    Description
    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.
    Time Frame
    Months 12, 24, and 36
    Title
    Change From Baseline to Month 36 or Early Termination Visit in Volume of T2-Lesions
    Description
    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.
    Time Frame
    Day 0, Month 36 or the early termination visit
    Title
    Change From Baseline to Month 36 or Early Termination Visit in Volume of Hypointense Lesions
    Description
    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.
    Time Frame
    Day 0, Month 36 or early termination visit

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    55 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Clinically definite multiple sclerosis (CDMS) according to Poser (Ann. Neurol. 1983) or McDonald (Ann. Neurol. 2001) Subjects eligible for GA treatment based on the investigator's clinical assessment and according to the current indication. Subjects must have a relapsing remitting disease course. Subjects must have had at least 1 documented relapse within the last year prior to study entry. 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. Subjects must be between the ages of 18 and 55 years inclusive. Subjects must be ambulatory, with a Kurtzke Expanded Disability Status Scale (EDSS) score between 0 and 5.0 inclusive. Subjects must be willing and able to give written informed consent prior to entering the study. Exclusion Criteria: 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. Previous use of cladribine. Previous use of mitoxantrone. Use of digitalis at study entry. Previous use of immunosuppressive agents (such as azathioprine, cyclophosphamide or mycophenolate mofetil) in the last 6 months prior to screening. Use of experimental or investigational drugs, including intravenous (IV) immunoglobulin within 6 months prior to screening. Use of interferon agents within 1 month prior to the baseline MRI. Use of corticosteroids (IV, intramuscular [IM] and/or by mouth [PO]) within 30 days prior to the baseline MRI. Chronic corticosteroid (IV, IM and/or PO) treatment (more than 30 consecutive days) in the 6 months prior to the screening visit. Subjects with diabetes. Previous total body irradiation or total lymphoid irradiation. Pregnancy or breast feeding. 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). Other diseases that can cause brain atrophy (ex. neurodegenerative disorder, cerebrovascular disease, history of alcohol abuse). Bone density less than -2.5 standard deviations (SD) (osteoporosis). A known history of sensitivity to mannitol. Contraindication to, or known history of, sensitivity or severe reaction to steroids. A known history of sensitivity to gadolinium. Inability to successfully undergo MRI scanning. Previous use of natalizumab.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Jean-Louis Stril, MD
    Organizational Affiliation
    Teva Neuroscience Canada
    Official's Role
    Study Chair

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    21111490
    Citation
    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.
    Results Reference
    result

    Learn more about this trial

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

    We'll reach out to this number within 24 hrs