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Relapsing Remitting Multiple SclerosisPhase 4ASSERTNCT00203047

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

A Phase 4 study testing Glatiramer Acetate and Prednisone in people with Relapsing Remitting Multiple Sclerosis, run by Teva Branded Pharmaceutical Products R&D, Inc..

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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

Who is it for?
Ages 18 to 55 years
Conditions the study is for
Relapsing Remitting Multiple Sclerosis
What is being tested?
Glatiramer Acetate and Prednisone
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
414 participants
Where
No sites listed yet
Study dates
Jan 2005to May 2009
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
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  • 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.

About this study

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)

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

Read the 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.

Being tested
Glatiramer Acetate, Placebo, Prednisone
Keywords
Multiple Sclerosis, brain atrophy, Glatiramer Acetate, Copaxone, Steroids, Prednisone
Medical subject headings
Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Glatiramer AcetateDrug

    Also called Copaxone

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

  • PlaceboDrug

    Placebo for prednisone given daily

  • PrednisoneDrug

    Also called corticosteroid

    Prednisone 1250 mg taken daily

Study groups in NCT00203047
Study groupRoleWhat they receive
GA + PlaceboActive comparatorGlatiramer acetate (GA) 10mg as a subcutaneous injection daily, plus a placebo to mimic prednisone given daily.
Receives: Drug: Glatiramer Acetate; Drug: Placebo
GA + PrednisoneExperimentalGlatiramer acetate (GA) 20mg daily as a subcutaneous injection, plus 1250 mg of prednisone daily.
Receives: Drug: Glatiramer Acetate; Drug: Prednisone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Day 0, latest scan at month 24, 36 or early termination visit

Secondary outcomes (3)

  1. 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.

    Measured: Months 12, 24, and 36

  2. 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.

    Measured: Day 0, Month 36 or the early termination visit

  3. 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.

    Measured: Day 0, Month 36 or early termination visit

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Sep 2005 (estimated)
  2. Study startJan 2005
  3. Primary completionMay 2009
  4. Study completionMay 2009

Why it stopped: Slow enrollment decreased sample size; No unexpected safety issues.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
414 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00203047
Sponsor's protocol ID
TNC GA MS 2004_01
Acronym
ASSERT
Status last verified
Nov 2013
First submitted
13 Sep 2005
Last updated
6 Jan 2014
Data monitoring committee
Yes

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.

    PubMed 21111490

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Glatiramer Acetate and Prednisone in people with Relapsing Remitting Multiple Sclerosis, run by Teva Branded Pharmaceutical Products R&D, Inc..

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 6 Jan 2014. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Jan 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00203047, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jan 2014.

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