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Comparison of Rituximab Induction Therapy Followed by Glatiramer Acetate (GATEWAYII)

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ClinicalTrials.gov Identifier: NCT01569451
Recruitment Status : Completed
First Posted : April 3, 2012
Results First Posted : June 7, 2018
Last Update Posted : June 8, 2018
Sponsor:
Collaborator:
Rocky Mountain MS Research Group, LLC
Information provided by (Responsible Party):
University of Colorado, Denver

Brief Summary:
The purpose of this study is (1) to determine if rituximab induction therapy followed by glatiramer acetate (GA) is substantially superior to placebo rituximab induction followed by GA for the treatment of clinically isolated syndrome (CIS) or relapsing forms of multiple sclerosis (RMS).

Condition or disease Intervention/treatment Phase
Multiple Sclerosis Drug: Rituximab Drug: Glatiramer Acetate Other: Placebo Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 53 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double Blinded, Randomized Study Comparing Rituximab Induction Therapy Followed by Glatiramer Acetate Therapy to Glatiramer Acetate Monotherapy in Patients With Relapsing Forms of Multiple Sclerosis
Study Start Date : February 2012
Actual Primary Completion Date : May 2015
Actual Study Completion Date : May 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: (Placebo and) Glatiramer Acetate
Subjects will receive an intravenous (IV) infusion of placebo (normal saline) on study days 1 (baseline visit) and 15 according to the infusion protocol. On study day 28, all subjects will initiate standard Glatiramer Acetate therapy, 20 mg injected subcutaneously daily.
Drug: Glatiramer Acetate
20 mg injected subcutaneously daily
Other Names:
  • Copolymer 1
  • Cop-1
  • Copaxone

Other: Placebo
Subjects will receive an intravenous (IV) infusion of 1000 mg of rituximab or placebo (normal saline) on study days 1 (baseline visit) and 15 according to the rituximab infusion protocol. On study day 28, all subjects will initiate standard GA therapy, 20 mg injected subcutaneously daily.

Experimental: Rituximab and Glatiramer Acetate (R-GA)
Subjects will receive an intravenous (IV) infusion of 1000 mg of rituximab on study days 1 (baseline visit) and 15 according to the rituximab infusion protocol. On study day 28, subjects will initiate standard Glatiramer Acetate therapy, 20 mg injected subcutaneously daily. There is no placebo arm.
Drug: Rituximab
intravenous (IV) infusion of 1000 mg of rituximab on study days 1 (baseline visit) and 15
Other Names:
  • Rituxan
  • MabThera

Drug: Glatiramer Acetate
20 mg injected subcutaneously daily
Other Names:
  • Copolymer 1
  • Cop-1
  • Copaxone




Primary Outcome Measures :
  1. Number of Disease-free Patients [ Time Frame: Baseline through 24 months ]
    Defined as patients without new lesions on brain MRI using the combined unique lesion approach (CUL), without sustained change in EDSS score over any 3-month period and without relapse. If a clear treatment effect is sustained in the R-GA arm, defined as a ≥ 70% decrease in brain lesions on MRI, using a CUL approach, attributable to MS and ≥ 70% reduction in annual relapse rates, compared to the GA arm, the study will continue under the extension protocol. If induction therapy fails to show superiority, at any point, the study will be stopped.


Secondary Outcome Measures :
  1. Time to Treatment Failure [ Time Frame: Baseline through 24 months ]
    Time itself is the outcome. Whenever treatment failure occurs for the first time within the follow up period of 24 months (2 years).

  2. Number of Subjects That Fail Treatment [ Time Frame: Baseline through 24 months ]
  3. Number of Relapse-free Subjects [ Time Frame: Baseline through 24 months ]
    Change in neurological symptoms in association with EDSS change is defined as relapse.

  4. Number of Patients Treated for Relapse With Corticosteroid [ Time Frame: Baseline through 24 months ]
  5. Number of Subjects Who Experience Multiple Relapses [ Time Frame: Baseline through 24 months ]
  6. Number of Patients That Develop Sustained Accumulation of Disability [ Time Frame: Baseline through 24 months ]
    Sustained accumulation of disability is defined as a 1 point change or more on the Expanded Disability Status Scale (EDSS); sustained for at least three months. Physicians assess patients' cerebral, optic, brainstem, pyramidal, sensory, cerebellar, and bowel and bladder neurological symptoms. The physician then subjectively rates the patient on the ordinal EDSS scale. The EDSS scale emphasizes ambulatory ability. The EDSS scale ranges in half integer increments from 0.0 to 10.0. Larger numbers mean more disability, with 0.0 being everything normal and 10.0 being death due to MS.

  7. Change From Baseline to 24 Months on the Multiple Sclerosis Functional Composite (MSFC) Z-score [ Time Frame: Observations were recorded at baseline and 24 months. ]
    The MSFC consists of Timed 25 Foot Walk Tests, 9 Hole Peg Tests, and the Paced Auditory Serial Addition Test (PASAT), administered by clinicians. The subscales are then converted into Z-scores and averaged to create the MSFC Z-score. Larger values denote improvements.

  8. Percentage of Subjects Worsening One Point or More on the Patient Determined Disease Steps (PDDS) Questionnaire [ Time Frame: Baseline through 24 months ]
    For PDDS the patient selects an integer 0-8 according to their personal assessment of their degree of ambulatory disability. Larger numbers mean more disability, with 0 being no disability and 8 being bedridden. There is an unclassifiable category as well.

  9. Change in Mean Score on Performance Scales (Baseline to 24 Months) [ Time Frame: Baseline through 24 months ]
    Performance scales measures patient assessments of disability in mobility (1-6), hand (1-5), vision (1-5), fatigue (1-5), cognitive (1-5), bladder and bowel, sensory (1-5), and spasticity (1-5). The overall measure of performance is the sum of subscales, ranging from 0 to 41. Larger numbers mean more disability, with 0 being no disability and the maximum number being total disability.



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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 18 through 55 years of age
  • Patients with CIS demonstrating one unifocal neurological event AND at least 2 T2-weighted brain lesions measuring a minimum of 6mm in diameter by MRI analysis; or a definite diagnosis of RMS, as defined by the 2005 revised McDonald criteria(1, 2), and have had at least one clinically defined relapse within the past year OR one GEL on an MRI within the past year
  • Women of child-bearing potential must agree to practice an acceptable method of birth control
  • No evidence of progressive multifocal leukoencephalopathy (PML) or primary central nervous system (PCNS) lymphoma
  • Neurologically stable with no evidence of relapse or corticosteroid treatment within 30 days prior to randomization
  • Subject must be able and willing to give meaningful, written informed consent prior to participation in the trial, in accordance with local regulatory requirements.

Exclusion Criteria:

  • ≥ 15 GELs on baseline MRI
  • Treatment with interferon β, natalizumab, or fingolimod within three months of randomization
  • Treatment with mitoxantrone, cyclophosphamide, or any other chemotherapeutic agent for MS or malignancy within 12 months of randomization
  • Attenuated live virus vaccination within 4 weeks of randomization
  • Positive urine and serum pregnancy test at screening or baseline visit
  • Any prior treatment with alemtuzumab or cladribine
  • Unable to tolerate GA
  • History of cardiac arrhythmias, angina or any other significant cardiac abnormalities
  • History of clinically significant chronic disease of the immune system or a known immunodeficiency syndrome (HIV) other than MS
  • White Blood Cell count of less than 2.5*10^9/L or lymphocyte count below 0.4*10^9/L
  • Positive for any evidence of past, or current, hepatitis B and/or C infection
  • History or presence of malignancy (except basal cell carcinoma)
  • Clinically significant alcohol or drug abuse within past two years
  • Any medical, psychiatric or other condition that could result in a subject not being able to give fully informed consent, or to comply with the protocol requirements
  • Inability to undergo MRI scans or history of hypersensitivity to gadolinium- diethylenetriamine penta-acetic acid (DTPA)
  • Participation in any clinical study evaluating another investigational drug or therapy within three months prior to randomization
  • Any other condition that, in the Investigator's opinion, makes the subject unsuitable for participation in the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01569451


Locations
United States, Colorado
University of Colorado Hospital
Aurora, Colorado, United States, 80045
Sponsors and Collaborators
University of Colorado, Denver
Rocky Mountain MS Research Group, LLC
Investigators
Principal Investigator: Timothy Vollmer, MD University of Colorado, Denver

Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT01569451     History of Changes
Other Study ID Numbers: 10-1143
First Posted: April 3, 2012    Key Record Dates
Results First Posted: June 7, 2018
Last Update Posted: June 8, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by University of Colorado, Denver:
Multiple Sclerosis
Glatiramer Acetate
Rituximab
Relapsing forms of Multiple Sclerosis
Relapsing Multiple Sclerosis

Additional relevant MeSH terms:
Sclerosis
Multiple Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Rituximab
Glatiramer Acetate
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Adjuvants, Immunologic
Immunosuppressive Agents