Comparison of Rituximab Induction Therapy Followed by Glatiramer Acetate Therapy to Glatiramer Acetate Monotherapy for MS (GATEWAY II)
This study is currently recruiting participants.
Verified November 2012 by University of Colorado, Denver
Sponsor:
University of Colorado, Denver
Collaborators:
University of Colorado Hospital
Rocky Mountain MS Research Group, LLC
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT01569451
First received: March 30, 2012
Last updated: November 20, 2012
Last verified: November 2012
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Purpose
The purpose of this study is (1) to determine if rituximab induction therapy followed by glatiramer acetate (GA) is substantially superior to placebo induction followed by GA for the treatment of clinically isolated syndrome (CIS) or relapsing forms of multiple sclerosis (RMS) and (2) to explore the changes in lymphocyte populations in the CNS as a consequence of treatment with rituximab followed by chronic GA therapy.
| Condition | Intervention | Phase |
|---|---|---|
|
Multiple Sclerosis |
Drug: Rituximab Drug: Glatiramer Acetate |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| Official Title: | A Double Blinded, Placebo Controlled, Randomized Study Comparing Rituximab Induction Therapy Followed by Glatiramer Acetate Therapy to Glatiramer Acetate Monotherapy in Patients With Relapsing Forms of Multiple Sclerosis |
Resource links provided by NLM:
Genetics Home Reference related topics:
multiple sclerosis
MedlinePlus related topics:
Multiple Sclerosis
U.S. FDA Resources
Further study details as provided by University of Colorado, Denver:
Primary Outcome Measures:
- Number of disease-free patients [ Time Frame: 1 year after the last patient is enrolled ] [ Designated as safety issue: Yes ]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:
- Time to treatment failure [ Time Frame: 1 year after the last patient is enrolled ] [ Designated as safety issue: Yes ]
- Percentage of subjects that fail treatment [ Time Frame: 1 year after the last patient is enrolled ] [ Designated as safety issue: Yes ]
- Proportion of relapse-free subjects [ Time Frame: 1 year after the last patient is enrolled ] [ Designated as safety issue: Yes ]
- Frequency of corticosteroid use (to treat relapses) [ Time Frame: 1 year after the last patient is enrolled ] [ Designated as safety issue: Yes ]
- Percentage of subjects who experience multiple relapses [ Time Frame: 1 year after the last patient is enrolled ] [ Designated as safety issue: Yes ]
- Number of patients that develop sustained accumulation of disability (SAD)c [ Time Frame: 1 year after the last patient is enrolled ] [ Designated as safety issue: Yes ]
- Change from baseline to the end of study on the Multiple Sclerosis Functional Composite (MSFC) z-score [ Time Frame: 1 year after the last patient is enrolled ] [ Designated as safety issue: Yes ]
- Percentage of subjects worsening one point or more on the Patient Determined Disease Steps (PDDS) questionnaire [ Time Frame: 1 year after the last patient is enrolled ] [ Designated as safety issue: Yes ]
- Change in mean score on Performance Scales [ Time Frame: 1 year after the last patient is enrolled ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 90 |
| Study Start Date: | February 2012 |
| Estimated Study Completion Date: | August 2014 |
| Estimated Primary Completion Date: | August 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: Glatiramer Acetate Therapy (GA)
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 GA therapy, 20 mg injected subcutaneously daily.
|
Drug: Glatiramer Acetate
20 mg injected subcutaneously daily
Other Names:
|
|
Experimental: Rituximab + Glatiramer Acetate Therapy (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 GA therapy, 20 mg injected subcutaneously daily.
|
Drug: Rituximab
intravenous (IV) infusion of 1000 mg of rituximab on study days 1 (baseline visit) and 15
Other Names:
Drug: Glatiramer Acetate
20 mg injected subcutaneously daily
Other Names:
|
Show Detailed Description Eligibility| Ages Eligible for Study: | 18 Years to 55 Years |
| Genders Eligible for Study: | Both |
| 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
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01569451
Contacts
| Contact: Mimi Burch | 303-724-6632 | Mimi.Burch@ucdenver.edu |
| Contact: Nicole Gendelman | 303-724-2197 | Nicole.Gendelman@ucdenver.edu |
Locations
| United States, Colorado | |
| University of Colorado Hospital | Recruiting |
| Aurora, Colorado, United States, 80045 | |
| Contact: Mimi Burch 303-724-6632 Mimi.Burch@ucdenver.edu | |
Sponsors and Collaborators
University of Colorado, Denver
University of Colorado Hospital
Rocky Mountain MS Research Group, LLC
Investigators
| Principal Investigator: | Timothy Vollmer, MD | University of Colorado, Denver |
More Information
No publications provided
| Responsible Party: | University of Colorado, Denver |
| ClinicalTrials.gov Identifier: | NCT01569451 History of Changes |
| Other Study ID Numbers: | 10-1143 |
| Study First Received: | March 30, 2012 |
| Last Updated: | November 20, 2012 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by University of Colorado, Denver:
|
Multiple Sclerosis Glatiramer Acetate Rituximab Relapsing forms of Multiple Sclerosis Relapsing Multiple Sclerosis |
Additional relevant MeSH terms:
|
Multiple Sclerosis Sclerosis Demyelinating Autoimmune Diseases, CNS Autoimmune Diseases of the Nervous System Nervous System Diseases Demyelinating Diseases Autoimmune Diseases Immune System Diseases Pathologic Processes Copolymer 1 |
Rituximab Adjuvants, Immunologic Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Immunosuppressive Agents Antirheumatic Agents Therapeutic Uses Antineoplastic Agents |
ClinicalTrials.gov processed this record on June 18, 2013