Comparison of Rituximab Induction Therapy Followed by Glatiramer Acetate
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Sclerosis
Intervention: Rituximab; Glatiramer Acetate; Placebo
Intervention description: intravenous (IV) infusion of 1000 mg of rituximab on study days 1 (baseline visit) and 15; 20 mg injected subcutaneously daily; 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.
Intervention MeSH terms: Rituximab; Glatiramer Acetate; (T,G)-A-L
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 53.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: No
Keywords: Multiple Sclerosis; Glatiramer Acetate; Rituximab; Relapsing forms of Multiple Sclerosis; Relapsing Multiple Sclerosis

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).
    

Eligibility 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