Comparison of Clinical Effects of Rituximab and Glatiramer Acetate in Secondary Progressive Multiple Sclerosis Patients

NCT ID: NCT03315923

Last Updated: 2019-05-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 84 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-01
• Study Completion Date: 2019-03-01

Brief Summary

The purpose of this study is to compare expanded disability status scale, annualized relapse rate, Gad-enhanced brain lesions, and side effects after administration of rituximab and glatiramer acetate among patients with active secondary progressive multiple sclerosis during a one year follow up through a randomized clinical trial.

Detailed Description

Multiple sclerosis (MS) is an autoimmune inflammatory demyelinative disease of central nervous system. Active secondary progressive MS means progressive accumulation of disability after an initial relapsing course which is also associated with clinical relapses and/or new/enlarged Gad-enhanced brain lesions. This form of the disease leads to high rates of morbidity and mortality among patients. Different immunosuppressive and immunomodulatory agents are recommended by researchers to decrease relapses and improve disability among MS patients. The effect of these medications on different phenotypes of MS are mostly investigated solely and very small number of comparative studies are conducted to evaluate the superiority of these medications on each other.

Glatiramer acetate is one of the known MS medications which is being used to control relapses from a long time ago and different clinical trials have shown its partial efficacy among MS patients. On the other hand, rituximab is one of the medications which is recently suggested for treatment of MS and currently phase II clinical trials are conducted to evaluate the efficacy of this medication among patients. As previously stated, there is a lack of clinical trials to compare the efficacy of suggested medications among secondary progressive patients. To fill this gap, we aimed to compare the efficacy of these two medications on disability, annualized relapse rate, and Gad-enhanced brain lesions among patients with active secondary progressive MS through a randomized clinical trial during a one-year follow-up period.

Conditions

Secondary Progressive Multiple Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Rituximab

Patients in this group will receive 1g of rituximab in 500 cc normal saline serum through intravenous infusion as one treatment course. The treatment course will be repeated in 6 months. Along with rituximab, 100 mg methylprednisolone, 10 mg chlorpheniramine, and 500 mg acetaminophen will also be injected to decrease side effects of rituximab.

Group Type: EXPERIMENTAL

Rituximab

Intervention Type: DRUG

Patients will receive 1 g of rituximab (two vials of Zytux 500 mg/50 ml) in 500 cc normal saline serum through intravenous infusion as one treatment cycle. This cycle will be repeated every 6 months. Along with rituximab, patients will receive 100 mg of methylprednisolone, 10 mg of chlorpheniramine, and 500 mg of acetaminophen. Before each cycle, patients will be evaluated regarding complete blood count (CBC)-diff, blood urea nitrogen (BUN), Cr, and liver function tests.

Glatiramer acetate

Patients in this group will receive 40 mg of glatiramer acetate three times per week through subcutaneous injection.

Group Type: EXPERIMENTAL

Glatiramer Acetate

Intervention Type: DRUG

Patients will receive 40 mg of glatiramer acetate three times per week through subcutaneous injection. Patients will undergo electrocardiography before starting the treatment to find any abnormal finding. Also, lab tests will be checked for them prior to the treatment, including CBC-diff, BUN, Cr, and liver function tests.

Interventions

Rituximab

Patients will receive 1 g of rituximab (two vials of Zytux 500 mg/50 ml) in 500 cc normal saline serum through intravenous infusion as one treatment cycle. This cycle will be repeated every 6 months. Along with rituximab, patients will receive 100 mg of methylprednisolone, 10 mg of chlorpheniramine, and 500 mg of acetaminophen. Before each cycle, patients will be evaluated regarding complete blood count (CBC)-diff, blood urea nitrogen (BUN), Cr, and liver function tests.

Intervention Type: DRUG

Glatiramer Acetate

Patients will receive 40 mg of glatiramer acetate three times per week through subcutaneous injection. Patients will undergo electrocardiography before starting the treatment to find any abnormal finding. Also, lab tests will be checked for them prior to the treatment, including CBC-diff, BUN, Cr, and liver function tests.

Intervention Type: DRUG

Other Intervention Names

Zytux®; Osvimer®

Eligibility Criteria

Inclusion Criteria

• age between 18 and 55 years old
• diagnosis of active secondary progressive multiple sclerosis based on the latest McDonald criteria in 2010
• experiencing at least one relapse during the last year
• expanded disability status scale ≤5
• diagnosis of secondary progressive MS for at least one year
• maintaining pregnancy prevention methods for women in reproductive ages
• filling the written informed consent prior to enrollment

Exclusion Criteria

• diagnosis of other subtypes of MS, including relapsing-remitting MS and primary progressive MS and inactive form of the disease
• experiencing relapse during the 30 days before starting the study
• receiving systemic corticosteroid therapy during the last 30 days
• undergoing plasmapheresis or receiving intravenous immunoglobulin during the last 1 months
• history of other demyelinative diseases of central nervous system such as neuromyelitis optica spectrum disorders
• history of other autoimmune diseases such as systemic lupus erythematosus, sjogren's syndrome, antiphospholipid syndrome, and behcet's disease
• presence of chronic or recurrent infections such as hepatitis B, hepatitis C, or syphilis
• pregnancy or lactation
• receiving live attenuated viral vaccines during the last 4 weeks
• history of cardiac arrhythmia, angina pectoris, or other cardiac diseases
• history of immunodeficiency syndromes such as HIV
• white blood cell count <2500 or lymphocyte count <400
• history of brain and spinal malignancies
• history of severe allergic reactions or anaphylaxis to monoclonal antibodies
• presence of active bacterial, viral, fungal, mycobacterial, or other infections
• alcohol or drug abuse during the last two years
• unable to undergo MRI
• presence of uncontrolled cardiac, respiratory, renal, hepatic, endocrine, or gastrointestinal disease
• presence of encephalopathy due to infectious (such as herpes, syphilis, ...) or metabolic (vitamin B12 deficiency) reasons
• history of bone marrow transplant, whole body radiotherapy, or other treatments leading to reduction of lymphocytes
• Cr>1.4 in women and >1.6 in men
• aspartate transaminase and alanine transaminase 2.5 times higher than the normal amount
• platelet count <100000
• Hb <8.5

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Isfahan University of Medical Sciences

OTHER

Sponsor Role: lead

Responsible Party

Vahid Shaygannejad

Professor of Neurology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Vahid Shaygannejad, M.D.

Role: STUDY_CHAIR

Isfahan University of Medical Sciences

Locations

Kashani Hospital

Isfahan, , Iran

Countries

Iran

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Other Identifiers

396514

Identifier Type: -

Identifier Source: org_study_id