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

Sponsor

Isfahan University of Medical Sciences (Other)

Overall Status

Completed

CT.gov ID

NCT03315923

Collaborator

(none)

Enrollment

Location

Arms

14.9

Actual Duration (Months)

5.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Secondary Progressive Multiple Sclerosis	Drug: Rituximab Drug: Glatiramer Acetate	Phase 2/Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

84 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Comparison of Expanded Disability Status Scale, Gad-enhanced Brain Lesions, Annualized Relapse Rate, and Side Effects Between Active Secondary Progressive Multiple Sclerosis Patients on Rituximab and Glatiramer Acetate

Actual Study Start Date :

Dec 1, 2017

Actual Primary Completion Date :

Feb 1, 2019

Actual Study Completion Date :

Mar 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: 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. Other Names: Zytux®
Experimental: Glatiramer acetate Patients in this group will receive 40 mg of glatiramer acetate three times per week through subcutaneous injection.	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. Other Names: Osvimer®

Arm

Intervention/Treatment

Experimental: 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.

Drug: 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.

Other Names:

Zytux®

Experimental: Glatiramer acetate

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

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.

Other Names:

Osvimer®

Outcome Measures

Primary Outcome Measures

Disability measured by Expanded Disability Status Scale [one year]
expanded disability status scale will be measured in the baseline and after 12 months of intervention. This scale measures the disability of patients with a score, ranging from 0 (normal neurological exam) to 10 (death due to MS). This score is assigned to the patient by the neurologist and after neurological examination. The patient will be given a score in this scale according to the observed disability. The scores will be compared at the end of study.

Secondary Outcome Measures

Adverse Drug Reactions [one year]
adverse drug reactions will be observed closely and reported during the intervention. We will compare the number of adverse drug reactions in two groups. Also, adverse drug reactions will be described by details in each group.
number of Gadolinium-enhanced brain lesions and neuroimaging findings [one year]
patients will undergo brain MRI before and after the study and number of Gad-enhanced brain lesions will compared before and after intervention.
Annualized relapse rate [one year]
annualized relapse rate will be measured in the baseline (according to patients' history in the last year) and after 12 months of intervention.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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