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

Primary Purpose

Secondary Progressive Multiple Sclerosis

Status

Completed

Phase

Phase 2

Locations

Iran, Islamic Republic of

Study Type

Interventional

Intervention

Rituximab

Glatiramer Acetate

About this trial

This is an interventional treatment trial for Secondary Progressive Multiple Sclerosis focused on measuring Active secondary progressive Multiple Sclerosis, Glatiramer acetate, Rituximab, Comparative study, Disability, Randomized clinical trial, Annualized relapse rate

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept 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

Sites / Locations

Kashani Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Rituximab

Glatiramer acetate

Arm Description

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.

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

Outcomes

Primary Outcome Measures

Disability measured by Expanded Disability Status Scale

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

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

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

annualized relapse rate will be measured in the baseline (according to patients' history in the last year) and after 12 months of intervention.

Full Information

NCT ID

NCT03315923

First Posted

October 17, 2017

Last Updated

May 22, 2019

Sponsor

Isfahan University of Medical Sciences

1. Study Identification

Unique Protocol Identification Number

NCT03315923

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2019

Overall Recruitment Status

Completed

Study Start Date

December 1, 2017 (Actual)

Primary Completion Date

February 1, 2019 (Actual)

Study Completion Date

March 1, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Isfahan University of Medical Sciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Secondary Progressive Multiple Sclerosis

Keywords

Active secondary progressive Multiple Sclerosis, Glatiramer acetate, Rituximab, Comparative study, Disability, Randomized clinical trial, Annualized relapse rate

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

84 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Rituximab

Arm Type

Experimental

Arm Description

Arm Title

Glatiramer acetate

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Rituximab

Other Intervention Name(s)

Zytux®

Intervention Description

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

Intervention Name(s)

Glatiramer Acetate

Other Intervention Name(s)

Osvimer®

Intervention Description

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.

Primary Outcome Measure Information:

Title

Disability measured by Expanded Disability Status Scale

Description

Time Frame

one year

Secondary Outcome Measure Information:

Title

Adverse Drug Reactions

Description

Time Frame

one year

Title

number of Gadolinium-enhanced brain lesions and neuroimaging findings

Description

patients will undergo brain MRI before and after the study and number of Gad-enhanced brain lesions will compared before and after intervention.

Time Frame

one year

Title

Annualized relapse rate

Description

annualized relapse rate will be measured in the baseline (according to patients' history in the last year) and after 12 months of intervention.

Time Frame

one year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Vahid Shaygannejad, M.D.

Organizational Affiliation

Isfahan University of Medical Sciences

Official's Role

Study Chair

Facility Information:

Facility Name

Kashani Hospital

City

Isfahan

ZIP/Postal Code

8174673461

Country

Iran, Islamic Republic of

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

We may share the individual participant data (anonymously) on request of qualified investigators.

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

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