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

NCT03315923 | Completed Phase 2

• 1 other identifier: 396514
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

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.

Conditions

Secondary Progressive Multiple Sclerosis

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  one year

Secondary Outcomes (3)

• Adverse Drug Reactions

  one year

• number of Gadolinium-enhanced brain lesions and neuroimaging findings

  one year

• Annualized relapse rate

  one year

Study Arms (2)

Rituximab

EXPERIMENTAL

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

Glatiramer acetate

EXPERIMENTAL

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

Drug: Glatiramer Acetate

Interventions

Rituximab 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.

Also known as: Zytux®

Rituximab

Glatiramer Acetate 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.

Also known as: Osvimer®

Glatiramer acetate

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Isfahan University of Medical Sciences: lead

Study Sites (1)

Kashani Hospital

Isfahan, 8174673461, Iran

Location

Related Publications (11)

• Calabresi PA. Diagnosis and management of multiple sclerosis. Am Fam Physician. 2004 Nov 15;70(10):1935-44.

  PMID: 15571060 BACKGROUND

• Leray E, Moreau T, Fromont A, Edan G. Epidemiology of multiple sclerosis. Rev Neurol (Paris). 2016 Jan;172(1):3-13. doi: 10.1016/j.neurol.2015.10.006. Epub 2015 Dec 21.

  PMID: 26718593 BACKGROUND

• Hurwitz BJ. The diagnosis of multiple sclerosis and the clinical subtypes. Ann Indian Acad Neurol. 2009 Oct;12(4):226-30. doi: 10.4103/0972-2327.58276.

  PMID: 20182569 BACKGROUND

• Tsang BK, Macdonell R. Multiple sclerosis- diagnosis, management and prognosis. Aust Fam Physician. 2011 Dec;40(12):948-55.

  PMID: 22146321 BACKGROUND

• Wingerchuk DM, Carter JL. Multiple sclerosis: current and emerging disease-modifying therapies and treatment strategies. Mayo Clin Proc. 2014 Feb;89(2):225-40. doi: 10.1016/j.mayocp.2013.11.002.

  PMID: 24485135 BACKGROUND

• Dhib-Jalbut S. Glatiramer acetate (Copaxone) therapy for multiple sclerosis. Pharmacol Ther. 2003 May;98(2):245-55. doi: 10.1016/s0163-7258(03)00036-6.

  PMID: 12725872 BACKGROUND

• Schrempf W, Ziemssen T. Glatiramer acetate: mechanisms of action in multiple sclerosis. Autoimmun Rev. 2007 Aug;6(7):469-75. doi: 10.1016/j.autrev.2007.02.003. Epub 2007 Mar 6.

  PMID: 17643935 BACKGROUND

• Khan O, Rieckmann P, Boyko A, Selmaj K, Ashtamker N, Davis MD, Kolodny S, Zivadinov R. Efficacy and safety of a three-times-weekly dosing regimen of glatiramer acetate in relapsing-remitting multiple sclerosis patients: 3-year results of the Glatiramer Acetate Low-Frequency Administration open-label extension study. Mult Scler. 2017 May;23(6):818-829. doi: 10.1177/1352458516664033. Epub 2016 Aug 8.

  PMID: 27503905 BACKGROUND

• Mao CP, Brovarney MR, Dabbagh K, Birnbock HF, Richter WF, Del Nagro CJ. Subcutaneous versus intravenous administration of rituximab: pharmacokinetics, CD20 target coverage and B-cell depletion in cynomolgus monkeys. PLoS One. 2013 Nov 12;8(11):e80533. doi: 10.1371/journal.pone.0080533. eCollection 2013.

  PMID: 24265828 BACKGROUND

• Bar-Or A, Calabresi PA, Arnold D, Markowitz C, Shafer S, Kasper LH, Waubant E, Gazda S, Fox RJ, Panzara M, Sarkar N, Agarwal S, Smith CH. Rituximab in relapsing-remitting multiple sclerosis: a 72-week, open-label, phase I trial. Ann Neurol. 2008 Mar;63(3):395-400. doi: 10.1002/ana.21363.

  PMID: 18383069 BACKGROUND

• Hawker K, O'Connor P, Freedman MS, Calabresi PA, Antel J, Simon J, Hauser S, Waubant E, Vollmer T, Panitch H, Zhang J, Chin P, Smith CH; OLYMPUS trial group. Rituximab in patients with primary progressive multiple sclerosis: results of a randomized double-blind placebo-controlled multicenter trial. Ann Neurol. 2009 Oct;66(4):460-71. doi: 10.1002/ana.21867.

  PMID: 19847908 BACKGROUND

MeSH Terms

Conditions

Multiple Sclerosis, Chronic Progressive

Interventions

Rituximab; Glatiramer Acetate

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Peptides

Study Officials

• Vahid Shaygannejad, M.D.

  Isfahan University of Medical Sciences

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurology

Study Record Dates

• First Submitted: October 17, 2017
• First Posted: October 20, 2017
• Study Start: December 1, 2017
• Primary Completion: February 1, 2019
• Study Completion: March 1, 2019
• Last Updated: May 23, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

IR (1)