Clinical trial NCT03315923: 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
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Secondary Progressive Multiple Sclerosis
Keywords: Active secondary progressive Multiple Sclerosis
Glatiramer acetate
Rituximab
Comparative study
Disability
Randomized clinical trial
Annualized relapse rate
Lead sponsor: Isfahan University of Medical Sciences
Sponsor class: OTHER
First posted: 2017-10-20
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Disability measured by Expanded Disability Status Scale
timeFrame: one year
Secondary outcomes:
measure: Adverse Drug Reactions
timeFrame: one year
measure: number of Gadolinium-enhanced brain lesions and neuroimaging findings
timeFrame: one year
measure: Annualized relapse rate
timeFrame: one year
Other outcomes:
Locations:
city: Isfahan
country: Iran, Islamic Republic of
facility: Kashani Hospital
Study officials:
affiliation: Isfahan University of Medical Sciences
name: Vahid Shaygannejad, M.D.
role: STUDY_CHAIR
References:
citation: Calabresi PA. Diagnosis and management of multiple sclerosis. Am Fam Physician. 2004 Nov 15;70(10):1935-44.
citation: 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.
citation: 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.
citation: Tsang BK, Macdonell R. Multiple sclerosis- diagnosis, management and prognosis. Aust Fam Physician. 2011 Dec;40(12):948-55.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.