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

Secondary Progressive Multiple Sclerosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03315923
• Other study ID #: 396514
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: December 1, 2017
• Est. completion date: March 1, 2019

Study information

• Verified date: May 2019
• Source: Isfahan University of Medical Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: March 1, 2019
• Est. primary completion date: February 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Chronic Progressive
• Neoplasm Metastasis
• Sclerosis
• Secondary Progressive Multiple Sclerosis

Intervention

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.
• 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.

Locations

Country	Name	City	State
Iran, Islamic Republic of	Kashani Hospital	Isfahan

Sponsors (1)

Lead Sponsor	Collaborator
Isfahan University of Medical Sciences

Country where clinical trial is conducted

Iran, Islamic Republic of, 

References & Publications (11)

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. Erratum in: Ann Neurol. 2008 Jun;63(6):803. Arnlod, Douglas [corrected to Arnold, Douglas]. — View Citation

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

Dhib-Jalbut S. Glatiramer acetate (Copaxone) therapy for multiple sclerosis. Pharmacol Ther. 2003 May;98(2):245-55. Review. — View 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. — View 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. — View 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. — View 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. — View Citation

Mao CP, Brovarney MR, Dabbagh K, Birnböck 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. — View Citation

Schrempf W, Ziemssen T. Glatiramer acetate: mechanisms of action in multiple sclerosis. Autoimmun Rev. 2007 Aug;6(7):469-75. Epub 2007 Mar 6. Review. — View Citation

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

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	one year
Secondary	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.	one year
Secondary	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.	one year