Combination Therapy With Avonex and BiMonthly High Dose Intravenous Methotrexate in Multiple Sclerosis (MTX01)

An Open Label Study of the Safety and Efficacy of Combination Therapy With AVONEX and Bi-Monthly High Dose Intravenous Methotrexate With Leucovorin Rescue in the Treatment of Multiple Sclerosis

The participant will receive weekly intramuscular treatment with AVONEX® (interferon beta 1-a) and bi-monthly high dose intravenous methotrexate with Leucovorin rescue.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: methotrexate; Drug: interferon beta 1a

Detailed Description

The participant will receive weekly intramuscular treatment with AVONEX® (interferon beta 1-a) and bi-monthly high dose intravenous methotrexate with Leucovorin rescue. Entrance into the study will be based on Multiple Sclerosis Functional Composite Score (MSFC) evaluations at -4 months, and - 1 month prior to study, where a decrease in score is noted. The composite score consists of the Timed 25-Foot Walk, Nine-Hole Peg Test (9HPT), and Paced Auditory Serial Addition Test 3 (PASAT 3). The patient must have been on AVONEX® for at least 6 months.

At study entrance, baseline lab work (complete blood count, platelet count, routine electrolytes, blood urea nitrogen, creatinine, liver function tests, 24 hour urine collection for creatinine clearance, and urine pH), an electrocardiogram (measurement of heart activity) and serum pregnancy test will be done. A complete physical examination will be performed, including measurements of vital signs (heart rate and blood pressure), as well as magnetic resonance imaging (MRI) to document status of disease. A self-administered questionnaire, the MSQLI (Multiple Sclerosis Quality of Life Instrument), will be completed at baseline and at the end of the study. MSFC and safety evaluations (previously mentioned blood and urine tests and electrocardiograms (EKG), will be conducted throughout the study at months 2, 4, 6, 8, 10, and 12. Blood tests of immune cells will also be drawn at these visits. The patient can continue this regimen of treatment at their own discretion and cost, and outside the parameters of this study, if there is apparent efficacy without serious adverse events. This treatment would be under the supervision of Dr. Rowe.

The patients will continue their AVONEX® intramuscular injections of 30 micrograms (administered by patient or caregiver) on a weekly basis with scheduled intravenous high dose methotrexate at 2 Gm/m2 followed by intravenous and oral leucovorin rescue once every 2 months. The methotrexate infusions will be performed in our outpatient infusion center. The patient will be required to complete a patient diary during the course of the trial, participate in and keep all scheduled appointments, and to inform the research staff and physician of any change in concomitant medications or adverse events that they may experience.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

To be eligible for entry into this study, candidates must meet the following eligibility criteria at the time of enrollment:

• Between the ages of 18 and 60 years, inclusive.
• Diagnosis of clinically definite relapsing MS.
• Must have been on AVONEX® therapy for at least six months.
• Brain MRI scans demonstrating lesions consistent with MS.
• Subject must have had at least one clinical exacerbation in the last year, and this must have occurred after having been on AVONEX® therapy for at least six to twelve (6-12) months. A clinical exacerbation is defined as a decrease of 0.1 in the MSFC composite or any of the subset domains scores administered 3 months apart.
• Give written informed consent prior to any testing under this protocol, including screening tests and evaluation that are not considered part of the subject's routine care.

To be eligible for treatment with methotrexate, subjects must have evidence for MS disease activity on their baseline screening MRI.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Collaborators and Investigators

• Sponsor: MidAmerica Neuroscience Research Foundation at Rowe Neurology Institute
• Collaborators: Biogen; Consultants in Neurology
• Investigators: Principal Investigator: Vernon D ROWE, MD, MidAmerica Research Foundation

Study record dates

Study Major Dates

• Study Start: July 1, 2001
• Primary Completion (Actual): December 1, 2003
• Study Completion (Actual): December 1, 2003

Study Registration Dates

• First Submitted: May 15, 2002
• First Submitted That Met QC Criteria: May 16, 2002
• First Posted (Estimate): May 17, 2002

Study Record Updates

• Last Update Posted (Actual): April 12, 2018
• Last Update Submitted That Met QC Criteria: April 10, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Multiple Sclerosis; Methotrexate; autoimmune; Relapsing; demyelinating; AVONEX; interferon beta 1a
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Adjuvants, Immunologic; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Interferons; Interferon beta-1a; Methotrexate; Interferon-beta
• Other Study ID Numbers: MANI-MTX01-001