Efficacy of Methotrexate in Myasthenia Gravis

NCT00814138 | Completed Phase 2 Results DMC

• 2 other identifiers: 11552FDA OOPD 003538
• Study Type: interventional
• Target: 50
• Locations: 2 countries
• Sites: 16

Brief Summary

Myasthenia gravis is a rare neuromuscular disorder characterized by weakness and fatigability of ocular, bulbar, and extremity musculature. The specific aim of this study is to determine if oral methotrexate is an effective therapy for myasthenia gravis (MG) patients who are prednisone dependent. Patients will be randomized to receive either methotrexate or placebo and those who are entered onto this trial will have symptoms and signs of the disease while on prednisone therapy. The hypothesis is that adding methotrexate therapy in these patients will improve the MG manifestations so that the prednisone dose can be reduced and clinical measures of MG severity will improve. Funding Source - FDA OOPD

Conditions

Myasthenia Gravis

Keywords

myasthenia gravis

Outcome Measures

Primary Outcomes (1)

• Total Prednisone Dose Area Under the Curve

  The primary outcome measure was the nine-month prednisone area under the dose-time curve (AUDTC, months 4-12). The AUDTC was chosen because it accounted for changes in the prednisone dose that could occur frequently during a month.

  9 months

Secondary Outcomes (6)

• Average Prednisone Daily Dose (mg/Day)

  Total length of time daily dose information was collected, i.e. 9 months.

• Quantitative Myasthenia Gravis (QMG) Score

  Change from Baseline to Month 12

• Manual Muscle Testing 12 Month Change

  Change from Baseline to Month 12

• MGQOL 12 Month Change

  Change from Baseline to Month 12

• MG-ADL 12 Month Change

  Change from Baseline to Month 12

Study Arms (2)

1

ACTIVE COMPARATOR

Methotrexate

Drug: Methotrexate

2

PLACEBO COMPARATOR

Placebo

Other: Placebo

Interventions

Methotrexate DRUG

10 mg weekly for 2 weeks and then increase to 15mg for 2 weeks and then 20mg weekly until the end of the study

1

Placebo OTHER

Weekly

2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have MGFA MG grades 2, 3, or 4 generalized myasthenia gravis, according to the MGFA classification system
• Elevated acetylcholine receptor antibody (AChR-Ab) titer.
• Patient's signs and symptoms should not be better explained by another disease process.
• Prednisone dose of at least 10 mg/day (or the equivalent in alternate days) and the subject must be on a stable dose of prednisone for 30 days prior to the screening visit.

You may not qualify if:

• A history of chronic degenerative, psychiatric, or neurologic disorder other than MG that can produce weakness or fatigue.
• Other major chronic or debilitating illnesses within six months prior to study entry.
• Female patients who are premenopausal and are: (a) pregnant on the basis of a serum pregnancy test, (b) breast-feeding, or (c) not using an effective method of double barrier (1 hormonal plus 1 barrier method or 2 simultaneous barrier methods) birth control (birth control pills, male condom, female condom, intrauterine device, Norplant, tubal ligation, or other sterilization procedures).
• Altered levels of consciousness, dementia, or abnormal mental status.
• Evidence of thymoma on chest CT or MRI. Such a finding could require immediate thymectomy and would preclude entry into the study.
• Thymectomy in the previous three months.
• Patients who have been medicated with azathioprine, cyclosporine, cyclophosphamide, mycophenolate mofetil, IVIg, or other immunosuppressive drugs within the last 60 days.
• Chest X-ray with evidence of tumor, infection, or interstitial lung disease.
• Clinical history of chronic or recurrent infections.
• Daily use of non-steroidal anti-inflammatory drugs (NSAIDs).
• History of renal or hepatic insufficiency or liver enzymes greater than the upper limit of normal.
• History of bone marrow hypoplasia, leucopenia, thrombocytopenia, significant anemia, clinical or laboratory evidence of immunodeficiency syndromes.
• Forced Vital Capacity (FVC) \<50% of predicted.
• MG Grade 1 (ocular only) or 5 (crisis, requiring ventilator).
• Prior use of methotrexate for any condition.

Sponsors & Collaborators

• University of Kansas Medical Center: lead

Study Sites (16)

Phoenix Neurological Associates

Phoenix, Arizona, 85018, United States

Location

University of California, San Francisco

Fresno, California, 93701, United States

Location

University of California-Irvine

Irvine, California, 92697, United States

Location

Forbes Norris MDA/ALS Research Center

San Francisco, California, 94115, United States

Location

University of Florida, Health Science Center Jacksonville

Jacksonville, Florida, 32209, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Massachusetts General Hospitals

Boston, Massachusetts, 02114, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Penn State College of Medicine, The Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

The Nerve and Muscle Center of Texas

Houston, Texas, 77030, United States

Location

University Health Sciences Center, San Antonio

San Antonio, Texas, 78229, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

University of Toronto

Toronto, Ontario, M5G 2C4, Canada

Location

MeSH Terms

Conditions

Myasthenia Gravis

Interventions

Methotrexate

Condition Hierarchy (Ancestors)

Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Neurodegenerative Diseases; Neuromuscular Junction Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Richard J. Barohn, MD/ Chairman of Neurology
• Organization: University of Kansas Medical Center

rbarohn@kumc.edu

913-588-6094

Study Officials

• Richard Barohn, MD

  University of Kansas Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Gertrude and Dewey Zeigler Professor of Neurology, Chairman Deptartment of Neurology

Study Record Dates

• First Submitted: December 23, 2008
• First Posted: December 24, 2008
• Study Start: April 1, 2009
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: May 26, 2016
• Results First Posted: December 23, 2015

Record last verified: 2016-04

Locations

CA (1); US (15)