Trial of Mycophenolic Acid Versus Azathioprine in the Treatment of Corticosteroid-refractory Myasthenia Gravis (Myfortic)

Randomized, Double-blind, Double-dummy Trial of Mycophenolic Acid Versus Azathioprine in the Treatment of Corticosteroid-refractory Myasthenia Gravis

This is an randomized, double-blind, double-dummy trial, and the objective is to compare the efficacy and safety of Mycophenolic acid (MA) and Azathioprine (AZA), immunosuppressive drugs, in myasthenia gravis patients. This prospective study will enroll 40 myasthenia gravis (MG) patients who are poor controlled under prior steroid therapy. All subjects should be randomly assigned to MA group and AZA group that will receive routine pyridostigmine and prednisolone in combination with MA or AZA.

Study Overview

• Status: Unknown
• Conditions: Myasthenia Gravis
• Intervention / Treatment: Drug: Mycophenolic acid; Drug: AZA

Detailed Description

This will be a double-dummy study to keep the blinded quality.

• MA group: 1 tablet AZA placebo and 4 tables MA (180 mg/tab,720 mg/day) twice daily.

• AZA group: 1 tablet AZA (50mg/tab) and 4 tables MA placebo twice daily.

  • When patients achieve minimal manifestation (MM, i.e. complete remission), which lead to normal daily routine, the dose of pyridostigmine should reduce to 240 mg/day (4 tablets) or less. The dose of steroid should be stepped down by 10 mg qod (every other day) for every 2 weeks until the dose achieves 40 mg qod. After that, the dose should be stepped down by 5 mg qod for every month.
  • When disease progresses and is no longer maintaining minimal manifestation, the dose of steroid will be stepped up by 10 mg qod for every 2 weeks until achieve clinical stable remission. The taper rule of steroid could start again 1 month after stabilization.
  • Every patient will be treated for 1 year. If the patient could not achieve MM within 1 year, the blind of individual patient will be opened and the patients will be crossed over to another medical treatment. The efficacy and safety of second medication will be observed openly until the end of study.
  • When the muscle weakness worsens under established study schedule, plasmapheresis could be conducted to improve the condition rapidly.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female age between 20-70 (including 20 and 70 years old).
• Osserman II and III Myasthenia Gravis.
• Positive serum anti-acetylcholine receptor antibodies.
• Poor control of disease with daily dose of prednisone ≥ 30 mg or 0.5 mg/kg at 3 months before enrollment.
• Without immunosuppressive therapy other than steroid.

Exclusion Criteria:

• Ocular MG or minimal clinical syndrome that would not require the therapy of steroids.
• Negative serum anti-acetylcholine receptor antibodies.
• Use immunosuppressants other than steroids in the preceding year.
• Previous use other investigational medication within 3 months or current participate other clinical study.
• Poor renal function: serum creatinine > 3.0 mg/dl or estimated creatinine clearance < 30 ml/min
• Females who are pregnancy or breast-feeding.
• Recent history, within 5 years, of malignancy
• Unwilling or unable to participate the necessary continuous visits and examinations.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MA; MA group: 1 tablet AZA placebo and 4 tablets MA (180mg/tab,720 mg/day) twice daily	Drug: Mycophenolic acid; 180 mg/tablet, 4 tablets twice daily
Active Comparator: AZA; AZA group: 1 tablet AZA (50mg/tab) and 4 tablets MA placebo twice daily	Drug: AZA; 1 tablet AZA (50 mg/tab) and 4 tablets MA placebo twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The ratio of two arms patients achieve minimal manifestation (MM, i.e. complete remission)	One year after treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Osserman clinical classification	One year after treatment
Myasthenia gravis (MG) score	One year after treatment

Collaborators and Investigators

• Sponsor: Qualitix Clinical Research Co., Ltd.
• Investigators: Principal Investigator: Jiann-Horng Yeh, M.D., Shin Kong Wu Ho-Su Memorial Hospital

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Anticipated): May 1, 2011
• Study Completion (Anticipated): May 1, 2011

Study Registration Dates

• First Submitted: October 16, 2009
• First Submitted That Met QC Criteria: October 16, 2009
• First Posted (Estimate): October 19, 2009

Study Record Updates

• Last Update Posted (Estimate): October 19, 2009
• Last Update Submitted That Met QC Criteria: October 16, 2009
• Last Verified: October 1, 2009

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Neoplasms; Autoimmune Diseases of the Nervous System; Autoimmune Diseases; Neoplasms by Site; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Neuromuscular Manifestations; Nervous System Neoplasms; Paraneoplastic Syndromes, Nervous System; Paraneoplastic Syndromes; Neuromuscular Junction Diseases; Muscle Weakness; Myasthenia Gravis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antitubercular Agents; Antibiotics, Antitubercular; Mycophenolic Acid
• Other Study ID Numbers: CERL080ATW07T