Overview

This trial is active, not recruiting.

Condition myasthenia gravis
Treatments rituximab, placebo
Phase phase 2
Target CD20
Sponsor Yale University
Start date May 2014
End date May 2017
Trial size 50 participants
Trial identifier NCT02110706, 1401013253-0

Summary

The specific primary objective of this study is to determine whether rituximab is a safe and beneficial therapeutic for Myasthenia Gravis (MG) that warrants further study in a phase III efficacy trial.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking double blind (subject, caregiver, investigator)
Primary purpose treatment
Arm
(Placebo Comparator)
The placebo group will receive a vehicle control infusion
placebo
The placebo group will receive a vehicle control infusion
(Experimental)
Intervention (rituximab): The treatment group will receive a total of two cycles of rituximab separated by 6 months. Each cycle is defined as one infusion (375mg/m2 IV) per week for four consecutive weeks
rituximab
Intervention (rituximab): The treatment group will receive a total of two cycles of rituximab separated by 6 months. Each cycle is defined as one infusion (375mg/m2 IV) per week for four consecutive weeks

Primary Outcomes

Measure
Percent of subjects that achieve a ≥ 75% reduction in mean daily prednisone dose in the 4 weeks prior to week 52
time frame: 4 weeks prior to week 52
Frequency of Study-Related Adverse Events
time frame: At the end of study-approximately 3 years

Eligibility Criteria

Male or female participants from 21 years up to 90 years old.

Inclusion Criteria: 1. Subjects 21 to 90 years old 2. Subjects must have generalized MG, defined as MGFA clinical classification grades 2 (mild), 3 (moderate), or 4 (severe, but not intubated) at the time of screening/randomization. 3. Elevated AChR antibody titer 4. Subject's signs and symptoms should not be better explained by another disease process. 5. Subjects must be on a stable standard immunosuppressive regimen: 1. Prednisone only: Prednisone dose must be at least 15mg/day (or the equivalent on alternate days), and the dose of prednisone must have been stable for at least 4 weeks (28 days) prior to the baseline visit. 2. Prednisone plus another immunosuppressive therapy (IST). Immunosuppressive therapies other than prednisone, specifically azathioprine, mycophenolate mofetil, cyclosporine, tacrolimus or methotrexate, are permitted, but the dose must have been stable for at least 6 months prior to the baseline visit. (Note: The prednisone dose must be stable as defined in the prednisone only group. The IST dose must remain stable throughout the course of the study). 6. Subjects must be willing to complete the study and return for follow-up visits. 7. No history of thymoma, tumor, infection, or interstitial lung disease on chest CT, MRI, or chest x-ray. Note: Chest x-ray will be completed at screening to look of interstitial lung disease. A chest CT or MRI to evaluate for thymoma must be completed as part of prescreening. 8. Able and willing to give written informed consent and comply with the requirements of the study protocol. 9. Subjects must be able to give written informed consent before participating in this study. A copy of the signed consent must be kept in the subject's medical record. 10. Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for twelve months (1 year) after completion of treatment. Exclusion Criteria: 1. A history of chronic degenerative, psychiatric, or neurologic disorder other than MG that can produce weakness or fatigue. 2. Other major chronic or debilitating illnesses within six months prior to study entry. 3. Female subjects who are premenopausal and are: 1. pregnant on the basis of a serum pregnancy test, 2. breast-feeding, or 3. not using an effective method of double barrier (1 hormonal plus 1 barrier method or 2 simultaneous barrier methods) or birth control (birth control pills, male condom, female condom, intrauterine device, Norplant, tubal ligation, or other sterilization procedures). 4. Altered levels of consciousness, dementia, or abnormal mental status. 5. Thymectomy in the previous six months. 6. Subjects who have been medicated with immunosuppressive drugs not listed in inclusion #5 within the last 8 weeks (56 days) prior to the baseline visit 7. Subjects who have been medicated with an immunosuppressive agent such as azathioprine, mycophenolate mofetil, cyclosporine, tacrolimus or methotrexate, that is withdrawn within 8 weeks (56 days) of the Baseline Visit. 8. Subjects who have received IVIg or PLEX treatment within the last 4 weeks (28 days) prior to the baseline visit. 9. Unstable dose or a stable dose of > 480 mg/day of pyridostigmine in 2 weeks prior to screening visit. 10. Daily use of non-steroidal anti-inflammatory drugs (NSAIDs). 11. History of renal or hepatic insufficiency or elevated liver enzymes (AST or ALT >2.5 x Upper Limit of Normal). 12. History of bone marrow hypoplasia, leucopenia, thrombocytopenia, significant anemia, clinical or laboratory evidence of immunodeficiency syndromes. 13. Forced Vital Capacity (FVC) <50% of percent predicted. 14. ANC < 1.5 x 103 cells/microliter 15. Hemoglobin: < 8.0 gm/dL 16. Platelets: < 100,000/mm 17. Positive Hepatitis B or C serology (Hep B surface antigen and Hep C antibody) 18. History of positive HIV (HIV conducted during screening if applicable) 19. Treatment with any investigational agent within 4 weeks of screening or 5 half-lives of the investigational drug (whichever is longer) 20. Receipt of a live vaccine within 4 weeks prior to randomization

Additional Information

Official title A Phase II Trial of Rituximab In Myasthenia Gravis
Principal investigator Richard J Nowak, MD, MS
Description Investigators plan on conducting a multicenter randomized, double-blind, placebo controlled Phase II clinical trial utilizing a futility design. The study would include acetylcholine receptor (AChR) antibody positive generalized MG subjects. This study also presents a unique opportunity to study both drug and disease mechanisms because unlike many other autoimmune diseases in which rituximab has been used, MG affords the investigation of antigen-specific components that participate in the immunopathology of the disease, namely autoantibodies, autoantibody-producing B cells, and antigen-specific T cells. This work will further our understanding of MG immunopathology and it represents the first step toward gaining a more complete understanding of the immune mechanisms underlying treatment of MG with rituximab leading to new ways to treat the disease. The specific aim of this study is to determine whether rituximab is a safe and effective treatment for subjects with MG.
Trial information was received from ClinicalTrials.gov and was last updated in July 2016.
Information provided to ClinicalTrials.gov by Yale University.