BeatMG: Phase II Trial of Rituximab In Myasthenia Gravis
B Cell Targeted Treatment In Myasthenia Gravis (BeatMG): A Phase II Trial of Rituximab In Myasthenia Gravis
4 other identifiers
interventional
52
1 country
26
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started May 2014
Typical duration for phase_2
26 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 7, 2014
CompletedFirst Posted
Study publicly available on registry
April 10, 2014
CompletedStudy Start
First participant enrolled
May 1, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2018
CompletedResults Posted
Study results publicly available
October 2, 2018
CompletedMarch 6, 2020
March 1, 2020
3.2 years
April 7, 2014
July 31, 2018
March 4, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Steroid Sparing Effect
Percent of subjects that achieve a ≥ 75% reduction in mean daily prednisone dose in the 4 weeks prior to week 52 and have clinical improvement or no significant worsening of symptoms (≤ 2 point increase in MGC score) as compared to 4-week period prior to randomization and initiation of treatment.
4 weeks prior baseline and 4 weeks prior to week 52
Safety:Percentage of Study Participants With Treatment-related Adverse Experiences
Evaluate treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs)
52 weeks
Secondary Outcomes (2)
Change in Myasthenia Gravis Composite (MGC) Scores From Baseline to Week 52
baseline and 52 weeks
Change in Quantitative Myasthenia Gravis(QMG) Scores From Baseline to Week 52
baseline and 52 weeks
Study Arms (2)
Placebo
PLACEBO COMPARATORThe placebo group will receive a vehicle control infusion
Rituximab
EXPERIMENTALIntervention (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
Interventions
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
Eligibility Criteria
You may qualify if:
- Subjects 21 to 90 years old
- 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.
- Elevated AChR antibody titer
- Subject's signs and symptoms should not be better explained by another disease process.
- Subjects must be on a stable standard immunosuppressive regimen:
- 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.
- 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).
- Subjects must be willing to complete the study and return for follow-up visits.
- 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.
- Able and willing to give written informed consent and comply with the requirements of the study protocol.
- 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.
- 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.
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 subjects who are premenopausal and are:
- pregnant on the basis of a serum pregnancy test,
- breast-feeding, or
- 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).
- Altered levels of consciousness, dementia, or abnormal mental status.
- Thymectomy in the previous six months.
- 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.
- Subjects who have received IVIg or PLEX treatment within the last 4 weeks (28 days) prior to the baseline visit.
- Unstable dose or a stable dose of \> 480 mg/day of pyridostigmine in 2 weeks prior to screening visit.
- Daily use of non-steroidal anti-inflammatory drugs (NSAIDs).
- History of renal or hepatic insufficiency or elevated liver enzymes (AST or ALT \>2.5 x 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 percent predicted.
- +21 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (26)
University of Alabama at Birmingham
Birmingham, Alabama, 35233, United States
University of California - Davis
Davis, California, 95616, United States
University of California - Los Angeles
Los Angeles, California, 90095, United States
University of Colorado - Denver
Denver, Colorado, 80217, United States
Yale School of Medicine, Department of Neurology
New Haven, Connecticut, 06510, United States
University of Miami School of Medicine
Miami, Florida, 33136, United States
Emory University
Atlanta, Georgia, 30322, United States
Northwestern University
Evanston, Illinois, 60208, United States
University of Kansas Medical Center
Kansas City, Kansas, 66160, United States
Brigham & Women's Hospital
Boston, Massachusetts, 02115, United States
Washington University
St Louis, Missouri, 63130, United States
SUNY Downstate Medical Center
Brooklyn, New York, 11203, United States
SUNY Buffalo
Buffalo, New York, 14260, United States
Columbia University Medical Center
New York, New York, 10032, United States
Weill Cornell Medical Center
New York, New York, 10065, United States
University of Rochester
Rochester, New York, 14627, United States
SUNY Stony Brook
Stony Brook, New York, 11790, United States
Montefiore Medical Center
The Bronx, New York, 10461, United States
University of Cincinnati
Cincinnati, Ohio, 45220, United States
Ohio State University
Columbus, Ohio, 43210, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
University of Pittsburgh
Pittsburgh, Pennsylvania, 15260, United States
University of Texas Southwestern Medical Center
Dallas, Texas, 75235, United States
University of Utah
Salt Lake City, Utah, 84112, United States
University of Virginia
Charlottesville, Virginia, 22904, United States
Swedish Medical Center
Seattle, Washington, 98107, United States
Related Publications (3)
Nowak RJ, Coffey CS, Goldstein JM, Dimachkie MM, Benatar M, Kissel JT, Wolfe GI, Burns TM, Freimer ML, Nations S, Granit V, Smith AG, Richman DP, Ciafaloni E, Al-Lozi MT, Sams LA, Quan D, Ubogu E, Pearson B, Sharma A, Yankey JW, Uribe L, Shy M, Amato AA, Conwit R, O'Connor KC, Hafler DA, Cudkowicz ME, Barohn RJ; NeuroNEXT NN103 BeatMG Study Team. Phase 2 Trial of Rituximab in Acetylcholine Receptor Antibody-Positive Generalized Myasthenia Gravis: The BeatMG Study. Neurology. 2022 Jan 25;98(4):e376-e389. doi: 10.1212/WNL.0000000000013121.
PMID: 34857535DERIVEDDi Stefano V, Lupica A, Rispoli MG, Di Muzio A, Brighina F, Rodolico C. Rituximab in AChR subtype of myasthenia gravis: systematic review. J Neurol Neurosurg Psychiatry. 2020 Apr;91(4):392-395. doi: 10.1136/jnnp-2019-322606. Epub 2020 Feb 25.
PMID: 32098874DERIVEDHehir MK, Hobson-Webb LD, Benatar M, Barnett C, Silvestri NJ, Howard JF Jr, Howard D, Visser A, Crum BA, Nowak R, Beekman R, Kumar A, Ruzhansky K, Chen IA, Pulley MT, LaBoy SM, Fellman MA, Greene SM, Pasnoor M, Burns TM. Rituximab as treatment for anti-MuSK myasthenia gravis: Multicenter blinded prospective review. Neurology. 2017 Sep 5;89(10):1069-1077. doi: 10.1212/WNL.0000000000004341. Epub 2017 Aug 11.
PMID: 28801338DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Richard Nowak, MD,MS
- Organization
- Yale School of Medicine
Study Officials
- PRINCIPAL INVESTIGATOR
Richard J Nowak, MD, MS
Yale University
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 7, 2014
First Posted
April 10, 2014
Study Start
May 1, 2014
Primary Completion
July 1, 2017
Study Completion
May 1, 2018
Last Updated
March 6, 2020
Results First Posted
October 2, 2018
Record last verified: 2020-03