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BeatMG: Phase II Trial of Rituximab In Myasthenia Gravis

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02110706
First Posted: April 10, 2014
Last Update Posted: March 3, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Yale University
  Purpose
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.

Condition Intervention Phase
Myasthenia Gravis Drug: Rituximab Drug: Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: B Cell Targeted Treatment In Myasthenia Gravis (BeatMG): A Phase II Trial of Rituximab In Myasthenia Gravis

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • 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 ]

Enrollment: 50
Study Start Date: May 2014
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: May 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
The placebo group will receive a vehicle control infusion
Drug: Placebo
The placebo group will receive a vehicle control infusion
Experimental: 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
Drug: 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

Detailed 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.

In order to assess safety in the B cell recovery during the repopulation period as well as the assess the long-term durability of response, there are two additional optional observational off study-intervention time points (weeks 72 and 96). The subjects will be treated per medical standard of care during this period.

The specific aim of this study is to determine whether rituximab is a safe and effective treatment for subjects with MG.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 90 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

    General Safety & Laboratory Exclusion Criteria

  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
  21. Previous treatment with rituximab (MabThera® / Rituxan®)
  22. Previous treatment with natalizumab (Tysabri®)
  23. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
  24. History of recurrent significant infection or history of recurrent bacterial infections
  25. Known active bacterial, viral fungal mycobacterial, or other infection (including tuberculosis or atypical mycobacterial disease, but excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening
  26. Unstable steroid dose in the past 4 weeks (28 days)
  27. Lack of peripheral venous access
  28. History of drug, alcohol, or chemical abuse within 6 months prior to screening
  29. Concomitant malignancies or previous malignancies, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or prostate.
  30. History of psychiatric disorder that would interfere with normal participation in this protocol
  31. Significant cardiac or pulmonary disease (including obstructive pulmonary disease)
  32. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the subject at high risk from treatment complications
  33. Subjects that do not record daily prednisone doses for at least 28 days before the Baseline Visit, or subjects whose prednisone dose varies by ≥6mg/day on average.
  34. Prednisone dose of more than 100 mg/day (or 200 mg over a two day period).
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02110706


  Show 26 Study Locations
Sponsors and Collaborators
Yale University
Investigators
Principal Investigator: Richard J Nowak, MD, MS Yale University
  More Information

Additional Information:
Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT02110706     History of Changes
Other Study ID Numbers: 1401013253-0
First Submitted: April 7, 2014
First Posted: April 10, 2014
Last Update Posted: March 3, 2017
Last Verified: July 2016

Keywords provided by Yale University:
Myasthenia Gravis
Rituximab

Additional relevant MeSH terms:
Rituximab
Muscle Weakness
Myasthenia Gravis
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Pathologic Processes
Signs and Symptoms
Autoimmune Diseases of the Nervous System
Neuromuscular Junction Diseases
Neuromuscular Diseases
Autoimmune Diseases
Immune System Diseases
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents