A Study Evaluating the Safety and Efficacy of Rituximab in Patients With Myasthenia Gravis (Rinomax)

March 12, 2020 updated by: Fredrik Piehl

A Randomized, Double-blind, Placebo-controlled Multicenter Study Evaluating the Safety and Efficacy of Rituximab (Mabthera®) in Patients With New Onset Generalized Myasthenia Gravis (MG)

A randomized, double-blind, placebo-controlled multicenter study evaluating the safety and efficacy of Rituximab (Mabthera®) in patients with new onset generalized myasthenia gravis (MG).

Study Overview

Detailed Description

Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction caused by auto-antibodies. MG is characterized by weakness in skeletal muscles and occurs in all ages, but mostly among young adult women and in people of both sexes over the age of 60 years. The disease has a wide variation in severity, where in milder cases only symptom-relieving choline esterase blockers may be sufficient. In many cases, however, immunomodulatory drugs are required. Traditionally MG has been treated with high doses of corticosteroids over longer time periods, which causes significant risks of side effects. Therefore, since several decades, oral immunosuppressive drugs have been used in order to reduce the need for steroids. This group includes azathioprine, cyclosporine and mycophenolate. However, none of these drugs has been approved for use in MG and the effect is usually delayed. There is thus a great need to develop newer treatment algorithms for MG, for example including more effective biological drugs. Several small observational studies have shown that rituximab, an anti-CD20 monoclonal antibody that eliminate B cells, can have good effects in treatment refractory MG. The aim of the present study is to study the effect of rituximab compared to placebo in the treatment of new onset MG of moderate to severe symptomatology.

Study Type

Interventional

Enrollment (Actual)

47

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Solna
      • Stockholm, Solna, Sweden, 171 76
        • Karolinska University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Patients with oculobulbar, bulbar or generalized MG ≥ 18 years of age and with onset of generalized symptoms or neurophysiological detection of generalized disease not more than 12 months ago.
  2. The diagnosis of MG should be determined with the following:

    Clinical neurological status with motor symptoms consistent with MG and at least two of the following:

    a positive serologic test for anti-acetylcholine receptor antibody (AChR) and/or b. typical MG findings on neurophysiological testing of neuromuscular transmission with single fiber electromyography (SFEMG) and / or repetitive nerve stimulation (RNS), and / or c. Positive anti-choline esterase-test, e.g. edrophoniumchloride or improvement of MG symptoms with oral cholinesterase inhibitors as judged by the treating physician.

  3. MGFA Class II to IV at screening.
  4. Quantitative MG score ≥ 6 at screening
  5. Women of childbearing potential must have a negative pregnancy test.
  6. Patients must have provided written informed consent.
  7. Patients must be able and willing to comply with all study procedures.

Exclusion Criteria:

  1. Weakness only affecting ocular or periocular muscles (MGFA Class I).
  2. MG crisis at screening (MGFA Class V)
  3. Thymectomy already carried out. In order to avoid difficulties to evaluate the effect of the study drug, thymectomy, where it is indicated, should be scheduled to the follow-up period, ie after the first 24 weeks.
  4. Strong suspicion of thymoma, where thymectomy as judged by the treating physician should be done within 24 weeks.
  5. Active malignancy, if not adequately treated
  6. Pregnancy or breast-feeding.
  7. Ongoing acute or chronic viral or systemic bacterial infections including HIV, latent hepatitis B, which is clinically significant, according to the study doctor's opinion and not treated with appropriate antibiotic / antiviral drugs.
  8. Severe heart failure (New York Heart Association Class IV) or severe, uncontrolled cardiac disease
  9. Previous use of immunosuppressive drugs, including rituximab, except prednisolone at a dose of up to 40mg daily for less than 3 months. This does not apply to treatment with immunosuppressive drugs / corticosteroids (except rituximab) for other indications than MG, provided at least 12 months have passed since treatment was terminated.
  10. Suspected hypersensitivity to the study drug
  11. Participation in another trial of study drug within 30 days prior to screening.
  12. Any medical condition which, according to the study physician's opinion, may interfere with the patient's participation in the study, poses additional risks for the patient, or that complicate the assessment of patients.
  13. Vaccination within 4 weeks before inclusion.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Rituximab
A single infusion at a dose of 500 mg of Mabthera/Rituximab.
A single infusion at a dose of 500 mg Mabthera/Rituximab.
Other Names:
  • Mabthera
Sham Comparator: Sodium Chloride solution
A single infusion with sodium chloride solution.
A single infusion of Placebo/Sham.
Other Names:
  • Sodium Chloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of patients with quantitative MG ascore (QMG) score ≤ 4 and a daily Prednisolon dose of ≤ 10mg at 16 weeks after administration of study drug/placebo.
Time Frame: 16 weeks
QMG is measured under standardized conditions with at least 12 hours since last intake of choline esterase inhibitors
16 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
QMG score at 24 weeks after administration of study drug/placebo.
Time Frame: 24 weeks
QMG is measured under standardized conditions with at least 12 hours since last intake of choline esterase inhibitors
24 weeks
MG-activities of daily living (ADL) score at 16 weeks after administration of study drug/placebo
Time Frame: 16 weeks
MG-ADL is a patient-reported outcome measured under standardized conditions with at least 12 hours since last intake of choline esterase inhibitors
16 weeks
MG-quality of life (QoL) score at 16 weeks after administration of study drug/placebo
Time Frame: 16 weeks
MG-QoL is a patient-reported outcome measured under standardized conditions with at least 12 hours since last intake of choline esterase inhibitors
16 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of patients with quantitative MG ascore (QMG) score ≤ 4 and a daily Prednisolon dose of ≤ 10mg at 24 weeks after administration of study drug/placebo.
Time Frame: 24 weeks
QMG is measured under standardized conditions with at least 12 hours since last intake of choline esterase inhibitors
24 weeks
QMG scores at 16, 36 and 48 weeks after administration of study drug/placebo.
Time Frame: 16, 36 and 48 weeks
QMG is measured under standardized conditions with at least 12 hours since last intake of choline esterase inhibitors
16, 36 and 48 weeks
MG-activities of daily living (ADL) score at 24, 36 and 48 weeks after administration of study drug/placebo
Time Frame: 24, 36 and 48 weeks
MG-ADL is a patient-reported outcome measured under standardized conditions with at least 12 hours since last intake of choline esterase inhibitors
24, 36 and 48 weeks
EQ5D score at 16, 24, 36 and 48 weeks after administration of study drug/placebo
Time Frame: 16, 24, 36 and 48 weeks
The EQ5D scale is a generic QoL score measured under standardized conditions with at least 12 hours since last intake of choline e
16, 24, 36 and 48 weeks
MG-QoL score at 24, 36 and 48 weeks after administration of study drug/placebo
Time Frame: 24, 36 and 48 weeks
MG-QoL is a patient-reported outcome measured under standardized conditions with at least 12 hours since last intake of choline esterase inhibitors
24, 36 and 48 weeks
Number of hospital admissions for MG worsening during week 0 to 48 after administration of study drug/placebo
Time Frame: 0 - 48 weeks
0 - 48 weeks
Rescue treatments during week 8 to 48 after administration of study drug/placebo
Time Frame: 8 - 48 weeks
Rescue treatments comprise i.v immunoglobulins, plasma exchange and high dose corticosteroids
8 - 48 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Principal Investigator: Fredrik Piehl, Professor, Dept Clinical Neuroscience Karolinska Institutet, Neuroimmunology Unit

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 16, 2016

Primary Completion (Anticipated)

January 30, 2021

Study Completion (Anticipated)

June 30, 2021

Study Registration Dates

First Submitted

October 28, 2016

First Submitted That Met QC Criteria

October 28, 2016

First Posted (Estimate)

October 31, 2016

Study Record Updates

Last Update Posted (Actual)

March 13, 2020

Last Update Submitted That Met QC Criteria

March 12, 2020

Last Verified

March 1, 2020

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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