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

NCT02950155 | Completed Phase 3 Results DMC

• 1 other identifier: EudraCT 2015-005749-30
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Generalized Myasthenia Gravis

Outcome Measures

Primary Outcomes (1)

• Percentage of Patients With Quantitative MG Score (QMG) Score ≤ 4 and a Daily Prednisolon Dose of ≤ 10mg at 16 Weeks After Administration of Study Drug/Placebo.

  The Quantitative Myasthenia Gravis (QMG) score is a physician rated disease activity score that ranges from 0 to 39, where lower indicates better outcome. QMG was measured at 16 weeks under standardized conditions with at least 12 hours since last intake of choline esterase inhibitors. Patients meeting the primary outcome had a QMG score of 4 or less whilst also requiring a daily oral Prednisolone dose of 10 mg or less.

  16 weeks

Secondary Outcomes (3)

• Change in QMG Score From Week 0 to Week 24 After Administration of Study Drug/Placebo.

  24 weeks

• Change in Myasthenia Gravis Activities of Daily Living (MG-ADL) Score From Week 0 to Week 16 After Administration of Study Drug/Placebo

  16 weeks

• Change in Myasthenia Gravis Quality of Life (QoL) Score From Week 0 to Week 16 After Administration of Study Drug/Placebo.

  16 weeks

Other Outcomes (7)

• 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.

  24 weeks

• QMG Scores at 16, 36 and 48 Weeks After Administration of Study Drug/Placebo.

  16, 36 and 48 weeks

• MG-activities of Daily Living (ADL) Score at 24, 36 and 48 Weeks After Administration of Study Drug/Placebo

  24, 36 and 48 weeks

Study Arms (2)

Rituximab

EXPERIMENTAL

A single infusion at a dose of 500 mg of Mabthera/Rituximab.

Drug: Rituximab

Sodium Chloride solution

SHAM COMPARATOR

A single infusion with sodium chloride solution.

Drug: Sodium Chloride solution

Interventions

Rituximab DRUG

A single infusion at a dose of 500 mg Mabthera/Rituximab.

Also known as: Mabthera

Rituximab

Sodium Chloride solution DRUG

A single infusion of Placebo/Sham.

Also known as: Sodium Chloride

Sodium Chloride solution

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Weakness only affecting ocular or periocular muscles (MGFA Class I).
• MG crisis at screening (MGFA Class V)
• 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.
• Strong suspicion of thymoma, where thymectomy as judged by the treating physician should be done within 24 weeks.
• Active malignancy, if not adequately treated
• Pregnancy or breast-feeding.
• 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.
• Severe heart failure (New York Heart Association Class IV) or severe, uncontrolled cardiac disease
• 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.
• Suspected hypersensitivity to the study drug
• Participation in another trial of study drug within 30 days prior to screening.
• 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.

Sponsors & Collaborators

• Fredrik Piehl: lead

Study Sites (1)

Karolinska University Hospital

Stockholm, Solna, 171 76, Sweden

Location

Related Publications (1)

• Piehl F, Eriksson-Dufva A, Budzianowska A, Feresiadou A, Hansson W, Hietala MA, Hakansson I, Johansson R, Jons D, Kmezic I, Lindberg C, Lindh J, Lundin F, Nygren I, Punga AR, Press R, Samuelsson K, Sundstrom P, Wickberg O, Brauner S, Frisell T. Efficacy and Safety of Rituximab for New-Onset Generalized Myasthenia Gravis: The RINOMAX Randomized Clinical Trial. JAMA Neurol. 2022 Nov 1;79(11):1105-1112. doi: 10.1001/jamaneurol.2022.2887.

  PMID: 36121672 DERIVED

MeSH Terms

Conditions

Myasthenia Gravis

Interventions

Rituximab; Sodium Chloride

Condition Hierarchy (Ancestors)

Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Neurodegenerative Diseases; Neuromuscular Junction Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Limitations and Caveats

Imbalances in some baseline characteristics, with a lower age, higher AChR antibody titres, a lower proportion treated with prednisolone, and a greater proportion with MGFA class III disease among those randomized to placebo compared with rituximab. On the other hand, late onset MG has been associated with worse disease, and one subject in the active arm suffered a condition (ALS) that effectively excluded the possibility to evaluate a treatment effect.

Results Point of Contact

• Title: Prof. Fredrik Piehl
• Organization: Karolinska Institutet

fredrik.piehl@ki.se

+46 736718101

Study Officials

• Fredrik Piehl, Professor

  Dept Clinical Neuroscience Karolinska Institutet, Neuroimmunology Unit

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, MD

Study Record Dates

• First Submitted: October 28, 2016
• First Posted: October 31, 2016
• Study Start: October 16, 2016
• Primary Completion: January 30, 2021
• Study Completion: January 31, 2022
• Last Updated: October 26, 2024
• Results First Posted: October 26, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)