Blinatumomab for Treatment of Refractory Myasthenia Gravis

Efficacy and Safety of Blinatumomab for Treatment of Refractory Myasthenia Gravis.

The goal of this clinical trial is to evaluate the efficacy and safety of Blinatumomab in the treatment of refractory myasthenia gravis, with the expectation of offering a new therapeutic option for refractory patients. The main questions it aims to answer are:

• Does Blinatumomab improve patients' clinical symptoms?
• Is Blinatumomab safe for the treatment of myasthenia gravis?

Participants will:

• Receive two cycles of intravenous Blinatumomab infusion, each lasting 5 days, with a 1-week interval between cycles.
• Visit the clinic once every 4 weeks for checkups and tests.
• Keep a diary of their symptoms and the types and dosages of medications.

Study Overview

• Status: Not yet recruiting
• Conditions: Myasthenia Gravis
• Intervention / Treatment: Drug: Blinatumomab

• Study Type: Interventional
• Enrollment (Estimated): 2
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Yuwei Da, M.D.; Phone Number: 00-86-010-83198493; Email: dayuwei100@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age at onset > 18 years old
• The diagnosis of MG was based on the presence of typical myasthenic symptoms and supported by positive autoantibodies, electrophysiological studies, and/or the neostigmine test.
• Positive or negative for anti-AChR, and/or anti-MuSK, and/or anti-LRP4 antibodies.
• Refractory myasthenia gravis (MG) patients are defined as those who meet any of the following criteria: For patients with ocular MG, the condition is defined as having no significant improvement in disease symptoms (QMG score improvement <25%) after adequate dosing and duration of existing immunosuppressive drugs and targeted biologics, with no change or worsening in the post-intervention status (PIS), or if the PIS improves but disease symptoms worsen or relapse during the regular tapering of immunosuppressive treatment, severely affecting daily quality of life. For generalized MG, the patient must meet the following conditions: no improvement or worsening in PIS after adequate dosing and duration of existing immunosuppressive drugs and targeted biologics; improvement in PIS, but with an MG-ADL score ≥6 persisting for at least six months; remission or improvement in PIS, but with ≥2 episodes of disease exacerbation (MG-ADL ≥6) per year during tapering of immunotherapy medications; patients who, after experiencing a myasthenic crisis, undergo multiple immunotherapies including intravenous efgartigimod, eculizumab, immunoglobulin, plasma exchange, and high-dose intravenous methylprednisolone, and active infection control, but still cannot be weaned off the ventilator due to respiratory muscle weakness from MG for more than 14 days. (Note: This includes patients who cannot tolerate existing treatment drugs due to contraindications, comorbidities, or adverse drug reactions.)
• Receiving stable doses of medication prior to enrollment
• Written informed consent

Exclusion Criteria:

• Patients who have thymoma or have undergone thymectomy within six months
• Patients who have used other biologics prior to enrollment that may affect the efficacy assessment of blinatumomab.
• Severe cardiovascular, hepatic, renal, respiratory, or endocrine diseases, malignancies, or uncontrolled acute or chronic infections
• Pregnancy or lactation, unwillingness to avoid pregnancy
• Patients with other diseases that may affect the assessment of muscle strength
• Other conditions that would preclude participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Blinatumomab	Drug: Blinatumomab; Blinatumomab is used at its starting dose of 9 µg per day and administered as continuous infusion for 5 days (total dose of 38.5 µg). After a 1-week pause, the patients receive a second 5-day infusion with blinatumomab of total 38.5 µg of the drug.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of Myasthenia Gravis Activities of Daily Living (MG-ADL) Score from baseline	The MG-ADL scale is an 8-item questionnaire. It is completed by trained interviewers based on the patients' subjective responses. The total score ranges from 0 to 24, with higher scores indicating greater impact of the disease on daily living activities.	From baseline to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of Quantitative Myasthenia Gravis (QMG) Scores from baseline	The QMG scale is a 13-item scale used to objectively assess muscle strength and fatigue in patients with myasthenia gravis. The total score ranges from 0 to 39, with higher scores indicating greater disease severity.	From baseline to 6 months
Time to achievement of minimal symptom expression (MSE)	The MSE is a quantifiable, patient-reported outcome measure that assesses treatment goals in myasthenia gravis. It is defined as achieving an MG-ADL score of ≤1, indicating that clinical symptoms of MG are at their minimal level.	From baseline to 6 months
Change of Myasthenia Gravis Quantity-of-Life Scale (MG-QoL15) from baseline	The MG-QOL15 scale is a 15-item questionnaire designed to assess the impact of myasthenia gravis on patients' daily life, physical function, social well-being, and mental health. The total score ranges from 0 to 60, with higher scores indicating poorer quality of life.	From baseline to 6 months
Change of Myasthenia Gravis Composite (MGC) scores from baseline	The MGC scale is a 10-item scale that combines patient self-assessment and physician examination results. Each item is assigned a weight based on factors such as health risks, quality of life, and prognosis. The total score of the scale is 50 points, with higher scores indicating more severe disease.	From baseline to 6 months
Change of antibody titers from baseline	MG antibodies are detected at enrollment and the titers of antibodies will be monitored monthly.	From baseline to 6 months
Treatment-Related Adverse Events (AEs)	Record all AEs reported by patients during the study period.	From baseline to 6 months

Collaborators and Investigators

• Sponsor: Da, Yuwei, M.D.

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2025
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: February 16, 2025
• First Submitted That Met QC Criteria: February 16, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 21, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Manifestations; Pathologic Processes; Neoplasms by Site; Neoplasms; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases; Autoimmune Diseases of the Nervous System; Neurodegenerative Diseases; Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Paraneoplastic Syndromes; Neuromuscular Junction Diseases; Muscle Weakness; Myasthenia Gravis; Antineoplastic Agents; Blinatumomab
• Other Study ID Numbers: LYS[2024]408-002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No