Efficacy and Safety of Low-dose Rituximab in the Treatment of Refractory Myasthenia Gravis

This study is designed to evaluate the effectiveness and safety of low-dose rituximab in patients with refractory myasthenia gravis.

The traditional treatment of MG is immunosuppressive therapy, usually beginning with corticosteroids. However, up to 70% of treated patients show an incomplete response, including 10 - 30% who are unresponsive. Corticosteroids and other immunosuppressive therapies presented also many side effects. The investigators propose to evaluate in a pilot, open, prospective, single central study, the interest of rituximab (RTX) in the treatment of patients with refractory MG. Fifty patients with refractory MG will be included in the study and divided into two stages: 14 patients in the first stage were followed up after using RTX according to the study protocol. The study will move into the second stage on if the number of effective cases is greater than 3, otherwise, the study will be discontinued (based on Simon's Optimal Two-stage Design). The remaining 36 patients were enrolled in the second stage. In the first and second stages, the treatment plan and follow-up plan were consistent. The therapeutical schema is rituximab 100-200 mg/week for a total of 2-4 times, followed by adequate organ function, laboratory parameters and assessment of MG after each injection and end of follow up for 24 weeks.

Study Overview

• Status: Recruiting
• Conditions: Refractory Myasthenia Gravis; Rituximab
• Intervention / Treatment: Drug: Rituximab

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangzhou, China, 510080
    • Recruiting
    • First Affiliated Hospital, Sun Yat-Sen University
    • Contact: Liu Weibin; Phone Number: 86+13826121596; Email: liuwb@mail.sysu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 80 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Aged 80 and under;

2. Myasthenia gravis:

   1. Patients who are diagnosed as generalized or ocular myasthenia gravis
   2. Patients must have disease refractory to treatment: the condition did not improve (QMG score decreased by less than 3 points after treatment) or even deteriorated after treatment with sufficient prednisone or other immunosuppressive agents.
3. Patients sign informed consent forms

Exclusion Criteria:

1. Over the age of 80
2. Patients with serious complications such as infection
3. Patients with active TB (during the screening period, a chest X-ray or chest CT would be performed unless the patient can provide chest X-ray or chest CT reports in the last month); or patients with active HBV, HBV DNA> 200
4. Patients suffering from cardiomyopathy, acute coronary events, or severe arrhythmia.
5. Patients who were allergic to rituximab
6. Pregnant or suckling period woman
7. Patients accompanied with mental disorders and have difficult to communication
8. Patients with a significant abnormality in white blood cells, hemoglobin, and platelet count.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Rituximab Treated; rituximab	Drug: Rituximab; The therapeutical schema is rituximab 100-200 mg/week for a total of 2-4 times

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to reach MM-1, the proportion of drug remission.	Mild clinical Manifestations（MM-1）was the primary efficacy endpoint observed. Record the time the patient appears from the time of medication to the time of MM-1，and calculate the percentage of Pharmacologic Remission (PR). Criteria for PR: The patient has had no symptoms or signs of MG and continues to take some form of therapy for MG. There is no weakness of any muscle on careful examination by someone skilled in the evaluation of neuromuscular disease. Isolated weakness of eyelid closure is accepted. Patients taking cholinesterase inhibitors are excluded from this category because their use suggests the presence of weakness.	27 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The changes of the disease severity	The magnitude by which the Quantitative Myasthenia Gravis (QMG) (0-39), the Myasthenia Gravis-specific Activities of Daily Living scale (MG-ADL) (0-24) , the MG Composite (MGC) (0-46) or the MG 15-item Quality of Life scale (MG-QOL15) (0-60) scores are changed. Higher scores mean a worse outcome.	27 weeks

Collaborators and Investigators

• Sponsor: First Affiliated Hospital, Sun Yat-Sen University

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 1, 2020
• Primary Completion (ANTICIPATED): July 1, 2022
• Study Completion (ANTICIPATED): July 1, 2022

Study Registration Dates

• First Submitted: December 4, 2021
• First Submitted That Met QC Criteria: April 12, 2022
• First Posted (ACTUAL): April 18, 2022

Study Record Updates

• Last Update Posted (ACTUAL): May 2, 2022
• Last Update Submitted That Met QC Criteria: April 26, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Neoplasms; Autoimmune Diseases of the Nervous System; Autoimmune Diseases; Neoplasms by Site; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Neuromuscular Manifestations; Nervous System Neoplasms; Paraneoplastic Syndromes, Nervous System; Paraneoplastic Syndromes; Neuromuscular Junction Diseases; Muscle Weakness; Myasthenia Gravis; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: [2020]414-1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No