Efficacy and Safety of Tocilizumab in the Treatment of Generalized Myasthenia Gravis (tMG)

A Multi-center, Randomized, Double-blind, Placebo-controlled Clinical Trial of the Efficacy and Safety of Tocilizumab in the Treatment of Generalized Myasthenia Gravis

Randomized, double-blind, placebo-controlled, parallel-group study with optional open-label extension.

Study Overview

• Status: Recruiting
• Conditions: Myasthenia Gravis, Generalized
• Intervention / Treatment: Drug: Tocilizumab Injectable Product

Detailed Description

This study is a randomized, double-blind, placebo-controlled study, to be conducted at 6 study sites. Approximately 64 subjects will be enrolled. Patients with MG who are positive for anti-AChR antibodies will be enrolled. Patients who do not have anti-AChR or anti-MuSK antibodies will not be enrolled. Patients with MGFA classification II, III, or IV disease, MG-ADL score ≥ 5, QMG score ≥ 11, and use of a corticosteroid and/or non-steroidal immunosuppressant will be included in the study.

All subjects who complete the randomized controlled period will have the option to enroll in a 1-year open-label period.

• Study Type: Interventional
• Enrollment (Estimated): 64
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ting Chang, MD,PHD; Phone Number: +86-29-84778845; Email: changting1981@163.com
• Study Contact Backup: Name: Zhe Ruan; Phone Number: +86-29-84778845; Email: ruanzhe573291596@126.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100050
      • Not yet recruiting
      • Beijing Tiantan Hospital, Capital Medical University
      • Contact: Fudong Shi, MD,PHD; Phone Number: +86-22-60817429; Email: fshi@tmu.edu.cn
  • Hunan
    • Changsha, Hunan, China, 410008
      • Not yet recruiting
      • Xiangya Hospital Central South University
      • Contact: Huan Yang, MD,PHD; Email: yxyx69@gahoo.com.cn
  • Shaanxi
    • Xi'an, Shaanxi, China, 710038
      • Recruiting
      • Tangdu Hospital, The Fourth Military Medical University
      • Contact: Ting Chang; Phone Number: 02984778845; Email: changting1981@163.com
      • Contact: Zhe Ruan; Email: ruanzhe573291596@126.com
  • Shanghai
    • Shanghai, Shanghai, China, 200040
      • Not yet recruiting
      • Huashan Hospital
      • Contact: Chongbo Zhao, MD,PHD; Phone Number: 86-21-52889999; Email: zhao_chongbo@fudan.edu.cn
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Not yet recruiting
      • West China Hospital of Sichuan University
      • Contact: Hongyu Zhou, MD,PHD; Email: zhouhy@scu.edu.cn
  • Tianjin
    • Tianjin, Tianjin, China, 300052
      • Not yet recruiting
      • Tianjin Medical University General Hospital
      • Contact: Chao Zhang, MD,PHD; Phone Number: +86-22-60362255

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Diagnosis of MG with anti-AChRantibody.
2. MGFA Clinical Classification Class II, III, or IV.
3. MG-ADL score of 5 or greater at screening and at randomization with > 50% of this score attributed to non-ocular items.
4. QMG score of 11 or greater.

5. Subjects must be on:

   1. Cholinesterase inhibitor, with no dose increase within 4 weeks prior to randomization;
   2. Corticosteroids, with no dose increase within 4 weeks prior to randomization; or/and c. non-steroidal IST (including azathioprine, mycophenolate mofetil, tacrolimus, cyclosporine A), with continuous use for at least 6 months prior to randomization and no dose increase within 4 months prior to randomization.

Exclusion Criteria:

1. Participants had clinically relevant active infections (such as sepsis, pneumonia, or abscess) or severe infections (resulting in hospitalization or requiring antibiotic treatment) in the 4 weeks before randomization;
2. Those with a history of high-risk tuberculosis infection, acquired tuberculosis infection, and chronic hepatitis;
3. Human immunodeficiency virus (HIV) infection;
4. Thymomas that have received thymectomy or planned thymectomy during RCP within 6 months before randomization, or require chemotherapy and/or radiotherapy at any time;
5. Received rituximab treatment in the past 6 months before randomization;
6. Received tocilizumab or eculizumab treatment within 3 months before randomization;
7. Received IVIG or plasma exchange within 4 weeks before randomization;
8. Unresected thymoma.
9. History of other tumor diseases.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tocilizumab; Participants will receive tocilizumab administered intravenously (IV) on weeks 1,5,9 and 13 of the randomized controlled period.	Drug: Tocilizumab Injectable Product; Participants will receive IV tocilizumab
Placebo Comparator: Placebo; Participants will receive placebo administered intravenously (IV) on weeks 1,5,9 and 13 of the randomized controlled period.	Drug: Tocilizumab Injectable Product; Participants will receive IV tocilizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in Quantitative Myasthenia Gravis (QMG) scores.	16 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of subjects with both (1) ≥ 3-point improvement in QMG and (2) lasts ≥4 weeks	16 weeks
Proportion of subjects with both (1) ≥ 2-point improvement in MG-ADL and (2) lasts ≥4 weeks	16 weeks
Change in Myasthenia Gravis Composite (MGC) score	16 weeks
Change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) Profile score.	16 weeks
Change in Myasthenia Gravis Quality of Life-15, revised (MGQOL-15r) score.	16 weeks
Change in Myasthenia Gravis Impairment Index (MGII) score.	16 weeks
Number of participants with treatment-emergent adverse events (TEAEs), adverse events of special interest (AESIs), and treatment-emergent serious adverse events (TESAEs) during the randomized controlled period and open-label period.	16 weeks

Collaborators and Investigators

• Sponsor: Tang-Du Hospital
• Investigators: Study Director: Ting Chang, MD,PHD, The Second Affiliated Hospital of Air Force Medical University

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2022
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): March 30, 2026

Study Registration Dates

• First Submitted: September 23, 2021
• First Submitted That Met QC Criteria: September 23, 2021
• First Posted (Actual): October 5, 2021

Study Record Updates

• Last Update Posted (Actual): May 1, 2025
• Last Update Submitted That Met QC Criteria: April 28, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Tocilizumab; Generalized Myasthenia Gravis
• 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
• Other Study ID Numbers: V4.0, 20220410

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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