Telitacicept and Low-dose Steroids in Refractory Myasthenia Gravis

Phase 4

Not yet recruiting

• Conditions: Myasthenia Gravis; Autoimmune Diseases
• Interventions: Drug: Telitacicept

• Registration Number: NCT06723548
• Lead Sponsor: First Affiliated Hospital of Wenzhou Medical University

Brief Summary

This study is designed to explore the efficacy and safety of Telitacicept combined with low-dose steroids for the treatment of refractory MG, and to investigate related biomarkers such as immunoglobulins, BlyS/APRIL, and AChR-Ab titers, in order to clarify whether Telitacicept can rapidly and effectively help achieve MG treatment goals and assist in steroid reduction.

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-11
• Study First Submitted: 2024-11-15
• Study Start: 2024-12
• Study First Submitted QC: 2024-12-03
• Last Update Submitted: 2024-12-03
• Study First Posted: 2024-12-09
• Last Update Posted: 2024-12-09
• Primary Completion: 2025-12
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• Age between 18-85 years, both genders included；

• Meet the diagnostic criteria of the 2020 Chinese MG guidelines, with positive serological testing for AChR-Ab;

• Clinical classification of Type I to Type IVa according to the MGFA;

• Meet the criteria for refractory MG in the 2022 Japanese MG guidelines: poor response to standard treatment, intolerance to standard treatment drugs due to adverse reactions, frequent relapses/exacerbations after reduction of standard treatment drugs, frequent need for rescue treatment due to disease fluctuations, frequent myasthenic crises, and comorbidities that limit the use of standard treatment;

• Patients with unstable symptoms (MG-ADL score ≥6 or QMG ≥8) despite treatment with standard therapeutic regimens before enrollment, defined as follows:

  1. Patients on monotherapy with corticosteroids: a corticosteroid dose ≤60mg/d, and a stable dose for at least 1 month before enrollment;
  2. Patients on combination therapy with corticosteroids and other immunosuppressants: a corticosteroid dose ≤60mg/d, and a stable dose for at least 1 month before enrollment, while other immunosuppressants such as azathioprine, methotrexate, tacrolimus, and mycophenolate mofetil have been stable for 6 months prior to the study start and will remain stable during the study period;

• Patients must provide written informed consent.

Exclusion Criteria

• Patients with active infections, such as herpes zoster, HIV, active pulmonary tuberculosis, or active hepatitis;
• Patients with thymic tumors or those who have undergone thymectomy within the past 6 months;
• Patients with coexisting malignant tumors;
• Patients with severe hepatic or renal insufficiency;
• Patients who have received intravenous immunoglobulin or undergone plasmapheresis within the last 2 months;
• Patients who have received any live vaccines within the last 3 months or plan to receive any vaccines during the study period;
• Women who are currently pregnant or breastfeeding, and patients who plan to conceive during the trial period;
• Patients with allergies to human-derived biological products;
• Patients who have participated in any clinical trial within the last 28 days or within 5 half-lives of the study medication (whichever is longer);
• Any other patients deemed unsuitable for enrollment by the investigator (e.g., severe psychiatric disorders).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Patients with refractory MG treated with Telitacicept combined with low-dose steroids	Telitacicept	This is an open-label, single-arm exploratory study of Telitacicept (240mg weekly, then every two weeks after achieving MMS or QMG reduction of ≥ 6 points) combined with a gradual reduction of steroids and other immunosuppressants. When the steroid dose is reduced to 5mg/day or 10mg/every other day, Telitacicept can be reduced to 160mg, administered subcutaneously every two weeks.

Primary Outcome Measures

Name	Time	Method
The change in patients' ADL scores	from baseline to week 52	The variation in ADL scores at 52 weeks compared to baseline in patients. Total MG -ADL scores range from 0 (normal) to 24 (severe).
The change in patients' QMG scores	from baseline to week 52	The variation in QMG scores at 52 weeks compared to baseline in patients. Total QMG scores range from 0 (none) to 39 (severe).

Secondary Outcome Measures

Name	Time	Method
MGFA-PIS	from baseline to week 52	Change in MGFA-PIS grading from baseline to week 52
the average daily corticosteroid usage	from baseline to week 24；from baseline to week 52	Change in the average daily corticosteroid usage from baseline to week 24 during follow-up；Change in the average daily corticosteroid usage from baseline to week 52 during follow-up
the usage of traditional non-steroidal immunosuppressants	from baseline at weeks 24 and 52	Change in the usage of traditional non-steroidal immunosuppressants from baseline to week 24 during follow-up; Change in the usage of traditional non-steroidal immunosuppressants from baseline to week 52 during follow-up. Medication usage logs or medical record reviews to document the changes in the use of traditional non-steroidal immunosuppressants (such as Azathioprine, Mycophenolate Mofetil, Tacrolimus, Methotrexate, Cyclosporine, etc.) from baseline to week 52. The change in the use of traditional non-steroidal immunosuppressants will be assessed by comparing the medication usage at baseline and at weeks 24 and 52. This includes details on the type of medication, dosage, frequency, and any adjustments or discontinuations.
Number of relapses	week 52	Number of relapses in both groups by the end of treatment (clinical relapse is defined as an increase in QMG score of ≥3 points);
AUDTC	week 52	Area under the corticosteroid dose-time curve (AUDTC) at week 52
Proportion of patients with a corticosteroid dose ≤10mg/d	at weeks 24 and 52	Proportion of patients with a corticosteroid dose ≤10mg/d at weeks 24 and 52 during follow-up;
Proportion of patients achieving MMS with a corticosteroid dose ≤ 5mg/d	week 24	Proportion of patients achieving MMS with a corticosteroid dose ≤5mg/d at week 24;
MG QoL15r scores	from baseline at weeks 24 and 52	Change in MG QoL15r scores from baseline at weeks 24 and 52 during follow-up
safety（Incidence, severity, and outcome of adverse events）	52 weeks	Incidence, severity, and outcome of adverse events
relevant biomarkers	from baseline at week 52	relevant biomarkers, such as immunoglobulins,lymphocyte subpopulation changes, BlyS/APRIL, and AChR-Ab titers.