Telitacicept and Low-dose Steroids in Refractory Myasthenia Gravis

Official title

The Efficacy and Safety of Telitacicept Combined With Low-dose Steroids in Patients With Refractory Myasthenia Gravis

Overview

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.

Interventions

• Drug Telitacicept
  Patients with MG who fulfill the inclusion criteria will receive Telitacicept 240mg weekly as an adjunct to their medication. Upon reaching MMS, significant symptom improvement, or a QMG score reduction of at least 6 points, Telitacicept is reduced to biweekly doses. Pyridostigmine and NSISTs are tapered based on patient response. Following this, Prednisone is tapered, starting with rapid reduction early and slowing later. If a patient on 60mg Prednisone daily achieves treatment goals within 6-8

Primary outcome measures

• The change in patients' ADL scores [Time frame: from baseline to week 52]
• The change in patients' QMG scores [Time frame: from baseline to week 52]

Secondary outcome measures (10)

• MGFA-PIS [Time frame: from baseline to week 52]
• the average daily corticosteroid usage [Time frame: from baseline to week 24；from baseline to week 52]
• the usage of traditional non-steroidal immunosuppressants [Time frame: from baseline at weeks 24 and 52]
• Number of relapses [Time frame: week 52]
• AUDTC [Time frame: week 52]
• Proportion of patients with a corticosteroid dose ≤10mg/d [Time frame: at weeks 24 and 52]
• Proportion of patients achieving MMS with a corticosteroid dose ≤ 5mg/d [Time frame: week 24]
• MG QoL15r scores [Time frame: from baseline at weeks 24 and 52]
• safety（Incidence, severity, and outcome of adverse events） [Time frame: 52 weeks]
• relevant biomarkers [Time frame: from baseline at week 52]

Eligibility criteria

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:

• Patients on monotherapy with corticosteroids: a corticosteroid dose ≤60mg/d, and a stable dose for at least 1 month before enrollment;
• 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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06723548 · 2024-ps-195

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗