A Phase II Study of SHR-2173 Injection in Patients With Myasthenia Gravis

Официальное название

A Phase II, Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Efficacy and Safety of SHR-2173 in Patients With Generalized Myasthenia Gravis

Обзор

This study is a multicenter, randomized, double-blind, placebo-controlled Phase II clinical trial designed to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of SHR-2173 compared to placebo as an add-on therapy to standard of care (SOC) for the treatment of generalized myasthenia gravis (gMG). The study consists of a 4-week screening period, a 24-week treatment period, and a 12-week safety follow-up period.

Вмешательства

• Препарат SHR-2173 injection
  SHR-2173 injection；High dose
• Препарат SHR-2173 injection
  SHR-2173 injection；Low dose
• Препарат Placebo
  Placebo

Первичные конечные точки

• Change from baseline in MG-ADL total score [Срок оценки: at Week 24]

Вторичные конечные точки (12)

• Change from baseline in Quantitative Myasthenia Gravis (QMG) score [Срок оценки: at Week 24]
• Change from baseline in Myasthenia Gravis Composite (MGC) total score [Срок оценки: at Week 24]
• Change from baseline in MG-ADL domain scores (ocular, bulbar, respiratory, limb) [Срок оценки: at Week 24]
• Change from baseline in QMG domain scores (ocular, bulbar, respiratory, limb) [Срок оценки: at Week 24]
• Proportion of participants with ≥3-point reduction from baseline in MG-ADL total score [Срок оценки: at Week 24]
• Proportion of participants with ≥50% reduction from baseline in MG-ADL total score [Срок оценки: at Week 24]
• Proportion of participants with ≥5-point reduction from baseline in QMG score [Срок оценки: at Week 24]
• Proportion of participants achieving Minimal Symptom Expression (MSE; MG-ADL total score 0 or 1) at Week 24 [Срок оценки: at Week 24]
• Change from baseline in Myasthenia Gravis Quality of Life 15-item revised (MG-QoL15r) total score [Срок оценки: at Week 24]
• Change from baseline in Neuro-QoL Fatigue subscale score [Срок оценки: at Week 24]
• Change from baseline in European Quality of Life 5-Dimensions 5-Levels (EQ-5D-5L) index score [Срок оценки: at Week 24]
• Proportion of participants without rescue therapy [Срок оценки: through Week 24]

Критерии участия

Критерии включения

• Male and female participants aged 18-75 years, confirmed diagnosis of generalized myasthenia gravis (gMG) (Myasthenia Gravis Foundation of America \[MGFA\] class II-IV).
• Positive for anti-AChR antibody or anti-MuSK antibody.
• MG-ADL total score ≥5 at screening and baseline, with >50% of the score attributable to non-ocular items.
• QMG score ≥11 at screening and baseline.
• Maintenance on stable standard of care (SOC) therapy.
• No contraindication to at least one rescue therapy: IVIg or PLEX.
• Provided written informed consent (ICF) after full understanding of the study content, procedures, and potential adverse reactions.
• Female subjects with fertility or male participants whose partners are women of childbearing age must avoid donating sperm/eggs from the date of signing the ICF until 12 weeks after the last study medication, and agree to take contraceptive measures as specified in the protocol

Критерии исключения

• Presence of any of the following medical histories or comorbidities:

• Any untreated thymic epithelial tumor, mediastinal germ cell tumor, or other malignant mediastinal mass; or any thymic cyst or other mass requiring immediate intervention per investigator judgment;
• Previous history of thymic tumor not meeting protocol requirements;
• Myasthenic crisis (MGFA Class V) within 3 months prior to randomization;
• Any known disease other than gMG that may interfere with study procedures and assessments;
• A history of progressive multifocal leukoencephalopathy (PML);
• A history of body irradiation or organ transplantation.
• Use of any of the following drugs/treatments or participation in a clinical study:

• Prior treatment with CAR-T or other cellular therapy, or T-cell engager (TCE) therapy;
• Anti-CD20 monoclonal antibody within 6 months prior to randomization; other B-cell or plasma cell-depleting therapy within 6-12 months prior to randomization;
• Alkylating agent within 12 weeks prior to randomization;
• Any biologic for MG treatment within 12 weeks prior to randomization;
• Neonatal Fc receptor antagonist therapy within 8 weeks prior to randomization;
• Janus kinase (JAK), Bruton tyrosine kinase (BTK), or tyrosine kinase 2 (TYK2) inhibitor within 12 weeks prior to randomization;
• IVIg, subcutaneous immunoglobulin, or PLEX therapy within 4 weeks prior to randomization;
• Live/attenuated live vaccine within 4 weeks prior to randomization, or planned vaccination during the study.
• A history of malignancy within 5 years prior to screening;
• Infection-related medical history and examinations:

• A history of herpes zoster meeting any of the following: 1) A history of disseminated herpes zoster, herpes zoster encephalitis, or ocular herpes zoster involving the retina; 2) Recurrent herpes zoster with 2 or more episodes within 2 years; 3) Herpes zoster infection not fully resolved within 12 weeks prior to screening;
• A history of tuberculosis (TB) or latent TB infection;
• A known history of primary immunodeficiency, splenectomy, or any underlying condition predisposing to infection;
• A history of recurrent infections requiring hospitalization and intravenous antibiotics;
• Any infection requiring hospitalization and/or intravenous antimicrobial therapy within 8 weeks prior to randomization, or any infection requiring oral antimicrobial therapy within 2 weeks prior to randomization;
• Positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody, treponemal pallidum antibody, or human immunodeficiency virus (HIV) antibody; for patients with HBsAg-negative but hepatitis B core antibody (HBcAb)-positive, regardless of the status of hepatitis B surface antibody (HBsAb), HBV-DNA testing is required to confirm their condition, with HBV-DNA-positive patients excluded and HBV-DNA-negative patients eligible to participate in the study.
• General situation:

• Pregnant or lactating females;
• A history of alcohol abuse or illicit drug abuse within 1 year prior to screening;
• A history of allergic diathesis, or known hypersensitivity/intolerance to any component of the investigational product;
• Major surgery within 3 months prior to the screening, or planned major surgery during the study;
• Any condition that, in the investigator's judgment, may affect evaluation of study drug safety and efficacy, or any other condition that renders the subject ineligible.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 2 центра

• Xiangya Hospital of Central South University — Чанша
• Huashan Hospital, Fudan University — Шанхай

Идентификаторы

NCT: NCT07622342 · SHR-2173-206

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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