NCT07818291尚未招募1 期
An Open-label, Dose-escalation Phase Ib Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of Multiple Doses of EA5 Humanized Monoclonal Antibody in Adult Patients With Anti-AChR Antibody-Positive Generalized Myasthenia Gravis
Shanghai Lanyi Therapeutics Co., Ltd.2 个研究点 分布在 1 个国家目标入组 18 人开始时间: 2026年9月15日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 18
- 试验地点
- 2
- 主要终点
- Incidence and Severity of Treatment Emergent Adverse Events (TEAEs)
研究概览
简要总结
This is a Phase Ib, open-label, dose-escalation, single-center/multicenter study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of multiple doses of EA5 (a humanized anti-complement C5 monoclonal antibody) in adult participants with anti-AChR antibody-positive generalized myasthenia gravis (gMG) who have not previously received complement inhibitor therapy. Approximately 18 participants will be enrolled. The study consists of a screening period (Day -42 to Day -1), a loading period (Day 1 to Day 14), a treatment observation period (Day 15/Week 3 to Day 99/Week 15), and an end-of-study visit (up to Day 155/Week 23). All participants receive a loading does , then are assigned to one of three maintenance dose cohorts: Cohort 1 (Low Dose), Cohort 2 (MID Dose), and Cohort 3 (High Dose). The primary objective is to assess safety and tolerability. Secondary objectives include preliminary efficacy, PK, PD (complement inhibition), and immunogenicity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female aged ≥18 years.
- •Diagnosis of myasthenia gravis (MG) confirmed by:
- •positive serology for anti-acetylcholine receptor (AChR) antibody at screening; and
- •any one of the following: abnormal neuromuscular transmission confirmed by repetitive nerve stimulation; history of positive anticholinesterase test (e.g., neostigmine test); or improvement in MG signs after oral cholinesterase inhibitors as assessed by the treating physician.
- •Body weight between 40 kg and 100 kg (inclusive) at screening.
- •MGFA clinical classification Class II to IVa at screening.
- •MG-ADL total score ≥5 at screening, with more than 50% of the total score from non-ocular symptoms.
- •For participants receiving immunosuppressive therapy (IST) (e.g., azathioprine [AZA], mycophenolate mofetil [MMF], methotrexate [MTX], cyclophosphamide [CY]): treatment for ≥6 months prior to screening and stable dose for ≥2 months (calculated as 30 days per month).
- •For participants receiving other IST (e.g., cyclosporine [CsA], tacrolimus [TAC]): treatment for ≥3 months prior to screening and stable dose for ≥1 month.
- •For participants receiving corticosteroid therapy at enrollment: stable dose (not exceeding 30 mg/day prednisone acetate or equivalent) for ≥28 days prior to screening.
- •For participants receiving cholinesterase inhibitor therapy: stable dose for ≥14 days prior to screening.
- •At screening, laboratory tests must meet: (a) Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) <1.5×ULN; (b) serum total bilirubin <1.5×ULN (<3×ULN for confirmed Gilbert's syndrome); (c) Hemoglobin ≥100 g/dL; (d) Platelet count >75×10⁹/L; (e) International normalized ratio (INR) and activated partial thromboplastin time (aPTT) <1.5×ULN; (f) serum creatinine <1.5×ULN and eGFR >90 mL/min/1.73m²; (g) basically normal immune function as assessed by the investigator (lymphocyte count ≥1×LLN, IgG ≥1×LLN).
- •To reduce the risk of meningococcal infection (Neisseria meningitidis): participants must be vaccinated at least 14 days prior to the first dose of study drug if not vaccinated within the valid coverage period; if vaccinated within 14 days before dosing, antibiotic prophylaxis must be provided until 2 weeks post-vaccination (penicillin V potassium recommended; cefaclor or other antibiotics may be used if penicillin is unavailable or the participant is allergic; fluoroquinolones and macrolides are not recommended).
- •To reduce the risk of pneumococcal infection: vaccination against Streptococcus pneumoniae is required; if previously vaccinated, vaccination may be waived during screening; if not previously vaccinated, vaccination must be given at least 14 days prior to the first dose (antibiotic prophylaxis as described in item 11).
- •For females of childbearing potential: serum β-HCG pregnancy test must be negative at screening; effective and reliable contraception must be used during the study and for at least 6 months after discontinuation of study intervention (women of childbearing potential are defined as premenopausal women who have not undergone sterilization; menopause is defined as amenorrhea for ≥12 months without alternative medical measures; FSH >40 mIU/mL confirms menopause).
- •Male participants must agree to use effective contraceptive measures (vasectomy, abstinence, condom use) throughout the study period (from screening to 6 months after study completion); female participants of childbearing potential must have negative blood pregnancy tests at screening and baseline, and female participants, male participants, and their sexual partners must agree to use contraceptive measures during the study and for 6 months after completion (both pharmacological and non-pharmacological methods are acceptable).
- •Capable of understanding the study procedures and methods, willing to sign the Informed Consent Form (ICF), and able to strictly adhere to the clinical study protocol to complete the study.
排除标准
- •Presence of untreated thymic epithelial tumors (including all types of thymoma or thymic carcinoma), extrathymic germ cell tumor, or other malignant mediastinal masses at the screening visit; or, as judged by the investigator, presence of thymic cysts or other space-occupying lesions requiring immediate intervention.
- •History of thymectomy or any other thymic surgery within 12 months prior to screening, or planned thymectomy during the trial period.
- •Prior history of thymic tumor is permitted for enrollment only if the subject meets all criteria in either of the following risk groups:
- •Low recurrence risk group: Subjects with histopathologically confirmed thymoma of Masaoka-Koga stages I-II (WHO types A, AB, B1, or B2) who meet all of the following criteria are eligible for enrollment in this study:
- •Curative treatment (e.g., R0 surgical resection) completed ≥ 12 months prior to the screening visit;
- •No clinical evidence of recurrence within 12 months prior to screening;
- •No radiological evidence of recurrence confirmed by contrast-enhanced chest CT or MRI within 6 months prior to randomization.
- •High recurrence risk group: Subjects with histopathologically confirmed thymic carcinoma (WHO type C) or Masaoka-Koga stages III-IV thymoma (including WHO type B3) who meet all of the following criteria are eligible for enrollment:
- •Curative treatment (surgery with or without radiotherapy/chemotherapy and other combined-modality therapy) completed > 5 years prior to the screening visit;
- •No clinical evidence of recurrence within 5 years;
- •No evidence of recurrence or distant metastasis confirmed by contrast-enhanced chest CT or MRI within 6 months prior to randomization.
- •[Note: If a participant cannot provide complete original histopathology reports or Masaoka-Koga staging records, they must be evaluated according to the high recurrence risk group criteria (i.e., treatment completed > 5 years with no evidence of recurrence).]
- •Weakness involving only ocular or periorbital muscles (MGFA Class I).
- •Occurrence of MG crisis (MGFA Class V) within 6 months prior to screening.
- •Known positive serology for muscle-specific receptor tyrosine kinase (MuSK) or lipoprotein receptor-related protein 4 (LRP4), or negative results for both anti-AChR and anti-MuSK antibodies.
- •Pregnant, lactating, or planning to become pregnant during the study period.
- •Any systemic bacterial infection or other infection deemed clinically significant by the investigator, or requiring intravenous antibiotic therapy within 28 days prior to the first dose.
- •Positive for hepatitis C virus (HCV) antibody at screening (except for those with negative HCV RNA); positive for human immunodeficiency virus (HIV) antibody; positive for anti-Treponema pallidum antibody (TP-Ab) (except for those with negative RPR or TRUST); or positive for hepatitis B virus (HBV) surface antigen (HBsAg) and/or HBV core antibody (HBcAb) with HBV-DNA above the upper limit of detection.
- •History of Neisseria meningitidis infection or unresolved meningococcal disease within 6 months prior to screening up to first dose.
- •Body temperature ≥38°C within 7 days prior to first treatment.
- •Use of intravenous immunoglobulin (IVIg) within 4 weeks prior to first treatment.
- •Use of plasma exchange or immunoadsorption within 4 weeks prior to first treatment.
- •Prior use of complement inhibitors (e.g., eculizumab, ravulizumab, crovalimab, or other complement inhibitors).
- •Use of telitacicept or other B-cell stimulating factor inhibitors within 3 months or 5 half-lives prior to screening (whichever is longer); use of rituximab, ocrelizumab, or other B-cell depletion therapies within 6 months prior to screening.
- •Use of human neonatal Fc receptor (FcRn) inhibitors within a period less than 5 half-lives prior to the first dose of study drug.
- •History of suicide attempt within the past 12 months, or suicidal ideation or behavior at screening, as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS).
- •Participation in any other investigational drug study or exposure to other investigational drugs, devices, or procedures within 30 days prior to screening (investational drugs for complement inhibitors, B-cell depletion therapies, and FcRn inhibitors are governed by exclusion criteria 12, 13, and 14, respectively).
- •Suspected allergy to any excipient of the product.
- •Any medical condition that, in the opinion of the investigator, may interfere with the participant's participation in the study, pose any additional risk to the participant, or interfere with the assessment of the participant.
研究组 & 干预措施
Administration of low-dose EA5
Experimental
First, administer the loading dose regimen intravenously, then maintain administration subcutaneously every 2 weeks(Q2W).
干预措施: EA5 (Drug)
Administration of mid-dose EA5
Experimental
First, administer the loading dose regimen intravenously, then maintain administration subcutaneously every 2 weeks(Q2W).
干预措施: EA5 (Drug)
Administration of high-dose EA5
Experimental
First, administer the loading dose regimen intravenously, then maintain administration subcutaneously every 4 weeks(Q4W).
干预措施: EA5 (Drug)
结局指标
主要结局
Incidence and Severity of Treatment Emergent Adverse Events (TEAEs)
时间窗: Baseline up to Week 14
次要结局
- Proportion of participants achieving an improvement of 4, 5, 6, 7, and ≥8 points from baseline in QMG total score without rescue therapy.(Weeks 2, 4, 8, and 12)
- Change and percentage change from baseline in MG-ADL total score.(Weeks 2, 4, 8, and 12)
- Change and percentage change from baseline in QMG total score.(Weeks 2, 4, 8, and 12)
- Change and percentage change from baseline in MGC total score.(Weeks 2, 4, 8, and 12)
- Change and percentage change from baseline in MG-QoL15r scale.(Weeks 2, 4, 8, and 12])
- Proportion of participants achieving MG-ADL response without rescue therapy.(Weeks 2, 4, 8, and 12)
- Maximum Observed Serum Concentration (Cmax) of EA5(Baseline up to Week 23)
- Area Under The Serum Concentration Versus Time Curve From Time Zero To The Time of The Last Quantifiable Concentration (AUC0-t) of EA5(Baseline up to Week 23)
- Area Under the Concentration-Time Curve from Time Zero to Infinity (AUC0-∞) of EA5(Baseline up to Week 23)
- Minimum Steady-State Concentration (Cmin,ss) of EA5(Baseline up to Week 23)
- Maximum Steady-State Concentration (Cmax,ss) of EA5(Baseline up to Week 23)
- Average Steady-State Concentration (Cav.ss) of EA5(Baseline up to Week 23)
- Steady-State Trough Concentration (Ctrough,ss) of EA5(Baseline up to Week 23)
- Time to Maximum Steady-State Concentration (Tmax,ss) of EA5(Baseline up to Week 23)
- Area Under the Concentration-Time Curve over One Dosing Interval at Steady State (AUC0-τ) of EA5(Baseline up to Week 23)
- Degree of Fluctuation of EA5(Baseline up to Week 23)
- Serum total complement hemolytic activity (CH50(Baseline up to Week 23)
- Serum total C5 concentration(Baseline up to Week 23)
- Serum free C5 concentration(Baseline up to Week 23)
- Concentrations of plasma soluble C5b-9 (sC5b-9)(Baseline up to Week 23)
- Anti-acetylcholine receptor antibody (AChR-Ab) titer(Baseline up to Week 23)
- Incidence of anti-drug antibodies (ADA) against the humanized monoclonal antibody EA5(Baseline up to Week 23)
- Incidence of Incidence of neutralizing antibodies (NAb) against the humanized monoclonal antibody EA5(Baseline up to Week 23)
研究者
研究点 (2)
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