2022-501147-32-00招募中3 期
A Phase 2/3, Multicenter, Randomized, Active-Controlled, Open-label Study to Evaluate the Efficacy and Safety of Zanubrutinib in Patients With Primary Membranous Nephropathy
Beigene Ltd.11 个研究点 分布在 4 个国家目标入组 32 人开始时间: 2023年9月7日最近更新:
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 32
- 试验地点
- 11
- 主要终点
- Part 1: The primary endpoint is change from baseline in urine protein creatinine ratio (UPCR) at Week 24.
研究概览
简要总结
Part 1 • Evaluate the efficacy of zanubrutinib as measured by proteinuria reduction in patients with primary membranous nephropathy who are on optimal supportive care Part 2 • Evaluate the efficacy of zanubrutinib compared with tacrolimus as measured by complete remission rate in patients with primary membranous nephropathy who are on optimal supportive care
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Part 1 and 2: 18 to 75 years of age (inclusive) on the day of signing the ICF
- •Part 1 and 2: Patients must sign the ICF and be capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in the protocol
- •Part 1 and 2: Biopsy-confirmed primary membranous nephropathy within 5 years before the initial screening (ie, the day the informed consent is signed)
- •Part 1 and 2: UPCR (based on 24-hour urine collection) > 3.5 at the initial screening and at the confirmation assessment.
- •Part 1 and 2: Female patients of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study and for ≥ 30 days after the last dose of treatment. They must also have a negative urine or serum pregnancy test result (Section 8.3.5). Note: a woman is considered of childbearing potential (ie, fertile, following menarche and until becoming postmenopausal) unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. Nonsterile male patients must be willing to use a highly effective method of birth control for the duration of the study and for ≥ 30 days after the last dose of study drug.
- •Part 1 only: Treatment with maximally tolerated or allowed dose of ACEI or ARB for ≥ 12 weeks before the first dose of zanubrutinib and with adequate blood pressure control (blood pressure < 130/80 mmHg, measured on ≥ 2 occasions [not on the same day] within 4 weeks before the assignment of study treatment).
- •Part 1 only: Anti-PLA2R antibody > 50 RU/mL at confirmation assessment
- •Part 2 only : Treatment with maximally tolerated or allowed dose of ACEI or ARB for ≥ 24 weeks before randomization and with adequate blood pressure control (blood pressure < 130/80 mmHg, measured on ≥ 2 occasions [not on the same day] within 4 weeks before randomization). See protocol for details.
排除标准
- •Part 1 and 2: Lactating or pregnant female patients
- •Part 1 and 2: A known history of a primary immunodeficiency or an underlying condition such as human immunodeficiency virus (HIV) infection or splenectomy that predisposes the patient to infections.
- •Part 1 and 2: Patients at risk for tuberculosis (see protocol for details)
- •Part 1 and 2: Unwilling or unable to follow the dietary guidance per investigator.
- •Part 1 only: The eGFR < 30 mL/min/1.73 m2 (according to the CKD-EPI formula), or initiation of dialysis.
- •Part 1 and 2: Severe hepatic insufficiency (Child-Pugh C).
- •Part 1 and 2: Current alcohol, drug, or chemical abuse, or a history of such abuse within 1 year before the assignment of study treatment.
- •Part 1 and 2: Known infection with serologic status reflecting active or chronic HBV, or presence of hepatitis C virus (HCV) antibody (see protocol for details)
- •Part 1 and 2: History of a cancer, apart from cervical cancer in situ, basal or squamous cell skin cancer treated with curative therapy ≥ 2 year prior to the assignment of study treatment.
- •Part 1 and 2: History of intracranial hemorrhage.
- •Part 1 and 2: Clinically significant cardio-cerebrovascular diseases (see protocol for details)
- •Part 2 only: Evidence of ≥ 50% reduction in 24-hour urine protein within 24 weeks before randomization
- •Part 1 and 2: History of severe bleeding disorder such as hemophilia A, hemophilia B, and von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention.
- •Part 2 only: The eGFR < 40 mL/min/1.73 m2 (according to the CKD-EPI formula), or initiation of dialysis.
- •Part 1 and 2: Patients with a secondary cause of membranous nephropathy (eg, diabetic nephropathy, lupus nephritis) or with other primary glomerular diseases, such as Immunoglobulin A (IgA) nephropathy, etc.
- •Part 1 and 2: Unable to understand the purpose and risks of the study and to provide a signed and dated ICF and authorization to use protected health information (in accordance with national and local patient privacy regulations), except to the extent that surrogate consents and assents are obtained in accordance with national and local laws and regulations. For clarity, the surrogate consents and assents may include, but are not limited to the following: court-appointed guardians, healthcare proxies, durable powers of attorney, or family members/next-of-kin.
- •Part 1 and 2: Major surgery within 4 weeks before the assignment of study treatment.
- •Part 1 and 2: Vaccination with a live vaccine within 4 weeks before the assignment of study treatment. See protocol for details on COVID 19 vaccination
- •Part 1 and 2: Concurrent participation in another therapeutic clinical trial.
- •Part 1 and 2: Positive test result for COVID-19 as determined by antigen testing or polymerase chain reaction (PCR) testing by a licensed method within 4 weeks before the assignment of study treatment.
- •Part 1 and 2: Unwilling or unable to participate in all required study evaluations and procedures.
- •Part 1 and 2: Active granulomatous infection before the assignment of study treatment; nontuberculous mycobacterial infection or opportunistic infection requiring hospitalization or parenteral antimicrobial treatment within 1 year before the assignment of study treatment.
- •Part 2 only: History of resistance or intolerance to tacrolimus.
- •Part 1 and 2: Any conditions that in the opinion of the investigator, will either alone or in combination (see protocol for the full list)
- •Part 1 and 2: Any of the following conditions within 14 days before the assignment of study treatment: Part 1 and 2: Alanine aminotransferase ≥ 3 x the upper limit of normal (ULN). Aspartate aminotransferase ≥ 3 x ULN. Total bilirubin ≥ 2 x ULN.
- •Part 1 only: Hypersensitivity to zanubrutinib, or its formulation excipients
- •Part 1 and 2: Type 1 or 2 diabetes mellitus with hemoglobin A1c (HbA1c) ≥ 7% at screening.
- •Part 1 only: Evidence of ≥ 50% reduction in 24-hour urine protein within 12 weeks before the assignment of zanubrutinib.
- •Part 1 and 2: Severe renal disease as determined by rapid decline in eGFR (defined as > 15 mL/min/1.73 m2 within 24 weeks prior to randomization, not otherwise explained)
- •Part 1 and 2: In the absence of colony-stimulating factor or blood transfusion, any of the following within 14 days before the assignment of study treatment: • hemoglobin ≤ 80 g/L (8.0 g/dL), • platelet count ≤ 100 x 10^9/L (100,000 cells/mm³), • white blood cell count ≤ 2.0 x 10^9/L (2,000 cells/mm³), • neutrophils ≤ 1.5 x 10^9/L (1500 cells/mm³), • CD4+ T cell count ≤ 0.4 x 10^9/L (400 cells/mm³)
- •Part 1 and 2: Unable to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery procedures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.
- •Part 2 only: Hypersensitivity to zanubrutinib, tacrolimus, or other macrolides, or their formulation excipients (eg, HCO-60 [polyoxyl 60 hydrogenated castor oil]).
- •Part 1 and 2: Ongoing treatment with a strong CYP3A inhibitor or inducer (refer to Appendix 4).
- •Part 1 and 2: Prior exposure to a BTK inhibitor.
- •Part 1 and 2: Any infections requiring hospitalization or treatment with intravenous anti-infectives not completed ≥ 4 weeks before the assignment of study treatment.
- •Part 1 and 2: Receipt of any prohibited drug within specified time (refer to Table 3 and Appendix 9).
结局指标
主要结局
Part 1: The primary endpoint is change from baseline in urine protein creatinine ratio (UPCR) at Week 24.
Part 1: The primary endpoint is change from baseline in urine protein creatinine ratio (UPCR) at Week 24.
Part 2: The primary endpoint is complete remission status (Yes/No) (for definition of complete remission, refer to Section 8.2.1 of the protocol) at Week 104.
Part 2: The primary endpoint is complete remission status (Yes/No) (for definition of complete remission, refer to Section 8.2.1 of the protocol) at Week 104.
次要结局
- Part 1: Treatment failure status (Yes/No) by Week 24
- Part 1: Immunological response status (Yes/No) at Week 24
- Part 1: Complete remission status (Yes/No) at Week 24, Week 52, Week 76, and Week 104
- Part 1: Overall remission status (Yes/No) at Week 24, Week 52, Week 76, and Week 104
- Part 1: Relapse status (Yes/No) by Week 104
- Part 1: Incidence and severity of treatment-emergent adverse events
- Part 2: overall remission status (Yes/No) (for definition of overall remission, refer to Section 8.2.3 of the protocol) at Week 104.
- Part 2: Complete remission status (Yes/No) at Week 24, Week 52, and Week 76
- Part 2: Overall remission status (Yes/No) at Week24, Week 52, and Week 76
- Part 2: Treatment failure status (Yes/No) by Week 24, Week 52, Week 76, and Week 104
- Part 2: Time to first complete remission: the time from the date of randomization to the date of the first complete remission
- Part 2: Time to first overall remission: the time from the date of randomization to the date of the first overall remission
- Part 2: Relapse status (Yes/No) by Week 104
- Part 2: Time to first relapse: the time from the date of first complete or partial remission to the date of the first relapse
- Part 2: Patient-reported symptoms and overall health status as measured using the Kidney Disease and Quality of Life instrument™ - 36 items (KDQoL-36) and European Quality of Life 5-Dimensions 5-Levels Health Questionnaire (EQ-5D- 5L)
- Part 2: ≥ 30% eGFR reduction from baseline to Week 52 and Week 104 (Yes/No)
- Part 2: Incidence and severity of treatment-emergent adverse events
研究者
BeOne Medical Officer
Scientific
BeOne Medicines AG
研究点 (11)
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