Study of YK012 in Primary Membranous Nephropathy

Официальное название

A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of YK012 in the Treatment of Primary Membranous Nephropathy

Обзор

The goal of this clinical trial is to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and preliminary efficacy of YK012 in participants with primary membranous nephropathy (PMN).

Подробное описание

This clinical trial consists of Phase Ia and Phase Ib. The goal of phase Ia is to evaluate the safety and tolerability of YK012 in participants with primary membranous nephropathy and to determine the maximum tolerated dose (MTD) and recommended dose for expansion (RDE). The goal of phase Ib is to assess the preliminary efficacy of YK012 in participants with primary membranous nephropathy and to establish the recommended Phase II dose (RP2D).

Вмешательства

• Препарат YK012
  YK012 is a bispecific antibody targeting CD19 on B cells and CD3 on T cells leading to T cell-mediated cytotoxicity of malignant B cells

Первичные конечные точки

• Ia: Dose-limiting Toxicity(DLT) [Срок оценки: up to 28 days after the first dose]
• Ia: Adverse Event (AE) [Срок оценки: From the first induction to the end of the trial at 53 weeks]
• Ia: Severe Adverse Event [Срок оценки: From the first induction to the end of the trial at 53 weeks]
• Ib: Proportion of participants achieving overall response [Срок оценки: From enrollment to the end of the trial at 76 weeks (if applicable)]

Вторичные конечные точки (12)

• Ia: Area Under the Curve (AUC) of a serum concentration versus time profile [Срок оценки: From 1 hour before the first infusion of YK012 to the end of trial at 53 weeks]
• Ia: Area Under the Curve of a serum concentration to infinite time (AUC0-infinity) [Срок оценки: From 1 hour before the first infusion of YK012 to the end of trial at 53 weeks]
• Ia: Maximum concentration (Cmax) of YK012 [Срок оценки: From 1 hour before the first infusion of YK012 to the end of trial at 53 weeks]
• Ia: Time to reach Cmax (Tmax) [Срок оценки: From 1 hour before the first infusion of YK012 to the end of trial at 53 weeks]
• Ia: Elimination half life (t1/2) [Срок оценки: From 1 hour before the first infusion of YK012 to the end of trial at 53 weeks]
• Ia: Total Apparent Clearance (CL) [Срок оценки: From 1 hour before the first infusion of YK012 to the end of trial at 53 weeks]
• Ia: Apparent volume of distribution(Vd) [Срок оценки: From 1 hour before the first infusion of YK012 to the end of trial at 53 weeks]
• Ia: Minimum Concentration (Cmin) of YK012 [Срок оценки: From 1 hour before the first infusion of YK012 to the end of trial at 53 weeks]
• Ia: The duration of peripheral blood B-cell depletion [Срок оценки: From 1 hour before the first infusion of YK012 to the end of trial at 53 weeks]
• Ia: The profile of peripheral blood NK cell changes [Срок оценки: From 1 hour before the first infusion of YK012 to the end of trial at 53 weeks]
• Ia: The profile of peripheral blood T-cell changes [Срок оценки: From 1 hour before the first infusion of YK012 to the end of trial at 53 weeks]
• Ia: The profile of cytokine changes [Срок оценки: From 1 hour before the first infusion of YK012 to the end of trial at 53 weeks]

Критерии участия

Критерии включения

• Aged 18 to 80 years (inclusive), regardless of gender.
• Kidney biopsy-confirmed diagnosis of primary (idiopathic) membranous nephropathy within the past 10 years.
• Elevated 24-hour urine protein, meeting the pre-defined criteria.
• Estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73m² as calculated by the CKD-EPI equation.
• If currently taking an angiotensin-converting enzyme inhibitor (ACEi), angiotensin II receptor blocker (ARB), or sodium-glucose cotransporter-2 (SGLT-2) inhibitor, the dose must have been stable for at least 4 weeks prior to enrollment or since initiation of therapy.
• Laboratory test results must meet the predefined criteria within 7 days prior to enrollment.
• Capable of understanding and voluntarily participating in this clinical trial, having provided written informed consent, and able to comply with scheduled visits, treatments, examinations, and other study procedures as required.

Критерии исключения

• Diagnosis of secondary membranous nephropathy.
• Any prior receipt of protocol-specified pharmacological treatment for membranous nephropathy.
• History of malignancy within 5 years prior to enrollment.
• Poorly controlled hypertension at enrollment.
• Severe renal dysfunction with prior dialysis or kidney transplantation within 6 months prior to enrollment.
• Prior kidney biopsy-confirmed diagnosis of diabetic nephropathy.
• History of severe or chronic infections within the 6 months before enrollment or current need for systemic antibiotic or antiviral therapy.
• Cardiovascular or cerebrovascular events requiring hospitalization within 6 months prior to enrollment.
• Severe or poorly controlled comorbidities that may affect protocol compliance or efficacy evaluation.
• Active Tuberculosis (TB) with documented evidence of infection.
• History of solid organ or bone marrow transplantation.
• Live vaccination, major surgery, or participated in other clinical trials with investigational drug use within 28 days prior to enrollment.
• HBsAg-positive, or HBcAb-positive with detectable HBV DNA above the normal range; HCV antibody-positive; HIV seropositive; Treponema pallidum antibody-positive.
• CD4+ T lymphocyte count <200 cells/μL
• Known hypersensitivity to any component of YK012.
• Pregnancy, breastfeeding, or positive pregnancy test at screening; or plans to become pregnant during the trial or within 12 months after study completion, or unwillingness to use physical contraceptive methods during the study and for 12 months thereafter.
• Other conditions deemed by the investigator to make the subject unsuitable for participation in this study.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Peking University First Hospital — Пекин

Идентификаторы

NCT: NCT06982729 · YK012-3-CN

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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