Study of YK012 in Primary Membranous Nephropathy

Phase 1RecruitingNCT06982729

Excyte Biopharma Ltd72 enrolled

Overview

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).

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Primary Membranous Nephropathy

Interventions

YK012DRUG

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

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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. Exclusion Criteria: * 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.

Locations (1)

Peking University First Hospital

Beijing, Beijing Municipality, China

RECRUITING

Outcomes

Primary Outcomes

Ia: Dose-limiting Toxicity(DLT)

Dose-limiting toxicities (DLTs) is defined as adverse events occurring within 28 days after the first dose and assessed by the investigator as related to the Investigational Medicinal Product (IMP).

Time frame: up to 28 days after the first dose

Ia: Adverse Event (AE)

An AE is defined as any untoward medical event that occurs after a participant receives the investigational drug, which may be manifested as symptoms, signs, diseases, or laboratory abnormalities, but may not necessarily have a causal relationship with the investigational drug.

Time frame: From the first induction to the end of the trial at 53 weeks

Ia: Severe Adverse Event

An SAE refers to any untoward medical occurrence after the participant receives the IMP that results in one or more of the following: death, life-threatening event, permanent or serious disability or loss of function, hospitalization or prolongation of hospitalization, congenital abnormalities or birth defects.

Time frame: From the first induction to the end of the trial at 53 weeks

Ib: Proportion of participants achieving overall response

Time frame: From enrollment to the end of the trial at 76 weeks (if applicable)

Secondary Outcomes

Ia: Area Under the Curve (AUC) of a serum concentration versus time profile

Time frame: 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)

Time frame: From 1 hour before the first infusion of YK012 to the end of trial at 53 weeks

Ia: Maximum concentration (Cmax) of YK012

Central Contacts

Minghui Zhao, M.D.

CONTACT

+86-010-83572388 mhzhao@bjmu.edu.cn

Data from ClinicalTrials.gov

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