Study of YK012 in Primary Membranous Nephropathy

NCT06982729 | Recruiting Phase 1

• 1 other identifier: YK012-3-CN
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Primary Membranous Nephropathy

Outcome Measures

Primary Outcomes (4)

• 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).

  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.

  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.

  From the first induction to the end of the trial at 53 weeks

• Ib: Proportion of participants achieving overall response

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

Secondary Outcomes (27)

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

  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)

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

• Ia: Maximum concentration (Cmax) of YK012

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

• Ia: Time to reach Cmax (Tmax)

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

• Ia: Elimination half life (t1/2)

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

Study Arms (2)

Ia: YK012

EXPERIMENTAL

Participants with primary membranous nephropathy will receive ascending doses of YK012 infusion to evaluate the safety and tolerability of YK012

Drug: YK012

Ib: YK012

EXPERIMENTAL

Participants will receive 2 different doses of YK012 infusion to assess the preliminary efficacy of YK012 in participants with primary membranous nephropathy and to establish the recommended Phase II dose (RP2D).

Drug: YK012

Interventions

YK012 DRUG

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

Also known as: YK012 Infusion

Ia: YK012; Ib: YK012

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Excyte Biopharma Ltd: lead

Study Sites (1)

Peking University First Hospital

Beijing, Beijing Municipality, 100034, China

RECRUITING

Study Officials

• Minghui Zhao, M.D.

  Peking University First Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Minghui Zhao, M.D.

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2025
• First Posted: May 21, 2025
• Study Start: March 8, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: November 17, 2025

Record last verified: 2025-11

Locations

CN (1)