A Phase I Study of YK012 in Primary Membranous Nephropathy

NCT07234474 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: YK012-3-FDA
• Study Type: interventional
• Target: 66
• Locations: 0 countries
• Sites: N/A

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 (3)

• Ia: Dose-Limiting Toxicity (DLT)

  up to 28 days after the first dose

• Adverse Event (AE)

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

• Severe Adverse Event

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

Secondary Outcomes (25)

• Area under the concentration-time curve (AUC0-t)

  From 1 hour before the first infusion of YK012 to the end of trial at 53 or 77 weeks

• Area under the concentration-time curve from time 0 to ∞ (AUC0-∞)

  From 1 hour before the first infusion of YK012 to the end of trial at 53 or 77 weeks

• Maximum plasma concentration (Cmax)

  From 1 hour before the first infusion of YK012 to the end of trial at 53 or 77 weeks

• Time to reach maximum concentration (Tmax)

  From 1 hour before the first infusion of YK012 to the end of trial at 53 or 77 weeks

• Half-life (t1/2)

  From 1 hour before the first infusion of YK012 to the end of trial at 53 or 77 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, and to determine the Maximum Tolerated Dose (MTD) and Recommended Dose for Expansion (RDE)

Drug: YK012

Ib: YK012

EXPERIMENTAL

Participants will receive 2 different doses of YK012 infusion to evaluate the safety and tolerability 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

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:

• Age 18-80 (inclusive), both gender.
• Diagnosed with primary (idiopathic) membranous nephropathy by renal biopsy within 10 years.
• Participants who meet the criteria of very high-risk primary (idiopathic) membranous nephropathy based on 2021 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Management of Glomerular Diseases and who have failed available therapies for the treatment of pMN.
• eGFR estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula is ≥45 mL/min/1.73 m².
• If taking angiotensin-converting enzyme inhibitor (ACEI), angiotensin II receptor blocker (ARB), or Sodium-Glucose Co-Transporter 2 (SGLT-2) inhibitor, the medication dosage must have been stable (≤50% change in dose) for at least 4 weeks prior to screening and continue being stable prior to the initiation of the investigational product.
• Laboratory tests within 7 days prior to enrollment meet the pre-defined criteria.
• Be able to understand and voluntarily participate in this clinical trial with written signed informed consent and available for scheduled visits, treatments, examinations, and other study procedures.

You may not qualify if:

• Diagnosed with secondary membranous nephropathy.
• Any prior receipt of protocol-specified pharmacological treatment for membranous nephropathy.
• History of malignant tumor within 5 years prior to screening.
• Poorly controlled hypertension.
• Participants with severe renal insufficiency who have received or require dialysis or kidney transplantation within 6 months prior to the initiation of the investigational product.
• History of diabetic nephropathy confirmed by renal biopsy.
• History of severe or chronic infections within 6 months prior to screening or currently infection requiring systemic antibiotic or antiviral therapy.
• History of cardiovascular event leading to hospitalization within 6 months prior to screening.
• Other severe or poorly controlled diseases that may affect the protocol compliance or efficacy assessments.
• Have active tuberculosis with clear evidence of infection.
• History of substantial organ or bone marrow transplantation.
• Received live vaccination, underwent major surgery, or participated in other clinical trials and applied any other study drugs within 28 days prior to the initiation of the investigational product.
• Hepatitis B surface antigen (HBsAg) positive, or hepatitis B core antibody (HBcAb) positive with hepatitis B virus (HBV) DNA quantification ≥ 1×103 copies/L or ≥ 50 IU/L (HBcAb positive participants require regular HBV DNA testing); Hepatitis C virus (HCV) antibody positive; Human immunodeficiency virus (HIV) seropositive; Syphilis helical antibody positive.
• Peripheral blood CD4+ T-lymphocyte count \< 200 cells/μL.
• The peripheral blood B-cell count is below the lower limit of normal.

Sponsors & Collaborators

• Excyte Biopharma Ltd: lead

Study Officials

• Minghui Zhao

  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: November 14, 2025
• First Posted: November 18, 2025
• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): February 1, 2028
• Last Updated: February 5, 2026

Record last verified: 2026-02