A Study of YKST02 in Participants With Primary IgA Nephropathy

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of YKST02 in Participants With Primary IgA Nephropathy

The goal of this clinical trial is to evaluate the safety and tolerability of YKST02 and to explore its potential to treat adults with primary IgA nephropathy (IgAN). The study will also assess how the drug moves through the body and how it affects the immune system.

The main questions it aims to answer are:

• Is YKST02 safe and well tolerated?
• Does YKST02 reduce protein levels in the urine?
• How does YKST02 behave in the body (pharmacokinetics, PK)?
• How does YKST02 affect the immune system (pharmacodynamics, PD)? Participants are adults with IgAN who have persistent proteinuria despite standard treatment.

Participants will:

• Receive YKST02 by intravenous (IV) infusion
• Be monitored after each dose for safety
• Attend clinic visits for safety assessments and laboratory tests
• Provide blood and urine samples during the study and follow-up period

Study Overview

• Status: Recruiting
• Conditions: Primary IgA Nephropathy
• Intervention / Treatment: Drug: YKST02

Detailed Description

This is a single-center, open-label, dose-escalation clinical trial designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and preliminary efficacy of YKST02 in adults with primary IgA nephropathy (IgAN).

Eligible participants are adults with IgAN and persistent proteinuria despite standard-of-care treatment.

The study consists of a screening period, a treatment period, and a follow-up period. During the treatment period, YKST02 will be administered by intravenous infusion. Dose levels and dosing schedules may be adjusted based on safety, tolerability, and emerging data to support dose escalation and determination of an appropriate dose level.

Safety assessments will include monitoring of adverse events, clinical laboratory evaluations, vital signs, and other relevant clinical parameters. Pharmacokinetic evaluations will characterize the concentration-time profile of YKST02. Pharmacodynamic and biomarker assessments will evaluate the biological activity of YKST02 and its effects on immune-related pathways.

Immunogenicity will be assessed by evaluating anti-drug antibodies. Preliminary efficacy will be explored using clinical measures relevant to IgAN.

Additional exploratory analyses may be performed to further characterize immune-related biomarkers and potential effects on renal pathology, as applicable.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Qiubai Li, MD, PhD; Phone Number: +86-27-85726338; Email: qiubaili@hust.edu.cn

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Recruiting
      • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
      • Contact: Qiubai Li, MD, PhD; Phone Number: +86-027-85726338; Email: qiubaili@hust.edu.cn
      • Principal Investigator: Qiubai Li, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of primary IgA nephropathy (IgAN)
• Proteinuria above a protocol-defined threshold at screening
• Receiving stable standard-of-care therapy for IgAN for an adequate duration prior to enrollment, unless contraindicated or not tolerated
• Women of childbearing potential must have a negative pregnancy test prior to study drug administration and agree to use effective contraception; male participants must agree to use effective contraception
• Able to understand the study procedures and provide written informed consent

Exclusion Criteria:

• Secondary IgA nephropathy (e.g., associated with liver disease, autoimmune disorders, infections, or other systemic conditions)
• Other clinically significant renal diseases unrelated to IgAN (e.g., diabetic nephropathy, lupus nephritis, vasculitis)
• Nephrotic syndrome considered unsuitable for study participation
• Rapidly progressive glomerulonephritis or rapidly declining renal function
• Estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m²
• Immunodeficiency or low immunoglobulin G (IgG) levels below normal
• Clinically significant abnormal laboratory findings (e.g., hematologic, hepatic, or coagulation abnormalities)
• Requirement for systemic corticosteroids for concomitant conditions
• Use of immunosuppressive, targeted, or biologic therapies within a defined period prior to screening or anticipated use during the study
• Prior treatment with B-cell-depleting or other targeted biologic therapies within a defined period
• History of demyelinating disorders (e.g., multiple sclerosis)
• Clinically significant cardiovascular or cerebrovascular disease within 6 months prior to screening
• History of organ transplantation or planned transplantation during the study
• Current dialysis or anticipated need for dialysis during the study
• Major surgery within 4 weeks prior to screening or planned during the study
• Active infection requiring systemic therapy, recent serious infection, or chronic/recurrent infections
• Known active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection
• Active or untreated latent tuberculosis
• History of splenectomy
• Uncontrolled comorbidities (e.g., poorly controlled hypertension or diabetes)
• Malignancy within the past 5 years, except adequately treated non-invasive cancers
• Known hypersensitivity to YKST02 or its components
• Receipt of another investigational product within 4 weeks or 5 half-lives (whichever is longer) prior to screening
• Receipt of live or attenuated vaccines within 4 weeks prior to screening or planned during the study
• Any condition that, in the investigator's judgment, would make the participant unsuitable for the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: YKST02; Participants receive YKST02 administered by intravenous infusion in this single-arm, open-label, dose-escalation study. Participants receive an initial dosing phase followed by subsequent administrations at escalating dose levels. Dose levels and dosing schedules may be adjusted based on safety, tolerability, and pharmacokinetic/pharmacodynamic (PK/PD) data. A follow-up period is included for safety and efficacy assessments.

Drug: YKST02; YKST02 is an investigational drug administered by intravenous infusion. It is provided as a sterile formulation for clinical use. Dosing may vary based on study design and ongoing evaluation of safety, tolerability, and pharmacokinetic/pharmacodynamic (PK/PD) data.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)	Safety will be assessed by the incidence and severity of adverse events (AEs) and serious adverse events (SAEs).	From first dose through Week 25
Change from Baseline in UPCR	Efficacy will be evaluated by the change from baseline in urine protein-to-creatinine ratio (UPCR).	From baseline through Week 25
Change from Baseline in eGFR	Efficacy will be evaluated by the change from baseline in estimated glomerular filtration rate (eGFR).	From baseline through Week 25
Change from Baseline in Urinary Red Blood Cells	Efficacy will be evaluated by the change from baseline in urinary red blood cells.	From baseline through Week 25

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration-Time Curve (AUC) of YKST02	Area under the concentration-time curve (AUC), including AUC0-t and AUC0-∞, of YKST02 will be evaluated.	From first dose through Week 25
Maximum Observed Concentration (Cmax) of YKST02	Maximum observed plasma concentration (Cmax) of YKST02 will be evaluated.	From first dose through Week 25
Half-life (t1/2) of YKST02	Terminal elimination half-life (t1/2) of YKST02 will be evaluated.	From first dose through Week 25
Change from Baseline in Gd-IgA1	Pharmacodynamic effects will be evaluated by the change from baseline in galactose-deficient IgA1 (Gd-IgA1).	From baseline through Week 24.
Change from Baseline in Serum Immunoglobulin Levels	Changes from baseline in serum immunoglobulin levels will be assessed, including IgA, IgG, and IgM.	From baseline through Week 24
Change from Baseline in Complement Levels	Changes from baseline in complement levels will be assessed, including complement components C3 and C4.	From baseline through Week 24
Immunogenicity of YKST02	Immunogenicity will be assessed by the incidence of anti-drug antibodies (ADAs). Neutralizing antibodies (NAbs) will be evaluated in participants who are ADA-positive.	From baseline through Week 25
Changes in Lymphocyte Subsets	Changes from baseline in peripheral blood lymphocyte subsets will be assessed, including B cell subsets and T cell subsets.	From baseline through Week 24
Changes in Lymphocyte Activation Markers	Changes from baseline in activation status of lymphocyte populations will be assessed using relevant activation markers, as applicable.	From baseline through Week 24
Changes in Cytokine Levels	Changes from baseline in cytokine levels relevant to immune and inflammatory responses will be assessed.	From baseline through Week 24

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Renal Histopathology	Pre-specified analyses will include evaluation of renal biopsy samples using histopathological methods.	From baseline through Week 24
Changes in Immune-Related Biomarkers	Pre-specified analyses will include assessment of immune-related biomarkers, such as gene expression profiles and immune repertoire characteristics.	From baseline through Week 24

Collaborators and Investigators

• Sponsor: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2026
• Primary Completion (Estimated): March 30, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: March 23, 2026
• First Submitted That Met QC Criteria: March 23, 2026
• First Posted (Actual): March 27, 2026

Study Record Updates

• Last Update Posted (Actual): May 12, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Autoimmune Diseases; Immune System Diseases; Glomerulonephritis; Nephritis; Glomerulonephritis, IGA
• Other Study ID Numbers: YKST02-N01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No