Primary IgA Nephropathy
Conditions
Brief summary
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
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.
Interventions
DRUGYKST02
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.
Sponsors
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in UPCR | From baseline through Week 25 | Efficacy will be evaluated by the change from baseline in urine protein-to-creatinine ratio (UPCR). |
| Change from Baseline in eGFR | From baseline through Week 25 | Efficacy will be evaluated by the change from baseline in estimated glomerular filtration rate (eGFR). |
| Change from Baseline in Urinary Red Blood Cells | From baseline through Week 25 | Efficacy will be evaluated by the change from baseline in urinary red blood cells. |
| Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) | From first dose through Week 25 | Safety will be assessed by the incidence and severity of adverse events (AEs) and serious adverse events (SAEs). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in Serum Immunoglobulin Levels | From baseline through Week 24 | Changes from baseline in serum immunoglobulin levels will be assessed, including IgA, IgG, and IgM. |
| Change from Baseline in Complement Levels | From baseline through Week 24 | Changes from baseline in complement levels will be assessed, including complement components C3 and C4. |
| Immunogenicity of YKST02 | From baseline through Week 25 | Immunogenicity will be assessed by the incidence of anti-drug antibodies (ADAs). Neutralizing antibodies (NAbs) will be evaluated in participants who are ADA-positive. |
| Area Under the Concentration-Time Curve (AUC) of YKST02 | From first dose through Week 25 | Area under the concentration-time curve (AUC), including AUC0-t and AUC0-∞, of YKST02 will be evaluated. |
| Changes in Lymphocyte Activation Markers | From baseline through Week 24 | Changes from baseline in activation status of lymphocyte populations will be assessed using relevant activation markers, as applicable. |
| Changes in Cytokine Levels | From baseline through Week 24 | Changes from baseline in cytokine levels relevant to immune and inflammatory responses will be assessed. |
| Changes in Lymphocyte Subsets | From baseline through Week 24 | Changes from baseline in peripheral blood lymphocyte subsets will be assessed, including B cell subsets and T cell subsets. |
| Maximum Observed Concentration (Cmax) of YKST02 | From first dose through Week 25 | Maximum observed plasma concentration (Cmax) of YKST02 will be evaluated. |
| Half-life (t1/2) of YKST02 | From first dose through Week 25 | Terminal elimination half-life (t1/2) of YKST02 will be evaluated. |
| Change from Baseline in Gd-IgA1 | From baseline through Week 24. | Pharmacodynamic effects will be evaluated by the change from baseline in galactose-deficient IgA1 (Gd-IgA1). |
Countries
China
Contacts
CONTACTQiubai Li, MD, PhD
Outcome results
None listed