Primary Membranous Nephropathy
Conditions
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).
Detailed description
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).
Interventions
DRUGYK012
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
Sponsors
Excyte Biopharma Ltd
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ia: Dose-limiting Toxicity(DLT) | up to 28 days after the first dose | 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). |
| Ia: Adverse Event (AE) | From the first induction to the end of the trial at 53 weeks | 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. |
| Ia: Severe Adverse Event | From the first induction to the end of the trial at 53 weeks | 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. |
| Ib: Proportion of participants achieving overall response | From enrollment to the end of the trial at 76 weeks (if applicable) | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ia: Elimination half life (t1/2) | From 1 hour before the first infusion of YK012 to the end of trial at 53 weeks | — |
| Ia: Total Apparent Clearance (CL) | From 1 hour before the first infusion of YK012 to the end of trial at 53 weeks | — |
| Ia: Apparent volume of distribution(Vd) | From 1 hour before the first infusion of YK012 to the end of trial at 53 weeks | — |
| Ia: Minimum Concentration (Cmin) of YK012 | From 1 hour before the first infusion of YK012 to the end of trial at 53 weeks | — |
| Ia: The duration of peripheral blood B-cell depletion | From 1 hour before the first infusion of YK012 to the end of trial at 53 weeks | — |
| Ia: The profile of peripheral blood NK cell changes | From 1 hour before the first infusion of YK012 to the end of trial at 53 weeks | — |
| Ia: The profile of peripheral blood T-cell changes | From 1 hour before the first infusion of YK012 to the end of trial at 53 weeks | — |
| Ia: The profile of cytokine changes | From 1 hour before the first infusion of YK012 to the end of trial at 53 weeks | — |
| Ia: ADA (anti-drug antibody) and Nab (Neutralizing antibody) positivity rate | From 1 hour before the first infusion of YK012 to the end of trial at 53 weeks | — |
| 24-hour urine protein change | From enrollment to the end of the trial at 53 or 77 (if applicable) weeks | — |
| eGFR (Glomerular Filtration Rate) change | From enrollment to the end of the trial at 53 or 77 (if applicable) weeks | — |
| 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: Proportion of participants achieving overall response | From enrollment to the end of the trial at 53 weeks | — |
| Proportion of participants achieving CR or PR | From enrollment to the end of the trial at 53 or 77 (if applicable) weeks | — |
| Proportion of anti-PLA2R antibody-positive participants achieving immunological remission | From enrollment to the end of the trial at 53 or 77 (if applicable) weeks | — |
| Time to achieve complete renal remission | From enrollment to the end of the trial at 53 or 77 (if applicable) weeks | — |
| Time to achieve overall renal response | From enrollment to the end of the trial at 53 or 77 (if applicable) weeks | — |
| Duration of complete renal response | From enrollment to the end of the trial at 53 or 77 (if applicable) weeks | — |
| Duration of overall renal response | From enrollment to the end of the trial at 53 or 77 (if applicable) weeks | — |
| Proportion of participants with treatment failure | From enrollment to the end of the trial at 53 or 77 (if applicable) weeks | — |
| Proportion of participants with relapse | From enrollment to the end of the trial at 53 or 77 (if applicable) weeks | — |
| Ib: Adverse Event (AE) | From the first induction to the end of the trial at 53 or 77 (if applicable) weeks | 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. |
| Ib: Severe Adverse Event | From the first induction to the end of the trial at 53 or 77 (if applicable) weeks | 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, need for hospitalization or prolongation of hospitalization, congenital abnormalities or birth defects. |
| Anti-PLA2R antibody titer change | From enrollment to the end of the trial at 53 or 77 (if applicable) 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 | — |
Countries
China
Contacts
Primary ContactMinghui Zhao, M.D.
Outcome results
None listed