Clinical trial NCT06982729: Study of YK012 in Primary Membranous Nephropathy
Official title: A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of YK012 in the Treatment of Primary Membranous Nephropathy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Primary Membranous Nephropathy
Lead sponsor: Excyte Biopharma Ltd
Sponsor class: INDUSTRY
First posted: 2025-05-21
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Ia: Dose-limiting Toxicity(DLT)
timeFrame: up to 28 days after the first dose
measure: Ia: Adverse Event (AE)
timeFrame: From the first induction to the end of the trial at 53 weeks
measure: Ia: Severe Adverse Event
timeFrame: From the first induction to the end of the trial at 53 weeks
measure: Ib: Proportion of participants achieving overall response
timeFrame: From enrollment to the end of the trial at 76 weeks (if applicable)
Secondary outcomes:
measure: Ia: Area Under the Curve (AUC) of a serum concentration versus time profile
timeFrame: From 1 hour before the first infusion of YK012 to the end of trial at 53 weeks
measure: Ia: Area Under the Curve of a serum concentration to infinite time (AUC0-infinity)
timeFrame: From 1 hour before the first infusion of YK012 to the end of trial at 53 weeks
measure: Ia: Maximum concentration (Cmax) of YK012
timeFrame: From 1 hour before the first infusion of YK012 to the end of trial at 53 weeks
measure: Ia: Time to reach Cmax (Tmax)
timeFrame: From 1 hour before the first infusion of YK012 to the end of trial at 53 weeks
measure: Ia: Elimination half life (t1/2)
timeFrame: From 1 hour before the first infusion of YK012 to the end of trial at 53 weeks
measure: Ia: Total Apparent Clearance (CL)
timeFrame: From 1 hour before the first infusion of YK012 to the end of trial at 53 weeks
measure: Ia: Apparent volume of distribution(Vd)
timeFrame: From 1 hour before the first infusion of YK012 to the end of trial at 53 weeks
measure: Ia: Minimum Concentration (Cmin) of YK012
timeFrame: From 1 hour before the first infusion of YK012 to the end of trial at 53 weeks
measure: Ia: The duration of peripheral blood B-cell depletion
timeFrame: From 1 hour before the first infusion of YK012 to the end of trial at 53 weeks
measure: Ia: The profile of peripheral blood NK cell changes
timeFrame: From 1 hour before the first infusion of YK012 to the end of trial at 53 weeks
measure: Ia: The profile of peripheral blood T-cell changes
timeFrame: From 1 hour before the first infusion of YK012 to the end of trial at 53 weeks
measure: Ia: The profile of cytokine changes
timeFrame: From 1 hour before the first infusion of YK012 to the end of trial at 53 weeks
measure: Ia: ADA (anti-drug antibody) and Nab (Neutralizing antibody) positivity rate
timeFrame: From 1 hour before the first infusion of YK012 to the end of trial at 53 weeks
measure: 24-hour urine protein change
timeFrame: From enrollment to the end of the trial at 53 or 77 (if applicable) weeks
measure: eGFR (Glomerular Filtration Rate) change
timeFrame: From enrollment to the end of the trial at 53 or 77 (if applicable) weeks
measure: Anti-PLA2R antibody titer change
timeFrame: From enrollment to the end of the trial at 53 or 77 (if applicable) weeks
measure: Ia: Proportion of participants achieving overall response
timeFrame: From enrollment to the end of the trial at 53 weeks
measure: Proportion of participants achieving CR or PR
timeFrame: From enrollment to the end of the trial at 53 or 77 (if applicable) weeks
measure: Proportion of anti-PLA2R antibody-positive participants achieving immunological remission
timeFrame: From enrollment to the end of the trial at 53 or 77 (if applicable) weeks
measure: Time to achieve complete renal remission
timeFrame: From enrollment to the end of the trial at 53 or 77 (if applicable) weeks
measure: Time to achieve overall renal response
timeFrame: From enrollment to the end of the trial at 53 or 77 (if applicable) weeks
measure: Duration of complete renal response
timeFrame: From enrollment to the end of the trial at 53 or 77 (if applicable) weeks
measure: Duration of overall renal response
timeFrame: From enrollment to the end of the trial at 53 or 77 (if applicable) weeks
measure: Proportion of participants with treatment failure
timeFrame: From enrollment to the end of the trial at 53 or 77 (if applicable) weeks
measure: Proportion of participants with relapse
timeFrame: From enrollment to the end of the trial at 53 or 77 (if applicable) weeks
measure: Ib: Adverse Event (AE)
timeFrame: From the first induction to the end of the trial at 53 or 77 (if applicable) weeks
measure: Ib: Severe Adverse Event
timeFrame: From the first induction to the end of the trial at 53 or 77 (if applicable) weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
Study officials:
affiliation: Peking University First Hospital
name: Minghui Zhao, M.D.
role: PRINCIPAL_INVESTIGATOR
References: