Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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).
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).
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ia: YK012 | Experimental | Participants with primary membranous nephropathy will receive ascending doses of YK012 infusion to evaluate the safety and tolerability of YK012 |
|
| Ib: YK012 | Experimental | Participants will receive 2 different doses of YK012 infusion to assess the preliminary efficacy of YK012 in participants with primary membranous nephropathy and to establish the recommended Phase II dose (RP2D). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Ia: Dose-limiting Toxicity(DLT) | 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). | up to 28 days after the first dose |
| Ia: Adverse Event (AE) | 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. | From the first induction to the end of the trial at 53 weeks |
| Ia: Severe Adverse Event | 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. | From the first induction to the end of the trial at 53 weeks |
| Ib: Proportion of participants achieving overall response | From enrollment to the end of the trial at 76 weeks (if applicable) |
| Measure | Description | Time Frame |
|---|---|---|
| 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: 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 |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Minghui Zhao, M.D. | Contact | +86-010-83572388 | mhzhao@bjmu.edu.cn |
| Name | Affiliation | Role |
|---|---|---|
| Minghui Zhao, M.D. | Peking University First Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Peking University First Hospital | Recruiting | Beijing | Beijing Municipality | 100034 | China |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| 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 |
| 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 |
| Anti-PLA2R antibody titer change | From enrollment to the end of the trial at 53 or 77 (if applicable) 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) | 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. | From the first induction to the end of the trial at 53 or 77 (if applicable) weeks |
| Ib: Severe Adverse Event | 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. | From the first induction to the end of the trial at 53 or 77 (if applicable) weeks |