Efficacy and Safety of VB119 in Subjects With Membranous Nephropathy

Study Overview
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Brief Summary
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This study is a Phase 1b/2a, open-label, sequential-cohort, dose escalation, and dose expansion study to evaluate the safety, tolerability, PK, and PD of VB119 in subjects with primary MN

Official Title
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A Phase 1b/2a Study of VB119 in Adult Subjects With Primary Membranous Nephropathy

Conditions
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Membranous Nephropathy

Intervention / Treatment
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* Drug: VB119


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is ≥ 18 years of age at the time of informed consent; Has a kidney biopsy-proven diagnosis of primary MN within the past 10 years; Note: It is preferable that subjects enrolled have kidney biopsy tissue samples that are positive for anti-PLA2R antibody staining. Subjects with kidney biopsy-proven diagnosis of primary MN >10 years and ≤20 years that meet all other eligibility criteria may be enrolled after discussion with the Medical Monitor. 3. Has a documented laboratory history of nephrotic range proteinuria (defined as either greater than or equal to 3.5 g total protein per 24-hour urine collection or greater than or equal to 3.5 g/g UPCR by spot collection) AND has proteinuria with a UPCR greater than or equal to 2.0 g/g based on 2 consecutive spot urine (first morning void) sample collections obtained within 14 days of each other during the Screening Period. Both samples must qualify; Has systolic blood pressure (BP) <160 mmHg or diastolic BP <100 mmHg after 5 minutes of rest at Screening; Is willing and able to provide written informed consent prior to Screening; Female subjects of non-childbearing potential must be either surgically sterile (hysterectomy, bilateral tubal ligation, salpingectomy, and/or bilateral oophorectomy at least 26 weeks before the Screening Visit) or postmenopausal, defined as spontaneous amenorrhea for at least 2 years, with follicle-stimulating hormone in the postmenopausal range at Screening, based on the central laboratory's ranges; Female subjects of childbearing potential (ie, ovulating, premenopausal, or not surgically sterile) and all male subjects must use a medically accepted, highly effective contraceptive regimen during their participation in the study and for 125 days after the last administration of study drug. Male subjects must agree to abstain from sperm donation through 125 days after administration of the last dose of study drug. Exclusion Criteria: Has an eGFR <45 mL/min/1.73 m2 at Screening utilizing the Chronic Kidney Disease Epidemiology Collaboration formula confirmed by the central laboratory; Has an absolute neutrophil count <1.5 x 10/L; Has a white blood cell count <3.0 x 10/L; Has secondary causes of MN (eg, malignancy, hepatitis B or C, human immunodeficiency virus [HIV], systemic lupus erythematosus [SLE], or other autoimmune diseases [eg, thyroiditis], drug-induced); Has a diagnosis or history of SLE (including non renal disease); Has type 1 or 2 diabetes mellitus; Has an acute, chronic, or latent infection, including tuberculosis, hepatitis, HIV, or chronic urinary tract infections;

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VB119 dose escalation<br>Dose escalation phase followed by a dose expansion phase. VB119 to be administered as intravenous infusions. | Drug: VB119<br>* Humanized, immunoglobin (Ig) G1 monoclonal antibody (mAb) to be administered as intravenous infusion at multiple timepoints during the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events | Safety and Tolerability | Through study completion, an average of 18 months | 
| Incidence of Clinical Laboratory Assessments | Safety and Tolerability | Through study completion, an average of 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| % of Patients with Anti-Drug Antibodies |  | Through study completion, an average of 18 months | 
| Maximum Plasma Concentration [Cmax] |  | Week 12 | 
| Time to Maximum Plasma Concentration [Tmax] |  | Week 12 | 
| % of patients achieving complete remission of proteinuria |  | Through study completion, an average of 18 months | 
| Anti-PLA2R Antibody Assessment |  | Through study completion, an average of 18 months | 
| Quality of Life as assessed by PROMIS |  | Through study completion, an average of 18 months |