Efficacy and Safety of VB119 in Subjects With Membranous Nephropathy

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Membranous Nephropathy
• Intervention / Treatment: Drug: VB119

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Paul Peloso, MD, MSc; Phone Number: 805-730-0327; Email: clinicaltrials@acelyrin.com

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 91324
      • Clinical Reserach Site
  • New York
    • Albany, New York, United States, 12209
      • Clinical Research Site
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18017
      • Clinical Research Site
  • Texas
    • Dallas, Texas, United States, 75208
      • Clinical Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Is ≥ 18 years of age at the time of informed consent;
2. 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. 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;
4. Has systolic blood pressure (BP) <160 mmHg or diastolic BP <100 mmHg after 5 minutes of rest at Screening;
5. Is willing and able to provide written informed consent prior to Screening;
6. 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;
7. 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.
8. Male subjects must agree to abstain from sperm donation through 125 days after administration of the last dose of study drug.

Exclusion Criteria:

1. Has an eGFR <45 mL/min/1.73 m2 at Screening utilizing the Chronic Kidney Disease Epidemiology Collaboration formula confirmed by the central laboratory;
2. Has an absolute neutrophil count <1.5 x 10/L;
3. Has a white blood cell count <3.0 x 10/L;
4. 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);
5. Has a diagnosis or history of SLE (including non renal disease);
6. Has type 1 or 2 diabetes mellitus;
7. Has an acute, chronic, or latent infection, including tuberculosis, hepatitis, HIV, or chronic urinary tract infections;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Tenet Medicines
• Investigators: Study Chair: Keenan, ValenzaBio, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2021
• Primary Completion (Actual): November 21, 2023
• Study Completion (Estimated): August 15, 2024

Study Registration Dates

• First Submitted: November 23, 2020
• First Submitted That Met QC Criteria: December 2, 2020
• First Posted (Actual): December 3, 2020

Study Record Updates

• Last Update Posted (Actual): February 16, 2024
• Last Update Submitted That Met QC Criteria: February 15, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Urologic Diseases; Nephritis; Glomerulonephritis; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Glomerulonephritis, Membranous
• Other Study ID Numbers: 119-01-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No