Efficacy and Safety of VB119 in Subjects With Membranous Nephropathy
Primary Purpose
Membranous Nephropathy
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
VB119
Sponsored by
About this trial
This is an interventional treatment trial for Membranous Nephropathy
Eligibility Criteria
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;
Sites / Locations
- Clinical Reserach SiteRecruiting
- Clinical Research SiteRecruiting
- Clinical Research SiteRecruiting
- Clinical Research SiteRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
VB119 dose escalation
Arm Description
Dose escalation phase followed by a dose expansion phase. VB119 to be administered as intravenous infusions.
Outcomes
Primary Outcome Measures
Incidence of Treatment-Emergent Adverse Events
Safety and Tolerability
Incidence of Clinical Laboratory Assessments
Safety and Tolerability
Secondary Outcome Measures
% of Patients with Anti-Drug Antibodies
Maximum Plasma Concentration [Cmax]
Time to Maximum Plasma Concentration [Tmax]
% of patients achieving complete remission of proteinuria
Anti-PLA2R Antibody Assessment
Quality of Life as assessed by PROMIS
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04652570
Brief Title
Efficacy and Safety of VB119 in Subjects With Membranous Nephropathy
Official Title
A Phase 1b/2a Study of VB119 in Adult Subjects With Primary Membranous Nephropathy
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 5, 2021 (Actual)
Primary Completion Date
October 2023 (Anticipated)
Study Completion Date
October 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ACELYRIN Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Membranous Nephropathy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
VB119 dose escalation
Arm Type
Experimental
Arm Description
Dose escalation phase followed by a dose expansion phase. VB119 to be administered as intravenous infusions.
Intervention Type
Drug
Intervention Name(s)
VB119
Intervention Description
Humanized, immunoglobin (Ig) G1 monoclonal antibody (mAb) to be administered as intravenous infusion at multiple timepoints during the study.
Primary Outcome Measure Information:
Title
Incidence of Treatment-Emergent Adverse Events
Description
Safety and Tolerability
Time Frame
Through study completion, an average of 18 months
Title
Incidence of Clinical Laboratory Assessments
Description
Safety and Tolerability
Time Frame
Through study completion, an average of 18 months
Secondary Outcome Measure Information:
Title
% of Patients with Anti-Drug Antibodies
Time Frame
Through study completion, an average of 18 months
Title
Maximum Plasma Concentration [Cmax]
Time Frame
Week 12
Title
Time to Maximum Plasma Concentration [Tmax]
Time Frame
Week 12
Title
% of patients achieving complete remission of proteinuria
Time Frame
Through study completion, an average of 18 months
Title
Anti-PLA2R Antibody Assessment
Time Frame
Through study completion, an average of 18 months
Title
Quality of Life as assessed by PROMIS
Time Frame
Through study completion, an average of 18 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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;
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Paul Peloso, MD, MSc
Phone
805-730-0327
Email
clinicaltrials@acelyrin.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Keenan
Organizational Affiliation
ValenzaBio, Inc.
Official's Role
Study Chair
Facility Information:
Facility Name
Clinical Reserach Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
91324
Country
United States
Individual Site Status
Recruiting
Facility Name
Clinical Research Site
City
Albany
State/Province
New York
ZIP/Postal Code
12209
Country
United States
Individual Site Status
Recruiting
Facility Name
Clinical Research Site
City
Bethlehem
State/Province
Pennsylvania
ZIP/Postal Code
18017
Country
United States
Individual Site Status
Recruiting
Facility Name
Clinical Research Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75208
Country
United States
Individual Site Status
Recruiting
12. IPD Sharing Statement
Learn more about this trial
Efficacy and Safety of VB119 in Subjects With Membranous Nephropathy
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