The purpose of this study is to evaluate the efficacy and safety of VIS649 in participants with immunoglobulin A (IgA) Nephropathy (IgAN)
This is a Phase 2, double-blind, randomized, placebo-controlled study in patients aged 18 years and above with biopsy confirmed diagnosis of IgAN. The study is designed to test the safety and effectiveness of multiple doses of VIS649. The main objectives are to evaluate the safety and tolerability of VIS649 and to evaluate the dose response of different doses of VIS649 by measuring proteinuria. The study is comprised of three main periods, Screening, Treatment (12 months) and Follow-Up (4 months). Approximately 144 patients will be enrolled. The findings from this study will form the basis for subsequent clinical development of VIS649. VIS649 is a humanized immunoglobulin G (IgG2) monoclonal antibody that binds to and blocks the biological actions of the cytokine A PRoliferation Inducing Ligand (APRIL), a key factor in the production of aberrantly glycosylated IgA1 (a-g- IgA1), which is critical to the pathogenesis of IgAN.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
155
Number of Participants With Adverse Events Graded by Severity
The number of participants who experienced adverse events, graded by maximum severity, are presented.
Time frame: Baseline to End of Study (16 months)
Changes From Baseline in Clinical Laboratory Tests
The number of participants who experience a shift from normal at baseline to Grade 3/4 (moderate/sever) at a postbaseline time point are presented.
Time frame: Baseline to End of Study (16 months)
Clinically Meaningful Changes From Baseline in Vital Signs
The number of participants who experienced clinically meaningful changes from baseline in vital signs (body mass index, diastolic blood pressure, height, heart rate, mean arterial pressure, respiratory rate, systolic blood pressure, temperature, and weight) are presented.
Time frame: Baseline to End of Study (16 months)
Clinically Significant Physical Examinations
Clinically significant physical examination findings are presented.
Time frame: Baseline to End of Study (16 months)
Change From Baseline in uPCR: Month 12
Natural Log 24-Hour uPCR (Schedule A Urine Collection) Change from Baseline at Month 12: mixed model with repeated measurements
Time frame: 12 months
Change From Baseline in uPCR: Months 9 and 16
Change from baseline in uPCR (Urine protein/creatinine ratio)
Time frame: Baseline to 9 months and 16 months (16 months total)
Change in 24-hour Urine Protein Excretion: Months 12 and 16
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Dose Level = High
Visterra Investigational Site
Birmingham, Alabama, United States
Visterra Investigational Site
Los Angeles, California, United States
Visterra Investigational Site
Oxnard, California, United States
Visterra Investigational Site
Palo Alto, California, United States
Visterra Investigational Site
Stanford, California, United States
Visterra Investigational Site
Denver, Colorado, United States
Visterra Investigational Site
Lawrenceville, Georgia, United States
Visterra Investigational Site
Baton Rouge, Louisiana, United States
Visterra Investigational Site
New Orleans, Louisiana, United States
Visterra Investigational Site
Baltimore, Maryland, United States
...and 83 more locations
Change in 24-hour urine protein excretion from baseline to Months 12 and 16
Time frame: 16 months
Participants Achieving a Greater Than or Equal to 30% Decline From Baseline in uPCR at Months 9, 12, and 16
Number of participants in each group achieving a greater than or equal to 30% decline from baseline in urinary protein/creatinine ratio (uPCR) at Months 9, 12, and 16
Time frame: Baseline to 9,12, and 16 months (16 months total)
Participants in Each Group Achieving Clinical Remission
Number of participants in each group achieving clinical remission. Clinical remission was defined as reduction in 24-hour urine protein excretion to less than 300 mg/day for at least 3 consecutive months.
Time frame: Baseline to End of Study (16 months)
Change From Baseline in eGFR at Months 9, 12, and 16
Change from baseline in (eGFR) at Months 9, 12, and 16
Time frame: Baseline to 12 and 16 months
Percent Change From Baseline in Total Serum IgA, IgG, and IgM Concentrations at Months 12 and 16
Percent change from baseline in total serum immunoglobin (Ig)A, IgG, and IgM concentrations at Months 12 and 16 in PD population
Time frame: Baseline to 12 and 16 months
Mean Serum PK Parameters at Month 0 and Month 11: Cmax
Serum PK parameters: maximum serum concentration (Cmax)
Time frame: Months 0 and 11
Median Serum PK Parameters at Month 0 and Month 11: Tmax
Serum PK parameters: time of maximum serum concentration (Tmax)
Time frame: Month 0 and Month 11
Mean Serum PK Parameters at Month 0: AUC0-inf and AUC0-30
Serum PK parameters of area under the concentration-time curve from time 0 to infinity (AUC0-inf) and area under the concentration-time curve from time 0 to Day 30 (AUC0-30)
Time frame: Month 0
Mean Serum PK Parameters at Month 0 and Month 11: t1/2z
Serum PK parameters: terminal elimination half-life(t1/2z)
Time frame: Month 0 and Month 11
Median Serum PK Parameters at Month 0: CL
Serum PK parameters of clearance. 8 mg/kg was not reported for this outcome measure. Other arms were not provided due to participants meeting exclusion criteria: %AUCext \> 20% and R2 Adjusted \< 0.8. Affected parameters at participant visits meeting this criteria were excluded.
Time frame: Month 0
Mean Serum PK Parameters at Month 0: Vz
Serum PK parameters of apparent volume of distribution (Vz). 8 mg/kg was not reported for this outcome measure. Other arms were not provided due to participants meeting exclusion criteria: %AUCext \> 20% and R2 Adjusted \< 0.8. Affected parameters at participant visits meeting this criteria were excluded.
Time frame: Month 0
Mean Serum PK Parameters at Month 11: AUCτ
Serum PK parameters: area under the concentration-time curve from time 0 to the end of the dosing period (AUCτ)
Time frame: Month 11
Mean Serum PK Parameters at Month 11: Vss
Serum PK parameters: volume of distribution at steady-state (Vss)
Time frame: Month 11
Mean Serum PK Parameters at Month 11: CLss
Serum PK parameters: clearance at steady-state (CLss)
Time frame: Month 11
Mean Serum PK Parameters at Month 11: Rac[AUC0-30]
Serum PK parameters: accumulation ratio of area under the concentration-time curve from time 0 to infinity (Rac\[AUC0-30\])
Time frame: Month 11