Study of Safety and Efficacy of AVB-S6-500 in Patients With IgA Nephropathy

An Open-Label Phase 2a Study to Evaluate the Safety and Efficacy of AVB-S6-500 in Patients With IgA Nephropathy

This is an open-label Phase 2a clinical study designed to evaluate the safety and efficacy of AVB-S6-500 in patients with IgA Nephropathy (IgAN). Approximately 24 patients will be enrolled. Several dose levels of AVB-S6-500 may be evaluated.

Study Overview

• Status: Terminated
• Conditions: IgA Nephropathy
• Intervention / Treatment: Drug: AVB-S6-500

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

Contacts and Locations

Study Locations

• Ukraine
  • Kyiv, Ukraine, 04050
    • Institute of Nephrology National Academy of Medical Science Ukraine
• United States
  • Florida
    • Doral, Florida, United States, 33166
      • Moonshine Clinical Research

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Diagnosis of biopsy-proven IgAN
• Proteinuria ≥ 1g to 3g/24hr
• Stable estimated glomerular filtration rate (eGFR) for at least 3 months prior to screening and ≥ 45 mL/min per 1.73 m2 using the Chronic Kidney Disease Epidemiology Collaboration formula
• Systolic BP lesser than or equal to 150 mmHg and diastolic BP lesser than or equal to 100 mmHg
• Patients who have been on a steady dose of ACE or ARB inhibitors for at least 3 months and throughout screening and who are not expected to have their dose adjusted during the study are allowed on study (patients who are not on ACEi/ARB due to inability to tolerate these therapies are also allowed)
• If a sexually-active patient, must agree to use a reliable method of birth control from at least 4 weeks prior to first dose of study drug, during the study and for 1 month following completion of therapy.

Exclusion Criteria:

• Patients with chronic urinary tract infections (UTIs) or taking prophylactic antibiotics to prevent recurrent UTIs
• Treatment with systemic immunosuppressants, including corticosteroids, within 8 weeks of the first dose of study drug
• Rapidly progressing nephropathy defined as falling GFR (≥ 15%) over past 3 mos
• Clinical or biological evidence of diabetes mellitus, systemic lupus erythematosus, IgA vasculitis (Henoch-Schonlein purpura), secondary IgAN, or other renal disease
• Hemoglobin < 9.0 g/dL
• History or clinical evidence of cirrhosis, or liver disease with serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3x upper limit of normal
• Organ transplant recipient (including bone marrow) or a planned transplant during the study
• Have a diagnosis of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection, or positive serology at screening
• Recent active infection requiring hospitalization or i.v. treatment within 30 days prior to the first dose of study drug
• Received transfusion, plasmapheresis or plasma exchange, IV immunoglobulin (IVIg) within 90 days prior to screening
• Malignancy within the past 5 years. Exceptions are squamous cell carcinoma of skin, basal cell carcinoma of skin, and cervical carcinoma in situ which have been excised and are considered cured
• Females who are nursing, pregnant, or intending to become pregnant during the time of the study, or who have a positive pregnancy test at baseline
• Exposure to an investigational drug or device within 90 days or 5 half-lives (whichever is longer) prior to the first dose of study drug
• Known sensitivity to any of the products to be administered during dosing
• Subject will not be available for follow-up assessment
• Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures
• Prior exposure to AVB-S6-500

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment with AVB-S6-500; Patients will receive AVB-S6-500 by intravenous infusion every 2 weeks for total of 6 doses.	Drug: AVB-S6-500; AVB-S6-500 is experimental drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events (AEs)	Measured by the number of patients with AEs	14 weeks
The Effect of AVB-S6-500 on Change From Baseline to End of Treatment in 24-hour Urine Protein Excretion (UPE) in g/Day.		12 weeks
The Effect of AVB-S6-500 on Change From Baseline to End of Treatment in 24-hour Urine Protein Excretion (UPE) in g/Day in the Subset of Patients With Baseline High Proteinuria.		12 weeks
The Effect of AVB-S6-500 on Proportion of Patients With Urinary Protein Equivalent of < 1 g/24 Hours at End of Treatment		12 weeks
The Effect of AVB-S6-500 on Proportion of Patients Who Had at Least a Decrease of 0.5 g/Day Proteinuria From Baseline to End of Treatment.		12 weeks
The Effect of AVB-S6-500 on Change From Baseline to End of Treatment in Urine Albumin/Creatinine Ratios (uACRs).		12 weeks
The Effect of AVB-S6-500 on Change From Baseline to End of Treatment in Estimated Glomerular Filtration Rate (eGFR).		12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Anti-drug Antibody (ADA)	The number of participants with anti-AVB-S6-500 antibodies	14 weeks
Titers of Anti-AVB-S6-500 Antibodies		14 weeks
Apparent Terminal Half-life (t1/2) of AVB-S6-500		12 weeks
Maximum Observed Plasma Concentration of AVB-S6-500 (Cmax)		12 weeks
Area Under Time-concentration Curve (AUC)		12 weeks
Time of Maximum Observed AVB-S6-500 Concentration (Tmax)		12 weeks

Collaborators and Investigators

• Sponsor: Aravive, Inc.
• Investigators: Study Director: Francoise Desir, Aravive, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 27, 2019
• Primary Completion (Actual): August 1, 2020
• Study Completion (Actual): August 1, 2020

Study Registration Dates

• First Submitted: July 31, 2019
• First Submitted That Met QC Criteria: July 31, 2019
• First Posted (Actual): August 2, 2019

Study Record Updates

• Last Update Posted (Actual): February 10, 2022
• Last Update Submitted That Met QC Criteria: January 18, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Kidney Disease; Proteinuria; IgAN; Berger's Disease; AXL inhibitor
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Urologic Diseases; Nephritis; Glomerulonephritis; Kidney Diseases; Glomerulonephritis, IGA
• Other Study ID Numbers: AVB500-IGA-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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