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

Phase 2

Terminated

Conditions: IgA Nephropathy

Interventions: Drug: AVB-S6-500

Registration Number: NCT04042623

Lead Sponsor: Aravive, Inc.

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 1

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment with AVB-S6-500	AVB-S6-500	Patients will receive AVB-S6-500 by intravenous infusion every 2 weeks for total of 6 doses.

Primary Outcome Measures

Name	Time	Method
Incidence of Adverse Events (AEs)	14 weeks	Measured by the number of patients with AEs
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

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

Trial Locations

Locations (2): Moonshine Clinical Research
🇺🇸
Doral, Florida, United States
Institute of Nephrology National Academy of Medical Science Ukraine
🇺🇦
Kyiv, Ukraine