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

Study Overview
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Brief Summary
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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.

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

Conditions
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IgA Nephropathy

Intervention / Treatment
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* Drug: AVB-S6-500


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IgAN, AXL inhibitor, Berger's Disease, Proteinuria, Kidney Disease