Clinical trial NCT04042623: Study of Safety and Efficacy of AVB-S6-500 in Patients With IgA Nephropathy
Official title: An Open-Label Phase 2a Study to Evaluate the Safety and Efficacy of AVB-S6-500 in Patients With IgA Nephropathy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: IgA Nephropathy
Keywords: IgAN
AXL inhibitor
Berger's Disease
Proteinuria
Kidney Disease
Lead sponsor: Aravive, Inc.
Sponsor class: INDUSTRY
First posted: 2019-08-02
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Incidence of Adverse Events (AEs)
timeFrame: 14 weeks
measure: The Effect of AVB-S6-500 on Change From Baseline to End of Treatment in 24-hour Urine Protein Excretion (UPE) in g/Day.
timeFrame: 12 weeks
measure: 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.
timeFrame: 12 weeks
measure: The Effect of AVB-S6-500 on Proportion of Patients With Urinary Protein Equivalent of < 1 g/24 Hours at End of Treatment
timeFrame: 12 weeks
measure: 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.
timeFrame: 12 weeks
measure: The Effect of AVB-S6-500 on Change From Baseline to End of Treatment in Urine Albumin/Creatinine Ratios (uACRs).
timeFrame: 12 weeks
measure: The Effect of AVB-S6-500 on Change From Baseline to End of Treatment in Estimated Glomerular Filtration Rate (eGFR).
timeFrame: 12 weeks
Secondary outcomes:
measure: Incidence of Anti-drug Antibody (ADA)
timeFrame: 14 weeks
measure: Titers of Anti-AVB-S6-500 Antibodies
timeFrame: 14 weeks
measure: Apparent Terminal Half-life (t1/2) of AVB-S6-500
timeFrame: 12 weeks
measure: Maximum Observed Plasma Concentration of AVB-S6-500 (Cmax)
timeFrame: 12 weeks
measure: Area Under Time-concentration Curve (AUC)
timeFrame: 12 weeks
measure: Time of Maximum Observed AVB-S6-500 Concentration (Tmax)
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Doral
country: United States
facility: Moonshine Clinical Research
state: Florida
city: Kyiv
country: Ukraine
facility: Institute of Nephrology National Academy of Medical Science Ukraine
Study officials:
affiliation: Aravive, Inc.
name: Francoise Desir
role: STUDY_DIRECTOR
References: