IgA Nephropathy
Conditions
Keywords
IgAN, AXL inhibitor, Berger's Disease, Proteinuria, Kidney Disease
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.
Interventions
DRUGAVB-S6-500
AVB-S6-500 is experimental drug
Sponsors
Aravive, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| 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 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| Incidence of Anti-drug Antibody (ADA) | 14 weeks | The number of participants with anti-AVB-S6-500 antibodies |
Countries
Ukraine, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment With AVB-S6-500 The subject received a single dose of AVB-S6-500 at 10 mg/kg (total dose 670 mg) | 1 |
| Total | 1 |
Baseline characteristics
| Characteristic | Treatment With AVB-S6-500 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Region of Enrollment Ukraine | 1 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 1 |
| other Total, other adverse events | 1 / 1 |
| serious Total, serious adverse events | 0 / 1 |
Outcome results
Primary
Incidence of Adverse Events (AEs)
Measured by the number of patients with AEs
Time frame: 14 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment With AVB-S6-500 | Incidence of Adverse Events (AEs) | 1 Participants |
Primary
The Effect of AVB-S6-500 on Change From Baseline to End of Treatment in 24-hour Urine Protein Excretion (UPE) in g/Day.
Time frame: 12 weeks
Population: The subject discontinued the study before data were collected, hence the outcome measure was not analyzed.
Primary
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.
Time frame: 12 weeks
Population: The subject discontinued the study before data were collected, hence the outcome measure was not analyzed.
Primary
The Effect of AVB-S6-500 on Change From Baseline to End of Treatment in Estimated Glomerular Filtration Rate (eGFR).
Time frame: 12 weeks
Population: The subject discontinued the study before data were collected, hence the outcome measure was not analyzed.
Primary
The Effect of AVB-S6-500 on Change From Baseline to End of Treatment in Urine Albumin/Creatinine Ratios (uACRs).
Time frame: 12 weeks
Population: The subject discontinued the study before data were collected, hence the outcome measure was not analyzed.
Primary
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.
Time frame: 12 weeks
Population: The subject discontinued the study before data were collected, hence the outcome measure was not analyzed.
Primary
The Effect of AVB-S6-500 on Proportion of Patients With Urinary Protein Equivalent of < 1 g/24 Hours at End of Treatment
Time frame: 12 weeks
Population: The subject discontinued the study before data were collected, hence the outcome measure was not analyzed.
Secondary
Apparent Terminal Half-life (t1/2) of AVB-S6-500
Time frame: 12 weeks
Population: Samples were not analyzed because the study was terminated by the Sponsor.
Secondary
Area Under Time-concentration Curve (AUC)
Time frame: 12 weeks
Population: Samples were not analyzed because the study was terminated by the Sponsor.
Secondary
Incidence of Anti-drug Antibody (ADA)
The number of participants with anti-AVB-S6-500 antibodies
Time frame: 14 weeks
Population: The subject discontinued the study before data were collected, hence the outcome measure was not analyzed.
Secondary
Maximum Observed Plasma Concentration of AVB-S6-500 (Cmax)
Time frame: 12 weeks
Population: Samples were not analyzed because the study was terminated by the Sponsor.
Secondary
Time of Maximum Observed AVB-S6-500 Concentration (Tmax)
Time frame: 12 weeks
Population: Samples were not analyzed because the study was terminated by the Sponsor.
Secondary
Titers of Anti-AVB-S6-500 Antibodies
Time frame: 14 weeks
Population: The subject discontinued the study before data were collected, hence the outcome measure was not analyzed.