Alport Syndrome, Diabetic Kidney Disease, Diabetic Nephropathy Type 2, Focal Segmental Glomerulosclerosis, IgA Nephropathy, Immunoglobulin A Nephropathy
Conditions
Brief summary
The AFFINITY Study is a phase 2, open-label, basket study to evaluate the efficacy and safety of atrasentan in patients with proteinuric glomerular disease who are at risk of progressive loss of renal function.
Detailed description
The AFFINITY Study is a phase 2, open-label, basket study to evaluate the efficacy and safety of atrasentan in patients with proteinuric glomerular disease who are at risk of progressive loss of renal function. Cohorts will consist of patients with: * IgA nephropathy (IgAN) with urine protein:creatinine ratio (UPCR) of 0.5 to less than 1.0 g/g * Focal segmental glomerulosclerosis (FSGS) * Alport syndrome * Diabetic kidney disease (DKD) on top of background care of a RAS inhibitor and SGLT2 inhibitor Additional cohorts may be added as data is available. Approximately 100 patients will be enrolled in the study. Approximately 20 patients will be enrolled in each cohort to receive 0.75 mg atrasentan QD for 52 weeks. The study will also evaluate efficacy and safety of 1.5 mg atrasentan QD in FSGS subjects who received 0.75 mg atrasentan and it was well tolerated. Patients will be allowed to continue into treatment extension and receive oral atrasentan QD for up to an additional 84 weeks (total maximum treatment of 188 weeks), The primary objective of the study is to evaluate the effect of atrasentan on proteinuria (for IgAN, FSGS, and Alport syndrome patients) or albuminuria (for DKD patients) levels. Exploratory objectives include evaluating the change in kidney function over time as measured by eGFR, safety and tolerability. To facilitate study participation over this time period, where allowed by local regulations, options for remote study visits using telemedicine and home health may be offered.
Interventions
DRUGAtrasentan
Film-coated tablet
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 years and older for patients in the IgAN, FSGS, and Alport Syndrome cohorts * Age 18-70 years for patients in the DKD cohort * Receiving a maximally tolerated dose of RAS inhibitor therapy (ACEi or ARB) that has been stable for at least 12 weeks. * For patients enrolling in IgAN Cohort: 1. Biopsy-proven IgA nephropathy 2. UPCR between 0.5 to less than 1.0 g/g 3. Screening eGFR ≥ 30 mL/min/1.73 m2 * For patients enrolling in FSGS Cohort: 1. Biopsy-proven FSGS or documented genetic mutation in a podocyte protein associated with FSGS 2. UPCR \> 1.0 g/g 3. Screening eGFR ≥ 30 mL/min/1.73 m2 4. Subjects receiving systemic corticosteroids or other immunosuppressants must be on a stable dose for at least 12 weeks. 5. BMI ≤ 40 kg/m2 * For patients enrolling in Alport syndrome Cohort: 1. Diagnosis of Alport syndrome by genetic testing 2. UPCR \> 0.5 g/g 3. Screening eGFR ≥ 30 mL/min/1.73 m2 * For patients enrolling in DKD Cohort: 1. Diagnosis of type 2 diabetes mellitus 2. UACR ≥ 0.5 g/g 3. Screening eGFR ≥ 45 mL/min/1.73 m2 4. Receiving a stable dose of SGLT2 inhibitor for at least 12 weeks * Willing and able to provide informed consent and comply with all study requirements
Exclusion criteria
* Current diagnosis of another cause of chronic kidney disease or another primary glomerulopathy. * History of kidney transplantation or other organ transplantation. * Except for FSGS patients, use of systemic immunosuppressant medications, such as steroids, for more than 2 weeks in the past 3 months. * Blood pressure above 150 mmHg systolic or 95 mmHg diastolic as evaluated by the Investigator. * History of heart failure or a previous hospital admission for fluid overload. * Clinically significant history of liver disease as assessed by the Investigator. * Hemoglobin below 9 g/dL as measured by the Investigator or blood transfusion for anemia within the past 3 months. * Clinical diagnosis of nephrotic syndrome * Malignancy within the past 5 years. Exception to the criteria include nonmelanoma skin cancer and curatively treated cervical carcinoma in situ. * For women, pregnant, breastfeeding, or intent to become pregnant during the study. * For men, intent to father a child or donate sperm during the study. * Recently received an investigational agent. * Clinically significant unstable or uncontrolled medical condition as assessed by the Investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in proteinuria for IgAN, FSGS, and Alport syndrome patients receiving 0.75 mg atrasentan QD | Up to Week 12 or approximately 3 months | The change in urine protein:creatinine ratio (UPCR) from baseline to Week 12 |
| Change in albuminuria for DKD patients | Up to Week 12 or approximately 3 months | The change in urine albumin:creatinine ratio (UACR) from baseline to Week 12 |
| Change in proteinuria for FSGS patients at 1.5 mg dose | Up to Week 24 or approximately 6 months | The change in urine protein:creatinine ratio (UPCR) from baseline to Week 24 |
Countries
Australia, Italy, South Korea, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Outcome results
None listed