Immunoglobulin A Nephropathy (IgAN)
Conditions
Interventions
Product Name: Atrasentan
Product Code: [Atrasentan]
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Atrasentan
CAS Number: 195733-43-8
Current Sponsor code: CHK-01
Concentration unit: mg
Sponsors
CHINOOK THERAPEUTICS, U.S., Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female subjects aged 18 and older at the time of signing the ICF prior to initiation of any study specific activities/procedures. 2. Biopsy-proven IgAN that, in the opinion of the Investigator, is not due to secondary causes. • Biopsy could have occurred at any point in time prior to study. • A diagnostic report must be available for review by the Sponsor or designee. 3. Receiving a maximally tolerated and optimized dose of a RAS inhibitor that has been stable for at least 12 weeks prior to screening. • Investigator discretion should be used in determining maximally tolerated and optimized dose. • Subjects who are intolerant to RAS inhibitors are eligible but will not exceed ~5% of total population randomized. 4. UPCR =1 g/g (=1000 mg/g) based on a central laboratory assessment of first morning void urine collected at screening. 5. eGFR of at least 30 mL/min/1.73 m2 at screening based on the CKD-EPI equation. 6. Willing to abide with highly effective forms of contraception, as specified in the protocol, throughout the study and for 1 month afterward. In WOCBP, use of hormonal contraceptive agents must have been started at least 1 month prior to baseline. 7. Willing and able to provide written informed consent and comply with all study visits and study procedures. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 305 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: 1. Concurrent diagnosis of another cause of chronic kidney disease including diabetic kidney disease or another primary glomerulopathy. 2. Clinical suspicion of rapidly progressive glomerulonephritis (RPGN) based on KDIGO guidelines or clinical suspicion of Henoch-Schonlein Purpura. 3. Diagnosis of nephrotic syndrome with serum albumin 200 pg/mL at screening. 5. Platelet count 2 weeks in the past 3 months. Use of rituximab within the past 6 months. 8. Confirmed blood pressure >150 mmHg systolic or >95 mmHg diastolic based on a mean of 3 measurements obtained at screening. 9. Known history of heart failure or prior hospital admissions for conditions relating to fluid overload such as pulmonary edema, uncontrolled peripheral edema, pleural effusion, or ascites. 10. Known history of clinically significant liver disease or transaminase or bilirubin values more than twice the upper limit of normal. Subjects with treated hepatitis C can be considered for inclusion into the study upon consultation with the Sponsor’s Medical Monitor (or designee). 11. Hemoglobin below 9 g/dL at screening or prior history of blood transfusion for anemia within 3 months of screening. 12. History of malignancy unless cancer free for at least 5 years or nonmelanoma skin cancer not requiring ongoing treatment. A subject with curatively treated cervical carcinoma in situ is eligible for this study. 13. Pregnancy, breast feeding, or intent to become pregnant during the study period and at least 1 month afterward for females. 14. Intent to father a child or donate sperm during the study period and at least 1 month afterward for males. 15. Have received any investigational agent within 1 month (or 5 half-lives of the agent, whichever is longer) prior to screening. If the investigational agent is a cytotoxic or immunosuppressive agent then this washout period is 6 months. 16. Concurrent clinically significant, unstable, or uncontrolled cardiovascular, pulmonary, hepatic, renal, gastrointestinal, genitourinary, hematological, coagulation, immunological, endocrine/metabolic, or other medical disorder that, in the opinion of the Investigator or Sponsor’s Medical Monitor (or designee), might confound the results of the study or pose additional risk to the subject by their participation in the study. 17. History of an alcohol or illicit drug-related disorder within the past 3 years.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of atrasentan versus placebo on proteinuria levels at Week 24;Secondary Objective: To evaluate the effect of atrasentan versus placebo on change from baseline to Week 136 (4 weeks post cessation of randomized treatment) in estimated glomerular filtration rate (eGFR) To compare 2-year on-treatment rates of change in eGFR between atrasentan and placebo (eGFR slope Week 12 to Week 120 of randomized treatment) To compare the total on-study rates of change in eGFR between atrasentan and placebo (eGFR slope from baseline to Week 136);Primary end point(s): The change in proteinuria (urine protein:creatinine ratio [UPCR] based on 24-hour urine collection) from baseline to Week 24.;Timepoint(s) of evaluation of this end point: Baseline to Week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Change from baseline to final study visit (Week 136) in eGFR, using the chronic kidney disease-epidemiology collaboration (CKD-EPI) creatinine equation Rate of change in eGFR during 2 years on treatment as measured through a chronic slope calculated from values at Week 12 through to Week 120 Rate of change in eGFR during the study as measured through a total slope calculated from values at baseline to Week 136;Timepoint(s) of evaluation of this end point: Baseline to final study visit (Week 136) 2 years | — |
Countries
Argentina, Australia, Brazil, Canada, China, Czech Republic, France, Germany, Hong Kong, India, Ireland, Italy, Japan, Korea, Republic of, New Zealand, Poland, Portugal, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactClinical Trial Information Desk
Chinook Therapeutics U.S., Inc.
Outcome results
None listed