Immunoglobulin A Nephropathy (IgAN)
Conditions
Interventions
Product Name: atrasentan
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: atrasentan
CAS Number: 195733-43-8
Current Sponsor code: CHK-01
Other descriptive name: ATRASENTAN
Concentration u
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. (applicable only to non- SGLT2i stratum) 4. Total urine protein =1 g/day as measured via 24-hour urine collection at a central laboratory collected at screening. 5. eGFR of at least 30 mL/min/1.73 m2 at screening based on the CKD-EPI equation. 6. All fertile men and WOCBP who engage in heterosexual intercourse must be 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. SGLT2i Stable Stratum Only 8. Receiving a stable dose of an SGLT2i (per Investigator choice) in addition to a maximally tolerated and optimized dose of a RAS inhibitor that have been stable for at least 12 weeks prior to Screening. Open Label Extension 9.Subjects who provided written informed consent for OL extension prior to initiation of any OL-specific activities/procedures and are willing to comply with all study visits and study procedures. 10.Subjects from the double-blind portion of study who have completed treatment through Week 132 and completed the Week 136 visit. Note: Subjects who were randomized to the non-SGLT2i stratum in the double-blind portion of the study may start SGLT2i during the OL extension 11.Subjects entering the OL extension must enroll and have their OL-Baseline visit within 14 days of Week 136 (OL Screening visit). Note: If enrollment in the OL extension was not possible due to administrative delays, patients who have completed the EOS visit in the double-blind portion of the study may be able to enroll in the open-label extension if less than 90 days have passed since their EOS visit after approval by Sponsor's Medical Monitor. If enrollment in the OL extension is > 30 days after Week 136, the patient must repeat the Week 136 laboratory assessments to confirm eligibility. 12. All fertile men and WOCBP who engage in heterosexual intercourse must be 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 contraceptive agents must have been continued after completing the double-blind portion of the study. 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 369 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. (IgA vasculitis). 3.Clinical diagnosis of nephrotic syndrome. 4. BNP value of > 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 or approved treatment for IgAN (other than RAS inhibitor) including SGLT2i (except for subjects in the SGLT2i stable stratum) 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. Refer to Sections 6.10.1 and 6.10.2 for details regarding prohibited and restricted medications, respectively. Open Label Extension: 18.Plan to receive any investigational agent (other than atrasentan) or approved treatment for IgAN (other than a RAS inhibitor or SGLT2i). Other ETA receptor antagonists will not be allowed during OL extension. Additional exclusion criteria included in the study protocol under Appendix 6, Section 3.2 (not included here due to character limit)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of atrasentan versus placebo on proteinuria Open Label Extension: to further characterize the safety of atrasentan;Secondary Objective: To evaluate the effect of atrasentan versus placebo in estimated glomerular filtration rate (eGFR) Additional efficacy outcomes Open Label Extension: to evaluate the effect of atrasentan on proteinuria (endpoint of change in UPCR based on 24-hour urine collection from OL baseline to OLE Week 36) Open Label Extension: to evaluate the effect of atrasentan on eGFR;Primary end point(s): The change in proteinuria (urine protein:creatinine ratio [UPCR] based on 24-hour urine collection) from baseline to Week 36 (non-SGLT2i stratum).;Timepoint(s) of evaluation of this end point: Baseline to Week 36 Open Label Extension: OL baseline to OL week 52 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Change from baseline to final study visit (Week 136, 4 weeks post end of treatment) in eGFR, using the chronic kidney disease-epidemiology collaboration (CKD-EPI) creatinine equation (non-SGLT2i stratum) • Percent of subjects meeting the composite endpoint of experiencing at least one of the following during the study (non-SGLT2i stratum): o At least a 30% reduction in eGFR sustained for at least 30 days o eGFR <15 mL/min/1.73m2, sustained for at least 30 days o Chronic dialysis, =30 days o Kidney transplantation o All-cause mortality • Percent of subjects meeting the composite endpoint of experiencing at least one of the following during the study (non-SGLT2i stratum): o At least a 40% reduction in eGFR sustained for at least 30 days o eGFR <15 mL/min/1.73m2, sustained for at least 30 days o Chronic dialysis, =30 days o Kidney transplantation o All-cause mortality • Percent of subjects achieving reduction of proteinuria to < 1 g/day at Week 36 and a 25% decrease in total urine protein from Baseline (non-SGLT2i stratum). Open Label Extension: •Change from OL Baseline to OL Week 36 in UPCR based on 24-hour urine collection •Change from OL Baseline to OL Week 52 in eGFR, using the chronic kidney disease-epidemiology collaboration (CKD-EPI) creatinine equation;Timepoint(s) of evaluation of this end point: Baseline to final study visit (Week 136, 4 weeks post end of treatment) Open Label Extension: •OL Baseline to OL Week 36 (UPCR) •OL Baseline to OL Week 52 (eGFR) | — |
Countries
Argentina, Australia, Brazil, Canada, China, Colombia, 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