ATRASENTAN HYDROCHLORIDE for Immunoglobulin A nephropathy (IgA nephropathy)

Stratification factors

• SGLT2 inhibitor use (SGLT2i stable stratum vs non-SGLT2i stratum)

Inclusion criteria

• {"criterion_text":"- Male and female subjects aged 18 and older at the time of signing the ICF prior to initiation of any study specific activities/procedures."}
• {"criterion_text":"- Open Label Extension - Subjects from the double-blind portion of study who have completed treatment throguh 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"}
• {"criterion_text":"- Open Label Extension - Subjects entering the OL extension must enroll and have their OLBaseline 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."}
• {"criterion_text":"- Open Label Extension - 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- Total urine protein ≥1 g/day as measured via 24-hour urine collection at a central laboratory collected at screening."}
• {"criterion_text":"- eGFR of at least 30 mL/min/1.73 m2 at screening based on the CKDXML File Identifier: NPqJMh0cM61lInVTZ7wGR8FZHeo= Page 10/23 EPI equation."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Willing and able to provide written informed consent and comply with all study visits and study procedures."}
• {"criterion_text":"- SGLT2i Stable Stratum Only - 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"}
• {"criterion_text":"- Open Label Extension - 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."}

Exclusion criteria

• {"criterion_text":"- Concurrent diagnosis of another cause of chronic kidney disease including diabetic kidney disease or another primary glomerulopathy."}
• {"criterion_text":"- Clinical suspicion of rapidly progressive glomerulonephritis (RPGN) based on KDIGO guidelines or clinical suspicion of Henoch-Schonlein Purpura (IgA vasculitis)."}
• {"criterion_text":"- Clinical diagnosis of nephrotic syndrome."}
• {"criterion_text":"- BNP value of > 200 pg/mL at screening."}
• {"criterion_text":"- Platelet count <80,000 per μL at screening."}
• {"criterion_text":"- History of organ transplantation (subjects with history of corneal transplant are not excluded)."}
• {"criterion_text":"- Use of systemic immunosuppressant medications including, systemic corticosteroids (e.g. prednisone, prednisolone, nefecon, etc.), mycophenolate, azathioprine, cyclosporine, tacrolimus, etc.; use of herbs such as Tripterygium Wilfordii Hook F, Caulis sinomenii and Sinomenium acutum; for > 2 weeks in the past 3 months. Use of rituximab within the past 6 months."}
• {"criterion_text":"- Confirmed blood pressure >150 mmHg systolic or >95 mmHg diastolic based on a mean of 3 measurements obtained at screening."}
• {"criterion_text":"- Known history of heart failure or conditions relating to fluid overload such as pulmonary edema, uncontrolled peripheral edema, pleural effusion, or ascites."}
• {"criterion_text":"- History of an alcohol or illicit drug-related disorder within the past 3 years."}
• {"criterion_text":"- Hemoglobin below 9 g/dL at screening or prior history of blood transfusion for anemia within 3 months of screening."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Pregnancy, breast feeding, or intent to become pregnant during the study period and at least 1 month afterward for females."}
• {"criterion_text":"- Intent to father a child or donate sperm during the study period and at least 1 month afterward for males."}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Refer to Sections 6.10.1 and 6.10.2 for details regarding prohibited and restricted medications, respectively."}
• {"criterion_text":"- Open Label Extension - 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"}

Primary endpoints

• {"endpoint_text":"- The change in proteinuria (urine protein:creatinine ratio [UPCR] based on 24-hour urine collection) from baseline to Week 36 (non-SGLT2i stratum).","definition_or_measurement_approach":"Change in urine protein:creatinine ratio (UPCR) measured by 24-hour urine collection from baseline to Week 36 in the non-SGLT2i stratum."}

Secondary endpoints

• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Change in estimated glomerular filtration rate (eGFR) from baseline to Week 136 calculated using the CKD-EPI creatinine equation (non-SGLT2i stratum)."}
• {"endpoint_text":"- Percent of subjects meeting the composite endpoint of experiencing at least one of the following during the study (non-SGLT2i stratum): 1) At least a 30% reduction in eGFR sustained for at least 30 days, 2) eGFR <15 mL/min/1.73m2, sustained for at least 30 days, 3) Chronic dialysis, ≥30 days, 4) Kidney transplantation, 5) All-cause mortality","definition_or_measurement_approach":"Composite clinical outcome defined as occurrence of any listed renal endpoint or death during study period; individual components as specified (sustained reductions in eGFR, dialysis ≥30 days, renal transplantation, all-cause mortality)."}
• {"endpoint_text":"- 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).","definition_or_measurement_approach":"Proportion of subjects with 24-hour urine total protein <1 g/day at Week 36 and ≥25% reduction from baseline total urine protein (non-SGLT2i stratum)."}
• {"endpoint_text":"- Open Label Extension: Change from OL Baseline to OL Week 36 in UPCR based on 24-hour urine collection","definition_or_measurement_approach":"Change in UPCR measured by 24-hour urine collection from Open Label baseline to Open Label Week 36."}
• {"endpoint_text":"- Open Label Extension: Change from OL Baseline to OL Week 52 in eGFR, using the chronic kidney disease-epidemiology collaboration (CKD-EPI) creatinine equation","definition_or_measurement_approach":"Change in eGFR from Open Label baseline to Open Label Week 52 calculated using CKD-EPI creatinine equation."}

Germany

Earliest CTIS Part Ii Submission Date

08-08-2024

Latest Decision Or Authorization Date

27-08-2025

Processing Time Days

384

Number Of Sites

6

Number Of Participants

9

Italy

Earliest CTIS Part Ii Submission Date

08-08-2024

Latest Decision Or Authorization Date

03-10-2025

Processing Time Days

421

Number Of Sites

4

Number Of Participants

8

France

Earliest CTIS Part Ii Submission Date

08-08-2024

Latest Decision Or Authorization Date

29-09-2025

Processing Time Days

417

Number Of Sites

4

Number Of Participants

9

Portugal

Earliest CTIS Part Ii Submission Date

08-08-2024

Latest Decision Or Authorization Date

22-09-2025

Processing Time Days

410

Number Of Sites

2

Number Of Participants

3

Poland

Earliest CTIS Part Ii Submission Date

08-08-2024

Latest Decision Or Authorization Date

08-09-2025

Processing Time Days

396

Number Of Sites

2

Number Of Participants

4

Primary sponsor

Full Name

Novartis Pharma AG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Switzerland

Contract research organisations

Name

Marken LLP

Responsibilities

Home health care, DFP (direct from patient)

Name

Q Squared Solutions Limited

Responsibilities

Central Lab

Name

Suvoda LLC

Responsibilities

3

Name

Emerald Clinical Trials B.V.

Responsibilities

Site retention / PI relationship management

Name

Medidata Solutions Inc.

Responsibilities

7

Name

Iqvia Biotech LLC

Responsibilities

Affiliates: -eCOA -Wingspan eTMF -Study Hub; 5

Name

Veeda Clinical Research Limited

Responsibilities

4

Name

Scout Clinical

Responsibilities

Patient Travel Arragements / Reimbursement

Third parties

• {"country":"United States","full_name":"Marken LLP","duties_or_roles":"Home health care, DFP (direct from patient)","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"Central Lab","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"3","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Emerald Clinical Trials B.V.","duties_or_roles":"Site retention / PI relationship management","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Patient Travel Arragements / Reimbursement","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Iqvia Biotech LLC","duties_or_roles":"Affiliates: -eCOA -Wingspan eTMF -Study Hub; 5","organisation_type":"Pharmaceutical company"}
• {"country":"India","full_name":"Veeda Clinical Research Limited","duties_or_roles":"4","organisation_type":"Pharmaceutical company"}