Randomized, Double-blind, Placebo-controlled, Crossover Study of Atrasentan in Subjects With IgA Nephropathy

Inclusion Criteria:

- Legal adults (per local and country specifications) ≥ 18 years of age at the time of
signing the informed consent form (ICF) prior to initiation of any study specific
activities/procedures.

- Biopsy-proven IgA nephropathy.

- Receiving a maximally tolerated and stable dose of a RASi for at least 12 weeks
prior to screening. Investigator discretion should be used in determining maximally
tolerated and optimized dose.

- eGFR of at least 30 mL/min/1.73 m^2 at screening based on the 2021 CKD-EPI equation.

- Willing to agree to highly effective forms of contraception, as specified in the
protocol, throughout the study and for up to 1 month afterward. In WOCBP, use of
hormonal contraceptive agents must have been started at least 1 month prior to
baseline.

- Willing and able to provide informed consent and comply with all study requirements.

- Inclusion Criteria for SGLT2i stable subjects

- Receiving a stable dose of an SGLT2i for at least 8 weeks prior to screening

- Must have a 24-hour urine protein of >0.5 grams/day.

- Inclusion Criteria for Run-In Subjects

- Must have a 24-hour total urine protein of >0.85 grams/day at screening

- Willing to participate in an 8-week run-in period with an SGLT2i (per
Investigator choice)

- Additional Inclusion Criteria for Run-in Subjects at the end of Run-In

- Must have completed the 8-week run-in period on a stable and well tolerated
dose of an SGLT2i

- Must have a 24-hour total urine protein of >0.5 grams/day confirmed at the
Run-in Week 8 visit.

- Must have an eGFR of ≥ 30 mL/min/1.73 m^2 based on the CKD-EPI equation at
their Run-in Week 8 visit.

Exclusion Criteria:

- Current diagnosis with another chronic kidney disease, including diabetic kidney
disease.

- History of kidney transplantation or other organ transplantation.

- 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.

- Known history of heart failure or prior hospital admissions for conditions relating
to fluid overload that in the opinion of the Principal Investigator or Sponsor might
confound the results of the study or pose additional risk to the participant by
their participation in the study.

- Clinically significant history of liver disease as assessed by the Investigator.

- Hemoglobin below 9 g/dL as measured by the Investigator or prior history of blood
transfusion for anemia within the past 3 months.

- Malignancy within the past 5 years. Exceptions to this criteria include nonmelanoma
skin cancer and curatively treated cervical carcinoma in situ.

- For women, pregnancy, breast feeding, or intent to become pregnant during the study.
and at least 1 month afterward.

- For men, intent to father a child or donate sperm during the study.

- Have received any investigational agent or approved treatment for IgAN (other than a
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.