Study to Assess the Efficacy, Pharmacokinetics, Safety and Tolerability of Atrasentan in Pediatric Patients With Primary IgAN

1. Signed informed consent by parent(s)/legal guardian(s) for the pediatric patient must be obtained before any study-specific assessment is performed. A consent or assent may also be required for some participants depending upon their age and local requirement.
2. Male and female participants 2 to \< 18 years of age as of Day 1.
3. eGFR ≥ 30 mL/min/1.73m2 where eGFR is calculated using the modified Schwartz formula at Screening and confirmed during the Run-in Period.
4. Kidney biopsy-proven primary IgAN*, with biopsy performed within 3 years of Screening with \< 50% tubulointerstitial fibrosis and \< 25% crescents. In case a kidney biopsy within 3 years from Screening is not available, a kidney biopsy may be performed if it is part of the planned diagnostic approach and clinical management of the participant.
5. Proteinuria due to primary diagnosis of IgAN as assessed by UPCR ≥ 1 g/g (113 mg/mmoL) sampled from FMV at Screening on Day -90 and Day -60 as well as during the Run-in Period despite treatment with maximum tolerated dose of ACE inhibitor/ARB for at least 120 days prior to Day 1. Note: UPCR will be assessed based on one FMV sample at Day -90 and based on the geometric mean of 2 FMV samples for the Day -60 visit and during the Run-in Period.
6. All participants must have been on supportive care including stable dose regimen of ACE inhibitor or ARB at either the locally approved maximal daily dose per body weight, or the maximally tolerated dose (per Investigator's judgment for pediatric use), for at least 120 days before first study drug administration. In addition, if participants are taking diuretics, other antihypertensive medication, or other background medication for IgAN (such as SGLT2 inhibitors), the doses should also be stabilized for at least 120 days prior to the first dosing of study treatment. Note: Participants with allergies or intolerance to ACE inhibitors and ARBs are eligible for the study. Participants with allergies or intolerance to RAS inhibitors are eligible but will not exceed \~5% of the total population treated (maximum of 2 participants).
7. The minimum body weight of enrolled pediatric participants is 10 kg at Screening and confirmed on Day 1.
8. Parent(s)/guardian(s) are to be able to communicate well with the investigator and to understand and comply with the study's requirements for their child.

Exclusion Criteria:

1. Participation in any other investigational drug trial or use of other investigational drugs at the time of enrollment, or within 5 elimination half-lives of enrollment, or within 30 days of enrollment, whichever is longer; or longer if required by local regulations.
2. History of hypersensitivity to any of the study drugs or its excipients or to drugs of similar chemical classes.
3. Any secondary IgAN as defined by the investigator; secondary IgAN can be associated with cirrhosis, celiac disease, Human Immunodeficiency Virus (HIV) infection, Herpes Simplex virus infection, dermatitis herpetiformis, seronegative arthritis, small-cell carcinoma, lymphoma, disseminated tuberculosis, bronchiolitis obliterans, inflammatory bowel disease, and familial mediterranean fever before treatment.
4. A clinical diagnosis of IgA vasculitis (IgAV or Henoch-Schoenlein purpura) based on typical palpable purpura with or without arthralgia and abdominal pain.
5. Evidence of significant urinary obstruction or difficulty in voiding, any urinary tract disorder causing significant urinary obstruction or difficulty in voiding at Screening and confirmed at Baseline/Day 1.
6. Concurrent diagnosis of CKD other than IgAN at Screening and before first study drug administration.
7. Current acute kidney injury (AKI) defined by Acute Kidney Injury Network (AKIN) criteria within 4 weeks of Screening.
8. Presence of rapidly progressive glomerulonephritis (RPGN) as defined by 50% decline in eGFR within 3 months prior to Screening or during Screening and Run-in periods.
9. Presence of nephrotic syndrome at Screening based on the investigator's judgement.
10. BNP value of >200 pg/mL at Screening.
11. Hemoglobin below 9 g/dL at Screening or prior history of blood transfusion for anemia within 3 months of Screening.
12. Platelet count \<80,000/μL at Screening.
13. On Day 1 participants' body weight falls below the lower limit of the cohort in which the participant was initially screened and lower body weight cohort is not open for enrollment.
14. Known history of congenital heart disease, heart failure or clinically significant fluid retention such as pulmonary edema, uncontrolled peripheral edema, pleural effusion, or ascites before treatment.
15. Current use of any homeopathic and/or herbal medications for the treatment of IgAN disease , such as but not limited to Tripterygium wilfordii (Lei Gong Teng), Caulis sinomenii and Sinomenium acutum before treatment.
16. History of an alcohol or illicit drug-related disorder within the past 3 years at Screening.
17. Confirmed blood pressure >150 mmHg systolic or >95 mmHg diastolic for 12 to \<18 years of age; >140 mmHg systolic or >90 mmHg diastolic for 6 to \<12 years of age; >120 mmHg systolic or >80 mmHg diastolic for 2 to \<6 years of age; based on the mean of 3 measurements obtained at Screening; or clinically significant hypotension at screening.

18. Participants previously treated with immunosuppressive or other immunomodulatory agents such as but not limited to cyclophosphamide, rituximab, infliximab, canakinumab, mycophenolate mofetil (MMF) or mycophenolate sodium (MPS), calcineurin inhibitors, complement inhibitors, oral budesonide in any dose, systemic corticosteroid exposure ≥0.5 mg/kg/day or > 7.5 mg total exposure in a single day of prednisone/prednisolone equivalent within 120 days (or 180 days for rituximab) prior to first study drug administration.

    Participants treated with endothelin (receptor) antagonists (including sparsentan) within 120 days prior to first study drug administration.

19. History of organ transplantation (subjects with history of corneal transplant are not excluded) before treatment.
20. Major concurrent comorbidities before treatment including but not limited to advanced cardiac disease (e.g., NYHA class III (for ages 6 to \<18 years), Ross class III (for ages 2 to \<6years)), severe pulmonary disease (e.g., WHO class III (for age 17 years); Pulmonary Vascular Research Institute (PVRI) class III (for 2-\<17 years)), or hepatic disease (e.g., active hepatitis) that in the opinion of the investigator precludes subject's participation in the study.
21. Any medical condition deemed likely to interfere with the subject's participation in the study before treatment.
22. Active systemic bacterial, viral (including COVID-19) or fungal infection within 14 days prior to study drug administration.
23. Presence of fever ≥ 38°C (100.4°F) within 7 days prior to study drug administration.
24. Human immunodeficiency virus (HIV) infection (known history of HIV or test positive for HIV antibody at Screening).

25. Liver disease, such as active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection defined as Hepatitis B surface antigen (HBsAg) positive or Hepatitis C virus ribonucleic acid (HCV-RNA) positive at Screening, or liver injury as indicated by abnormal liver function tests at Screening and Baseline as defined below:

    • Any single parameter of ALT, AST, GGT, alkaline phosphatase must not exceed 3X upper limit of normal (ULN)
    • Serum bilirubin must not exceed 2X ULN
26. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in situ cervical cancer treated with curative intent), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases; for children aged 2 to \<5 years of age, history of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in situ cervical cancer), treated or untreated, inclusive of malignancies diagnosed at birth and during the neonatal and childhood time, regardless of whether there is evidence of local recurrence or metastases.
27. Pregnant or nursing (lactating) female participants (of childbearing potential), where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test at Screening.
28. Subjects taking prohibited therapies before treatment.
29. Women of childbearing potential, defined as all women physiologically capable of becoming pregnant from menarche until becoming post-menopausal, unless they are using highly effective methods of contraception (failure rate \< 1% per year) while taking study treatment and for 1 month after stopping study treatment.

Highly effective contraception methods include:

• Total abstinence (when this is in line with the preferred and usual lifestyle of the participant). Note that periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
• Bilateral oophorectomy with or without hysterectomy, total hysterectomy or bilateral salpingectomy at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment are they considered to be not of childbearing potential.
• Bilateral tubal occlusion, Bilateral tubal ligation (at least six weeks before taking study treatment).
• Sterilization (vasectomy) of male partner(s) of the female participant at least 6 months prior to screening provided partner(s) has(have) received medical confirmation of surgical success.
• Use of hormonal contraception methods:
• Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation; oral, intravaginal or transdermal.
• Progestogen-only hormonal contraception (where inhibition of ovulation is not the primary or only mode of action): oral, injectable or implantable.
• Intrauterine device (IUD) or intrauterine hormone-releasing system (IUS) In case of use of hormonal contraception, women should have been stable on the same method for a minimum of 3 months before taking study treatment. If local regulations are more stringent than the contraception methods listed above, local regulations apply and will be described in the ICF. 30. For fertile male participants, participants must not intend to father a child or donate sperm while taking study treatment and at least 1 month afterward for males.
• All fertile male participants in a sexual relationship with a WOCBP must agree to the use of a condom during the trial and for up to one month after last study drug administration. A male participant is considered fertile after puberty unless permanently sterile by bilateral orchidectomy/orchiectomy.