A Study of the Safety and Activity of Sparsentan for the Treatment of Patients With Immunoglobulin A Nephropathy

For Cohort A (Patients with Incident IgAN) Inclusion Criteria: * The patient is willing and able to provide signed informed consent. * The patient can understand written and spoken English. * The patient is male or female, aged ≥18 years. * The patient has been diagnosed with biopsy-proven IgAN within the last 6 months (calculated from the date of kidney biopsy, upon which the IgAN-positive diagnosis was made, to the signing of the informed consent form). * The patient has a urine total protein value ≥0.5 g/day at screening. * The patient has an eGFR value ≥30 mL/min/1.73 m2 at screening. * The patient has not previously been treated with ACEI and/or ARB therapy for IgAN OR has not received ACEI and/or ARB therapy within the last 12 months. * The patient has a systolic BP ≤150 mmHg and ≥100 mmHg, and diastolic blood pressure ≤100 mmHg and ≥60 mmHg at screening. * Women of childbearing potential (WOCBP), beginning at menarche, must agree to the use of one highly reliable (ie, can achieve a failure rate of \<1% per year) method of contraception from 7 days prior to the first dose of trial medication until 90 days after the last dose of trial medication. Highly reliable contraception methods include stable oral, implanted, transdermal, or injected contraceptive hormones associated with inhibition of ovulation, or an intrauterine device (IUD) in place for at least 3 months. One additional barrier method must also be used during sexual activity, such as a diaphragm or diaphragm with spermicide (preferred), or male partner's use of male condom or male condom with spermicide), from Day 1 until 90 days after the last dose of trial medication. WOCBP are defined as those who are fertile, following menarche and until becoming postmenopausal unless permanently sterile; permanent sterilisation methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. A postmenopausal state is defined as amenorrhoea for more than 24 consecutive months without an alternative medical cause; women on hormone replacement therapy must have a documented plasma follicle-stimulating hormone level ≥40 mIU/mL. All WOCBP must have a negative pregnancy test at Visit 1 (serum test) and Visit 2 (urine, with positive results confirmed by serum). Exclusion Criteria: * The patient has IgAN secondary to another condition (eg, systemic lupus erythematosus, liver cirrhosis). * The patient, in the opinion of the Investigator, has a rapidly progressive glomerulonephritis (rapid decline in GFR and crescents on biopsy). * The patient has a history of type 1 diabetes mellitus, uncontrolled type 2 diabetes mellitus (haemoglobin A1c \[HbA1c\] \>8%), or nonfasting blood glucose \>10 mmol/L (180 mg/dL) at screening. * The patient has undergone any organ transplantation, with the exception of corneal transplants. * The patient requires any of the prohibited concomitant medications (see Section 14.4). * The patient has been taking any systemic immunosuppressive medications for \>2 weeks within 6 months prior to screening. * The patient has a documented history of heart failure (New York Heart Association Class II-IV) and/or previous hospitalisation for heart failure or unexplained dyspnoea, orthopnoea, paroxysmal nocturnal dyspnoea, ascites, and/or peripheral oedema. * The patient has clinically significant cerebrovascular disease (transient ischemic attack or stroke) and/or coronary artery disease (hospitalisation for myocardial infarction or unstable angina, new onset of angina with positive functional tests, coronary angiogram revealing stenosis, or a coronary revascularisation procedure) within 6 months prior to screening. * The patient has jaundice, hepatitis, or known hepatobiliary disease (including asymptomatic cholelithiasis), or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2 times the upper limit of the normal range at screening. * The patient has a history of malignancy other than adequately treated basal cell or squamous cell skin cancer or cervical carcinoma within the past 2 years. * The patient has a screening haematocrit value \<27% or haemoglobin value \<90 g/L (9 g/dL). * The patient has a screening potassium value of \>5.5 mmol/L (5.5 mEq/L). * The patient has a history of alcohol or illicit drug use disorder (as defined in the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition). * The patient has a history of serious side effects or allergic response to any AngII or ERA, including sparsentan, or has a hypersensitivity to any of the excipients in the IMP. * The female patient is pregnant, plans to become pregnant during the course of the trial, or is breastfeeding. * The patient has participated in a trial of any investigational product within 28 days prior to screening, or plans to participate in such a trial during the course of this trial. * The patient, in the opinion of the Investigator, is unable to adhere to the requirements of the trial, including the ability to swallow the IMP whole. * The patient, in the opinion of the Investigator, has a medical condition or abnormal clinically significant laboratory screening value not listed above that may interfere with the evaluation of sparsentan safety or activity. * Patients with a medical condition or abnormal clinically significant laboratory screening value not listed above that may interfere with the evaluation of sparsentan safety or activity will be reviewed before consideration of the patient for enrolment. For Cohort B (Recurrent IgAN following kidney transplantation) Inclusion Criteria: * Male and female aged ≥18 years * Diagnosis of recurrent IgAN based on histological analysis of a transplanted kidney biopsied within the last 6 months * A time period of \>12 months since kidney transplantation * UPCR ≥50 mg/mmol (≥0.44 g/g) and eGFR value ≥25 mL/min/1.73 m2 * For patients on an ACEI and/or ARB, and/or SGLT2 inhibitor, the dosing regimen is stable for at least 6 weeks prior to and during the screening period * Tacrolimus treatment as part of standard of care immunosuppression following kidney transplantation * Systolic BP ≤150 mmHg and ≥100 mmHg, and diastolic blood pressure ≤100 mmHg and ≥60 mmHg at screening. * Female patients not of childbearing potential, or of childbearing potential and agreeing to use the contraceptive methods listed in Section 5.1 Exclusion Criteria: * The patient has recurrent IgAN secondary to another condition or cause (eg, systemic lupus erythematosus, liver cirrhosis). * Evidence of alternative pathology on the kidney transplant biopsy as the main cause for proteinuria (e.g. diabetic nephropathy, chronic transplant glomerulopathy, mTORi treatment) * Patient has multiorgan transplants (with the exception of corneal transplants) * Immunosuppressive therapy (IST) regimen for kidney transplant or other chronic immunosuppressive therapies that is not stable for \>6 weeks prior to Day 1. Exceptions include routine protocol tapering and for tacrolimus, changes in dose to meet target level * Treatment with enteric budesonide (nefecon) within 6 months prior to screening, or planned use of enteric budesonide (nefecon) at any time during the study. * Current treatment for surgical complications * \<3 months after anti-rejection treatment or active rejection * Active bacterial, fungal or viral infection and/or active treatment of infection including BKV, CMV, HIV, Hepatitis B and C \<3 months prior to and during the screening period * Current treatment for surgical complications * Uncontrolled diabetes mellitus (defined by HbA1C \>8% (\>64 mmol/mol) * History of heart failure (New York Heart Association (NYHA) Class II-IV) * Jaundice, hepatitis, or known hepatobiliary disease * Malignancy within the past 2 years with the exception of adequately treated basal cell carcinoma or non-metastatic squamous cell carcinoma of the skin, with no evidence or recurrence * Haematocrit \<27%, haemoglobin \<90 g/L (9 g/dL), or potassium \>5.5 mmol/L (5.5 mEq/L) * History of alcohol or illicit drug use disorder (as defined in the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition) * History of serious side effects or allergic response to any angiotensin II antagonist or endothelin receptor antagonist (ERA) or dual endothelin and angiotensin receptor antagonist (DEARA e.g. sparsentan) * The female patient is pregnant, plans to become pregnant during the course of the study, or is breastfeeding. * The patient has participated in a study of any investigational product within 28 days prior to screening, or plans to participate in such a study during the course of this study. * The patient, in the opinion of the Investigator, is unable to adhere to the requirements of the study, including the ability to swallow the IMP whole. * The patient, in the opinion of the Investigator, has a medical condition or abnormal clinically significant laboratory screening value not listed above that may interfere with the evaluation of sparsentan safety or activity.