| Eligibility |
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.
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