Effectiveness and Safety of Sparsentan as treatment for Immunoglobulin A Nephropathy (IgAN)

Phase 1

• Conditions: Immunoglobulin A Nephropathy (IgAN); MedDRA version: 20.0Level: PTClassification code 10021263Term: IgA nephropathySystem Organ Class: 10038359 - Renal and urinary disorders; Therapeutic area: Diseases [C] - Symptoms and general pathology [C23]

• Registration Number: EUCTR2017-004605-41-ES
• Lead Sponsor: Retrophin, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-07-30
• Last Update Posted: 26 November 2018

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 280

Inclusion Criteria

1. The patient is willing and able to provide signed informed consent.
2. The patient is male or female, aged >=18 years.
3. The patient has biopsy-proven primary IgAN. The biopsy may have been performed at any time in the past.
4. The patient has a urine total protein value >=1.0 g/day at screening.
5. The patient has an eGFR >=30 mL/min/1.73 m2 at screening.
6. The patient has been on a stable dose of ACEI and/or ARB therapy for at least 12 weeks prior to screening that is:
A. the patient’s maximum tolerated dose, AND
B. at least one-half of the maximum labeled dose (according to approved labeling).
7. In the Investigator’s opinion, the patient’s blood pressure has been managed in accordance with standard of care using ACEI and/or ARB therapy as described in Inclusion Criterion #6 and additional antihypertensive agents if needed. At screening, the patient’s systolic blood pressure must be <=150 mmHg and diastolic blood pressure must be <=100 mmHg.
8. The patient is willing to undergo a change in ACEI and/or ARB and antihypertensive medications.
9. Women of childbearing potential (WOCBP) must agree to the simultaneous use of 2 medically accepted methods of contraception from randomization until 90 days after the last dose of study medication. At least one method of contraception must be highly reliable (ie, can achieve a failure rate of <1% per year), such as 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. The other method of contraception must be a barrier method, such as a diaphragm with spermicide or male partner’s use of male condom with spermicide. WOCBP are defined as those who are fertile, following menarche and until becoming postmenopausal unless permanently sterile; permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as amenorrhea 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 (urine, with positive results confirmed by serum) at screening and randomization.
10. Males must be surgically sterile (more than 3 months post-vasectomy) or must agree to the use of medically accepted methods of contraception that are considered highly reliable from randomization until 90 days after the last dose of study medication.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 260
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion Criteria

1. The patient has IgAN secondary to another condition (eg, systemic lupus erythematosus, liver cirrhosis) or Henoch-Schonlein purpura.
2. The patient has cellular glomerular crescents present in >25% of glomeruli on renal biopsy within 6 months prior to screening.
3. The patient has a history of type 1 diabetes mellitus, uncontrolled type 2 diabetes mellitus (hemoglobin A1c [HbA1c] >8%), or nonfasting blood glucose >180 mg/dL at screening.
4. The patient has undergone any organ transplantation, with the exception of corneal transplants.
5. The patient requires any of the prohibited concomitant medications.
6. The patient has been taking any systemic immunosuppressive medications (including corticosteroids) for >2 weeks within 3 months prior to screening.
7. The patient has a documented history of heart failure (New York Heart Association Class II-IV) and/or previous hospitalization for heart failure or unexplained dyspnea, orthopnea, paroxysmal nocturnal dyspnea, ascites, and/or peripheral edema.
8. The patient has clinically significant cerebrovascular disease (transient ischemic attack or stroke) and/or coronary artery disease (hospitalization for myocardial infarction or unstable angina, new onset of angina with positive functional tests, coronary angiogram revealing stenosis, or a coronary revascularization procedure) within 6 months prior to screening.
9. The patient has jaundice, hepatitis, or known hepatobiliary disease (including asymptomatic cholelithiasis), or alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >2 times the upper limit of the normal range at screening.
10. 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.
11. The patient has a screening hematocrit value <27% or hemoglobin value <9 g/dL.
12. The patient has a screening potassium value of >5.5 mEq/L.
13. 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).
14. The patient has a history of serious side effect or allergic response to any angiotensin II antagonist or endothelin receptor antagonist, including sparsentan or irbesartan, or has a hypersensitivity to any of the excipients in the study medications.
15. The female patient is pregnant, plans to become pregnant during the course of the study, or is breastfeeding.
16. The male patient plans to father a child during the course of the study.
17. The patient has participated in a study of another investigational product within 28 days prior to screening, or plans to participate in such a study during the course of this study.
18. The patient, in the opinion of the Investigator, is unable to adhere to the requirements of the study, including the ability to swallow the study medication capsules whole.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified