A Study of the Effect and Safety of Sparsentan in the Treatment of Patients With IgA Nephropathy (PROTECT)

• Sponsor: Retrophin, Inc.
• Information provided by (Responsible Party): Retrophin, Inc.

Study Description

Brief Summary:

To determine the long-term (approximately 2 years) nephroprotective potential of treatment with sparsentan as compared to an angiotensin receptor blocker in patients with immunoglobulin A nephropathy (IgAN).

Condition or disease	Intervention/treatment	Phase
Immunoglobulin A Nephropathy	Drug: sparsentan; Drug: irbesartan	Phase 3

Detailed Description:

This is a randomized, multicenter, double-blind, parallel-group, active-control study. Approximately 280 patients aged ≥18 years will be enrolled in the study globally. The investigational drug (sparsentan) is a dual acting angiotensin receptor blocker and endothelin receptor antagonist. The active control is irbesartan.

The purpose of the study is to evaluate the potential benefit of sparsentan on kidney function by analyzing change in proteinuria (protein in urine) and estimated glomerular filtration rate (eGFR) as compared to current standard treatment.

Patients enrolled in the PROTECT study (Protocol 021IGAN17001) will be those at high risk of progressing to renal failure. They will be randomly assigned n a 1:1 ratio to either sparsentan or irbesartan, as the active control (current standard treatment) at the Day 1 (Randomization) visit. Study medication (sparsentan and irbesartan) will be administered as a single oral morning dose.

The primary analysis is change in proteinuria (urine protein/creatinine ratio) from baseline at Week 36 in sparsentan-treated patients as compared to irbesartan-treated patients.

Study Design

Layout table for study information

Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	280 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Investigator)
Primary Purpose:	Treatment
Official Title:	A Randomized, Multicenter, Double-blind, Parallel-group, Active-control Study of the Efficacy and Safety of Sparsentan for the Treatment of Immunoglobulin A Nephropathy
Actual Study Start Date :	December 20, 2018
Estimated Primary Completion Date :	March 2023
Estimated Study Completion Date :	April 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: sparsentan; Sparsentan will be administered daily as a 200-mg oral tablet, over-encapsulated (blinded) size 00 capsule for the first 2 weeks of the study following randomization. For patients who tolerate the initial dose of 200 mg after 2 weeks will increase their dose to 400 mg and continue treatment to Week 110.	Drug: sparsentan; Target dose of 400 mg daily; Other Name: RE-021
Active Comparator: irbesartan; Irbesartan will be administered daily as a 150-mg oral tablet, over-encapsulated (blinded) size 00 capsule for the first 2 weeks of the study following randomization. For patients who tolerate the initial dose of 150 mg after 2 weeks will increase their dose to 300 mg and continue treatment to Week 110.	Drug: irbesartan; Target dose of 300 mg daily; Other Name: Irbesartan Tablets USP

Outcome Measures

Primary Outcome Measures :

1. Urine protein/creatinine ratio (UP/C) at Week 36 [ Time Frame: After the last patient randomized has undergone the Week 36 visit ]
   The primary efficacy endpoint is the change from baseline in the urine protein/creatinine ratio (UP/C), based on a 24-hour urine sample, at Week 36.

Secondary Outcome Measures :

1. Overall eGFR change from baseline [ Time Frame: Week 114 post-randomization ]
   Change in eGFR from baseline (Week 0) to 4 weeks post-cessation of randomized treatment (Week 114).
2. eGFR over a 52-week period [ Time Frame: Week 58 post-randomization ]
   The rate of change in estimated glomerular filtration rate (eGFR) over a 52-week period following the initial acute effect of randomized therapy (the initial acute effect of randomized therapy is defined as the first 6 weeks of randomized treatment with study medication; thus, the analysis is from 6 weeks post-randomization to 58 weeks post-randomization).
3. eGFR over a 104-week period [ Time Frame: Week 110 post-randomization ]
   The rate of change in estimated glomerular filtration rate (eGFR) over a 104-week period following initial acute effect of randomized therapy (the initial acute effect of randomized therapy is defined as the first 6 weeks of randomized treatment with study medication; thus, the analysis is from 6 weeks post-randomization to 110 weeks post-randomization).

Eligibility Criteria

Layout table for eligibility information

Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Key Inclusion Criteria:

• Age 18 years or older at screening
• Biopsy-proven primary IgAN
• Proteinuria of >=1 g/day at screening
• eGFR >=30 mL/min/1.73 m2 at screening
• Currently on stable dose of ACEI and/or ARB therapy, for at least 12 weeks prior to screening (maximum tolerated dose and at least one-half of the maximum labeled dose)
• Systolic BP <=150 mmHg and diastolic BP <=100 mmHg at screening
• Agree to contraception

Key Exclusion Criteria:

• IgAN secondary to another condition
• Presence of cellular glomerular crescents in >25% of glomeruli on renal biopsy (if biopsy available within 6 months of screening)
• History of type 1 diabetes mellitus, uncontrolled type 2 diabetes mellitus (HbA1c >8%), or nonfasting blood glucose >180 mg/dL at screening
• History of organ transplantation, with exception of corneal transplants
• Require any prohibited medications
• Treatment of systemic immunosuppressive medications (including corticosteroids) for >2 weeks within 3 months of screening
• History of heart failure or previous hospitalization for heart failure or unexplained dyspnea, orthopnea, paroxysmal nocturnal dyspnea, ascites, and/or peripheral edema
• Clinically significant cerebrovascular disease or coronary artery disease within 6 months of screening
• Jaundice, hepatitis, or known hepatobiliary disease or elevations of transaminases (ALT/AST) >2 times upper limit of normal at screening
• History of malignancy other than adequately treated basal cell or squamous cell skin cancer or cervical carcinoma within the past 2 years
• Hematocrit value <27% or hemoglobin value <9 g/dL at Screening
• Potassium >5.5 mEq/L at Screening
• History of alcohol of illicit drug use disorder
• 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
• For female: Pregnancy, or planning to become pregnant during the course of the study, or breastfeeding
• For male: planning to father a child during the course of the study
• Participation in a study of another investigational product within 28 days of screening

Contacts and Locations

Contacts

Layout table for location contacts

Contact: Retrophin Call Center	1-877-659-5518	medinfo@retrophin.com
Contact: Michelle Greenman	1-760-288-8062	michelle.greenman@retrophin.com

  Show 66 Study Locations

Sponsors and Collaborators

Retrophin, Inc.

Investigators

Layout table for investigator information

Study Director:	Radko Komers, MD, PhD	Retrophin, Inc.

More Information

Additional Information:

Sponsor Website 

Layout table for additonal information

Responsible Party:	Retrophin, Inc.
ClinicalTrials.gov Identifier:	NCT03762850 History of Changes
Other Study ID Numbers:	021IGAN17001
First Posted:	December 4, 2018
Last Update Posted:	April 5, 2019
Last Verified:	April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Layout table for additional information

Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

Additional relevant MeSH terms:

Layout table for MeSH terms

Kidney Diseases; Glomerulonephritis, IGA; Urologic Diseases; Glomerulonephritis; Nephritis; Autoimmune Diseases	Immune System Diseases; Irbesartan; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Molecular Mechanisms of Pharmacological Action