A Study of the Effect and Safety of Sparsentan in the Treatment of Patients With IgA Nephropathy (PROTECT)
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|ClinicalTrials.gov Identifier: NCT03762850|
Recruitment Status : Active, not recruiting
First Posted : December 4, 2018
Last Update Posted : April 27, 2023
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|Condition or disease||Intervention/treatment||Phase|
|Immunoglobulin A Nephropathy||Drug: sparsentan Drug: irbesartan Drug: Dapagliflozin||Phase 3|
This is a 114-week,randomized, multicenter, double-blind, parallel-group, active-control study with an open-label extension period of up to 156 weeks, for a total duration of up to 270 weeks in patients with IgAN who have persistent overt proteinuria and remain at high risk of disease progression despite being on a stable dose (or doses) of an angiotensin-converting enzyme inhibitor (ACEI) and/or angiotensin receptor blocker (ARB) that is (are) a maximum tolerated dose that is at least one half of the maximum labeled dose (MLD) (according to approved labeling. Approximately 380 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 in 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.
Primary completion date represents the anticipated completion date of the double-blind portion of the study. Study completion date represents the anticipated completion date of the open-label extension portion of the study.
Patients participating in the open-label extension period may be evaluated for eligibility to participate in a randomized, open-label, controlled Sub study evaluating the safety and efficacy of an SGLT2 inhibitor in addition to stable sparsentan treatment (OLE Sub study). The SGLT2 inhibitor, dapagliflozin will be provided as "study medication" for the OLE Sub study. Following completion of the visit 12 weeks after the OLE baseline visit, eligible patients may receive open-label dapagliflozin for at least 12 weeks but up to 24 additional weeks, or through the end of the open-label extension period, whichever is shortest. Approximately 60 patients from the open-label extension period will be enrolled into the OLE Sub study.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||380 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|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 11, 2018|
|Estimated Primary Completion Date :||August 2023|
|Estimated Study Completion Date :||July 2026|
Double-blind: 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.
Target dose of 400 mg daily
Other Name: RE-021
Active Comparator: irbesartan
Double-blind: 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.
Target dose of 300 mg daily
Other Name: Irbesartan Tablets USP
Experimental: dapagliflozin + sparsentan (Sub study)
OLE Sub study: Dapagliflozin will be administered daily as a 5-mg oral tablet, in addition to 400-mg of Sparsentan, for a period of 12 weeks.
Target dose of 400 mg daily
Other Name: RE-021
Target dose of 10 mg daily
Experimental: sparsentan (Sub Study)
OLE Sub study: Sparsentan will be administered daily as a dose of 400-mg for a period of 12 weeks.
Target dose of 400 mg daily
Other Name: RE-021
- 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 (Day 1) in the UP/C based on a 24-hour urine sample at Week 36.
- eGFR over a 52-week period [ Time Frame: Week 58 postrandomization ]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 postrandomization to 58 weeks postrandomization eGFR chronic slope at 1 year.)
- eGFR over a 104-week period [ Time Frame: Week 110 postrandomization ]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 postrandomization to 110 weeks postrandomization eGFR chronic slope at 2 years.)
- eGFR over a 110-week period [ Time Frame: Week 110 postrandomization ]The rate of change in eGFR over a 110-week (approximately 2 years) period following the initiation of randomized therapy (thus, the analysis is from Day 1 to 110 weeks postrandomization eGFR total slope at 2 years).
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
Key Inclusion Criteria for the Double-Blind Period:
- 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
- Willing to undergo change in ACEI and/or ARB and anti-hypertensive medications
- Agree to contraception
Key Exclusion Criteria for the Double-Blind Period:
- 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)
- Chronic kidney disease (CKD) in addition to IgAN
- 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% (0.27 V/V) or hemoglobin value <9 g/dL (90 g/L) at Screening
- Potassium >5.5 mEq/L (5.5 mmol/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
- Participation in a study of another investigational product within 28 days of screening
Key Inclusion Criteria for the Open-Label Extension Period based on assessments at the Week 110 visit:
- Completed participation in the double-blind period, including the Week 114 visit
- Did not permanently discontinue study medication during the double-blind period
- Agree to contraception
Key Exclusion Criteria for the Open-Label Extension Period based on assessments at the Week 110 and Week 114 visits:
- Progression to end-stage renal disease (ESRD) requiring renal replacement therapy (RRT)
- Development of any criteria for discontinuation of study medication or discontinuation from the study, between Week 110 and Week 114
- Patient was unable to initiate, or developed contraindications to, treatment with RAAS inhibitors between Week 110 and Week 114
- eGFR ≤20 mL/min/1.73 m2 at Week 110
- Female patient is pregnant or breastfeeding
Key Inclusion Criteria for the OLE Sparsentan + SGLT2 Inhibitor Sub study:
- Participating in the open-label extension and is willing and able to provide signed informed consent for participation in the open-label extension period Sub study
- A urine protein excretion value of ≥0.3 g/day.
- An eGFR of ≥25 mL/min/1.73m2
- On a stable dose of sparsentan for ≥8 weeks in the open-label extension period that is the maximum tolerated dose.
Key Exclusion Criteria for the OLE Sparsentan + SGLT2 Inhibitor Sub study:
- Progressed to ESRD requiring RRT
- Initiated or changed dose of a systemic immunosuppressive medication (including systemic steroids) within 12 weeks
- Taking an SGLT2 inhibitor within 12 weeks
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03762850
|Study Director:||Priscila Preciado, MD||Travere Therapeutics, Inc.|
|Responsible Party:||Travere Therapeutics, Inc.|
|Other Study ID Numbers:||
2017-004605-41 ( EudraCT Number )
|First Posted:||December 4, 2018 Key Record Dates|
|Last Update Posted:||April 27, 2023|
|Last Verified:||February 2023|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
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