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

Phase 3

Active, not recruiting

• Conditions: Immunoglobulin A Nephropathy
• Interventions: Drug: sparsentan; Drug: irbesartan; Drug: Dapagliflozin

• Registration Number: NCT03762850
• Lead Sponsor: Travere Therapeutics, Inc.

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).

Detailed Description

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 Timeline

• Study First Submitted: 2018-11-27
• Study First Submitted QC: 2018-11-30
• Study First Posted: 2018-12-04
• Study Start: 2018-12-11
• Primary Completion: 2023-08-07
• Results First Submitted: 2024-06-11
• Results First Submitted QC: 2024-06-11
• Results First Posted: 2024-07-03
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-30
• Last Update Posted: 2024-11-18
• Study Completion: 2026-07

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 406

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
dapagliflozin + sparsentan (Sub study)	sparsentan	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.
dapagliflozin + sparsentan (Sub study)	Dapagliflozin	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.
irbesartan	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.
sparsentan	sparsentan	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.
sparsentan (Sub Study)	sparsentan	OLE Sub study: Sparsentan will be administered daily as a dose of 400-mg for a period of 12 weeks.

Primary Outcome Measures

Name	Time	Method
Percent Change From Baseline in the Urine Protein/Creatinine (UP/C) at Week 36	Baseline (Day 1) and at Week 36	24-hour urine sample was collected for analysis of UP/C via a mixed-model repeated-measures (MMRM) analysis. Missing responses were imputed prior to analysis using multiple imputation. Change from Baseline during the double-blind period in UP/C on the log scale was the dependent variable. Log Baseline UP/C was included as a covariate along with fixed effects for randomized treatment, time (ie, nominal visit in weeks), randomized treatment-by-time interaction, and randomization strata with participants as random effect. Estimates in log scale were back transformed. Baseline was defined as the last non-missing observation on or prior to the start of the dosing. Using Rubin's approach, estimated treatment effects are combined across all imputations to obtain overall estimates.

Secondary Outcome Measures

Name	Time	Method
Annualized Slope of eGFR Following the Initial Acute Effect of Randomized Treatment (Chronic Slope)	From Week 6 to Week 110 post randomization	The rate of change in eGFR from Week 6 to Week 110 (ie, over 104 weeks following the initial acute effect of randomized therapy) was analyzed via a mixed-model random coefficients analysis. Missing responses were imputed prior to analysis using multiple imputation. Fixed effects for randomized treatment, Baseline eGFR, time (in weeks), randomized treatment-by-time interaction, and randomization strata were included. In addition, the model also included a random intercept and random slope for each participant. Using Rubin's approach, the estimated treatment effects are combined across all imputations to obtain the overall estimates.
Total Slope of Estimated Glomerular Filtration Rate (eGFR) Over a 110-week Period	From Day 1 to Week 110	The rate of change in eGFR from Day 1 to Week 110 (ie, over 110 weeks) was analyzed via a mixed-model random coefficients analysis. Missing responses were imputed prior to analysis using multiple imputation. Fixed effects for randomized treatment, Baseline eGFR, time (in weeks), randomized treatment-by-time interaction, and randomization strata were included. In addition, the model also included a random intercept and random slope for each participant. Using Rubin's approach, the estimated treatment effects are combined across all imputations to obtain the overall estimates.

Trial Locations

Locations (1)

Travere Investigational Site; 🇬🇧 London, United Kingdom