Study of Sparsentan in Patients With Primary Focal Segmental Glomerulosclerosis (FSGS)

Phase 3

Active, not recruiting

• Conditions: Focal Segmental Glomerulosclerosis
• Interventions: Drug: Irbesartan; Drug: sparsentan

• Registration Number: NCT03493685
• Lead Sponsor: Travere Therapeutics, Inc.

Brief Summary

To determine the long-term nephroprotective potential of treatment with sparsentan as compared to an angiotensin receptor blocker in patients with primary and genetic focal segmental glomerulosclerosis (FSGS).

Detailed Description

This is a randomized, multicenter, double-blind, parallel, active-control study. Approximately 300 patients aged 8 to 75 years (inclusive) will be enrolled in the study. The study will be conducted in approximately 300 study centers, globally. The investigational drug (sparsentan) is a dual-acting angiotensin receptor blocker and endothelin receptor antagonist. The active control is irbesartan. Patients who meet eligibility criteria will require washout from renin-angiotensin-aldosterone system (RAAS) blockers, if applicable prior to their first dose of study drug.

Patients will be randomly assigned in a 1:1 ratio to receive either sparsentan or active control (irbesartan).

After completing the double-blind portion of the study, patients may participate in the open-label extension for treatment with sparsentan if they meet eligibility criteria.

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations
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Related News

Study Timeline

• Study First Submitted: 2018-04-03
• Study First Submitted QC: 2018-04-03
• Study First Posted: 2018-04-10
• Study Start: 2018-04-17
• Primary Completion: 2023-03-20
• Results First Submitted: 2024-03-15
• Results First Submitted QC: 2024-04-27
• Results First Posted: 2024-04-30
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-30
• Last Update Posted: 2024-11-18
• Study Completion: 2026-02

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 371

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Irbesartan	Irbesartan	Irbesartan will be administered as a single oral dose; an initial dose of 150 mg daily titrating up to a target dose of 300 mg, daily
sparsentan for double-blind and open-label extension	sparsentan	Sparsentan will be administered as a single oral dose; an initial dose of 400 mg daily titrating up to a target dose of 800 mg, daily

Primary Outcome Measures

Name	Time	Method
Slope of Estimated Glomerular Filtration Rate (eGFR)	From Day 1 to Week 108	The total eGFR slope over 2 years, defined as the slope of eGFR following initiation of randomized treatment (ie, Day 1 to Week 108). Estimates are calculated from a mixed-effects model with treatment, Baseline eGFR, analysis visit, treatment-by-analysis visit, randomization stratification factors as fixed effects, and intercept and slope for each participant as a random effect.
Percentage of Participants Achieving FSGS Partial Remission Endpoint (FPRE)	Week 36	Percentage of participants achieving FPRE, defined as urine protein-to-creatinine ratio (UP/C) ≤1.5 grams/gram (g/g) (170 milligrams per millimoles \[mg/mmol\]) and a \>40% reduction from Baseline was analyzed using a generalized linear model to model probability of achieving FPRE. Missing responses were imputed prior to analysis using multiple imputation. A generalized linear model with appropriate link function was implemented with Baseline log (UP/C), treatment, analysis visit, treatment by analysis visit interaction, and randomization strata as fixed effects. For estimates of probability of achieving FPRE, risk difference, and odds ratio, binomial distribution with logit link was used. For relative risk, Poisson distribution with log link was used. Using Rubin's approach, estimated treatment effects are combined across all imputations to obtain overall estimates for probabilities.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in eGFR to 4 Weeks Post-cessation of Randomized Treatment	Baseline (Day 1) to Week 112	The change from Baseline to 4 weeks post-cessation of randomized treatment (Week 112) was analyzed via an analysis of covariance (ANCOVA) model on the natural log(eGFR) with treatment, Baseline eGFR, and randomization strata as fixed effects. Only participants who completed the 108-week treatment period were included. Estimated LS Mean and 95% CI are converted to percentages as follows: \[exponential (LS mean change from baseline in natural log(eGFR)) minus 1\] multiplied by 100. Baseline (Day 1) was defined as the last non-missing assessment prior to and including the first administration of study medication in the study including unscheduled assessments. Percent change from Baseline was calculated as "\[(Post Baseline minus Baseline value)/ Baseline value\] multiplied by 100.
Slope of eGFR Following the Initial Acute Effect of Randomized Treatment	From Week 6 to Week 108	The chronic eGFR slope over 2 years, defined as the slope of eGFR following the initial acute effect of randomized treatment (ie, Week 6 to Week 108). Estimates were calculated from a mixed-effects model with linear spline (ie, change point at Week 6), which included treatment, Baseline eGFR, time from Baseline (TFB) (weeks), time from change point (TFCP) (weeks), treatment-by-TFB and treatment-by-TFCP interactions, and randomization stratification factors as fixed effects, intercept and slopes as random effects. The slope difference was tested by the null hypothesis that the sum of the treatment-by-TFB and treatment-by-TFCP interactions = 0.

Trial Locations

Locations (1)

Travere Investigational Site; 🇬🇧 York, United Kingdom