Study of Sparsentan in Patients With Primary Focal Segmental Glomerulosclerosis (FSGS) (DUPLEX)
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| ClinicalTrials.gov Identifier: NCT03493685 |
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Recruitment Status :
Active, not recruiting
First Posted : April 10, 2018
Last Update Posted : October 31, 2022
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Focal Segmental Glomerulosclerosis | Drug: sparsentan Drug: Irbesartan | Phase 3 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 371 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | A Randomized, Multicenter, Double-blind, Parallel, Active-control Study of the Effects of Sparsentan, a Dual Endothelin Receptor and Angiotensin Receptor Blocker, on Renal Outcomes in Patients With Primary FSGS |
| Actual Study Start Date : | April 17, 2018 |
| Estimated Primary Completion Date : | February 2023 |
| Estimated Study Completion Date : | February 2026 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: sparsentan for double-blind and open-label extension
Sparsentan will be administered as a single oral morning dose; an initial dose of 400 mg daily titrating up to a target dose of 800 mg, daily
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Drug: sparsentan
Double-blind period: target dose of 800 mg daily; Open-label extension: target dose based on dosage from week 114 daily
Other Name: RE-021 |
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Active Comparator: Irbesartan
Irbesartan will be administered as a single oral morning dose; an initial dose of 150 mg daily titrating up to a target dose of 300 mg, daily
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Drug: Irbesartan
target dose of 300 mg daily
Other Name: Irbesartan Tablets USP |
- Slope of estimated glomerular filtration rate (eGFR) [ Time Frame: Week 108 ]The slope of eGFR from Day 1 to Week 108. (Secondary outcome measure in non-US countries)
- Proportion of patients achieving a urine protein/creatinine (UP/C) ≤1.5 g/g and a >40% reduction [ Time Frame: Week 36 ]Proportion of patients achieving a UP/C ≤1.5 g/g and a >40% reduction from baseline in UP/C at Week 36
- Slope of eGFR [ Time Frame: Week 6 to Week 108 ]The slope of eGFR from 6 weeks post randomization at Week 108. (Primary outcome in non-US countries)
- Change in eGFR from baseline [ Time Frame: Week 112 ]Change in eGFR from baseline to 4 weeks post-cessation of treatment at Week 112. (Percent change in eGFR in non-US countries)
- Non-US countries: Percent change in eGFR [ Time Frame: Week 6 to Week 108 ]Percent change from Week 6 in eGFR at Week 108
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 8 Years to 75 Years (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Key Inclusion Criteria for the Double-blind Period:
- Sites within the US and UK: The patient is male or female aged 8 to 75 years, inclusive, weighing ≥20 kg at screening
- Sites outside the US and UK: The patient is male or female aged 18 to 75 years, inclusive, weighing ≥20 kg at screening
- Biopsy-proven focal segmental glomerulosclerosis (FSGS) lesion(s) or documentation of a genetic mutation in a podocyte protein associated with FSGS.
- Urine protein/creatinine (UP/C) ≥1.5 g/g (170 mg/mmol) at screening
- eGFR ≥30 mL/min/1.73 m2 at screening.
- Women of childbearing potential must agree to the use of one highly reliable method of contraception from 7 days prior to the first dose of study medication until 90 days after the last dose of study medication, plus one additional barrier method during sexual activity
Key Exclusion Criteria for the Double-blind Period:
- FSGS secondary to another condition
- Positive serological tests of another primary or secondary glomerular disease not consistent with a diagnosis of primary or genetic FSGS
- History of type 1 diabetes mellitus, uncontrolled type 2 diabetes mellitus, or nonfasting blood glucose >180 mg/dL (10.0 mmol/L)
- Treated with rituximab, cyclophosphamide, or abatacept within ≤3 months prior to screening; if taking other chronic immunosuppressive medications, the dosage must be stable prior to screening
- Documented history of heart failure, coronary artery disease, or cerebrovascular disease
- Significant liver disease
- Positive at screening for the human immunodeficiency virus or markers indicating acute or chronic hepatitis B virus infection or hepatitis C infection
- History of malignancy other than adequately treated basal cell or squamous cell skin cancer or cervical carcinoma within the past 2 years
- Screening hematocrit value <27% (0.27 L/L) or hemoglobin value <9 g/dL (90 g/L)
- Screening potassium value of >5.5 mEq/L (5.5 mmol/L)
- Extreme obesity (ie, ≥18 years of age with a body mass index (BMI) >40, or is <18 years of age with a BMI in the 99th percentile plus 5 units at screening, in whom there is a causal relationship between obesity and the development of FSGS
- History of alcohol or illicit drug use disorder
- History of serious side effect or allergic response to any angiotensin II antagonist or endothelin receptor antagonist
- Female patient is pregnant, plans to become pregnant during the course of the study, or is breastfeeding.
Key Inclusion Criteria for the Open-label Extension Based on assessments at the Week 108 visit:
- Complete participation in the double-blind period, including the Week 112 visit.
- Patient received blinded study medication through the duration of the double-blind period (ie, did not permanently discontinue study medication)
Key Exclusion Criteria for the Open-label Extension Based on Assessments at Week 108 and 112 visits:
- Progression to end-stage renal disease requiring replacement therapy
- The patient developed criteria for discontinuation between Week 108 and Week 112
- The patient was unable to initiate, or developed contraindications to, treatment with RAAS inhibitors between Week 108 and Week 112
- eGFR ≤20 mL/min/1.73 m2 at Week 108
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): NCT03493685
Show 225 study locations
| Study Director: | Priscila Preciado, MD | Travere Therapeutics, Inc. |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Travere Therapeutics, Inc. |
| ClinicalTrials.gov Identifier: | NCT03493685 |
| Other Study ID Numbers: |
021FSGS16010 |
| First Posted: | April 10, 2018 Key Record Dates |
| Last Update Posted: | October 31, 2022 |
| Last Verified: | October 2022 |
| 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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Glomerulosclerosis, Focal Segmental Glomerulonephritis Nephritis Kidney Diseases Urologic Diseases |
Irbesartan Antihypertensive Agents Angiotensin II Type 1 Receptor Blockers Angiotensin Receptor Antagonists Molecular Mechanisms of Pharmacological Action |