A Phase 3 interventional study of sparsentan and irbesartan in Immunoglobulin A Nephropathy, sponsored by Travere Therapeutics, Inc.. Completed at 162 sites in 18 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-14.
Sponsored by Travere Therapeutics, Inc. · Phase 3, Interventional, and Treatment
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).
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.
275 studies on the registry are indexed under Glomerulonephritis, IGA; 107 are open to participants now.
This study's enrollment of 406 is above the median of 62 across 221 interventional studies indexed under Glomerulonephritis, IGA.
Browse Glomerulonephritis, IGA studies →Travere Therapeutics, Inc. is the lead sponsor of 14 studies on the registry; 4 are open to participants now.
Of its 5 completed or terminated interventional studies of FDA-regulated products, 4 (80%) have results posted.
Counted across the registry records on this site, refreshed daily.
Key Inclusion Criteria for the Double-Blind Period:
Key Exclusion Criteria for the Double-Blind Period:
Key Inclusion Criteria for the Open-Label Extension Period based on assessments at the Week 110 visit:
Key Exclusion Criteria for the Open-Label Extension Period based on assessments at the Week 110 and Week 114 visits:
Key Inclusion Criteria for the OLE Sparsentan + SGLT2 Inhibitor Sub study:
Key Exclusion Criteria for the OLE Sparsentan + SGLT2 Inhibitor Sub study:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Drug: sparsentan
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.
Drug: irbesartan
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.
Drug: sparsentan · Drug: Dapagliflozin
OLE Sub study: Sparsentan will be administered daily as a dose of 400-mg for a period of 12 weeks.
Drug: sparsentan
Target dose of 400 mg daily
Also known as: RE-021
Target dose of 300 mg daily
Also known as: Irbesartan Tablets USP
Target dose of 10 mg daily
Percent Change From Baseline in the Urine Protein/Creatinine (UP/C) 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.
Time frame: Baseline (Day 1) and at Week 36
Total Slope of Estimated Glomerular Filtration Rate (eGFR) Over a 110-week Period
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.
Time frame: From Day 1 to Week 110
Annualized Slope of eGFR Following the Initial Acute Effect of Randomized Treatment (Chronic Slope)
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.
Time frame: From Week 6 to Week 110 post randomization
The PROTECT study is a 114-week, randomized, multicenter, double-blind (DB), parallel-group, active control study, in participants with Immunoglobulin A nephropathy (IgAN) who had persistent overt proteinuria and remained at high risk of disease progression despite being on a stable dose (or doses) of an Angiotensin converting enzyme inhibitor (ACEI) and/or Angiotensin II receptor blocker (ARB) that was (were) a maximum tolerated dose
| Milestone | Sparsentan | Irbesartan |
|---|---|---|
| Started | 203 | 203 |
| Received at least 1 dose of study drug | 202 | 202 |
| Completed | 199 | 191 |
| Not completed | 4 | 12 |
| Withdrew: Death | 0 | 1 |
| Withdrew: Lost to follow-up | 0 | 1 |
| Withdrew: Physician decision | 0 | 1 |
| Withdrew: Withdrawal by subject | 4 | 9 |
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.
| Percent change | Sparsentan | Irbesartan |
|---|---|---|
| Percent Change From Baseline in the Urine Protein/Creatinine (UP/C) at Week 36 | -49.77 (-54.98 to -43.95) | -15.05 (-23.72 to -5.39) |
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.
| milliliters/minute/1.73square meter/year | Sparsentan | Irbesartan |
|---|---|---|
| Total Slope of Estimated Glomerular Filtration Rate (eGFR) Over a 110-week Period | -2.9 (-3.58 to -2.24) | -3.9 (-4.59 to -3.13) |
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.
| milliliters/minute/1.73square meter/year | Sparsentan | Irbesartan |
|---|---|---|
| Annualized Slope of eGFR Following the Initial Acute Effect of Randomized Treatment (Chronic Slope) | -2.7 (-3.43 to -2.05) | -3.8 (-4.60 to -3.07) |
Collected over Up to Week 114. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Sparsentan | 0/202 (0%) | 75/202 (37.1%) | 187/202 (92.6%) |
| Irbesartan | 1/202 (0.5%) | 71/202 (35.1%) | 177/202 (87.6%) |
| Event | Sparsentan | Irbesartan |
|---|---|---|
| COVID-19Infections and infestations | 42/202 | 38/202 |
| Chronic kidney diseaseRenal and urinary disorders | 6/202 | 6/202 |
| Acute kidney injuryRenal and urinary disorders | 4/202 | 1/202 |
| AppendicitisInfections and infestations | 1/202 | 2/202 |
| COVID-19 pneumoniaInfections and infestations | 1/202 | 2/202 |
| CellulitisInfections and infestations | 1/202 | 2/202 |
| IgA nephropathyRenal and urinary disorders | 1/202 | 2/202 |
| ProteinuriaRenal and urinary disorders | 1/202 | 2/202 |
| DizzinessNervous system disorders | 2/202 | 1/202 |
| Meniscus injuryInjury, poisoning and procedural complications | 1/202 | 2/202 |
| Event | Sparsentan | Irbesartan |
|---|---|---|
| COVID-19Infections and infestations | 53/202 | 46/202 |
| HyperkalaemiaMetabolism and nutrition disorders | 32/202 | 26/202 |
| Oedema peripheralGeneral disorders | 31/202 | 24/202 |
| DizzinessNervous system disorders | 30/202 | 13/202 |
| HypertensionVascular disorders | 22/202 | 28/202 |
| HeadacheNervous system disorders | 27/202 | 26/202 |
| HypotensionVascular disorders | 26/202 | 8/202 |
| DiarrhoeaGastrointestinal disorders | 10/202 | 19/202 |
| Upper respiratory tract infectionInfections and infestations | 18/202 | 18/202 |
| Muscle spasmsMusculoskeletal and connective tissue disorders | 14/202 | 17/202 |
Full Analysis Set comprised of all participants who were randomized and received at least 1 dose of randomized therapy
| Age, Continuous(Years) | Sparsentan | Irbesartan | Total |
|---|---|---|---|
| Mean | 46.6 ± 12.76 | 45.4 ± 12.12 | 46.0 ± 12.44 |
| Sex: Female, Male(Participants) | Sparsentan | Irbesartan | Total |
|---|---|---|---|
| Female | 63 | 59 | 122 |
| Male | 139 | 143 | 282 |
| Ethnicity (NIH/OMB)(Participants) | Sparsentan | Irbesartan | Total |
|---|---|---|---|
| Hispanic or Latino | 17 | 16 | 33 |
| Not Hispanic or Latino | 185 | 183 | 368 |
| Unknown or Not Reported | 0 | 3 | 3 |
| Race/Ethnicity, Customized(Participants) | Sparsentan | Irbesartan | Total |
|---|---|---|---|
| Asian | 67 | 48 | 115 |
| Black or African American | 1 | 3 | 4 |
| White | 130 | 142 | 272 |
| Other | 4 | 8 | 12 |
| Multiple | 0 | 1 | 1 |
| American Indian or Alaska Native | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
Showing the first 100 of 162 sites across 18 countries. Choose a country and city above to see the rest.
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — Requests for clinical trial data, including language stating its intended use, should be directed to datarequest@travere.com. If approved, the requested information will be provided to the requestor after signing a data access agreement. Requests can be made following completion of the study and full publication of the study data in a peer reviewed journal for up to 36 months following its publication. Travere reserves the right to decline or recommend modifications to a request if it does not comply with the data sharing policy or if it is determined that the request is made by a biased source.
Time frame: Requests can be made following completion of the study and full publication of the study data in a peer reviewed journal for up to 36 months following its publication.
Access criteria: Requires submission and approval of intended use and a data sharing agreement.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is completed, as verified in Sep 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Sparsentan
Travere Therapeutics, Inc.