Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as RE-021, Sparsentan
RE-021, sparsentan · 7 trials · 12 indications
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.
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 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.
The change from baseline in UA/C at Week 24 based on first morning void (FMV) samples
Change from baseline to week 6 in acetylcholine-mediated forearm blood flow vasodilatation
The incidence of TEAEs, SAEs, AEs leading to treatment discontinuation, and AEOIs
Change from baseline in UP/C over 108 weeks
The primary efficacy endpoint is the change from baseline in the urine protein/creatinine ratio (UP/C), based on a 24-hour urine sample, at Week 36.
Primary efficacy objective is to determine the change in UP/C in FSGS patients receiving RE-021 (Sparsentan) from baseline to 8 weeks over a range of dose levels compared to treatment with irbesartan as active control.
| Arm | Type | Description |
|---|---|---|
| sparsentan | EXPERIMENTAL | 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. |
| irbesartan | ACTIVE_COMPARATOR | 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. |
| dapagliflozin + sparsentan (Sub study) | EXPERIMENTAL | 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. |
| sparsentan (Sub Study) | EXPERIMENTAL | OLE Sub study: Sparsentan will be administered daily as a dose of 400-mg for a period of 12 weeks. |
| sparsentan for double-blind and open-label extension | EXPERIMENTAL | 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 |
| Population 1: FSGS and/or MCD | EXPERIMENTAL | Subjects with selected proteinuric glomerular diseases associated with FSGS and MCD histological patterns |
| Population 2: IgAN, IgAV, or AS | EXPERIMENTAL | Subjects with kidney biopsy-confirmed immunoglobulin A nephropathy (IgAN), immunoglobulin A vasculitis (IgAV), or Alport syndrome (AS) |
| Population 3: IgAN | EXPERIMENTAL | Subjects with kidney biopsy-confirmed IgAN |
| RE-021 (Sparsentan) 200 mg - Double-Blind Period | EXPERIMENTAL | RE-021 (Sparsentan) will be administered as a single oral morning dose. In this ARM the RE-021 (Sparsentan) dose will be 200mg. Patients at \</= 50kg will receive half of the RE-021 (Sparsentan) dose for the 8 week duration. |
| RE-021 (Sparsentan) 400 mg - Double-Blind Period | EXPERIMENTAL | RE-021 (Sparsentan) will be administered as a single oral morning dose. In this ARM the RE-021 (Sparsentan) dose will be 400mg. Patients at \</= 50kg will receive half of the RE-021 (Sparsentan) dose for the 8 week duration. |
| RE-021 (Sparsentan) 800 mg - Double-Blind Period | EXPERIMENTAL | RE-021 (Sparsentan) will be administered as a single oral morning dose. In this ARM the RE-021 (Sparsentan) dose will be 800mg. Patients at \</= 50kg will receive half of the RE-021 (Sparsentan) dose for the 8 week duration. |
| Irbesartan 300 mg - Double-Blind Period | ACTIVE_COMPARATOR | The control will be administered irbesartan as a single oral dose of 150mg for the first week before escalating to 300mg for the remaining 7 weeks. Patients at \</= 50kg will receive 150mg irbesartan for the 8 week duration. |
| RE-021 (Sparsentan) - Open-Label Extension Period | EXPERIMENTAL | Includes all subjects who completed the Double-Blind period and enrolled in the Open-Label Extension period of the study. All subjects who completed the Double-Blind period were evaluated for response and safety at the Week 8 visit to determine eligibility for continued treatment on their assigned doses in an Open-Label Extension period for up to 496 additional weeks. Subjects treated with irbesartan during the Double-Blind period were offered sparsentan treatment at the dose they would have received according to the Double-Blind dose cohort in which they were enrolled. |
| Name | Type | Description |
|---|---|---|
| sparsentan | DRUG | Target dose of 400 mg daily |
| irbesartan | DRUG | Target dose of 300 mg daily |
| Dapagliflozin | DRUG | Target dose of 10 mg daily |
| RE-021 (Sparsentan) | DRUG | Oral, once-daily |
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 (maximu...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Apellis Pharmaceuticals, Inc. | APLS | 1 | PHASE2 | APL-2 |
| Sanofi SA Sponsored ADR | SNY | 1 | PHASE2 | Frexalimab, Brivekimig, Rilzabrutinib |
| Novartis AG Sponsored ADR | NVS | 1 | PHASE2 | Atrasentan |
| Akebia Therapeutics, Inc. | AKBA | 1 | PHASE2 | Praliciguat |
| Travere Therapeutics, Inc. | TVTX | 1 | PHASE2 | Sparsentan |
| Vera Therapeutics, Inc. Class A | VERA | 1 | PHASE2 | Atacicept |
RE-021, also known as sparsentan, is being studied for the treatment of focal segmental glomerulosclerosis (FSGS), a rare kidney disorder. It is an investigational small molecule in Phase 2 development for this nephrology indication. The completed Phase 2 trial evaluated its safety and efficacy in patients with FSGS.
RE-021 (sparsentan) is being developed by Travere Therapeutics, Inc., which trades on the Nasdaq under the ticker TVTX. The company is responsible for the clinical development of this investigational therapy for focal segmental glomerulosclerosis.
RE-021 (sparsentan) is in Phase 2 clinical development for focal segmental glomerulosclerosis. The Phase 2 trial has been completed. It is an investigational drug and has not been approved by the FDA for any indication.
RE-021 (sparsentan) has been studied in one completed Phase 2 clinical trial, NCT01613118, titled "Randomized, Double-Blind, Safety and Efficacy Study of RE-021 (Sparsentan) in Focal Segmental Glomerulosclerosis." The trial enrolled 109 participants across the United States, Czechia, and Italy.
Yes, RE-021 and sparsentan are the same investigational drug. RE-021 is an alternative name for sparsentan, which is being developed by Travere Therapeutics for focal segmental glomerulosclerosis.