Selonsertib phase 3. Selonsertib (an inhibitor of apoptosis signal-regulating kinase 1), elafibranor (a PPAR α/δ agonist), and cenicriviroc (a chemokine receptor type 2 and 5 antagonist) all failed to show benefit in phase 3 trials. Executive Summary Selonsertib, developed by Gilead Sciences, aimed to reduce liver fibrosis in patients with NASH by inhibiting ASK1, a key protein in stress-induced inflammatory and fibrotic pathways. Participants will be randomized with a 1:1:1:1 allocation to receive 1 of 3 doses of selonsertib (2 mg, 6 mg, or 18 mg) or matching placebo. Healthy subjects received 1 Two randomized, double-blind, placebo-controlled phase III trials have evaluated the safety and anti-fibrotic efficacy of the selective ASK1 inhibitor, selonsertib, in patients with nonalcoholic Selonsertib once daily for 24 weeks did not lead to a significant reduction in pulmonary vascular resistance or to clinical improvement in patients with PAH, but appeared to be safe and well tolerated. Patients were randomized 2:2:1 to receive selonsertib 18 mg, selonsertib 6 mg, or placebo once daily for 48 weeks. Patients taking selonsertib had slower eGFR decline but were more likely to reach a composite kidney outcome and report AKI. Gilead’s NASH candidate selonsertib has disappointed in yet another phase 3 trial. Methods: We conducted 2 randomized, double-blind, placebo-controlled, phase III trials of selonsertib in patients with NASH and bridging fibrosis (F3, STELLAR-3) or compensated cirrhosis (F4, STELLAR-4). We evaluated the safety and antifibrotic effect of selonsertib, a selective inhibitor of ASK1, in patients with advanced fibrosis due to NASH. Selonsertib has failed to meet the pre-specified week 48 primary endpoint of a ≥ 1-stage histologic improvement in fibrosis without worsening of NASH. OVERVIEW MOSAIC - A Phase 2b, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multicenter Study Evaluating the Efficacy and Safety of Selonsertib in Subjects With Moderate to Advanced Diabetic Kidney Disease (MOSAIC). Stellar-4 is a phase 3 randomized, double-blind and placebo-controlled study designed to assess the safety and efficacy of selonsertib in patients with compensated cirrhosis (F4) due to NASH. Methods We conducted 2 randomized, double-blind, placebo-controlled, phase III trials of selonsertib in patients with NASH and bridging fibrosis (F3, STELLAR-3) or compensated cirrhosis (F4, STELLAR-4). In this study, we investigated whether selonsertib could reverse MDR-mediated by ABC transporters, including ABCB1, ABCG2, ABCC1 and ABCC10. A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Selonsertib in Subjects With Nonalcoholic Steatohepatitis (NASH) and Bridging (F3) Fibrosis Feb 13, 2026 · Gilead's top late-stage drug selonsertib, for patients with compensated cirrhosis due to nonalcoholic steatohepatitis (NASH), has failed a phase 3 trial. 21 However, in a double-blind, placebo-controlled phase 2 clinical trial (ENCORE-NF, NCT02686762) involving 318 MASH patients with Topline data from the Phase 3 STELLAR-4 trial showed that selonsertib, an investigational treatment for patients with compensated cirrhosis due to nonalcoholic steatohepatitis (NASH), was not associated with a significant improvement in fibrosis without worsening of NASH. Phase 2b trials frequently evaluate treatment combinations and liver histology outcomes in a limited patient group, providing insights into the potential for advancement to phase 3. MASH PHASE 3 TRIALS Table 1 provides a summary of selected drugs that have undergone phase 3 testing for the treatment of MASH. Feb 11, 2019 · The STELLAR-4 study is a Phase 3, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of selonsertib in patients with compensated cirrhosis (F4) due to NASH. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. Selonsertib, a highly selective small-molecule inhibitor of ASK1, has been tested in two Phase 3 clinical trials for severe nonalcoholic steatohepatitis (NASH; NCT03053050 and NCT03053063) and was found to be ineffective [19]. In a randomized, dose-ranging, placebo-controlled phase 2 trial Gilead’s chances of winning the first-to-market nonalcoholic steatohepatitis (NASH) race has dwindled after one of its key candidates selonsertib failed in a crucial phase 3 test. Since beneficial effects, without any apparent hepatic or systemic adverse effects, were demonstrated with emricasan, further clinical evaluation in the treatment of advanced chronic liver disease was encouraged. Selonsertib, a serine/threonine kinase inhibitor, targets apoptosis signal-regulating kinase 1 (ASK1) and is now in phase III clinical trial for the treatment of non-alcoholic steatohepatitis (NASH). 21 However, in a double-blind, placebo-controlled phase 2 clinical trial (ENCORE-NF, NCT02686762) involving 318 MASH patients with Official Title A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Selonsertib, GS-0976, GS-9674, and Combinations in Subjects With Bridging (F3) Fibrosis or Compensated Cirrhosis (F4) Due to Nonalcoholic Steatohepatitis (NASH) Selonsertib targets a novel, nonhemodynamic pathway in CKD. Our data suggest that ASK1 inhibition, when combined with ACEI, has additive effects to reduce progression of glomerulosclerosis, attenuate kidney function decline, and reduce podocyte loss. announced that STELLAR-4, a Phase 3, placebo-controlled study evaluating the safety and efficacy of selonsertib, oral inhibitor of apoptosis signal-regulating kinase 1, did not meet the pre-specified week 48 primary endpoint of a ≥ 1-stage histologic improvement in fibrosis… Methods: We conducted 2 randomized, double-blind, placebo-controlled, phase III trials of selonsertib in patients with NASH and bridging fibrosis (F3, STELLAR-3) or compensated cirrhosis (F4, STELLAR-4). Despite promising preclinical and Phase 2 data, the larger Phase 3 trials, STELLAR-3 and STELLAR-4, failed to meet their primary endpoints. Gilead's top late-stage drug selonsertib, for patients with compensated cirrhosis due to nonalcoholic steatohepatitis (NASH), has failed a phase 3 trial. Gilead has reported selonsertib failed to meet the primary endpoint in the Phase III STELLAR-3 trial in patients with bridging fibrosis caused due to NASH. AI generated definition based on: Pharmacological Research, 2018 This guide provides a detailed comparative analysis of the efficacy of Selonsertib, a selective inhibitor of apoptosis signal-regulating kinase 1 (ASK1), in patients with nonalcoholic steatohepatitis (NASH) and bridging fibrosis (F3) versus those with compensated cirrhosis (F4). Topline data from the Phase 3 STELLAR-4 trial showed that selonsertib, an investigational treatment for patients with compensated cirrhosis due to nonalcoholic steatohepatitis (NASH), was not associated with a significant improvement in fibrosis without worsening of NASH. Gilead Sciences announced that STELLAR-3, a Phase 3, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of selonsertib, an investigational, once daily, oral inhibitor of apoptosis signal-regulating kinase 1 (ASK1), for patients with bridging fibrosis (F3) due to nonalcoholic steatohepatitis (NASH), did not The primary objective of this study is to determine the effect of selonsertib (formerly GS-4997) on estimated glomerular filtration rate (eGFR) decline in participants with diabetic kidney disease (DKD). Selonsertib in adults with pulmonary arterial hypertension (ARROW): a randomised, double-blind, placebo-controlled, phase 2 trial Prof Stephan Rosenkranz MD a , Prof Jeremy Feldman MD b , Prof Vallerie V McLaughlin MD c , Prof Franz Rischard d , Dr Tobias J Lange MD e , Prof R James White MD f , Prof Andrew J Peacock MD g , Dr Felix Gerhardt MD Methods We conducted 2 randomized, double-blind, placebo-controlled, phase III trials of selonsertib in patients with NASH and bridging fibrosis (F3, STELLAR-3) or compensated cirrhosis (F4, STELLAR-4). Abstract Key Points: In a randomized, placebo-controlled, phase 2b study, we compared the effects of selonsertib with placebo on eGFR decline in people with type 2 diabetes and CKD. About Selonsertib and the STELLAR-3 Study Selonsertib is an investigational small molecule inhibitor of ASK1, a protein that promotes inflammation, apoptosis (cell death) and fibrosis in settings of oxidative stress. Oxidative stress can be increased in many pathological conditions including liver diseases such as NASH. This phase I study evaluated the safety, tolerability, pharmacokinetics (PK), and food effect of selonsertib in healthy subjects. This time, two different doses of the drug did worse than placebo at reducing scarring in patients with The STELLAR-3 study is a Phase 3, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of selonsertib in patients with bridging fibrosis (F3) due to NASH. The STELLAR-3 study is a Phase 3, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of selonsertib in patients with bridging fibrosis (F3) due to NASH. During the STELLAR-3 trial, the apoptosis signal-regulating kinase 1 (ASK1) inhibitor failed to meet its primary In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. The analysis is based on the results of the two pivotal Phase 3 clinical trials, STELLAR-3 and Jul 28, 2025 · Current Research and Status Gilead Sciences developed selonsertib, which progressed through Phase 2 and Phase 3 clinical trials. The model demonstrates fibrosis reduction for known clinical compounds tested by pharma companies that have that effect in humans, while revealing lack of fibrosis reduction for compounds that failed in phase 2 or phase 3 for NASH. OVERVIEW MOSAIC - A Phase 2b, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multicenter Study Evaluating the Efficacy and Safety of Selonsertib in Subjects With Moderate to Advanced Diabetic Kidney Disease (MOSAIC) Methods: We analyzed data from 1667 patients (58 ± 9 years, 40% male, 52% with cirrhosis, 74% with diabetes) with NASH and bridging fibrosis or compensated cirrhosis (metavir scores, F3 or F4) enrolled in the phase 3 STELLAR trials of selonsertib (NCT03053050 and NCT03053063) who completed PRO questionnaires (SF-36, CLDQ-NASH, EQ-5D, or WPAI Selonsertib Terminated Phase 3 Trials for Metabolic Dysfunction-associated Steatohepatitis (MASH) Treatment Back to Selonsertib The STELLAR Phase 3 trial program evaluating selonsertib among NASH patients with bridging fibrosis (F3) or cirrhosis (F4) is ongoing. A phase 3 trial of Gilead’s NASH prospect selonsertib has bombed. We evaluated the safety and antifibrotic effect of selonsertib, a selective inhibitor of ASK1, in patients with advanced fibrosis due to NASH. METHODS: We conducted 2 randomized, double-blind, placebo-controlled, phase III trials of selonsertib in patients with NASH and bridging fibrosis (F3, STELLAR-3) or compensated cirrhosis (F4, STELLAR-4). The primary objective of this study is to determine the effect of selonsertib (formerly GS-4997) on estimated glomerular filtration rate (eGFR) decline in participants with diabetic kidney disease (DKD). Gilead is to take its selonsertib into late stage trials in the hotly-contested fatty liver disease, non-alcoholic steatohepatitis (NASH) market, but abandoned further development in two other A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Selonsertib in Subjects with Compensated Cirrhosis due to Nonalcoholic Steatohepatitis (NASH) Gilead Sciences, Inc. Based on this mechanistic rationale, pre-clinical data, and promising phase II data, we conducted the STELLAR-3 and STELLAR-4 phase III trials to evaluate whether ASK1 inhibition with selonsertib could cause fibrosis regression and reduce clinical disease progression in patients with bridging fibrosis or compensated cirrhosis due to NASH. Gilead Sciences, Inc. The drug, an apoptosis signal-regulating Selonsertib is defined as an inhibitor of apoptosis signal-regulating kinase 1 (ASK-1) and MAP3 kinase, which are targets that promote hepatic steatosis and fibrosis. announced that STELLAR-4, a Phase 3, placebo-controlled study evaluating the safety and efficacy of selonsertib, oral inhibitor of apoptosis signal-regulating kinase 1, did not meet the pre-specified week 48 primary endpoint of a ≥ 1-stage histologic improvement in fibrosis… Based on this mechanistic rationale, pre-clinical data, and promising phase II data, we conducted the STELLAR-3 and STELLAR-4 phase III trials to evaluate whether ASK1 inhibition with selonsertib could cause brosis regression and reduce fi clinical disease progression in patients with bridging brosis or fi compensated cirrhosis due to NASH. Findings in animal models of diabetic kidney disease identified selonsertib, a selective inhibitor of apoptosis signal–regulating kinase 1 (ASK1), as a potential therapeutic agent. Phase 3 trials include large numbers of people to make sure that the result is valid. Gilead Sciences announced that STELLAR-3, a Phase 3, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of selonsertib, an investigational, once daily, oral inhibitor of apoptosis signal-regulating kinase 1 (ASK1), for patients with bridging fibrosis (F3) due to nonalcoholic steatohepatitis (NASH), did not The STELLAR-4 study is a Phase 3, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of selonsertib in patients with compensated cirrhosis (F4) due to NASH. Two randomized, double- blind, placebo- controlled phase III trials have evaluated the safety and anti- fibrotic efficacy of the selective ASK1 inhibitor, selonsertib, in patients with The primary objective of this study is to determine the effect of selonsertib (formerly GS-4997) on estimated glomerular filtration rate (eGFR) decline in participants with diabetic kidney disease (DKD). The drug, an apoptosis signal-regulating Gilead Sciences, Inc. The ASK1 inhibitor was no better than placebo at improving fibrosis, wiping out hopes that selonsertib would spearhead Gilead We evaluated the safety and antifibrotic effect of selonsertib, a selective inhibitor of ASK1, in patients with advanced fibrosis due to NASH. GS-9674 and GS-0976 are currently in Phase 2 studies in NASH. Background Selonsertib is a first-in-class inhibitor of apoptosis signal-regulating kinase 1 (ASK1) with therapeutic potential for fibrotic diseases. In Phase 2 trials for NASH, selonsertib showed promising anti-fibrotic activity, with patients improving in fibrosis stage and other liver injury measures after 24 weeks. Eligible adults ages 18 to 70 years were randomized and received selonsertib 18 mg (n=354), selonsertib 6 mg (n=351) or placebo (n=172) for up to 240 weeks. The STELLAR-4 study is a Phase 3, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of selonsertib in patients with compensated cirrhosis (F4) due to NASH. Although these data do not support the clinical use of selonsertib in PAH, further study of the potential of targeting the ASK1–p38 pathway in PAH is warranted. Blood and urine (single-dose cohorts only) samples for selonsertib PK were collected and safety was assessed throughout the study. They also compare the safety of the new treatment with that of current treatments. Its safety and efficacy are currently being investigated in Phase 3 clinical trials. Methods This was a double-blinded, randomized, placebo-controlled dose-escalation study. Healthy subjects received 1, 3, 10, 30, or 100 mg of selonsertib or placebo as single or multiple doses once daily for 14 days in the fasted state, or 30 mg or placebo single dose in the fed state. 4kgdw, ujnzd, hxdl, 9xdg, ciqr, wdtt, jzl5, sfu5r2, oeqy, p4eqkk,