お知らせ • Jul 15
Pliant Therapeutics, Inc. Announces Positive Long-Term Data from the INTEGRIS-PSC Phase 2a Trial Demonstrating
Pliant Therapeutics, Inc. announced positive 24-week data from the 320 mg cohort of INTEGRIS-PSC, a multinational, randomized, double-blind, placebo-controlled Phase 2a clinical trial of bexotegrast in patients with primary sclerosing cholangitis (PSC) and suspected moderate to severe liver fibrosis. The 320 mg treatment group met its primary endpoint of safety, demonstrating that bexotegrast was well tolerated up to 40 weeks of treatment. Pruritus and cholangitis occurred in lower proportions on bexotegrast than on placebo, consistent with previous findings. The trial’s exploratory efficacy endpoints assessed changes in liver stiffness as measured by transient elastography (TE) at 24 weeks, changes in the liver fibrosis markers including Enhanced Liver Fibrosis (ELF) score, as well as liver biochemistry and magnetic resonance imaging (MRI). Bexotegrast at 320 mg demonstrated improvement in liver stiffness compared to placebo at Week 24. A reduction in ELF score was observed at Week 24 in patients at higher risk of disease progression (baseline ELF > 9.8) compared to an increase in ELF on placebo. Stable ELF score was observed from Week 12 to Week 24 in the overall bexotegrast-treated population compared to placebo. Bexotegrast improved markers and symptoms of cholestasis including alkaline phosphatase (ALP), MRI, self-reported itch, and common adverse events associated with PSC. Bexotegrast-treated patients showed decreased ALP levels over 24 weeks, compared to increased ALP on placebo. MRI of the liver demonstrated evidence of further improvement of hepatocyte function and bile flow with bexotegrast at the 320 mg dose from Week 12 to 24.INTEGRIS-PSC was a multinational, randomized, dose-ranging, double-blind, placebo-controlled Phase 2a trial designed to evaluate bexotegrast at once-daily oral doses of 40 mg, 80 mg, 160 mg or placebo up to 12 weeks and 320 mg or placebo for up to 48 weeks in 121 patients with PSC and suspected liver fibrosis. The 320 mg cohort enrolled 27 patients in the active arm and 9 patients in placebo arm. The primary endpoint of the INTEGRIS-PSC trial was the evaluation of the safety and tolerability of bexotegrast. Bexotegrast at 320 mg was well tolerated up to 40 weeks of treatment with no treatment-related severe or serious adverse events (SAE). Most treatment-emergent adverse events (TEAEs) were mild or moderate in severity and consistent with PSC disease symptoms. The exploratory endpoints of the INTEGRIS-PSC trial included changes in liver stiffness as measured by transient elastography (TE) at 24 weeks, changes in liver fibrosis markers including ELF, liver biochemistry and MRI imaging. These data suggest stabilization of liver fibrosis. Bexotegrast at 320 mg demonstrated a numerical reduction in liver stiffness at Week 24 compared to an increase on placebo, as measured by TE. Liver stiffness is a marker of liver fibrosis that increases over time in patients with PSC. Measurement of liver stiffness by TE can be used to predict the severity and progression of liver fibrosis. In patients at high risk for disease progression (baseline ELF ? 9.8), bexotegrast-treated patients showed a reduction in ELF score at Week 24 compared to an increase in placebo at Week 24. Across all bexotegrast-treated patients, ELF remained stable on treatment from Week 12 to 24 compared to placebo. Bexotegrast-treated patients demonstrated statistically significant reduction in ALP over 24 weeks compared to increased levels on placebo, with greater reductions observed in bexotegrast-treated patients with elevated baseline ALP values. At Week 12, in the MRI sub-study, bexotegrast-treated patients showed increased relative enhancement compared to decreased relative enhancement in the placebo group. At Week 24, bexotegrast-treated patients displayed a further increase in relative enhancement, suggesting continued improvement in hepatocyte function from Week 12 to 24. At Week 12, bexotegrast-treated patients showed decreased time to arrival to the common bile duct compared to placebo, suggesting improved bile flow.2 At Week 24, bexotegrast-treated patients showed faster time to arrival to the common bile duct, suggesting further improvement in bile flow from Week 12 to 24. Interpretation of placebo findings at Week 24 was limited due to the small number of placebo participants (n=?2) enrolled in the MRI sub-study of the 320 mg cohort.Pruritus and cholangitis are common symptoms of cholestasis in PSC patients.3 Adverse events of pruritus and cholangitis occurred in a lower proportion of bexotegrast-treated patients at 320 mg compared to placebo. Bexotegrast-treated patients demonstrated a stable score on the Itch Numerical Rating Scale relative to a numerical increase on placebo. These findings are consistent with previously reported data from Week 12 across all doses. INTEGRIS-PSC was a Phase 2a, multinational randomized, dose-ranging, double-blind, placebo-controlled trial evaluating the safety, tolerability, and pharmacokinetics of bexotegrast administered over 12 weeks in patients with PSC. Patients were enrolled in doses of 40 mg, 80 mg, 160 mg or 320 mg, with a 3:1 randomization ratio (active:placebo) and stratification based on use of ursodeoxycholic acid (UDCA). The primary endpoint was the evaluation of bexotegrast safety and tolerability, and the secondary endpoint is the assessment of pharmacokinetics across the range of doses. Exploratory endpoints measured changes in liver fibrosis markers, ELF and PRO-C3, liver biochemistry and liver imaging.