Scholarlink

<p>Thyroid hormone receptor-β (THRβ) agonism is a validated mechanism for treating metabolic dysfunction-associated steatohepatitis (MASH). DUET was a 12-week, randomized, double-blind, placebo-controlled, multicenter phase 2a study investigating the efficacy, safety and pharmacodynamics and pharmacokinetics of once-daily TERN-501 (THRβ agonist) as monotherapy or combined with TERN-101 (farnesoid X receptor agonist), in patients with presumed MASH. Overall, 162 patients were randomized to: TERN-501 monotherapy (1 mg (<i>n</i> = 23), 3 mg (<i>n</i> = 23) or 6 mg (<i>n</i> = 22)), TERN-101 10-mg monotherapy (<i>n</i> = 24), TERN-501 (3 mg (<i>n</i> = 23) or 6 mg (<i>n</i> = 23)) plus TERN-101 10-mg combination therapy or placebo (<i>n</i> = 24). The primary endpoint was relative change from baseline at week 12 in liver fat content with TERN-501 monotherapy versus placebo, using magnetic resonance imaging proton density fat fraction (MRI-PDFF). Least squares mean (s.e.) changes from baseline at week 12 in MRI-PDFF with TERN-501 were: −15.4% (5.2%) with 1 mg, −27.5% (5.7%) with 3 mg (<i>P</i> = 0.0036) and −44.8% (5.9%) with 6 mg (<i>P</i> &lt; 0.0001), versus −4.0% (5.4%) with placebo. The incidence of adverse events was similar with TERN-501 monotherapy or placebo. In conclusion, TERN-501 treatment resulted in dose-dependent, significant reductions from baseline in MRI-PDFF compared to placebo in patients with MASH. ClinicalTrials.gov registration: <a href="https://clinicaltrials.gov/study/NCT05415722">NCT05415722</a>.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

TERN-501 monotherapy and combination therapy with TERN-101 in metabolic dysfunction-associated steatohepatitis: the randomized phase 2a DUET trial

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年6月11日

查看全文
  • Mazen Noureddin,
  • Naim Alkhouri,
  • Eric J. Lawitz,
  • Kris V. Kowdley,
  • Rohit Loomba,
  • Lois Lee,
  • Christopher Jones,
  • Amnon Schlegel,
  • Tonya Marmon,
  • Kacey Anderson,
  • Yizhao Li,
  • Erin Quirk,
  • Stephen A. Harrison

摘要

Thyroid hormone receptor-β (THRβ) agonism is a validated mechanism for treating metabolic dysfunction-associated steatohepatitis (MASH). DUET was a 12-week, randomized, double-blind, placebo-controlled, multicenter phase 2a study investigating the efficacy, safety and pharmacodynamics and pharmacokinetics of once-daily TERN-501 (THRβ agonist) as monotherapy or combined with TERN-101 (farnesoid X receptor agonist), in patients with presumed MASH. Overall, 162 patients were randomized to: TERN-501 monotherapy (1 mg (n = 23), 3 mg (n = 23) or 6 mg (n = 22)), TERN-101 10-mg monotherapy (n = 24), TERN-501 (3 mg (n = 23) or 6 mg (n = 23)) plus TERN-101 10-mg combination therapy or placebo (n = 24). The primary endpoint was relative change from baseline at week 12 in liver fat content with TERN-501 monotherapy versus placebo, using magnetic resonance imaging proton density fat fraction (MRI-PDFF). Least squares mean (s.e.) changes from baseline at week 12 in MRI-PDFF with TERN-501 were: −15.4% (5.2%) with 1 mg, −27.5% (5.7%) with 3 mg (P = 0.0036) and −44.8% (5.9%) with 6 mg (P < 0.0001), versus −4.0% (5.4%) with placebo. The incidence of adverse events was similar with TERN-501 monotherapy or placebo. In conclusion, TERN-501 treatment resulted in dose-dependent, significant reductions from baseline in MRI-PDFF compared to placebo in patients with MASH. ClinicalTrials.gov registration: NCT05415722.