A Multi-center, Randomized, Double-blind, Placebo-controlled, Phase IIa Clinical Trial to Evaluate the Safety and Explore the Efficacy of J2H-1702 for Non-alcoholic Steatohepatitis

The study aims to evaluate the safety of J2H-1702 compared to the placebo and explore the efficacy of J2H-1702 at Week 12 timepoint after administration compared to baseline in patients with NASH.

开始日期2023-02-15

申办/合作机构

J2H Biotech, Inc.

KCT0007904 / Recruiting临床2期

A Multi-center, Randomized, Double-blind, Placebo-controlled, Phase IIa Clinical Trial to Evaluate the Safety and Explore the Efficacy of J2H-1702 for Non-alcoholic Steatohepatitis

开始日期2023-02-15

申办/合作机构

J2H Biotech, Inc.

KCT0008007 / Completed临床1期

A Double-Blind, Placebo Controlled, Single Dosing, Dose-Escalation Phase 1 Clinical Trial to Investigate the Safety, Tolerability, Pharmacokinetics/Pharmacodynamics Characteristics of J2H-1702 (Nonalcoholic Steatohepatitis Treatment Candidate) after Oral Administration in Healthy Female Subjects

开始日期2023-01-02

申办/合作机构

J2H Biotech, Inc.

100 项与 J2H-1702 相关的临床结果

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100 项与 J2H-1702 相关的转化医学

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100 项与 J2H-1702 相关的专利（医药）

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项与 J2H-1702 相关的文献（医药）

2023-12-01·Alimentary Pharmacology & Therapeutics

First in human randomised trial of J2H‐1702: A novel 11β‐hydroxysteroid dehydrogenase type 1 inhibitor for non‐alcoholic steatohepatitis treatment

Article

作者: Lee, Sang Won ; Lee, Shi-Ra ; Kim, Yun

SummaryBackground11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1), which is an enzyme that converts cortisone to cortisol, plays a role in the regulation of glucose metabolism and inflammation. J2H‐1702 is a novel 11β‐HSD1 inhibitor, and the inhibition of 11β‐HSD1 has been shown to improve insulin sensitivity, reduce inflammation, and prevent the development of nonalcoholic steatohepatitis (NASH) in preclinical models.AimsWe aimed to assess the pharmacokinetics (PKs), pharmacodynamics (PDs), safety, and tolerability of J2H‐1702 after a single‐dose oral administration.MethodsA randomised, double‐blinded, placebo‐controlled, single‐dose, dose‐escalation study was conducted on 50 healthy volunteers. Blood and urine samples were collected to assess the PK and PD of J2H‐1702.ResultsThe peak plasma concentration of J2H‐1702 was observed at 2–2.9 h after a single‐dose oral administration. J2H‐1702 reduced 11β‐HSD1 activity compared to the placebo at all dose levels. The drug reached its maximal inhibitory effect within 12–24 h post‐dose administration, and the inhibitory effect was maintained till 1 day after administration of the study drug. The drug showed typical first‐order elimination kinetics, with a mean elimination half‐life of 9.8–14.7 h. Systemic exposure to J2H‐1702 increased in a dose‐dependent manner. J2H‐1702 was well tolerated after a single oral administration of up to 300 mg. A total of 11 treatment‐emergent adverse events (TEAEs) occurred in seven (14%) participants, all of which were mild and resolved spontaneously. The most common TEAE was diarrhoea (8%), followed by dizziness (4%).ConclusionsThe results of this study suggest that J2H‐1702 could be developed as an effective therapeutic option for NASH.

Cell Death & Disease

Inhibition of 11β-hydroxysteroid dehydrogenase 1 relieves fibrosis through depolarizing of hepatic stellate cell in NASH

Article

作者: Ryu, Hyung Chul ; Kim, Namjeong ; Kim, Jason ; Choi, Inhee ; Lim, Jee Woong ; Seo, Haeng Ran ; Kim, Sanghwa ; Lee, Su-Yeon ; Kang, Hyo Jin ; Song, Yeonhwa

Abstract11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) is a key enzyme that catalyzes the intracellular conversion of cortisone to physiologically active cortisol. Although 11βHSD1 has been implicated in numerous metabolic syndromes, such as obesity and diabetes, the functional roles of 11βHSD1 during progression of nonalcoholic steatohepatitis (NASH) and consequent fibrosis have not been fully elucidated. We found that pharmacological and genetic inhibition of 11βHSD1 resulted in reprogramming of hepatic stellate cell (HSC) activation via inhibition of p-SMAD3, α-SMA, Snail, and Col1A1 in a fibrotic environment and in multicellular hepatic spheroids (MCHSs). We also determined that 11βHSD1 contributes to the maintenance of NF-κB signaling through modulation of TNF, TLR7, ITGB3, and TWIST, as well as regulating PPARα signaling and extracellular matrix accumulation in activated HSCs during advanced fibrogenesis in MCHSs. Of great interest, the 11βHSD1 inhibitor J2H-1702 significantly attenuated hepatic lipid accumulation and ameliorated liver fibrosis in diet- and toxicity-induced NASH mouse models. Together, our data indicate that J2H-1702 is a promising new clinical candidate for the treatment of NASH.

100 项与 J2H-1702 相关的药物交易

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