A Randomized, Double-blind, Placebo-controlled, Multicenter, Phase 2 Study to Evaluate the Efficacy and Safety of HY209 Gel in Patients With Mild to Moderate Atopic Dermatitis(AD)

This is a randomized, double-blind, placebo-controlled, multi-center, phase 2 study in patients with mild to moderate Atopic Dermatitis(AD), which consists of 2 parts.

开始日期2024-03-01

申办/合作机构

Shaperon, Inc.

NCT06533878 / Enrolling by invitation临床1期

(Part A) A Non-randomized, Open, Single-dose Escalation to Evaluate Tolerability and Safety of Single Oral Dose of HY209; (Part B) A Block-randomized, Double-blinded, Placebo-controlled, Multiple-dose Escalation to Evaluate Tolerability and Safety of Multiple Oral Doses of HY209 Phase 1 Clinical Trial in Healthy Volunteers

* Primary study objectives in Parts A and B To determine the Maximum Tolerable Dose(MTD) of the study drug (repeated or single dose).
* Endpoint: • Adverse event(AEs), including objective and subjective symptoms, after the IP dosing as well as physical examinations, vital signs, ECGs, and laboratory tests findings related to the IP dosing
• Dose-limiting toxicities (DLTs)
* Justification for endpoints: The safety will be assessed comprehensively by performing safety assessment and evaluating relevant variables by dose group.
The tolerability will be assessed in DLT analysis set. In a first-in-human clinical trial, tolerability of the drug administered is usually assessed through determination of dose-limiting toxicity (DLT). An accurate dose proportionality of toxicity was not observed, but toxicity was found at high doses, not at low doses following IV and oral administrations, except transdermal treatment. Thus, a relationship between toxicity and doses was confirmed.
In addition, HY209 showed a dose dependence in some efficacy endpoints, including dose-dependent inhibition of release of Tumor Necrosis Factor(TNF)-α and Il-1β, key inflammation factors related to inflammatory bowel disease. Thus, evaluating the occurrence of DLTs through sequential dose escalation is determined appropriate to assess the tolerability and safety of HY209.
* Primary study objectives in Part A (Dose levels 4-6): To evaluate the effects of food on HY209 bioavailability (absorption rate and volume) following a single oral dose in healthy volunteers.
* Endpoint: PK of HY209 at a fasting condition and after a high-fat meal Point estimates for the geometric mean ratio of variables (Area under concentration-time curve;AUC₀-₆, AUCₗₐₛₜ, AUC₀-∞, and Cmax) and the 90% confidence interval(CI) and Tmax .
* Justification for endpoints: For oral drugs, effects of food on bioavailability of the drugs are usually evaluated. Especially, a systemic exposure to bile acid drugs of enterohepatic circulation can be explained with a spillover from the liver to systemic circulatory system. Thus, a systemic exposure is thought to be affected by food, but the actual effects of food are triggered by combination of factors that affect in vivo elution of a drug and absorption of the active pharmaceutical ingredient(API) of the drug. As estimating the extent of effects on bioavailability is difficult without conducting an actual food effect study, there is a need for clinical evaluation.

开始日期2023-09-13

申办/合作机构

Kukjeon Pharm Co., Ltd.

NCT04530643 / Completed临床2期

A Randomized, Double-blinded, Placebo-controlled, Parallel, Multi-Center Phase II Clinical Study to Evaluate the Efficacy and Safety of HY209 Gel for Patients With Atopic Dermatitis

A Randomized, Double-blinded, Placebo-controlled, Parallel, Multi-Center Phase II Clinical Study to Evaluate the Efficacy and Safety of HY209 gel for Patients with Atopic Dermatitis

开始日期2020-08-26

申办/合作机构

Shaperon, Inc.

100 项与牛磺脱氧胆酸钠(Shaperon Co., Ltd.) 相关的临床结果

登录后查看更多信息

100 项与牛磺脱氧胆酸钠(Shaperon Co., Ltd.) 相关的转化医学

登录后查看更多信息

100 项与牛磺脱氧胆酸钠(Shaperon Co., Ltd.) 相关的专利（医药）

登录后查看更多信息

211

项与牛磺脱氧胆酸钠(Shaperon Co., Ltd.) 相关的文献（医药）

2024-12-01·Journal of Trace Elements in Medicine and Biology

Effects of tauroursodeoxycholate on arsenic-induced hepatic injury in mice: A comparative transcriptomic analysis

Article

作者: Wang, Ningning ; Li, Haonan ; Wang, He ; Li, Xuying ; Zheng, Xiujuan ; Wang, Kewei ; Nian, Shijing ; He, Rui ; Li, Mingqi ; Cao, Jianbin ; Zhang, Hua ; Jin, Baiming ; Liu, Lele

BACKGROUNDProlonged exposure to excessive arsenic (As) and its compounds can cause damage to multiple systems, including respiratory, cardiovascular, immune, nervous, and endocrine systems. Manifestations include changes in skin pigmentation, excessive keratosis on palms and soles, gastrointestinal symptoms, and anemia. The liver as an important detoxification organ of the body, is a significant target organ for arsenic toxicity, and liver diseases are common. So far, the molecular mechanism has not been fully elucidated. Evidence suggests that taurodeoxycholic acid (TUDCA) has a protective role in arsenic-induced liver injury. This study aims to reveal potential target genes at the transcriptional level following TUDCA intervention, providing insights for the intervention of arsenic-induced liver injury.METHODSThe TUDCA intervention model of arsenic liver injury in C57BL/6 N mice was established. The experiment was divided into two phases and lasted for 24 weeks. The phase I trial (12 weeks) was divided into control, low, middle and high groups according to the dose of As. The phaseⅡtrial (12 weeks) was administered in combination with 10 mg/L sodium arsenite (the first stage high arsenic group) and TUDCA, so subsequent groups was named with H indicating high arsenic. Divide into four groups: control group(C), TUDCA solvent control group(H-Vehicle), TUDCA combined with As group(H-TUDCA), arsenic group (As). As was ingested through free water and TUDCA was administered to mice by gavage at a dose of 0.1 mL/10 g.b.w (100 mg/kg) once a day for 12 weeks. The differential expression gene (DEG) profile was obtained from the second batch of mouse liver tissues by RNA sequencing technology. Comparative transcriptomic analysis methods were used to identify co-varying DEGs between arsenic induction and TUDCA intervention, along with their associated pathways. QRT-PCR was utilized for validation.RESULTSTranscriptome results showed that 487 DEGs were identified after arsenic induction. TUDCA intervention identified 231 DEGs (p-values < 0.05 and | log2(fold change) | > 1). The comparison of "AS vs C" and "H_TUDCA vs AS" identified 65 covariant DEGs, and further screened the TUDCA pathways and related genes among these genes，six pathways and 11 genes (Ccl21a, Ccr7, Mdm2, Slc2a4, Akr1b7, Pnpla3, Dusp8, Hspa1a, Cyp7a1, Cybrd1, Trpm6) were obtained. Next, we screened for covariant DEGs among the top 50 potential hub genes in arsenic-induced DEGS, and obtained 7 (Hbb-bs, Hspa1a, Mdm2, Slc2a4, Ptk6, Egr1, and Dusp8). Finally, the intersection of Hub gene and pathway gene was selected as the target genes Dusp8, Hspa1a, Mdm2 and Slc2a4. The sequencing results showed that the mRNA expressions of Dusp8, Hspa1a and Mdm2 were significantly increased after arsenic induction, while the expression of Slc2a4 was significantly decreased (P<0.05). Conversely, TUDCA intervention reversed these DEGs changes, consistent with QRT-PCR validation results.CONCLUSIONThis study contributes to understanding the potential health effects of arsenic-induced liver injury, identifying new potential targets, and providing references for TUDCA intervention.

2024-11-01·Journal of Dairy Science

Altered bile acid and correlations with gut microbiome in transition dairy cows with different glucose and lipid metabolism status

Article

作者: Zhang, Xia ; Yao, Junhu ; Li, Lei ; Liu, Huifeng ; Wang, Peiyue ; Zhang, Jun ; Bionaz, Massimo ; Lin, Pengfei

The transition from pregnancy to lactation is critical in dairy cows. Among others, dairy cows experience a metabolic stress due to a large change in glucose and lipid metabolism. Recent studies revealed that bile acids (BA), other than being involved in both the emulsification and solubilization of fats during intestinal absorption, can also affect the metabolism of glucose and lipids, both directly or indirectly by affecting the gut microbiota. Thus, we used untargeted and targeted metabolomics and 16S rRNA gene sequencing approaches to investigate the concentration of plasma metabolites and BA, the composition of the rectum microbial community, and assess their interaction in transition dairy cows. In Experiment 1, we investigated BA and other blood parameters and gut microbiota in dairy cows without clinical diseases during the transition period, which can be seen as well adapted to the challenge of changed glucose and lipid metabolism. As expected, we detected an increased plasma concentrations of BHB and nonesterified fatty acids (NEFA) but decreased concentrations of glucose, cholesterol, and triglycerides (TG). Untargeted metabolomic analysis of the plasma revealed primary BA biosynthesis was one of the affected pathways, and was consistent with the increased concentration of BA in the plasma. A correlation approach revealed a complex association between BA and microbiota with the host plasma concentration of glucose and lipid metabolites. Among BA, chenodeoxycholic acid derivates such as glycolithocholic acid, taurolithocholic acid, lithocholic acid, taurochenodeoxycholic acid, and taurodeoxycholic acid were the main hub nodes connecting microbe and blood metabolites (such as glucose, TG, and NEFA). In Experiment 2, we investigated early postpartum dairy cows with or without hyperketonemia (HPK). As expected, HPK cows had increased concentration of NEFA and decreased concentrations of glucose and triglycerides. The untargeted metabolomic analysis of the plasma revealed that primary BA biosynthesis was also one of the affected pathways. Even though the BA concentration was similar among the 2 groups, the profiles of taurine-conjugated BA changed significantly. A correlation analysis also revealed an association between BA and microbiota with the concentration in plasma of glucose and lipid metabolites (such as BHB). Among BA, cholic acid and its derivates such as taurocholic acid, tauro α-muricholic acid, and taurodeoxycholic acid were the main hub nodes connecting microbe and blood metabolites. Our results indicated an association between BA, intestinal microbe, and glucose and lipid metabolism in transition dairy cows. These findings provide new insight into the adaptation mechanisms of dairy cows during the transition period.

2024-08-01·Cell Host & Microbe

A small intestinal bile acid modulates the gut microbiome to improve host metabolic phenotypes following bariatric surgery

Article

作者: Mathur, Vasundhara ; Roberts, Cullen F ; Moscalu, Andrei ; Devlin, A Sloan ; Zhao, Lei ; Chen, Yingjia ; Harris, David A ; Chaudhari, Snehal N ; Tavakkoli, Ali ; Sheu, Eric G

Bariatric surgical procedures such as sleeve gastrectomy (SG) provide effective type 2 diabetes (T2D) remission in human patients. Previous work demonstrated that gastrointestinal levels of the bacterial metabolite lithocholic acid (LCA) are decreased after SG in mice and humans. Here, we show that LCA worsens glucose tolerance and impairs whole-body metabolism. We also show that taurodeoxycholic acid (TDCA), which is the only bile acid whose concentration increases in the murine small intestine post-SG, suppresses the bacterial bile acid-inducible (bai) operon and production of LCA both in vitro and in vivo. Treatment of diet-induced obese mice with TDCA reduces LCA levels and leads to microbiome-dependent improvements in glucose handling. Moreover, TDCA abundance is decreased in small intestinal tissue from T2D patients. This work reveals that TDCA is an endogenous inhibitor of LCA production and suggests that TDCA may contribute to the glucoregulatory effects of bariatric surgery.

项与牛磺脱氧胆酸钠(Shaperon Co., Ltd.) 相关的新闻（医药）

2024-06-30

·生物探索

Nat Metab | 洪尚宇/郑琰合作揭示生酮饮食通过调控肠道微生物-胆汁酸代谢抗肥胖的分子机制

引言生酮饮食（ketogenic diet，KD）是一种高脂肪、适量蛋白质和极低碳水化合物占比的特殊配方饮食【1】。KD能够在短期内降低体重和血糖水平，是肥胖管理中的一种饮食选择【2,3】。然而，KD抗肥胖和调控能量平衡的分子机制十分复杂，至今仍不明确。 2024年6月27日，复旦大学生命科学学院洪尚宇研究员团队和郑琰研究员团队联合在Nature Metabolism杂志上发表了题为Ketogenic diet-induced bile acids protect against obesity through reduced calorie absorption的研究论文，发现牛磺脱氧胆酸（taurodeoxycholic acid, TDCA）和牛磺熊去氧胆酸（tauroursodeoxycholic acid, TUDCA）是KD发挥抗肥胖作用的关键内源性代谢物，并进一步揭示了KD通过调控肠道微生物结构，影响胆汁酸成分，并最终降低体重的分子机制。既往人群和动物研究表明，肠道菌群及其次级代谢产物可能在调节KD诱导的代谢变化中发挥至关重要的作用【4, 5】。作者首先研究了KD诱导的肠道微生物及其代谢物变化与介导的体重减轻之间是否存在因果关系，运用广谱靶向代谢组学检测技术、鸟枪法宏基因组测序技术、肠道转录组测序技术并结合代谢物回补、抗生素干预、微生物移植、BODIPY荧光探针标记等体内外实验，发现受肠道微生物调控的特异性胆汁酸TDCA和TUDCA是KD发挥抗肥胖作用的关键小分子代谢物。机制上，KD通过降低编码胆盐水解酶（bile salt hydrolase, BSH）的肠道微生物丰度（如Lactobacillus murinus ASF361），导致TDCA和TUDCA的解偶联减少和循环水平上调。TDCA和TUDCA进一步通过抑制肠道碳酸酐酶1（carbonic anhydrase 1, Car1）的表达，降低肠道对摄入能量的吸收水平来减轻体重。此外，作者利用多种肥胖/糖尿病小鼠模型、自然人群队列数据和低碳水化合物生酮饮食干预试验数据对上述发现的临床适用性进行了探索。研究发现，口服TDCA和TUDCA能够显著降低肥胖/糖尿病小鼠的体重和空腹血糖水平，且无明显副作用；人体循环TDCA和TUDCA水平与身体质量指数（body mass index, BMI）和空腹血糖水平呈显著负相关；低碳水化合物生酮饮食干预导致参与者体重减轻的同时，伴随循环TDCA和TUDCA水平的上调。上述结果表明，TDCA和TUDCA能够独立于KD发挥抗肥胖的作用，有望成为治疗肥胖及其并发症的候选小分子。综上，本研究揭示了KD通过调控肠道微生物-胆汁酸代谢抗肥胖的分子机制：KD诱导肠道微生物依赖性TDCA和TUDCA的循环水平上调，抑制肠道Car1的表达，进而通过降低肠道能量吸收水平导致体重减轻。该研究为肥胖的预防和治疗提供了潜在的新靶点和新药物。 KD通过TDCA和TUDCA抗肥胖的机制示意图（Credit: Nature Metabolism）参考文献 https://www.nature.com/articles/s42255-024-01072-1 责编|探索君排版|探索君文章来源|“BioArt” End 往期精选围观一文读透细胞死亡(Cell Death) | 24年Cell重磅综述（长文收藏版）热文 Cell | 是什么决定了细胞的大小？热文 Nature | 2024年值得关注的七项技术热文 Nature | 自身免疫性疾病能被治愈吗？科学家们终于看到了希望热文 CRISPR技术进化史 | 24年Cell综述

临床研究

2022-04-19

·PR Newswire

Bridge Biotherapeutics Enters into an Exclusive License Agreement with Shaperon to Strengthen Its IPF Franchise

Bridge Biotherapeutics (KQ288330), a South Korean clinical-stage biotechnology company focused on developing novel drugs for fibrosis, inflammation, and cancer, today announced that the company has signed an exclusive in-license agreement with Shaperon, a South Korean clinical-stage biotech company, for its GPCR19 (G protein-coupled receptor 19) agonist, coded "BBT-209", in order to develop a novel therapy for the treatment of idiopathic pulmonary fibrosis (IPF). Shaperon, the originator, has identified that BBT-209, a first-in-class GPCR19 agonist, controls GPCR19-P2X7 expressions and downregulates component proteins of NLRP3 so that inflammation signaling networks can be significantly suppressed by the compound's mode of action. Through IPF animal models, Bridge Biotherapeutics has confirmed that the drug candidate shows treatment efficacy through its robust anti-inflammatory activities. The company will utilize this data when developing monotherapy and/or combination therapy strategies. By entering into the license agreement, Bridge will make an upfront payment of approximately USD 1.63 million (KRW 2 billion). The potential deal value equates to approximately USD 24.4 million (KRW 30 billion) including upfront, milestone, and royalty payments. "We are highly excited to in-license BBT-209, which is known to be the first-in-class GPCR19 agonist for the treatment of idiopathic pulmonary fibrosis," said James Lee, CEO of Bridge Biotherapeutics. "By jointly working with Shaperon, our development team will make the best effort to ensure the rapid advancement for our novel drug candidate, along with the other pipeline assets under the company's IPF franchise," James added. "We hope that BBT-209 will become a breakthrough therapy for patients with IPF, who are currently lacking treatment options" and "We will accelerate the development of innovative treatments, to help improve the quality of life for patients suffering from rare diseases, such as IPF, through our partnership with Bridge Biotherapeutics, which has a proven track record in both global drug development and business development," said Seung-Yong Seong, M.D., Ph.D., and Myung-Sea Lee M.D., M.B.A., co-CEOs of Shaperon. Bridge Biotherapeutics reinforces its strategic focus on disease areas with significant unmet medical needs and lacks novel approved therapies, including cancers and various fibrotic diseases. Relating to idiopathic pulmonary fibrosis, the company has been accelerating the development of BBT-877 (an autotaxin inhibitor), BBT-301 (an ion channel modulator), and BBT-209 (a GPCR19 agonist).

特发性肺纤维化引进/卖出合作突破性疗法First in Class

100 项与牛磺脱氧胆酸钠(Shaperon Co., Ltd.) 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
轻度特应性皮炎	临床2期	美国	Shaperon, Inc.	2024-03-01
中度特应性皮炎	临床2期	美国	Shaperon, Inc.	2024-03-01
特应性皮炎	临床2期	韩国	Shaperon, Inc.	2020-08-26
脓毒症	临床2期	韩国	Shaperon, Inc.	2019-12-05
痴呆	临床1期	韩国	Kukjeon Pharm Co., Ltd.	2023-09-13

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03492398 (Shaperon, CTgov)	临床1期	特应性皮炎	56	HY209 (Cohort A HY209 0.05% Gel)	壓糧積範蓋願顧鏇蓋範(範齋鹹簾製繭鏇鹹膚網) = 蓋餘選鹽鹽鏇觸簾構獵鏇願齋艱夢製廠膚鹽淵 (簾襯廠憲糧願壓襯鏇選, 願窪遞網淵繭範願築夢 ~ 簾範衊蓋襯膚繭糧廠艱) 更多	-	2020-10-19
				HY209 (Cohort A HY209 0.1% Gel)	壓糧積範蓋願顧鏇蓋範(範齋鹹簾製繭鏇鹹膚網) = 憲簾壓蓋製鏇艱獵顧顧鏇願齋艱夢製廠膚鹽淵 (簾襯廠憲糧願壓襯鏇選, 鑰鹽範餘鹹艱夢夢壓廠 ~ 構糧鹽築憲艱憲製衊襯) 更多