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.

EUCTR2022-001152-42-BG

/ Not yet recruiting临床2/3期

A Randomized, Double-blinded, Placebo-controlled, Parallel-treatment Group, Adaptive Design, Multi-center, Phase 2b/3 Trial to Evaluate Efficacy and Safety of NuSepin® Intravenous Infusion in COVID-19 Pneumonia Patients

开始日期2022-09-05

申办/合作机构

Shaperon, Inc.

100 项与牛磺脱氧胆酸钠相关的临床结果

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100 项与牛磺脱氧胆酸钠相关的转化医学

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100 项与牛磺脱氧胆酸钠相关的专利（医药）

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3,632

项与牛磺脱氧胆酸钠相关的文献（医药）

2025-12-31·Gut Microbes

The microbiota-derived bile acid taurodeoxycholic acid improves hepatic cholesterol levels in mice with cancer cachexia

Article

作者: Piron, Edwige ; Neyrinck, Audrey M. ; Roumain, Martin ; Thissen, Jean-Paul ; Bonetto, Andrea ; Pin, Fabrizio ; Huot, Joshua R. ; Muccioli, Giulio G. ; Loriot, Axelle ; Thibaut, Morgane M. ; Delzenne, Nathalie M. ; Rodriguez, Julie ; Massart, Isabelle ; Gillard, Justine ; Bindels, Laure B.

Alterations in bile acid profile and pathways contribute to hepatic inflammation in cancer cachexia, a syndrome worsening the prognosis of cancer patients. As the gut microbiota impinges on host metabolism through bile acids, the current study aimed to explore the functional contribution of gut microbial dysbiosis to bile acid dysmetabolism and associated disorders in cancer cachexia. Using three mouse models of cancer cachexia (the C26, MC38 and HCT116 models), we evidenced a reduction in the hepatic levels of several secondary bile acids, mainly taurodeoxycholic (TDCA). This reduction in hepatic TDCA occurred before the appearance of cachexia. Longitudinal analysis of the gut microbiota pinpointed an ASV, identified as Xylanibacter rodentium, as a bacterium potentially involved in the reduced production of TDCA. Coherently, stable isotope-based experiments highlighted a robust decrease in the microbial 7α-dehydroxylation (7α-DH) activity with no changes in the bile salt hydrolase (BSH) activity in cachectic mice. This approach also highlighted a reduced microbial 7α-hydroxysteroid dehydrogenase (7α-HSDH) and 12α-hydroxysteroid dehydrogenase (12α-HSDH) activities in these mice. The contribution of the lower production of TDCA to cancer cachexia was explored in vitro and in vivo. In vitro, TDCA prevented myotube atrophy, whereas in vivo hepatic whole transcriptome analysis revealed that TDCA administration to cachectic mice improved the unfolded protein response and cholesterol homeostasis pathways. Coherently, TDCA administration reversed hepatic cholesterol accumulation in these mice. Altogether, this work highlights the contribution of the gut microbiota to bile acid dysmetabolism and the therapeutic interest of the secondary bile acid TDCA for hepatic cholesterol homeostasis in the context of cancer cachexia. Such discovery may prove instrumental in the understanding of other metabolic diseases characterized by microbial dysbiosis. More broadly, our work demonstrates the interest and relevance of microbial activity measurements using stable isotopes, an approach currently underused in the microbiome field.

2025-04-01·ENVIRONMENTAL RESEARCH

Maternal per- and polyfluoroalkyl substances exposure, cord blood lipidomics and infant anthropometry: A mediation analysis

Article

作者: Li, Likang ; Liu, Xiaofang ; Miao, Maohua ; Yuan, Wei ; Xi, Jianya ; Xie, Zhenzhen ; Yang, Lan ; Ji, Honglei ; Liang, Hong ; Wang, Yan

Maternal exposure to per- and polyfluoroalkyl substances (PFAS) has been associated with offspring adiposity; however, underlying mechanisms remain unclear. In this study, we quantified 11 PFAS in maternal plasma collected between 12 and 16 gestational weeks and 104 lipid metabolites in the cord blood of 525 mother-infant pairs. Principal components of multiple PFAS compounds, extracted by principal component analysis, were employed to investigate the effect of the PFAS mixture. Infant anthropometric indicators included weight, length, waist/arm circumference, and abdominal/triceps/subscapular skinfold thickness at birth and 6 and 12 months old. Multiple linear regression showed that maternal PFAS exposure was primarily associated with increased glycerophospholipids and decreased fatty acyls and bile acids in cord blood. Four glycerophospholipids (16:0 PI, 16:0-18:1 PI, 18:0-20:4 PI, and 18:0-18:1 PS), fatty acyls (5(S)-HETE, 15(S)-HETE, 13-HDoHE, and dhkPGF2), and bile acids (GCA, TCA, TCDA, and TDCA) partially mediated the positive associations of the first principle component of PFAS compounds (with positive loadings for all PFAS compounds), PFNA, and PFUdA with infant skinfold thickness with mediating proportions ranging from 15.24% to 33.39%. Our findings provide novel insights into mechanisms underlying the effects of maternal PFAS exposure on infant growth.

2025-03-01·Animal Nutrition

Folic acid alleviates the negative effects of dexamethasone induced stress on production performance in Hyline Brown laying hens

Article

作者: Wang, Yumeng ; Liu, Yanli ; Li, Sijing ; Niu, Yuxin ; Liu, Xiaoying ; Wang, Chaohui ; Yang, Xiaojun ; Yang, Xin ; Sun, Xi ; Ren, Zhouzheng ; Li, Yun

Multiple stressors are believed to deteriorate production performance and cause substantial economic losses in commercial poultry farming. Folic acid (FA) is an antioxidant compound that can improve oocyte function and regulate gut microbiota composition. The current study was conducted to investigate the role of FA in alleviating stress and improving production performance. Sixty Hyline Brown laying hens at 21 weeks of age were randomly divided into three groups, with 10 replicates in each group and each replicate containing two chickens. Each group received basic diet and saline injection (Con group), basic diet with dexamethasone (DXM) injection (DXM group), or basic diet supplemented with FA (13 mg/kg in the premix) with DXM injection (FA group). The feeding trial lasted five weeks. Birds in the DXM and FA groups receiving subcutaneous DXM injections at a dosage of 4.50 mg/kg per day during the first seven days of the trial. Results showed that the levels of corticosterone, triglyceride, total cholesterol, and malondialdehyde in serum were significantly increased in the DXM group (P < 0.05), while the concentrations of FA and 5-methyltetrahydrofolate were decreased in the DXM group (P < 0.05). Laying hens in the DXM group had lower laying rates and egg quality, including egg weight, eggshell thickness, eggshell strength, albumen height, and Haugh units (P < 0.05). Conversely, FA alleviated these negative impacts. Through transcriptome analysis, a total of 247 and 151 differentially expressed genes were identified among the three groups, and 32 overlapped genes were further identified. Moreover, 44 and 59 differential metabolites were influenced by DXM and FA, respectively. Kyoto Encyclopedia of Genes and Genomes enrichment from the transcriptome and metabolomics showed that the reduced production performance may be due to the disturbance of oocyte production, calcium metabolism, and oxidative stress. Analysis of 16S rRNA gene amplicon sequences revealed the differential microbial composition and potential functional changes among the different groups. LEfSe analysis showed that Mucispirillum and Nautella were the predominant bacteria in the DXM group, while Clostridium was the predominant bacteria in the FA group. Functional prediction demonstrated that stressors enhanced fatty acid biosynthesis, while betaine biosynthesis and retinol metabolism were elevated in the FA group. Dietary FA reversed the elevated levels of bile acids (BA), including cholic acid, taurodeoxycholic acid, and taurochenodeoxycholic acid (P < 0.05). The DXM group showed an overall decrease in short-chain fatty acids (SCFA), but FA restored the concentrations of acetic acid, propionic acid, and isobutyric acid (P < 0.05). In conclusion, this study reveals that dietary FA can alleviate the degradation of production performance caused by stress through improving circulating antioxidant capacity, maintaining intestinal microbiota homeostasis, and regulating SCFA and BA biosynthesis. Thus, highlighting the prominent role of gut microbe-host interactions in alleviating multi-stresses.

项与牛磺脱氧胆酸钠相关的新闻（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.libproxy1.nus.edu.sg/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

2024-03-18

·BioSpace

Shaperon Enrolls Its First Patient in Phase 2 U.S. Clinical Trial for Atopic Dermatitis Therapy 'Nugel'

210 Patients With Multi-Racial Atopic Dermatitis...Phase 2 Clinical Trial Begins CAMBRIDGE, Mass. & SEOUL, South Korea--(BUSINESS WIRE)-- Shaperon, Inc. (Kosdaq: 378800), a biotechnology company developing innovative immune drugs, announced the enrollment of the first patient in the Phase 2 clinical trial for Nugel, its therapy for Atopic Dermatitis. This milestone marks the start of a crucial phase in Shaperon’s effort to advance treatment for patients globally. With FDA approval secured for the Global Phase 2 Clinical Trials (IND) of Nugel in September 2023, Shaperon is dedicated to evaluating its efficacy in improving the Eczema Area Severity Index (EASI) across a diverse cohort of 210 patients with mild to moderate atopic dermatitis. Employing a rigorous double-blind, placebo-controlled methodology, the trial is anticipated to conclude by the first half of 2026. Market research forecasts indicate a robust growth of over 8.7%, projecting the global atopic dermatitis market to reach $19.1 billion by 2030. Presently, patients rely on steroids and FDA-approved medications, yet there remains a pressing need for novel drugs due to their adverse effects and limited efficacy. Of particular note, more than 70% of patients exhibit positive responses to the biomarker discovered during Shaperon's phase 2 clinical trials in Korea, categorized as "A type A atopic patients." This treatment, distinguished by its superior safety and efficacy compared to existing JAK inhibitors or PDE4 inhibitors in the market, has garnered attention at U.S. and European forums. Shaperon has already initiated patent applications for this biomarker, enabling tailored treatments for patients showing exceptional responses to Nugel. Nugel represents a paradigm shift in atopic dermatitis therapy as the world's first inflammation control drug targeting 'GPCR19' action. Its unique mechanism of action, exclusive to immune-related cells, offers minimal side effects while effectively addressing inflammatory pathways. Beyond atopic dermatitis, Nugel holds promise for treating a spectrum of skin conditions, further underscoring its potential impact on global healthcare. Dr. Seung-Yong Seong, CEO of Shaperon, reaffirms Shaperon's commitment to advancing Nugel's global presence and facilitating technology transfer through the Phase 2 clinical trials. Leveraging innovative approaches such as a smartwatch-based AI medication management system demonstrates Shaperon's dedication to optimizing patient outcomes and data reliability. The establishment of Hudson Therapeutics, Shaperon's U.S.-based subsidiary, reinforces its strategic vision for global expansion and technology exports. ABOUT SHAPERON Shaperon is a clinical stage biotech company developing novel inflammasome inhibitors. Its unique mechanism of action of GPCR19-P2X7 modulation suppresses a broad spectrum of inflammatory cytokines including IL-1β, IL-18, IL-6, and TNF-α by controlling both priming and activation phase of inflammasome, whereas conventional approaches are designed to suppress only the activation phase. With this unique and novel modality which is best suited to address complex immune-mediated inflammatory disorders, Shaperon is currently developing multiple clinical programs in atopic dermatitis, cytokine release syndrome, Alzheimer’s disease, Obesity and MASH. ABOUT Hudson Therapeutics Hudson Therapeutics, a US subsidiary of Shaperon, was founded in 2023 to lead global clinical trials and business development of assets from Shaperon. Hudson’s pipeline includes immunology clinical assets in Atopic Dermatitis, Covid-19, Alzheimer’s Disease and preclinical programs focused in Obesity and other indications, combined with their nanobody platform. View source version on businesswire.com: Contacts Ellie Jung (ellie@hudsontherapeutics.com) Source: Shaperon View this news release online at:

临床2期

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).

Bridge Biotherapeutics, Inc.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相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
新型冠状病毒感染	临床3期	韩国	Shaperon, Inc.	2022-04-12
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
痴呆	临床1期	韩国	Kukjeon Pharm Co., Ltd.	2023-09-13
脓毒症	临床1期	美国	Shaperon, Inc.	2019-12-05
阿尔茨海默症	临床1期	韩国	Shaperon, Inc.	-
特发性肺纤维化	临床前	美国	BridgeBio Pharma, Inc.	2025-02-01
特发性肺纤维化	临床前	韩国	Shaperon, Inc.	2025-02-01

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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)	壓鹹網糧鬱簾憲夢壓廠 = 築醖遞艱網願繭鹽膚膚艱獵積顧選遞遞選顧蓋 (衊願鹹夢夢願簾願構淵, 鹽網廠夢蓋醖觸遞網選 ~ 膚製鹽鹽鹽繭獵鹹衊鹽) 更多	-	2020-10-19
				HY209 (Cohort A HY209 0.1% Gel)	壓鹹網糧鬱簾憲夢壓廠 = 廠衊選艱觸鑰遞醖鬱簾艱獵積顧選遞遞選顧蓋 (衊願鹹夢夢願簾願構淵, 觸鏇積範襯鏇鏇願餘鏇 ~ 醖顧鏇製範製鏇廠夢窪) 更多