This is a multicenter, interventional, non-randomized study among patients with a relapsed or refractory Wilms tumor. The study will aim to assess efficacy of metronomic chemotherapy, in terms of disease control after two cycles of metronomic chemotherapy.

开始日期2022-09-14

申办/合作机构

Centre Oscar Lambret

KCT0006687

/ Completed临床4期IIT

A multicenter, open-label, single-arm, investigator-initiated clinical trial to evaluate the efficacy and safety of alitretinoin in patients with chronic hand eczema in real patient encounter

开始日期2022-01-28

申办/合作机构-

NCT05077813

/ Unknown status临床2期IIT

Utilizing the Crosstalk Among Chicoric Acid, 13-Cis Retinoic Acid(Aerosolized), Minocycline and Vitamin D as a Potent Quadrate Therapy for Treating Patients With Multidrug-resistant TB and Patient With Both Multidrug-resistant TB and COVID-19

Utilizing the Crosstalk Among Chicoric Acid, 13-Cis Retinoic Acid(Aerosolized), Minocycline and Vitamin D as a Potent Quadrate Therapy for treating patients with Multidrug-resistant TB and patient with both Multidrug-resistant TB and COVID-19 . A double-edged sword Clinical Study
I)Part of Tuberculosis
Tuberculosis (TB) is a major infectious disease killer globally. It affected 10 million and killed 1.4 million people in 2019 alone. The predicted impact of the COVID-19 pandemic is an additional 190,000 TB deaths in 2020, and it is expected in the next 5 y that there will be up to a 20% increase in the global TB disease burden , stressing the critical need for new safe and effective drugs against Mycobacterium tuberculosis (Mtb). In addition, controlling multidrug-resistant TB (MDR-TB) presents a huge public health challenge . New drug discovery could require several years with no guarantee but repurposing established may be useful to treat patients with tuberculosis . Here we demonstrate that we could utilize the crosstalk among Chicoric Acid, 13-Cis Retinoic Acid, Minocycline , and vitamin D as a novel quadrate therapy against TB.Drug-resistant tuberculosis represents a global emergency, requiring new drugs. Recently Minocycline was found to be highly potent in laboratory strains of Mycobacterium TB, and 30 drug-sensitive and multidrug/extensively drug-resistant clinical strains were susceptible to clinically attainable dosages. The lung concentration-time profiles of a 7 mg/kg/day human-equivalent minocycline dosage yielded bacterial kill rates comparable to first-line antituberculosis drugs. Extracellular bacilli were destroyed directly by minocycline. Minocycline also killed intracellular bacilli indirectly through granzyme A-driven apoptosis. Furthermore, minocycline showed dose-dependent antiinflammatory effect, suggesting that it may protect tuberculosis patients against immunopathology. A study showed that M. tuberculosis induced the expression of indoleamine 2,3-dioxygenase (IDO), an enzyme involved in tryptophan catabolism, in macrophages and in the lungs of animals (mice and macaque) with active disease. In a macaque model of inhalation TB, suppression of IDO activity reduced bacterial burden, pathology, and clinical signs of TB disease, leading to increased host survival. This increased protection was accompanied by increased lung T cell proliferation, induction of inducible bronchus-associated lymphoid tissue and correlates of bacterial killing . A recent study showed that Minocycline-induced significantly inhibition of IDO expression. But Minocycline-induced inhibition of IDO expression is retinoid-dependent. The combined treatment with minocycline and retinol, however, resulted in a striking, statistically significant decrease in IDO. Co-treatment with minocycline and retinol again resulted in decreased TNF-α and IL-6 levels. A study showed that IL-6 inhibits IFN-γ induced autophagy in Mycobacterium (TB) H37Rv infected macrophages. As well as neutralization of endogenous IL-6 by anti-IL-6 antibody significantly enhances the IFN-γ mediated killing of the intracellular bacteria. Minocycline's anti-inflammatory effects are mediated through RAR signaling. Therefore, The combined treatment with minocycline and retinol is expected to effectively inhibit (TB) and its inflammatory complication, Fortunately, Retinoic Acid significantly inhibits the in vivo growth of M. tuberculosis and the development of tuberculosis. In addition to, 13-Cis RA and Chicoric Acid ( CA ) enhanced the cell surface expression of HLA-DR and CD14 molecules on U937 macrophages and prevented the growth of Mtb within macrophages. Moreover, 13-cis RA and CA, have increased NO generation compared to untreated control macrophages, significantly . Both drugs have a significant inhibitory effect on Mtb growth but CA at the highest concentration was more potent than 13-cis RA . Therefore we will use retinoic acid to induce the effect of Minocycline as well as its ability to inhibit tuberculosis in combination with CA .Recent data showed that Vitamin D support innate immune responses to Mycobacterium TB and Low vitamin D levels were associated with a 5-fold increased risk for progression to tuberculosis. Deficiency of vitamin D has long been implicated in activation of (TB) . Serum vitamin D in TB patients are lower than in healthy controls . Vitamin D has been found to speed up the clearance of (TB) bacteria from the lungs of people with multi-drug resistant TB, according to a study of 1,850 patients. It was showed that Vitamin D receptor (VDR) must form a heterodimer complex with retinoid X receptor (RXR) to regulate gene transcription. Retinol plays a crucial role in lung development and signaling the vitamin D pathway. 9-cis-retinoic acid, an active vitamin A metabolite and the ligand of RXR, assists VDR signaling and suppresses the degradation of circulating vitamin D.

开始日期2021-12-01

申办/合作机构

Kafrelsheikh University

100 项与阿利维A酸相关的临床结果

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100 项与阿利维A酸相关的转化医学

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100 项与阿利维A酸相关的专利（医药）

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2,686

项与阿利维A酸相关的文献（医药）

2025-06-01·AQUACULTURE

Dietary methionine requirement of postlarval shrimp (litopenaeus vannamei): Based on growth performance, antioxidant capacity, and lipid metabolism

作者: Liu, Yucheng ; Liu, Hongyu ; Yang, Qihui ; Song, Jiahao ; Qu, Kangyuan ; Zhang, Shuang ; Tan, Beiping ; Li, Yunzhen ; Ma, Yuxuan ; Xie, Shiwei

A 25-day experiment assessed the optimal methionine requirements for postlarval shrimp litopenaeus vannamei (initial weight: 1.3 mg) using five diets with consistent protein and lipid content but different methionine levels (0.86-1.32%).Dietary methionine levels did not significantly impact growth performance and body composition; however, the control group exhibited higher survival rates.Groups M1 and M2 showed increased antioxidant enzyme activities (SOD and T-AOC) and decreased MDA levels.Dietary methionine supplementation activates immune-related genes (toll, dorsal, relish, and myd88), potentially enhancing immune function.The lipid metabolism genes (srebp, acc1, ampk, and cpt-1) exhibited significant upregulation in the M2 and M3 groups, indicating metabolic changes to meet energy demands.In the M1 group, odc-antizym was upregulated while sam-synth was downregulated, indicating alterations in methionine cycle regulation and cellular methylation.Metabolomic anal. revealed that the synthesis of unsaturated fatty acids, the pathway of arachidonic acid metabolism, and other metabolic pathways associated with bile acid metabolism exhibited enhanced activity in the M2 group relative to the M0 group.Concurrently, the levels of methionine and cholesterol were markedly diminished in the M2 group.When the low salt stress lasted for 4 h, there was a significant difference in survival rate among the groups.Quadratic polynomial regression anal. was conducted on the percent weight gain (WG), and a folded model anal. was performed on the survival rate after low salt stress to determine the ideal dietary methionine levels as 1.13% and 1.19%, resp.

2025-05-01·AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE

Exploring the Varied Clinical Presentation of Pediatric Asthma through the Metabolome

Article

作者: Chen, Liang ; Kelly, Rachel S ; Prince, Nicole ; Sharma, Rinku ; McGeachie, Michael ; Broadhurst, David I ; Mendez, Kevin M ; Huang, Mengna ; Chu, Su H ; Chen, Yulu ; Hecker, Julian ; Lasky-Su, Jessica A ; Celedón, Juan C ; Clish, Clary ; Reinke, Stacey N ; Weiss, Scott T ; Gerszten, Robert ; Kachroo, Priyadarshini ; Wheelock, Craig E ; Avila, Lydiana ; Cote, Margaret

RATIONALE:

Pediatric asthma is heterogeneous, with varied clinical presentations and treatment responses. Metabolomic profiling may uncover shared and unique biological mechanisms across clinical traits that characterize pediatric asthma.

OBJECTIVES:

To characterize the varied clinical presentation of pediatric asthma by examining the metabolome's relationship with 22 clinical traits, categorized into 5 phenotypic domains: airway hyperresponsiveness (AHR), atopy, lung function (LF), blood eosinophil (B-EOS), and blood neutrophil (B-NEU).

METHODS:

Metabolomic profiling was conducted on plasma samples from children in the Childhood Asthma Management Program (CAMP) (n=953) and the Genetic Epidemiology of Asthma in Costa Rica Study (GACRS) (n=1,155) studies. We identified domain-specific and multi-domain metabolites using a fixed-effect meta-analysis of generalized linear models between metabolites and 22 clinical traits. Metabolomic Risk Scores (MRSs) were developed to summarize the metabolic processes for each domain at the patient level.

MEASUREMENTS AND MAIN RESULTS:

There were 154 unique metabolites significantly associated with at least one of 22 clinical traits (q-value<0.05). Histamine and kynurenine were significant across 4 domains, while 7 metabolites-12,13-diHOME, azelate, sebacate, PC(P-36:0)/PC(O-36:1), taurine, nudifloramide, and niacinamide-were significant across 3. Notable domain-specific metabolites include n-oleoyl dopamine for AHR, 9-cis-retinoic acid for lung function, phosphatidylcholines for B-EOS, and 2-hydroxybutyric acid for B-NEUT. We then applied the domain-specific MRSs to previously identified patient clusters, enabling a more comprehensive characterization of each endotype.

CONCLUSION:

This study demonstrated the power of the metabolome to capture the heterogeneity in the clinical presentation of pediatric asthma and to develop clinically relevant MRSs that inform our understanding of specific metabotypes to guide targeted treatment approaches.

2025-05-01·LANCET

Efficacy and safety of topical delgocitinib cream versus oral alitretinoin capsules in adults with severe chronic hand eczema (DELTA FORCE): a 24-week, randomised, head-to-head, phase 3 trial

Article

作者: Mellerup, Natja ; Plohberger, Ursula ; Reguiai, Ziad ; Sondermann, Wiebke ; Woolf, Richard ; Giménez-Arnau, Ana Maria ; Lynde, Charles ; Costanzo, Antonio ; Pinter, Andreas ; Silvestre, Juan F ; Østerdal, Marie Louise ; Bauer, Andrea ; Legat, Franz J ; Ryttig, Lasse

BACKGROUND:

Chronic hand eczema is a heterogeneous, fluctuating, and long-lasting disease affecting the hands and wrists that substantially affects quality of life. For severe chronic hand eczema, topical corticosteroids are often unsatisfactory and systemic treatment can be required. The aim of the head-to-head, phase 3 DELTA FORCE trial was to evaluate the efficacy and safety of topical delgocitinib cream versus oral alitretinoin, the only currently approved systemic drug for severe chronic hand eczema.

METHODS:

This randomised, assessor-masked, trial was conducted at 102 trial centres in Austria, Canada, France, Germany, Italy, Norway, Poland, Slovakia, Spain, and the UK. Adults (aged ≥18 years) with severe chronic hand eczema were randomly assigned (1:1) via an interactive response technology system to delgocitinib cream 20 mg/g (twice daily) or alitretinoin 30 mg (once daily) for up to 24 weeks. The primary endpoint was change in Hand Eczema Severity Index (HECSI) score from baseline to week 12. Efficacy of delgocitinib cream versus alitretinoin was assessed in all eligible randomly assigned patients who had available data at baseline, and safety was assessed in all patients exposed to trial treatment. The trial is registered with ClinicalTrials.gov (NCT05259722) and is complete.

FINDINGS:

Between June 15, 2022, and Dec 5, 2023, 513 (334 [65%] female and 179 [35%] male) patients were randomly assigned to receive delgocitinib cream (n=254) or alitretinoin (n=259). Ten patients were excluded after randomisation due to not meeting eligibility criteria, so the full analysis set consisted of 250 patients in the delgocitinib group and 253 in the alitretinoin group. One patient in the delgocitinib group and three in the alitretinoin group were excluded from the primary analysis as they had missing HECSI data at baseline. A significantly greater least squares mean change in HECSI score from baseline to week 12 was observed with delgocitinib cream (-67·6 [SE 3·4]; n=249) versus alitretinoin (-51·5 [3·4]; n=250; difference -16·1 [95% CI -23·3 to -8·9], p<0·0001). Fewer patients reported adverse events in the delgocitinib group (125 [49%] of 253 patients) than in the alitretinoin group (188 [76%] of 247). The most frequent adverse events were headache (ten [4%] in the delgocitinib group vs 80 [32%] in the alitretinoin group), nasopharyngitis (30 [12%] vs 34 [14%]), and nausea (one [<1%] vs 14 [6%]).

INTERPRETATION:

Delgocitinib cream showed superior efficacy and a more favourable safety profile versus oral alitretinoin over 24 weeks. These results support the benefit of delgocitinib cream in patients with severe chronic hand eczema.

FUNDING:

LEO Pharma.

项与阿利维A酸相关的新闻（医药）

2025-04-24

·Business Wire

LEO Pharma Announces Publication of Head-to-Head DELTA FORCE Study Results in The Lancet

TORONTO--(BUSINESS WIRE)--LEO Pharma A/S, a global leader in medical dermatology, is pleased to share that The Lancet, which is considered one of the most influential peer-reviewed medical journals in the world, has published an article discussing the findings of the DELTA FORCE trial for investigational delgocitinib cream. The publication summarizes the results of DELTA FORCE, a phase 3, two-arm trial (N=513) that compares the efficacy and safety of delgocitinib cream with alitretinoin capsules.1 Alitretinoin is the only treatment currently approved in Canada to treat severe CHE in patients who do not respond to topical corticosteroids.2 In Canada and the US, delgocitinib cream is currently under review and has not been approved by Health Canada or the FDA. Delgocitinib cream achieved the primary outcome measure of the DELTA FORCE trial, assessing the Hand Eczema Severity Index (HECSI) scores from baseline to Week 12 compared to alitretinoin capsules. Delgocitinib cream also met all key secondary outcome measures, including Investigator’s Global Assessment (IGA)-CHE treatment success, a reduction in HECSI scores from baseline to Week 24, and improvement in health-related quality of life, as measured by the Dermatology Life Quality Index (DLQI). Furthermore, patients receiving delgocitinib cream had fewer treatment-emergent adverse events (AEs) compared to those receiving alitretinoin capsules. “The discussion of delgocitinib and the presentation of DELTA FORCE data in The Lancet is an exciting moment for the LEO Pharma team,” said Robert Spurr, EVP, LEO Pharma, North America and President, LEO Pharma, US. “We are proud to contribute to the overall understanding of moderate to severe chronic hand eczema, helping uncover potentially new treatment options for those living with skin conditions like CHE.” “We know that CHE is an under researched condition,” commented Dr. Charles Lynde, Chief Medical Director, The Lynde Institute for Dermatology & Lynderm Research Inc. and Associate Professor, University of Toronto, Department of Medicine. “We hope that discussions of the DELTA FORCE program, like that published in The Lancet, will continue to raise awareness of the disease, inspire new research, and ultimately help improve the quality of life of those living with CHE.” About The Lancet The Lancet is a world-leading source of clinical, public health, and global health knowledge. Lancet journals have an extensive global reach with more than 36.6 million annual visits and 108.1 million downloaded articles.3 About the DELTA FORCE Trial DELTA FORCE was a 24-week, randomized, assessor-blinded, active-controlled, parallel-group, phase 3, two-arm trial to compare the efficacy and safety of delgocitinib cream twice-daily with alitretinoin capsules once-daily in adult participants with severe chronic hand eczema.1 The primary endpoint of the trial was the change in Hand Eczema Severity Index (HECSI) score from baseline to Week 12. Participants assigned to receive delgocitinib cream applied the drug to the skin twice a day for 16 weeks. Participants assigned to receive alitretinoin capsules took the drug orally once a day for 12 weeks. All participants were permitted to continue for up to 24 weeks if the doctor considered that they were benefiting from the treatment.1 All 14 North American DELTA FORCE clinical trial sites were located in Canada.4 About Chronic Hand Eczema Chronic Hand Eczema (CHE) is defined as hand eczema (HE) that lasts for more than three months or relapses twice or more within a year.5,6 HE is the most common skin disorder of the hands7 with a prevalence rate of approximately 4.7%.8 In a substantial number of patients, HE can develop into a chronic condition.7 CHE is a fluctuating disorder characterized by itch and pain, and patients may experience signs such as erythema, scaling, lichenification, hyperkeratosis, vesicles, edema, and fissures on hands and wrists.2 CHE has been shown to cause psychological and functional burdens that impact patient quality of life,9 with approximately 70% of individuals who live with severe CHE admitting to problems in performing everyday activities, and suffering disruption in their daily life due to the condition.10 Furthermore, careers and earning potential have also been shown to be impacted by the burden of living with CHE.11 About delgocitinib cream Delgocitinib cream is a topical pan-Janus kinase (JAK) inhibitor for the treatment of moderate to severe CHE. It inhibits the activation of JAK-STAT signaling, which plays a key role in the pathogenesis of CHE.12 The pathophysiology is characterized by skin barrier dysfunction, inflammation of the skin, and alterations of the skin microbiome.13 In 2014, LEO Pharma A/S and Japan Tobacco Inc. (JT) entered into a license agreement in which LEO Pharma gained exclusive rights to develop and commercialize delgocitinib cream for topical use in dermatological indications worldwide, excluding Japan, where JT retains rights. Delgocitinib cream is currently approved and marketed under the trade name Anzupgo® in the European Union, United Kingdom, Switzerland and the United Arab Emirates for the treatment of moderate to severe chronic hand eczema (CHE) in adults for whom topical corticosteroids are inadequate or inappropriate. Delgocitinib is under investigation in Canada and the United States. About LEO Pharma LEO Pharma is a global leader in medical dermatology. We deliver innovative solutions for skin health, building on a century of experience with breakthrough medicines in healthcare. We are committed to making a fundamental difference in people’s lives, and our broad portfolio of treatments serves close to 100 million patients in over 70 countries annually. Headquartered in Denmark, LEO Pharma has a team of 4,000 people worldwide. LEO Pharma is co-owned by majority shareholder the LEO Foundation and, since 2021, Nordic Capital. For more information, visit www.leo-pharma.com. LEO Pharma Canada is located in Toronto, Ontario. References: 1 ClinicalTrials.gov. National Library of Medicine (U.S.). A 24 Week Trial to Compare the Efficacy and Safety of Delgocitinib Cream 20 mg/g Twice-daily With Alitretinoin Capsules Once-daily in Adult Participants With Severe Chronic Hand Eczema. Identifier: NCT05259722. https://classic.clinicaltrials.gov/ct2/show/NCT05259722. 2 Thyssen JP, et al. Guidelines for diagnosis, prevention, and treatment of hand eczema. Contact Dermatitis 2022;86:357–378. 3 The Lancet. About The Lancet. Published: 2024. Last assessed: Jun 25, 2024. Available at: https://www.thelancet.com/lancet/about. 4 Giménez-Arnau, Ana Maria et al. Efficacy and safety of topical delgocitinib cream versus oral alitretinoin capsules in adults with severe chronic hand eczema (DELTA FORCE): a 24-week, randomised, head-to-head, phase 3 trial The Lancet, April 16, 2025 Available at https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)00001-7/abstract 5 Diepgen TL, Andersen KE, Chosidow O, et al. Guidelines for diagnosis, prevention and treatment of hand eczema. J Dtsch Dermatol Ges. 2015;13(1):e1-e22. 6 Lynde C, Guenther L, Diepgen TL, et al. Canadian hand dermatitis management guidelines. J Cutan Med Surg. 2010;14(6):267-284. Erratum in: J Cutan Med Surg. 2011 Nov-Dec;15(6):360. 7 Bissonnette R, Diepgen TL, Elsner P, et al. Redefining treatment options in chronic hand eczema (CHE). J Eur Acad Dermatol Venereol. 2010;24 Suppl 3:1-20. 8 Apfelbacher C, Bewley A, Molin S, et al. Prevalence of Chronic Hand Eczema in adults: A cross-sectional multi-national study of 60,000 respondents in the general population. Presented at the 2024 European Society of Contact Dermatitis (ESCD) congress; September 04-07 2024; Dresden, Germany. Poster presentation #3. 9 Grant L, Seiding Larsen L, Burrows K, et al. Development of a Conceptual Model of Chronic Hand Eczema (CHE) Based on Qualitative Interviews with Patients and Expert Dermatologists. Adv Ther. 2020;37(2):692-706. 10 Cortesi PA, Scalone L, Belisari A, et al. Cost and quality of life in patients with severe chronic hand eczema refractory to standard therapy with topical potent corticosteroids. Contact Dermatitis. 2014;70(3):158-168. 11 Voorberg AN, Loman L, Schuttelaar MLA. Prevalence and Severity of Hand Eczema in the Dutch General Population: A Cross-sectional, Questionnaire Study within the Lifelines Cohort Study. Acta Derm Venereol. 2022;102:adv00626. 12 Dubin C, Del Duca E, Guttman-Yassky E. Drugs for the Treatment of Chronic Hand Eczema: Successes and Key Challenges. Ther Clin Risk Manag. 2020;16:1319-1332. Erratum in: Ther Clin Risk Manag. 2021 Mar 18;17:233. 13 Lee GR, Maarouf M, Hendricks AK, Lee DE, Shi VY. Current and emerging therapies for hand eczema. Dermatol Ther. 2019;32(3):e12840. MAT- 81870 April 2025

临床3期临床结果引进/卖出上市批准

2025-04-17

·医学新视点

《柳叶刀》：一周见效，效果持续半年！新药有望让手部湿疹患者告别反复瘙痒、疼痛

手部红斑、丘疹、水疱、糜烂、渗出等，伴或不伴有瘙痒等症状的手部湿疹皮炎样改变，临床称为手部湿疹或手部皮炎，终生患病率约为15%。多达2/3的手部湿疹会演变为慢性病，即持续3个月以上或在12个月内复发2次及以上。目前，外用糖皮质激素是治疗慢性手部湿疹的一线策略，但长期使用可能引起皮肤萎缩、皲裂等问题，且对于重度慢性手部湿疹患者而言，外用药的疗效较为有限。Delgocitinib是一款外用泛Janus激酶（JAK）抑制剂，可抑制造成慢性炎症皮肤疾病病变的JAK-STAT信号通路的激活。既往DELTA 1、DELTA 2和DELTA 3研究均证实，在中重度慢性手部湿疹成年患者中，相比于乳膏样安慰剂，使用delgocitinib疗效显著，患者耐受性高。近日，《柳叶刀》（The Lancet）发表DELTA FORCE研究结果，表明相比于活性对照药物，使用delgocitinib治疗24周，患者手部湿疹严重程度指数较基线显著降低67.6分，且delgocitinib的优势从治疗第1周即开始显现，并维持至治疗结束，患者皮肤病生活质量指数明显改善且耐受性高。The Lancet发表的同期社论指出：“这项具有前景的头对头研究结果，标志着重度慢性手部湿疹的治疗迈出了重要的一步，为患者提供了新的选择。未来可考虑评估delgocitinib在不同类型的慢性手部湿疹之间疗效是否存在差异，如水疱型和角化过度型。”截图来源：The LancetDELTA FORCE是一项随机、评估者盲法、活性对照药物、平行组、多中心的3期研究，纳入全球多个国家和地区的102家医学中心重度慢性手部湿疹成人患者。研究人员将患者以1：1的比例随机分配至delgocitinib组（外涂，20 mg/g，每天2次）和活性对照药物组（alitretinoin，口服，30 mg，每日一次）。delgocitinib组和活性对照药物组的平均用药时长分别为21周和17周。主要研究终点为基线至治疗第12周时，手部湿疹严重程度指数（HECSI）评分变化。研究结果显示，治疗第12周时，delgocitinib组和活性对照药物组HECSI评分分别较基线降低67.6分和51.5分（差值-16.1分，95%CI：-23.3分~-8.9分，P＜0.0001）。如下图所示，24周治疗期内，delgocitinib组HECSI评分较基线降幅始终比活性对照药物组更大，治疗第1周时即可观察到这种差异，且这种差异持续维持至治疗结束。▲delgocitinib组（红色）和活性对照药物组（蓝色）治疗期间HECSI评分较基线变化趋势（图片来源：参考文献[1]）HECSI 评分主要对6种手部湿疹症状（红斑、浸润或丘疹、水疱、皲裂、鳞屑、水肿）进行0到3分的评分，分数越高症状越严重；同时对5个部位（指尖、手指、手掌、手背、手腕）的皮损范围进行0到4分的评分，分数越高皮损面积越大。HECSI总分为每个部位皮损面积评分×症状严重程度评分，总分范围0~360分。次要终点方面，delgocitinib组的表现也均优于活性对照药物组，其中delgocitinib组中39%患者手部湿疹症状和严重程度改善90%：▲两组患者次要结局指标对比（内容来源：参考文献[1]；图表制作：药明康德团队）安全性方面，delgocitinib组的不良事件发生率为49%，低于活性对照药物组的76%，主要不良事件为头痛、鼻咽炎和恶心。未发现新的安全性问题。总之，本次研究结果显示，在重度慢性手部湿疹患者中，相比于活性对照药物，delgocitinib治疗24周的疗效更好，从治疗第1周即可观察到两组间明显疗效差异，药物安全性特征良好。点击文末“阅读原文/Read more”，即可访问The Lancet官网阅读完整论文。推荐阅读欢迎投稿：学术成果、前沿进展、临床干货等主题均可，点此了解投稿详情。参考资料[1] Ana Maria Giménez-Arnau, Andreas Pinter, Wiebke Sondermann, et al. Efficacy and safety of topical delgocitinib cream versus oral alitretinoin capsules in adults with severe chronic hand eczema (DELTA FORCE): a 24-week, randomised, head-to-head, phase 3 trial. Published April 16, 2025. The Lancet. DOI: 10.1016/S0140-6736(25)00001-7 [2] Yael Renert-Yuval. Chronic hand eczema treatment: exploring topical JAK inhibition further. Published April 16, 2025. The Lancet. DOI: 10.1016/S0140-6736(25)00554-9免责声明：本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「医学新视点」微信公众号留言联系。如有其他合作需求，请联系wuxi_media@wuxiapptec.com分享，点赞，在看，传递医学新知

临床结果临床3期临床成功

2025-02-04

·Business Wire

LEO Pharma Achieves Positive DELTA TEEN Trial Results with Anzupgo® (delgocitinib) Cream in Adolescents with Moderate to Severe Chronic Hand Eczema (CHE)

BALLERUP, Denmark--( BUSINESS WIRE )-- NOT FOR UK USE – NOT INTENDED FOR UK MEDIA LEO Pharma A/S, a global leader in medical dermatology, today announced the positive results of the DELTA TEEN trial. DELTA TEEN is a pivotal phase 3 clinical trial with Anzupgo ® (delgocitinib) 20mg/g cream, a topical pan-Janus kinase (JAK) inhibitor, for the potential treatment of adolescents (aged 12-17) with moderate to severe Chronic Hand Eczema (CHE) for whom topical corticosteroids are inadequate or inappropriate. 1 This is the fifth phase 3 Anzupgo trial to achieve primary and all key secondary endpoints, validating the results of the previous clinical trials from the DELTA program. 1,3-10 DELTA TEEN expands LEO Pharma’s growing portfolio of scientific evidence for the treatment of moderate to severe CHE, offering insight into a new patient population. Currently, no treatment options are approved specifically for moderate to severe CHE in the adolescent population. " Research on adolescents with CHE has revealed that the condition can considerably affect their quality of life, including psychosocial well-being, school performance and leisure activities," said Professor Sonja Molin, Academic Dermatologist at Charite Universitätsmedizin Berlin and Adjunct Associate Professor of Dermatology at Queen’s University and coordinating investigator. " These findings further our understanding of how moderate to severe CHE manifests in adolescents and how to support this underserved patient group." The trial met the primary endpoint with a statistically significant improvement in CHE symptoms after 16 weeks of treatment with Anzupgo compared to cream vehicle. 1 Furthermore, the safety profile of Anzupgo was consistent with previous pivotal trials. 1 “ The positive results from DELTA TEEN are encouraging and in line with LEO Pharma’s purpose of serving more and more people living with this debilitating condition,” said Christophe Bourdon, Chief Executive Officer, LEO Pharma . “ Anzupgo is already available to adults in some markets, including Germany, and it is a critical next step to address the unmet need in this younger patient population.” Currently, Anzupgo is approved for adults in the European Union, United Kingdom, Switzerland and the United Arab Emirates for the treatment of moderate to severe CHE for whom topical corticosteroids are inadequate or inappropriate, and is under investigation in other markets, including the United States. Detailed results from DELTA TEEN are planned to be submitted for scientific presentation and publication at a later date. For more information on the DELTA TEEN trial (NCT05355818) go to clinicaltrials.gov . Notes to editors About Anzupgo ® (delgocitinib) cream Anzupgo is currently approved in the European Union, United Kingdom, Switzerland and the United Arab Emirates for the treatment of moderate to severe chronic hand eczema (CHE) in adults for whom topical corticosteroids are inadequate or inappropriate. Anzupgo is under investigation in other markets, including the United States. Anzupgo ® (delgocitinib) cream is a topical pan-Janus kinase (JAK) inhibitor for the treatment of moderate to severe CHE. It inhibits the activation of JAK-STAT signaling, which plays a key role in the pathogenesis of CHE. 11 The pathophysiology is characterized by skin barrier dysfunction, inflammation of the skin, and alterations of the skin microbiome. 12 In 2014, LEO Pharma A/S and Japan Tobacco Inc. (JT) entered into a license agreement in which LEO Pharma gained exclusive rights to develop and commercialize delgocitinib cream for topical use in dermatological indications worldwide, excluding Japan, where JT retains rights. About the DELTA TEEN Trial DELTA TEEN was a 16-week, phase 3, randomized, double-blind, vehicle-controlled, parallel group, multi-site trial to evaluate the efficacy and safety of twice-daily applications of Anzupgo compared with cream vehicle in adolescents 12-17 years of age with moderate to severe CHE. 1 The primary endpoint of DELTA TEEN was the Investigator’s Global Assessment for chronic hand eczema treatment success (IGA-CHE TS) at Week 16. Treatment success was defined as an IGA-CHE score of 0 (clear) or 1 (almost clear) with at least a two-step improvement from baseline. 1 About Chronic Hand Eczema Chronic Hand Eczema (CHE) is defined as hand eczema (HE) that lasts for more than three months or relapses twice or more within a year. 13,14 HE is the most common skin disorder of the hands 15 with a prevalence rate of approximately 4.7%. 16 In a substantial number of patients, HE can develop into a chronic condition. 15 CHE is a fluctuating disorder characterized by itch and pain, and patients may experience signs such as erythema, scaling, lichenification, hyperkeratosis, vesicles, edema, and fissures on hands and wrists. 17 CHE has been shown to cause psychological and functional burdens that impact patient quality of life, 18 with approximately 70% of individuals who live with severe CHE admitting to problems in performing everyday activities, and suffering disruption in their daily life due to the condition. 19 Furthermore, careers and earning potential have also been shown to be impacted by the burden of living with CHE. 20 About LEO Pharma LEO Pharma is a global company dedicated to advancing the standard of care through innovation for the benefit of people with skin conditions. LEO Pharma is co-owned by majority shareholder the LEO Foundation and, since 2021, Nordic Capital. LEO Pharma offers a broad portfolio of treatments, serving 100 million patients annually. Headquartered in Denmark, LEO Pharma has a global team of 4,000 people. In 2023, the company generated net sales of EUR 1.5 billion. References ClinicalTrials.gov. National Library of Medicine (U.S.). Efficacy and Safety of Delgocitinib Cream in Adolescents 12-17 Years of Age With Moderate to Severe Chronic Hand Eczema (DELTA TEEN). Identifier: NCT05355818. https://clinicaltrials.gov/study/NCT05355818 . Haft MA, Park HH, Lee SS, Sprague JM, Eichenfield LF. Pediatric chronic hand eczema: Epidemiology, clinical presentation, and management. JAAD Int. 2023;11:165-173. ClinicalTrials.gov. National Library of Medicine (U.S.). Efficacy and Safety of Delgocitinib Cream in Adults With Moderate to Severe Chronic Hand Eczema (DELTA 1). Identifier: NCT04871711. https://clinicaltrials.gov/ct2/show/NCT04871711 . ClinicalTrials.gov. National Library of Medicine (U.S.). Efficacy and Safety of Delgocitinib Cream in Adults With Moderate to Severe Chronic Hand Eczema (DELTA 2). Identifier: NCT04872101. https://clinicaltrials.gov/ct2/show/NCT04872101 . ClinicalTrials.gov. National Library of Medicine (U.S.). Open-label Multi-site Extension Trial in Subjects Who Completed the DELTA 1 or DELTA 2 Trials (DELTA 3). Identifier: NCT04949841 https://clinicaltrials.gov/ct2/show/NCT04949841 . Bissonnette R, Warren RB, Pinter A, et al. Efficacy and safety of delgocitinib cream in adults with moderate to severe chronic hand eczema (DELTA 1 and DELTA 2): results from multicentre, randomised, controlled, double-blind, phase 3 trials. Lancet. 2024;404(10451):461-473. doi:10.1016/S0140-6736(24)01027-4. Schliemann S, et al. Efficacy and safety of delgocitinib cream in adults with moderate to severe chronic hand eczema: results of the Phase 3 DELTA 2 trial. Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2023. Berlin, Germany. 11– 14 October. Poster Presentation #P0395. Bissonnette R, et al. Efficacy and safety of delgocitinib cream in adults with moderate to severe chronic hand eczema: results of the Phase 3 DELTA 1 trial. Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2023. Berlin, Germany. 11– 14 October. Poster Presentation #P0369. ClinicalTrials.gov. National Library of Medicine (U.S.). A 24 Week Trial to Compare the Efficacy and Safety of Delgocitinib Cream 20 mg/g Twice-daily With Alitretinoin Capsules Once-daily in Adult Participants With Severe Chronic Hand Eczema. Identifier: NCT05259722. https://clinicaltrials.gov/study/NCT05259722 . Giménez-Arnau AM, Pinter A, Sondermann W et al. DELTA FORCE trial: 24-week Phase 3 trial comparing the efficacy and safety of topical delgocitinib cream with oral alitretinoin capsules in adults with severe CHE. Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024. Amsterdam, Netherlands. 25-28 September. Late Breaking News Session. D1T01 Dubin C, Del Duca E, Guttman-Yassky E. Drugs for the Treatment of Chronic Hand Eczema: Successes and Key Challenges. Ther Clin Risk Manag. 2020;16:1319-1332. Erratum in: Ther Clin Risk Manag. 2021 Mar 18;17:233. Lee GR, Maarouf M, Hendricks AK, Lee DE, Shi VY. Current and emerging therapies for hand eczema. Dermatol Ther. 2019;32(3):e12840. Diepgen TL, Andersen KE, Chosidow O, et al. Guidelines for diagnosis, prevention and treatment of hand eczema. J Dtsch Dermatol Ges. 2015;13(1):e1-e22. Lynde C, Guenther L, Diepgen TL, et al. Canadian hand dermatitis management guidelines. J Cutan Med Surg. 2010;14(6):267-284. Erratum in: J Cutan Med Surg. 2011 Nov-Dec;15(6):360. Bissonnette R, Diepgen TL, Elsner P, et al. Redefining treatment options in chronic hand eczema (CHE). J Eur Acad Dermatol Venereol. 2010;24 Suppl 3:1-20. Apfelbacher C, Bewley A, Molin S, et al. Prevalence of Chronic Hand Eczema in adults: A cross-sectional multi-national study of 60,000 respondents in the general population. Presented at the 2024 European Society of Contact Dermatitis (ESCD) congress; September 04-07 2024; Dresden, Germany. Poster presentation #3. Thyssen JP, Schuttelaar MLA, Alfonso JH, et al. Guidelines for diagnosis, prevention, and treatment of hand eczema. Contact Dermatitis. 2022;86(5):357-378. Grant L, Seiding Larsen L, Burrows K, et al. Development of a Conceptual Model of Chronic Hand Eczema (CHE) Based on Qualitative Interviews with Patients and Expert Dermatologists. Adv Ther. 2020;37(2):692-706. Cortesi PA, Scalone L, Belisari A, et al. Cost and quality of life in patients with severe chronic hand eczema refractory to standard therapy with topical potent corticosteroids. Contact Dermatitis. 2014;70(3):158-168. Voorberg AN, Loman L, Schuttelaar MLA. Prevalence and Severity of Hand Eczema in the Dutch General Population: A Cross-sectional, Questionnaire Study within the Lifelines Cohort Study. Acta Derm Venereol. 2022;102:adv00626. MAT-79328 February 2025

临床3期引进/卖出临床结果上市批准

100 项与阿利维A酸相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D02815	阿利维A酸	L01XX22 D11AH04	DB00523

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适应症	国家/地区	公司	日期
艾滋病相关性卡波西肉瘤	美国	Advanz Pharma Corp. Ltd.	1999-02-02

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适应症	最高研发状态	国家/地区	公司	日期
慢性湿疹	临床3期	法国	Basilea Pharmaceutica AG	2007-05-01
慢性湿疹	临床3期	德国	Basilea Pharmaceutica AG	2007-05-01
慢性皮炎	临床3期	德国	Basilea Pharmaceutica AG	2004-12-01
手皮肤病	临床3期	德国	Basilea Pharmaceutica AG	2004-12-01
急性早幼粒细胞白血病	临床3期	美国	Ligand Pharmaceuticals, Inc.	1999-06-30
皮肤红斑狼疮	临床2期	德国	Basilea Pharmaceutica International Ltd.	2011-08-01
盘状红斑狼疮	临床2期	德国	Basilea Pharmaceutica International Ltd.	2011-08-01
脓疱型银屑病	临床2期	法国	Basilea Pharmaceutica AG	2011-04-26
脓疱型银屑病	临床2期	德国	Basilea Pharmaceutica AG	2011-04-26
脓疱型银屑病	临床2期	荷兰	Basilea Pharmaceutica AG	2011-04-26

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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


NCT00817063 (HANDEL, CTgov)	临床3期	慢性湿疹	599	Placebo	鑰鹹廠壓鹽襯構艱夢壓 = 衊廠膚壓積糧餘窪艱獵築繭積獵積淵醖淵齋醖 (衊鹽築獵鏇觸簾繭夢鬱, 繭蓋夢範製襯餘繭艱衊 ~ 範鑰鬱範艱簾獵鹹淵襯) 更多	-	2017-11-09
NCT01245140 (CTgov)	临床2期	手掌和足底脓疱病 \| 脓疱型银屑病	33	placebo (Matching Placebo)	衊顧壓襯鹽選鏇憲淵顧(網廠範範繭夢窪鹹網窪) = 襯鏇夢膚壓繭糧構餘遞淵齋積憲蓋願窪蓋鬱窪 (遞鏇鹽鹹壓觸觸簾廠簾, 45.9) 更多	-	2017-04-04
NCT01245140 (CTgov)	临床2期	手掌和足底脓疱病 \| 脓疱型银屑病	33	Alitretinoin (Alitretinoin 30 mg)	衊顧壓襯鹽選鏇憲淵顧(網廠範範繭夢窪鹹網窪) = 顧積選鹽壓鬱衊蓋夢窪淵齋積憲蓋願窪蓋鬱窪 (遞鏇鹽鹹壓觸觸簾廠簾, 32.8) 更多	-	2017-04-04
NCT00817063 (Pubmed)	临床3期	湿疹	596	Alitretinoin 30 mg	餘餘艱獵積襯鹽製觸膚(簾餘壓淵壓餘醖醖夢艱) = 選鹹繭顧窪鹹憲範鑰襯觸鑰獵膚築鏇餘鏇醖膚 (製夢醖壓積鹹蓋願鹹鹹 ) 更多	积极	2014-10-01
NCT00817063 (Pubmed)	临床3期	湿疹	596	Placebo	壓構網鏇鑰艱獵夢製範(積襯衊襯選餘憲簾壓範) = 鬱淵壓積選鬱選鹹繭觸選範顧齋繭齋獵餘鬱夢 (憲鹽鏇廠蓋築願鑰積鏇 )	积极	2014-10-01
NCT00609739 (CTgov)	临床1/2期	幼年型骨髓单核细胞白血病	1	umbilical cord blood transplantation+cyclosporine+methylprednisolone+Cis-Retinoic acid+Filgrastim+mitoxantrone hydrochloride+methotrexate+Cytarabine	淵構顧淵遞鹽衊夢選選 = 窪製獵積廠築艱簾鏇襯衊繭餘簾鑰顧鏇淵構鬱 (鹽夢鹽窪積鹹鬱廠廠積, 築製壓構蓋願齋築壓蓋 ~ 遞餘憲製襯鑰網簾窪繭) 更多	-	2012-03-02