A Multi-center, Double-blinded, Randomized, Placebo-controlled, Phase II Study to Evaluate the Safety, Tolerability and Efficacy of a Topical Application of DLX105 Onto Lesional Skin in Patients With Mild-to-moderate Psoriasis Vulgaris

In this study, the safety, tolerability and efficacy of DLX105 administered topically onto the psoriatic lesion of mild-to-moderate psoriasis patients will be investigated.

开始日期2013-08-01

申办/合作机构

Cell Medica Switzerland AG

EUCTR2013-001885-41-DE / Not yet recruitingN/A

A multi-center, double-blinded, randomized, placebo-controlled, phase II study to evaluate the safety, tolerability and efficacy of a topical application of DLX105 onto lesional skin in patients with mild-to-moderate psoriasis vulgaris

开始日期2013-07-11

申办/合作机构

Cell Medica Switzerland AG

NCT01624376 / Completed临床2期

A Randomized, Double-blind, Placebo-controlled Phase I/IIa Study in Patients With Abdominal or Perianal Fistulizing Crohn's Disease to Explore the Safety, Tolerability and Preliminary Efficacy of Locally Administered DLX105.

The primary objective of this study is to investigate the safety and tolerability of locally administered DLX105 in treating enterocutaneous fistulas in Crohn's Disease patients.
The study will consist of a screening period of approx. 2 weeks, a 4-week treatment period and a 2-week follow-up period. An end-of study visit is scheduled on Day 43, 2 weeks after the last study visit.

开始日期2012-06-01

申办/合作机构

Cell Medica Switzerland AG

100 项与 DLX-105 相关的临床结果

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100 项与 DLX-105 相关的转化医学

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项与 DLX-105 相关的文献（医药）

2013-07-01·Ophthalmology1区 · 医学

Penetration of a Topically Administered Anti–Tumor Necrosis Factor Alpha Antibody Fragment into the Anterior Chamber of the Human Eye

1区 · 医学

Article

作者: Andreas Wild ; Oliver Job ; Frank Bochmann ; Michael A. Thiel ; Martin K. Schmid ; Dominik Escher ; Annette Schmidt ; Wolfan Alcantara ; Peter Lichtlen ; Vlasios Loukopoulos

OBJECTIVETo determine whether topically applied ESBA105, a single-chain antibody fragment against tumor necrosis factor (TNF)-α, could efficiently penetrate into the anterior chamber of the human eye.DESIGNMulticenter, interventional cohort study.PARTICIPANTSOtherwise healthy patients undergoing cataract surgery (cohorts I-III) or combined cataract surgery and vitrectomy (cohort IV).METHODSESBA105 (n = 57) or placebo (n = 22) was preoperatively applied as eye drops to 1 eye in patients scheduled for cataract surgery (n = 73) or combined cataract surgery and vitrectomy (n = 6). ESBA105 was administered on the day of surgery at 1-hour intervals (last dose 1 hour preoperatively) as 1.6 mg in 4 drops for cohort I (n = 15) and as 3.2 mg in 8 drops for cohorts II (n = 15) and IV (n = 6). Cohort III (n = 43) was randomized 1:1 in double-masked fashion to receive either ESBA105 6.4 mg or placebo over 4 days using 4 drops per day at 4-hour intervals (last dose 12 hours preoperatively). Aqueous humor (all cohorts), vitreous humor (cohort IV only), and blood samples (all cohorts) were collected for measurement of ESBA105.MAIN OUTCOME MEASURESESBA105 intraocular concentration.RESULTSBoth 4 times daily over 4 days dosing (cohort III) and 8 times daily dosing (cohorts II and IV) resulted in reliably high ESBA105 concentrations in aqueous humor. Mean molar excess of intraocular ESBA105 over its target (intraocular TNF-α) was calculated as 96-fold (cohort III) to 359-fold (cohorts II and IV). Results from the cohorts receiving 4 and 8 hourly drops per 1 day (cohorts I, II, and IV) indicated that dose-dependent intraocular concentrations of ESBA105 were achieved within hours of dosing. After 8 times daily dosing, 5 of 6 vitreous samples (cohort IV) had undetectable ESBA105 levels. ESBA105 was detected in 17 of 55 preoperative serum samples but no longer detectable in serum 1 day after surgery (0 of 19 samples). In cohort III, treatment-emergent adverse events were identical between ESBA105 and placebo groups (2 cases each of eye irritation).CONCLUSIONSThese results demonstrate that the topically applied single-chain antibody fragment ESBA105 penetrated into the anterior chamber of the human eye at therapeutic levels.

2010-09-01·Investigative Opthalmology & Visual Science2区 · 医学

Relative Contribution of VEGF and TNF-α in the Cynomolgus Laser-Induced CNV Model: Comparing the Efficacy of Bevacizumab, Adalimumab, and ESBA105

2区 · 医学

ArticleOA

作者: Urech, David M. ; Streit, Tim ; Nork, T. Michael ; Lam, Tim T. ; Lichtlen, Peter

PURPOSETo compare the relative contribution of VEGF and TNF-alpha in the development of laser-induced choroidal neovascularization (CNV) in monkeys and to exploit the feasibility of topical use of suitable antibody fragments for the prevention of experimental CNV.METHODSTo induce experimental CNV, small high-energy laser spots were used to treat several areas of the macula in the retinas of cynomolgus monkeys according to previously published protocols. To prevent abnormalities, bevacizumab (a potent VEGF inhibitor) and adalimumab or ESBA105 (potent TNF-alpha inhibitors) were given by intravitreal injection 1 week before and 1 week and 3 weeks after laser treatment. ESBA105 was also applied topically in a separate group. Control animals were treated with either intravitreal or topical saline. Eyes were monitored by ophthalmic examination, color photography, and fluorescein angiography.RESULTSInhibition of VEGF by bevacizumab completely blocked the formation of CNV. Both TNF-alpha inhibitors also significantly reduced laser-induced CNV abnormalities after intravitreal administration. Most important, topical use of the anti-TNF-alpha single-chain antibody fragment ESBA105 also reduced the formation of CNV.CONCLUSIONSTNF-alpha contributes to laser-induced CNV formation, and its inhibition can be a new therapeutic target for CNV. This study suggests TNF-alpha as another therapeutic target for the prevention and treatment of CNV and adds to the emerging clinical data suggesting the therapeutic value of TNF-alpha inhibitors in age-related macular degeneration (AMD). Further, this study shows that topical therapy with suitable antibody fragments has the potential of being introduced to retinal disease treatment regimens.

2010-02-01·Annals of the Rheumatic Diseases1区 · 医学

Anti-inflammatory and cartilage-protecting effects of an intra-articularly injected anti-TNFα single-chain Fv antibody (ESBA105) designed for local therapeutic use

1区 · 医学

Article

作者: Lichtlen, P. ; Polzer, K. ; Ottiger, M. ; Feige, U. ; Urech, D. M. ; Schlosser, V. ; Ewert, S. ; Schett, G.

Objectives:(1) To show that a single-chain Fv antibody (scFv) against tumour necrosis factor α (TNFα) (ESBA105) has efficacy comparable to a full length anti-TNFα IgG (infliximab); (2) to evaluate whether ESBA105 has all the properties required for the local treatment of arthritis; and (3) to investigate its discriminative tissue penetration properties.Methods:In vivo efficacy was measured in arthritis of the knee joint induced by the intra-articular injection of recombinant human TNFα (rhTNFα) in Lewis rats. Cartilage penetration of scFv (ESBA105) and full length IgG (infliximab) were studied in bovine cartilage specimens ex vivo. Tissue penetration, biodistribution and pharmacokinetics of ESBA105 were followed and compared after intra-articular and intravenous administration.Results:In cell culture, ESBA105 showed similar TNFα inhibitory potency to infliximab. In vivo, ESBA105 inhibited rhTNFα-induced synovial inflammation in rats with efficacy again comparable to infliximab. An 11-fold molar excess of ESBA105 over rhTNFα resulted in 90% inhibition of knee joint swelling, inflammatory infiltrates and proteoglycan loss from cartilage. In ex vivo studies of bovine cartilage, ESBA105 penetrated well into the cartilage whereas infliximab remained on the surface. In vivo, rapid penetration into the synovial tissue, cartilage and surrounding tissues was observed following intra-articular injection of [125I]-ESBA105 into the knee joint of rabbits.Conclusions:ESBA105 potently inhibits inflammation and prevents cartilage damage triggered by TNFα. In contrast to a full length IgG, ESBA105 also penetrates into cartilage and can be expected to reverse the TNFα-induced catabolic state of articular cartilage in arthritides.

项与 DLX-105 相关的新闻（医药）

2022-05-26

·BioSpace

Arrivo BioVentures Closes Enrollment in Large Phase 2 Clinical Trial for Major Depressive Disorder

May 26, 2022 12:10 UTC SP-624 has a novel epigenetic mechanism to enhance neuroplasticity in brain regions involved in depression, namely the hippocampus and prefrontal cortex MORRISVILLE, N.C.--(BUSINESS WIRE)-- Arrivo BioVenturesannounced today that the company has closed enrollment of a phase 2 clinical study with its most advanced program, SP-624, after having enrolled more than 300 patients with major depressive disorder. Arrivo expects top-line data in early Q4 2022. The study is a multicenter, double-blind, randomized, placebo-controlled study of the safety and efficacy of SP-624 in the treatment of adults with major depressive disorder. The trial is being conducted across 39 clinical trial sites in the United States with a total of 319 patients enrolled. Patients were randomized to either SP-624 or placebo once daily for four weeks. The primary endpoint is the change from baseline to Week 4 in the Montgomery Asberg Depression Rating Scale (MADRS) total score. There are also a number of standard measures as secondary endpoints for the study. SP-624 is a novel, small molecule that selectively activates a novel epigenetic mechanism known to modulate gene expression, metabolism and DNA repair. SP-624 enhances neuroplasticity in the hippocampus and augments neurotransmitter release in the prefrontal cortex in animal studies. Augmented neurotransmitter release is understood to be a key feature of many first line anti-depressants while enhanced neuroplasticity holds the potential to reprogram cell function and produce long-lasting effects. Arrivo’s portfolio also includes three other promising drug candidates. DLX-105 is single-chain variable fragment the company is delivering topically to directly treat mild to moderate plaque psoriasis. DLX-105 is currently in a small proof-of-concept study with data readout expected in mid-2022. DLX-2323 is a single-chain variable fragment inhibitor of IL-1β. IL-1β is a potent cytokine and an important mediator of acute and chronic inflammation. Finally, Arrivo is developing RABI-767, potentially the first treatment for severe acute pancreatitis. Arrivo has now taken over the lead from its strategic development partner, Lamassu Pharma, LLC, and the drug is entering the clinic in 2022. About Arrivo BioVentures, LLC Working in partnership with investors, innovators, and pharmaceutical companies, Arrivo is always seeking solutions for unmet medical needs. Arrivo has built a portfolio of diverse drug candidates with the potential to be first-in-class or best-in-class. The company stands on a solid foundation as the team has an average of more than 25 years of experience in drug development. Arrivo is founded and led by a team that has built and sold four companies in the last 15 years. Two products are currently commercially available and helping patients. Arrivo is propelled forward by its insatiable curiosity and drive to solve complex problems and help millions of patients globally. Arrivo is based in Morrisville, N.C., on the edge of Research Triangle Park. For more information, visit .

First in Class小分子药物合作

100 项与 DLX-105 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
白塞病/贝赫切特综合征	临床2期	瑞士	Kuur Therapeutics Ltd.	-
克罗恩病	临床2期	-	ESBATech, a Novartis Co. GmbH	-
干眼综合征	临床2期	美国	ESBATech, a Novartis Co. GmbH	-
眼部炎症	临床2期	瑞士	ESBATech, a Novartis Co. GmbH	-
银屑病	临床2期	-	ESBATech, a Novartis Co. GmbH	-
葡萄膜炎	临床2期	-	Cell Medica Switzerland AG	-
干眼症	临床2期	-	Cell Medica Switzerland AG	-
干眼症	临床2期	-	ESBATech, a Novartis Co. GmbH	-
干眼症	临床2期	-	ESBATech, a Novartis Co. GmbH	-
干眼症	临床2期	-	Cell Medica Switzerland AG	-

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分期

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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


NCT01338610 (CTgov)	临床2期	干眼症	334	ESBA105 ophthalmic solution (ESBA105)	顧蓋簾醖齋窪範選遞鬱(範廠憲顧顧糧築醖鑰鹹) = 鹹衊襯壓製餘艱壓壓鏇膚膚窪獵獵廠築簾製鑰 (淵繭壓憲鏇醖鬱衊餘鹽, 鏇製齋齋鑰糧鏇鹽積蓋 ~ 願醖壓鑰網築獵膚蓋鏇) 更多	-	2013-04-19
				ESBA105 vehicle (Vehicle)	顧蓋簾醖齋窪範選遞鬱(範廠憲顧顧糧築醖鑰鹹) = 鏇鬱鹽鬱簾簾鏇廠醖鏇膚膚窪獵獵廠築簾製鑰 (淵繭壓憲鏇醖鬱衊餘鹽, 鹹醖範壓膚鬱襯鬱築壓 ~ 鹽襯壓網顧壓膚鏇壓繭) 更多