Phase III Multi-center, Randomized, Double-masked, Active- and Placebo-controlled Study of Trabodenoson in Adults With Ocular Hypertension or Primary Open-angle Glaucoma
Phase III trial involving topical application, in both eyes, of trabodenoson ophthalmic formulation 3.0% or 6.0% once per day or 4.5% twice per day, placebo twice per day, or timolol 0.5% twice per day for 12 weeks in adult subjects with Ocular Hypertension or Primary Open-Angle Glaucoma. All subjects who meet the study's enrollment criteria following Screening will undergo washout of all prohibited medications, including their routine glaucoma medications. During the Placebo Run-In Period, placebo is administered twice daily to both eyes in all subjects. During the Treatment Period, study drug is applied to both eyes for a total of 12 weeks followed by an Observation Period of approximately 7 days wherein no study eye drops are instilled. The purpose of the study is to assess the efficacy, tolerability, and safety of binocular topical application of trabodenoson ophthalmic formulation 3.0% or 6.0% QD or 4.5% BID for 12 weeks. Timolol is being included in the trial in order to have an active control to ensure the integrity of the trial from an efficacy perspective; the primary comparator for all statistical purposes is the placebo arm.
A Phase II Multi-center, Randomized Study to Evaluate the Monocular Addition of Trabodenoson (INO-8875) Ophthalmic Formulation to Latanoprost Ophthalmic Solution Therapy in Adults With Ocular Hypertension or Primary Open-Angle Glaucoma
The purpose of this study is to evaluate the intraocular pressure (IOP) lowering efficacy and the safety and tolerability profile of trabodenoson ophthalmic formulation compared to timolol maleate ophthalmic solution 0.5% in adults with ocular hypertension (OHT) or primary open-angle glaucoma (POAG) who are already receiving treatment with latanoprost ophthalmic solution 0.005% once every evening (QPM).
Adenosine: The common target between cancer immunotherapy and glaucoma in the eye.
3区 · 医学
作者: Shahin Hallaj ; Mohammad Mirza-Aghazadeh-Attari ; Amin Arasteh ; Anahita Ghorbani ; Daniel Lee ; Farhad Jadidi-Niaragh
Adenosine, an endogenous purine nucleoside, is a well-known actor of the immune system and the inflammatory response both in physiologic and pathologic conditions. By acting upon particular, G-protein coupled adenosine receptors, i.e., A1, A2- a & b, and A3 receptors mediate a variety of intracellular and immunomodulatory actions. Several studies have elucidated Adenosine's effect and its up-and downstream molecules and enzymes on the anti-tumor response against several types of cancers. We have also targeted a couple of molecules to manipulate this pathway and get the immune system's desired response in our previous experiences. Besides, the outgrowth of the studies on ocular Adenosine in recent years has significantly enhanced the knowledge about Adenosine and its role in ocular immunology and the inflammatory response of the eye. Glaucoma is the second leading cause of blindness globally, and the recent application of Adenosine and its derivatives has shown the critical role of the adenosine pathway in its pathophysiology. However, despite a very promising background, the phase III clinical trial of Trabodenoson failed to achieve the non-inferiority goals of the study. In this review, we discuss different aspects of the abovementioned pathway in ophthalmology and ocular immunology; following a brief evaluation of the current immunotherapeutic strategies, we try to elucidate the links between cancer immunotherapy and glaucoma in order to introduce novel therapeutic targets for glaucoma.
2021-01-21·Expert Opinion on Investigational Drugs2区 · 医学
Trabodenoson on trabecular meshwork rejuvenation: a comprehensive review of clinical data
2区 · 医学
作者: Qiu, Tina Guanting
Trabodenoson is an adenosine mimetic acting selectively at the A1 receptor (A1R) subtype, involved in multiple signaling pathways including matrix metalloproteinase (MMP-2) associated with glaucoma pathological processes. It has been developed as a Phase 3 candidate for the treatment of patients with primary open-angle glaucoma (POAG) or ocular hypertension (OH).
This review summarizes the molecular traits of Trabodenoson in intraocular pressure (IOP) regulations and provides a scientific interpretation of the Phase 2 clinical study results. This article sheds light on the root causes of the two pivotal Phase 3 clinical trial failures in patients with POAG or OH; it further highlights the discovery of MMP-2 in trabecular meshwork (TM) rejuvenation, which has strategic importance in long-term glaucoma patient care.
Trabodenoson is a BID glaucoma eye drop with a possible QD dose as maintenance. Its Phase 3 pivotal clinical trials failed at the wrong dose and dosing regimen because of the misinterpretation of the complex IOP results from the Phase 2 monotherapy and combination studies. The future development should focus on the TM benefits whilst unleashing its potential of neural protection through nanoparticle eye drops, medical coating, and sustained release drug delivery.
2020-06-01·FEBS letters3区 · 生物学
Knowledge-based structural models of SARS-CoV-2 proteins and their complexes with potential drugs.
The World Health Organization (WHO) has declared the coronavirus disease 2019 (COVID-19) caused by the novel coronavirus SARS-CoV-2 a pandemic. There is, however, no confirmed anti-COVID-19 therapeutic currently. In order to assist structure-based discovery efforts for repurposing drugs against this disease, we constructed knowledge-based models of SARS-CoV-2 proteins and compared the ligand molecules in the template structures with approved/experimental drugs and components of natural medicines. Our theoretical models suggest several drugs, such as carfilzomib, sinefungin, tecadenoson, and trabodenoson, that could be further investigated for their potential for treating COVID-19.
LEXINGTON, MA--(Marketwire - June 10, 2010) - Highlighted Links
Inotek Pharmaceuticals Corp. Inotek Pharmaceuticals Corp., a leader in the development of innovative drug candidates to address significant diseases of the eye, today announced it has closed an $18 million preferred stock financing. Proceeds from the financing will be used to advance Inotek's novel eye-drop INO-8875 through multiple-dose Phase 2 clinical trials in glaucoma. In an earlier Phase 1/2 clinical trial, INO-8875 was shown to significantly reduce intraocular pressure in glaucoma patients. Devon Park Bioventures, a new investor, led the round with participation from existing investors Rho Ventures, Care Capital, Pitango Venture Capital, MedImmune Ventures, and Bio*One Capital.
"We are pleased to receive such financial support from Devon Park and our current investors to advance the clinical development of INO-8875, including the initiation of a multiple-dose Phase 2 clinical trial later this month," stated Paul G. Howes, President and Chief Executive Officer of Inotek. "INO-8875 is a first-in-class product candidate with an elegant mechanism of action that differentiates it from currently approved products for glaucoma as well as other candidates in development. As a highly selective adenosine-1 receptor agonist, INO-8875 enhances outflow through the major pathway used by healthy elderly eyes -- the trabecular meshwork -- to reduce intraocular pressure. With continued clinical success, we believe INO-8875 could play an important role in meeting the need for improved treatments for glaucoma."
"We believe INO-8875 is one of the most promising glaucoma product candidates in clinical development today," said John Leaman, M.D., Principal at Devon Park Bioventures. "The Inotek team has made considerable progress advancing the candidate to date and we look forward to working with them as INO-8875 moves into later-stage clinical trials."
In conjunction with the financing, John Leaman has joined Inotek's Board of Directors.
About INO-8875 for Glaucoma
Glaucoma is a leading cause of blindness globally, and it is broadly accepted that lowering intraocular pressure (IOP) in glaucoma patients is the only clinically reliable means of slowing the progression of vision loss. Current products for glaucoma, such as prostaglandins, lower IOP by reducing inflow of fluid in the eye or increasing its drainage through a secondary pathway in the eye -- the uveoscleral pathway. As glaucoma advances with age, the eye's trabecular meshwork grows increasingly clogged with protein debris, and the eye can become less responsive to these mechanisms. As such, a significant percentage of patients do not respond adequately to currently approved products, and up to 40% of patients are treated with a combination of products in the hope of achieving targeted reductions in IOP. There remains an unmet need for innovative glaucoma products acting on the trabecular meshwork to provide improved IOP-lowering efficacy.
The Company believes INO-8875 has significant potential as an IOP-lowering medicine, either as monotherapy or in combination with other glaucoma products, because it restores outflow of aqueous humor through the trabecular meshwork. As validation of its complementary mechanism to other glaucoma products, INO-8875 has shown substantial additivity of IOP-lowering efficacy when combined with the leading glaucoma product (Xalatan®, Pfizer) in a preclinical model. As a highly selective adenosine-1 receptor agonist, INO-8875 has a novel mechanism differentiating it from currently approved products and other candidates in development for glaucoma in that INO-8875 enhances a natural cellular signaling pathway to clear debris from the trabecular meshwork, resulting in improved outflow.
Inotek is a leader in the development of innovative drug candidates to address significant diseases of the eye, with a major focus on glaucoma. Inotek's lead product candidate INO-8875 is a potential first-in-class eye-drop product for glaucoma that significantly reduced intraocular pressure (IOP) in glaucoma subjects following single doses applied to the eye in a Phase 1/2 clinical trial. The Company believes INO-8875 will be a breakthrough treatment that can be used alone or combined with other IOP-lowering products because it increases the outflow of aqueous humor through the trabecular meshwork, the primary drainage system used by healthy elderly eyes to maintain normal IOP. The Company is also advancing a broad pipeline of PARP inhibitors and SOD mimetics that alleviate oxidative injury and inflammation, which it believes may address significant unmet medical needs in retinal diseases, such as the dry form of age-related macular degeneration (dry AMD). The Company is located in Lexington, MA. For further information on Inotek, please visit .
About Devon Park Bioventures
Founded in 2006, Devon Park Bioventures is a healthcare venture capital firm with a primary focus on therapeutics companies. Based in the Philadelphia area, the firm seeks to invest in companies which have significant commercial potential based on proprietary products, attractive clinical development plans and superior management teams. The General Partners of Devon Park have a longstanding history in the biotechnology business, having been lead or co-lead investor in over 25 biotechnology companies over the past 18 years. For additional information, please visit .
Adam L. Muzikant, Ph.D.
Senior Director, Business Development
MacDougall Biomedical Communications
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