A Randomized, Open-Label, Multi-Center, Active-Controlled, Parallel Group Study To Determine the Efficacy and Safety of the REG1 Anticoagulation System Compared to Bivalirudin in Patients Undergoing Percutaneous Coronary Intervention

This study is designed to determine the efficacy of REG1 compared to bivalirudin in preventing periprocedural ischemic complications and major bleeding in patients undergoing PCI as a treatment for CAD. Bivalirudin has been studied in patients undergoing PCI in both ACS (NSTEMI and unstable angina [UA]) and elective PCI. In comparison to UFH, bivalirudin has shown similar rates of ischemic events while demonstrating a significant reduction in bleeding and an improved net clinical benefit.
Evidence from previous studies indicates that pegnivacogin represents an extremely potent, chemically unique anticoagulant that can be reversed by anivamersen across multiple populations (refer to Section 1.2.2). The question that still remains is whether Factor IX (FIX) inhibition by pegnivacogin can result in fewer ischemic events than a previously studied agent while active control with anivamersen can preserve the benefit of reduced bleeding. The purpose of this study is to evaluate REG1 in an adequately powered definitive study with an open-label, multi-center, active-controlled, randomized design to answer that question.

开始日期2013-09-01

申办/合作机构

Regado Biosciences, Inc.

[+5]

NCT01872572 / Completed临床1期

A Phase 1 Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RB006 Administered Subcutaneously, With and Without IV RB007, in Healthy Young Volunteers

This was a Phase 1a, single-center, double-blind, randomized, placebo-controlled study of the safety, tolerability, PK, and PD of single ascending doses of RB006 administered as an SC injection, with and without IV RB007 (an active control agent for RB006), in healthy young volunteers. The study originally planned to enroll 4 cohorts of 8 subjects each (N=32); however, upon review cohort (Cohort 1-A) was necessary in order to fully define the PK profile of SC RB006. Therefore, 36 subjects were enrolled in this study.
Each cohort was balanced by sex with no more than 2/3 of one sex enrolled in any particular cohort (i.e., 5 of 8 subjects in each cohort). No subject participated in >1 dose group, and progression to the next higher dose only occurred if the prior dose level was well tolerated, as assessed by a Safety Review Committee (SRC)

开始日期2009-08-01

申办/合作机构

Regado Biosciences, Inc.

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100 项与 Anivamersen-pegnivacogin 相关的专利（医药）

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项与 Anivamersen-pegnivacogin 相关的文献（医药）

2024-09-01·Biochemical Pharmacology

Reg2 treatment is protective but the induced Reg2 autoantibody is destructive to the islets in NOD mice

Article

作者: Li, Xin ; Luo, Chen ; Yu, Lu-Ting ; Xie, Fei-Lu ; Wang, Xiao-Nan ; Pu, Chun-Cheng ; Xie, Bing-Bing ; Zhou, Yi-Han ; Xu, Ke-Yi ; Gao, Yan ; Li, You-Jie

Regenerating family protein 2 (Reg2) is a trophic factor which stimulates β-cell replication and resists islet destruction. However, Reg2 also serves as an islet autoantigen, which makes it complicated to judge the effectiveness in treating diabetes. How Reg2 treatment behaves in non-obese diabetic (NOD) mice is to be investigated. NOD mice were treated with recombinant Reg2 protein, Complete Freund's adjuvant (CFA) + PBS and CFA+Reg2 vaccinations, CFA+PBS- and CFA+Reg2-immunized antisera, and single chain variable fragment (scFv)-Reg2 and mIgG2a-Reg2 antibodies. Glycemic level, bodyweight, serum Reg2 antibody titer, glucose tolerance, and insulin secretion were determined. Islet morphological characteristics, insulitis, cell apoptosis, islet cell components, and T cell infiltration were analyzed by histological examinations. The autoantigenicity of constructed Reg2C and Reg2X fragments was determined in healthy BALB/c mice, and the bioactivity in stimulating cell proliferation and survival was assessed in insulinoma MIN6 cells. Reg2 administration alleviated diabetes in NOD mice with improved glucose tolerance and insulin secretion but elevated serum Reg2 autoantibodies. Histomorphometry showed reduced inflammatory area, TUNEL signal and CD8 + T cell infiltration, and increased β-cell proportion in support of the islet-protective effect of Reg2 treatment. CFA+PBS and CFA+Reg2 immunizations prevented diabetic onset and alleviated insulitis while injections of the antisera offered mild protections. Antibody treatments accelerated diabetic onset without increasing the overall incidence. Reg2C fragment depletes antigenicity, but reserves protective activity in streptozotocin (STZ)-treated MIN6 cells. In conclusion, Reg2 treatment alleviates type 1 diabetes (T1D) by preserving islet β-cells, but induces Reg2 autoantibody production which poses a potential risk of accelerating diabetic progression.

2023-04-01·Antioxidants (Basel, Switzerland)

Interdependencies of Gene Expression and Function between Two Redox Enzymes and REG Family Proteins in Murine Pancreatic Islets and Human Pancreatic Cells

Article

作者: Vatamaniuk, Marko Z ; Wang, Hong ; Lei, Xin Gen ; Zhao, Zeping

Our laboratory previously revealed that regenerating islets-derived protein 2 (REG2) was diminished in pancreatic islets of glutathione peroxidase-1-overexpressing mice (Gpx1-OE). It remained unknown if there is an inverse relationship between the expression and function of all Reg family genes and antioxidant enzymes in the pancreatic islets or human pancreatic cells. This research was to determine how altering the Gpx1 and superoxide dismutase-1 (Sod1) genes alone or together (dKO) affected the expression of all seven murine Reg genes in murine pancreatic islets. In Experiment 1, Gpx1^-/-, Gpx1-OE, their wild-type (WT), Sod1^-/-, dKO, and their WT (male, 8-wk old, n = 4-6) were fed a Se-adequate diet and their islets were collected to assay the mRNA levels of Reg family genes. In Experiment 2, islets from the six groups of mice were treated with phosphate-buffered saline (PBS), REG2, or REG2 mutant protein (1 µg/mL), and/or GPX mimic (ebselen, 50 µM) and SOD mimic (copper [II] diisopropyl salicylate, CuDIPS, 10 µM) for 48 h before the proliferation assay using bromodeoxyuridine (BrdU). In Experiment 3, human pancreatic cells (PANC1) were treated with REG2 (1 µg/mL) and assayed for REG gene expression, GPX1 and SOD1 activities, viability, and responses to Ca²⁺. Compared with the WT, knockouts of Gpx1 and/or Sod1 up-regulated (p < 0.05) the mRNA levels of most of the murine Reg genes in islets whereas the Gpx1 overexpression down-regulated (p < 0.05) Reg mRNA levels. REG2, but not the REG2 mutant, inhibited islet proliferation in Gpx1 or Sod1-altered mice. Such inhibition was abolished by co-incubation the Gpx1^-/- islets with ebselen and the Sod1^-/- islets with CuDIPS. Treating PANC1 cells with murine REG2 protein induced expression of its human orthologue REG1B and three other REG genes, but decreased SOD1 and GPX1 activities and cell viability. In conclusion, our results revealed an interdependence of REG family gene expression and/or function on intracellular GPX1 and SOD1 activities in murine islets and human pancreatic cells.

2016-02-01·European Journal of Cardio-Thoracic Surgery2区 · 医学

Inhibition of factor IXa by the pegnivacogin system during cardiopulmonary bypass: a potential substitute for heparin. A study in baboons

2区 · 医学

Article

作者: Menasché, Philippe ; Zelenkofske, Steven ; Alexander, David ; Fremes, Stephen ; Alexander, John ; Borik, Wasseem ; Davidson, Simon ; Rusconi, Christopher ; Pepper, John ; Helies, Jean-Marie ; Bel, Alain ; Stimmer, Lev

OBJECTIVESHeparin and protamine are standard for anticoagulation and reversal for cardiopulmonary bypass (CPB). The REGADO biosciences protocol 1 (REG1) anticoagulant system, consisting of the Factor IXa (FIXa)-inhibitor pegnivacogin and its reversal agent (anivamersen), has been studied in patients undergoing coronary catheterization and in CPB in sheep and pigs. Prior to first human use in CPB, we wanted to test the safety and efficacy of REG1 in a primate model.METHODSFourteen baboons undergoing 2 h of CPB followed by 1 h of reperfusion were studied. Three received heparin/protamine and 11 received 1 of 2 doses of pegnivacogin followed by anivamersen. Thrombin-generating capacity was tested in additional in vitro experiments.RESULTSTargeted drug levels and near-complete FIXa inhibition were achieved. Bypass was run uneventfully in all animals without any clotting in the circuit and bleeding was minimal in the two groups. However, in contrast to heparin-treated baboons, those receiving pegnivacogin/anivamersen displayed thrombi in the bypass cannulae upon cannulation and kidney cortical infarcts. Inter-species comparisons revealed that in the presence of high levels of FIXa inhibition, tissue factor-mediated thrombin generation in baboons was much higher than that in other species.CONCLUSIONSThese data highlight the limitations of the baboon model for assessing factor-specific coagulation inhibitors during CPB. The justification for Phase 1 human studies using REG1 for CPB is unclear.

项与 Anivamersen-pegnivacogin 相关的新闻（医药）

2014-10-10

·BioSpace

Regado Biosciences, Inc. CEO Steps Down

Regado Biosciences, Inc. Appoints Michael A. Metzger CEO BASKING RIDGE, N.J., Oct. 10, 2014 /PRNewswire/ -- Regado Biosciences, Inc. (NASDAQ: RGDO), today announced the appointment of Michael A. Metzger, president of Regado, to the additional post of chief executive officer and as a member of the Board of Directors effective immediately. Mr. Metzger previously served as president and chief operating officer of Regado. He replaces David J. Mazzo, Ph.D., who has resigned from the company. "On behalf of the entire Board, I would like to thank Dr. Mazzo for his many years of service and all his contributions to Regado," said Dennis Podlesak, chairman of Regado's Board of Directors. "In addition, we are very pleased to have Michael Metzger in the CEO role. Michael has a proven track record of effectively growing companies, and his extensive business development and transactional experience is ideal as Regado focuses on evaluating strategic alternatives to optimize value for shareholders." Mr. Metzger joined Regado in December 2013 and has nearly 20 years of experience within the life sciences sector. He was previously chief operating officer at Mersana Therapeutics, where he was one of the architects of the strategic direction and growth plans of the business and drove the establishment and management of key business alliances. Prior to joining Mersana in 2011, Mr. Metzger led mergers and acquisitions at Forest Laboratories and held senior positions within business development. At Forest, Mr. Metzger developed and completed several high impact transactions with specialty pharmaceutical and biotechnology companies. Mr. Metzger earned his BA from George Washington University and an MBA in Finance from New York University's Stern School of Business. ABOUT REGADO BIOSCIENCES Regado Biosciences, Inc., is a biopharmaceutical company focused on the discovery and development of novel, oligonucleotide-based actively controllable therapeutics. Our initial focus is on applications in the acute and sub-acute cardiovascular therapeutic area. The company's lead product candidate, Revolixys Kit, is a two-component system consisting of pegnivacogin, an anticoagulant aptamer specifically targeting coagulation Factor IXa, and its complementary oligonucleotide active control agent, anivamersen. Regado's actively controllable product candidates have the potential to improve patient outcomes and enhance the patient experience, provide direct therapeutic control to physicians and reduce overall treatment costs. More information can be found at . Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements reflect management's current expectations, as of the date of this press release, and involve certain risks and uncertainties. Forward-looking statements include statements herein with respect to management transition matters, including the future success of members of management in fulfilling their roles and the impact of such success on the Company. The Company's actual results could differ materially from those anticipated in these forward-looking statements as a result of various factors. Factors that could cause future results to materially differ from those projected in forward-looking statements include the actual success of the management transition matters described above, as well as the "Risk Factors" described in the Company's Annual Report on Form 10-K filed with the Securities and Exchange Commission on March 12, 2014, and in the Company's other periodic filings with the SEC. All forward-looking statements are expressly qualified in their entirety by this cautionary notice. You are cautioned not to place undue reliance on any forward-looking statements, which speak only as of the date of this release. The Company has no obligation, and expressly disclaim any obligation, to update, revise or correct any of the forward-looking statements, whether as a result of new information, future events or otherwise. Investor Relations Contact: Don Elsey, CFO Regado Biosciences, Inc. 908-580-2113 delsey@regadobio.com SOURCE Regado Biosciences, Inc. Help employers find you! Check out all the jobs and post your resume.

寡核苷酸并购

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外链

KEGG	Wiki	ATC	Drug Bank
D10059	-	-	DB16089

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
冠心病	临床3期	美国	Regado Biosciences, Inc.	2013-09-01
急性冠状动脉综合征	临床3期	-	Archemix Corp.	-
急性冠状动脉综合征	临床3期	加拿大	Tobira Therapeutics, Inc.	-
急性冠状动脉综合征	临床3期	-	Allergan Ltd. (Ireland)	-
急性冠状动脉综合征	临床3期	美国	Tobira Therapeutics, Inc.	-
静脉血栓形成	临床3期	美国	Tobira Therapeutics, Inc.	-