This is a multicenter, two-stage trial with the goal of evaluating up to 100 subjects. This trial will be performed to initiate identification of a safe and effective dose of twice-weekly, subcutaneous rNAPc2 for the second-line treatment of metastatic colorectal carcinoma in combination with contemporary 5-FU-based chemotherapy.

开始日期2006-12-01

申办/合作机构

ARCA biopharma, Inc.

100 项与 Recombinant nematode anticoagulant protein c2(ARCA Biopharma) 相关的临床结果

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100 项与 Recombinant nematode anticoagulant protein c2(ARCA Biopharma) 相关的转化医学

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100 项与 Recombinant nematode anticoagulant protein c2(ARCA Biopharma) 相关的专利（医药）

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项与 Recombinant nematode anticoagulant protein c2(ARCA Biopharma) 相关的文献（医药）

2022-04-01·American Heart Journal2区 · 医学

Rationale and design of a study to assess the safety and efficacy of rNAPc2 in COVID-19: the Phase 2b ASPEN-COVID-19 trial

2区 · 医学

Article

作者: Hsia, Judith ; Graybill, Christopher A ; Morrow, David A ; Szarek, Michael ; Marshall, Debra ; Hess, Connie N ; Bristow, Michael R ; Nicolau, Jose C ; Bonaca, Marc P ; Ruf, Wolfram ; Capell, Warren H

BACKGROUNDThe interaction between thrombosis and inflammation appears central to COVID-19-associated coagulopathy and likely contributes to poor outcomes. Tissue factor is a driver of disordered coagulation and inflammatory signaling in viral infections and is important for viral replication; therefore, tissue factor may be an important therapeutic target in COVID-19.STUDY DESIGNASPEN-COVID-19 (NCT04655586) is a randomized, prospective open-label blinded endpoint (PROBE), active comparator Phase 2b trial to evaluate the safety and efficacy of recombinant Nematode Anticoagulant Protein c2 (rNAPc2), a potent tissue factor inhibitor, in patients hospitalized with COVID-19 with elevated D-dimer levels. This report describes the design of the Phase 2b dose ranging and proof of concept study. Participants are randomly assigned, in a 1:1:2 ratio, to lower or higher dose rNAPc2 by subcutaneous injection on days 1, 3, and 5 or to heparin according to local standard of care; randomization is stratified by baseline D-dimer level (at 2X upper limit of normal). The primary efficacy endpoint for Phase 2b is proportional change in D-dimer concentration from baseline to Day 8 or day of discharge, whichever is earlier. The primary safety endpoint is major or non-major clinically relevant bleeding through Day 8. Phase 2b enrollment began in December 2020 and is projected to complete ∼160 participants by Q4 2021.CONCLUSIONSASPEN-COVID-19 will provide important data on a novel therapeutic approach that may improve outcomes in hospitalized COVID-19 patients beyond available anticoagulants by targeting tissue factor, with potential effects on not only thrombosis but also inflammation and viral propagation.

2015-04-01·Oncology Reports3区 · 医学

Recombinant nematode anticoagulant protein c2 inhibits cell invasion by decreasing uPA expression in NSCLC cells

3区 · 医学

Article

作者: Zhou, Jing ; Tong, Yu ; Liu, Qingqing ; Yang, Jiyun ; Mao, Meng ; Yue, Jun

Nematode anticoagulant protein c2 (NAPc2) is an 85-residue polypeptide originally isolated from the hematophagous hookworm, Ancylostoma caninum. Several studies have shown that rNAPc2 inhibits the growth of primary and metastatic tumors in mice independently of its ability to initiate coagulation. We obtained bioactive recombinant rNAPc2 by splicing of the rNAPc2-intein-CBD fusion proteins expressed in E. coli ER2566. In the in vitro assay, rNAPc2 obviously inhibited the invasive ability of non-small cell lung cancer (NSCLC) cells in a dose-dependent manner. Furthermore, rNAPc2 suppressed tumor growth in vivo by daily intraperitoneal injection of rNAPc2 in an NSCLC cell xenograft model of nude mice. Respectively, rNAPc2 downregulated the production of urokinase plasminogen activator (uPA) (P<0.05) and suppressed nuclear factor-κB (NF-κB) activity. We also identified that inhibition of NF-κB activity impaired cell invasion and reduced the uPA production in NSCLC cells. Meanwhile, NF-κB was found to directly bind to the uPA promoter in vitro. These results demonstrated that rNAPc2 inhibits cell invasion at least in part through the downregulation of the NF-κB-dependent metastasis-related gene expression in NSCLC. Our results also suggest that uPA, a known metastasis-promoting gene, is indirectly regulated by rNAPc2 through NF-κB activation. These results indicate that rNAPc2 may be a potent agent for the prevention of NSCLC progression.

2012-04-01·Critical Care Medicine1区 · 医学

Tissue factor/factor VIIa pathway mediates coagulation activation in induced-heat stroke in the baboon

1区 · 医学

Article

作者: Tarek Owaidah ; Falah Al-Mohanna ; Engin Baturcam ; Abdelmoneim Eldali ; Mohammed Dehbi ; Lina Assad ; Abderrezak Bouchama

OBJECTIVEExcessive activation of coagulation, which can culminate in overt disseminated intravascular coagulation, is a prominent feature of heat stroke. However, neither the mechanism that initiates the coagulation activation nor its pathogenic role is known. We examined whether the tissue factor/factor VIIa complex initiates the coagulation activation in heat stroke and, if so, whether upstream inhibition of coagulation activation through its neutralization may minimize cellular injury and organ dysfunction. We also examined whether coagulation inhibition influences heat stroke-induced fibrinolytic and inflammatory responses.DESIGNRandomized controlled study.SETTINGComparative Medicine Department, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.SUBJECTSBaboons (Papio Hamadryas).INTERVENTIONSTwelve anesthetized baboons assigned randomly to recombinant nematode anticoagulant protein c2, a powerful inhibitor of tissue factor/factor VIIa-dependent coagulation (n = 6), or a control group (n = 6) were heat-stressed in a prewarmed neonatal incubator at 44-47°C until systolic blood pressure fell <90 mm Hg, signaling the onset of severe heat stroke. Recombinant nematode anticoagulant protein c2 was administered as a single intravenous dose of 30 μg/kg body weight at onset of heat stroke. The control group received an equivalent volume of sterile saline intravenously.MEASUREMENTS AND MAIN RESULTSHeat stroke was associated with coagulation activation and fibrin formation as evidenced by the increased plasma thrombin-antithrombin complexes, endogenous thrombin potential, and D-dimer levels. Recombinant nematode anticoagulant protein c2 induced significant inhibition of thrombin generation and fibrin formation. Inhibition of coagulation in recombinant nematode anticoagulant protein c2-treated animals did not influence either fibrinolysis (assessed by tissue plasminogen activator, plasmin-α2-antiplasmin complexes, and plasminogen activator inhibitor) or the release of pro- and anti-inflammatory cytokines. No difference in markers of cell injury and organ dysfunction was observed between recombinant nematode anticoagulant protein c2-treated and control groups.CONCLUSIONSTissue factor/factor VIIa-dependent pathway initiates coagulation activation in induced-heat stroke in the baboon without an effect on fibrinolysis and inflammation. The findings suggest also that coagulation activation is not a prerequisite of cell injury and organ dysfunction.

100 项与 Recombinant nematode anticoagulant protein c2(ARCA Biopharma) 相关的药物交易

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