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

登录后查看更多信息

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

登录后查看更多信息

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

登录后查看更多信息

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

BACKGROUND:

The 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 DESIGN:

ASPEN-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.

CONCLUSIONS:

ASPEN-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.

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

OBJECTIVE:

Excessive 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.

DESIGN:

Randomized controlled study.

SETTING:

Comparative Medicine Department, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

SUBJECTS:

Baboons (Papio Hamadryas).

INTERVENTIONS:

Twelve 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 RESULTS:

Heat 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.

CONCLUSIONS:

Tissue 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.

2007-11-15·The Journal of infectious diseases2区 · 医学

Marburg Virus Angola Infection of Rhesus Macaques: Pathogenesis and Treatment with Recombinant Nematode Anticoagulant Protein c2

2区 · 医学

Article

作者: Elizabeth A. Fritz ; Howard A. Young ; Pierre Formenty ; Kathleen M. Daddario-DiCaprio ; Thomas W. Geisbert ; Tom Larsen ; Lisa E. Hensley ; Joan B. Geisbert

BACKGROUND:

The procoagulant tissue factor (TF) is thought to play a role in the coagulation disorders that characterize filoviral infections. In this study, we evaluated the pathogenesis of lethal infection with the Angola strain of Marburg virus (MARV-Ang) in rhesus macaques and tested the efficacy of recombinant nematode anticoagulant protein c2 (rNAPc2), an inhibitor of TF/factor VIIa, as a potential treatment.

METHODS:

Twelve rhesus macaques were challenged with a high dose (1000 pfu) of MARV-Ang. Six macaques were treated with rNAPc2, and 6 macaques served as control animals.

RESULTS:

All 6 control animals succumbed to MARV-Ang challenge by day 8 (mean, 7.3 days), whereas 5 of 6 rNAPc2-treated animals died on day 9 and 1 rNAPc2-treated animal survived. The disease course for MARV-Ang infection appeared to progress more rapidly in rhesus macaques than has been previously reported for other strains of MARV. In contrast to Ebola virus (EBOV) infection in macaques, up-regulation of TF was not as striking, and deposition of fibrin was a less prominent pathologic feature of disease in these animals.

CONCLUSIONS:

These data show that the pathogenicity of MARV-Ang infection appears to be consistent with the apparent increased human virulence attributed to this strain. The apparent reduced efficacy of rNAPc2 against MARV-Ang infection, compared with its efficacy against EBOV infection, appears to be associated with differences in TF induction and fibrin deposition.

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

登录后查看更多信息