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Waltham, MA, United States

Hye R.J.,Kaiser Permanente | Peden E.K.,Methodist Hospital | Browne B.J.,California Institute of Renal Research | Dixon B.S.,University of Iowa | And 5 more authors.
Journal of Vascular Surgery | Year: 2014

Objective This study explored the safety and efficacy of recombinant type I pancreatic elastase (PRT-201) topically applied once to the external surface of an arteriovenous fistula. Methods This was a randomized, double-blind, placebo-controlled trial. Adults with kidney disease undergoing creation of a radiocephalic fistula (RCF) or brachiocephalic fistula were randomized to treatment with placebo (n = 51), PRT-201 at 10 μg (n = 51), or PRT-201 at 30 μg (n = 49). The primary efficacy measure was unassisted primary patency (PP) over 1 year. Secondary efficacy measures were secondary patency (SP), unassisted maturation by ultrasound interrogation, use for hemodialysis, and hemodynamically significant lumen stenosis. Results Median PP was 224 days for placebo and >365 days for the PRT-201 groups. At 1 year, 45%, 54%, and 53% of placebo, 10-μg, and 30-μg patients retained PP. The risk of PP loss was nonsignificantly reduced for 10 μg (hazard ratio [HR], 0.69; P =.19) and 30 μg (HR, 0.67; P =.17) vs placebo. In the subset (44% of patients) with a RCF, the median PP was 125 days for placebo and >365 days for the PRT-201 groups. At 1 year, 31%, 50%, and 63% of placebo, 10-μg, and 30-μg RCFs retained PP. The risk of RCF PP loss was nonsignificantly reduced by 10 μg (HR, 0.59; P =.18) and significantly reduced by 30 μg (HR, 0.37; P =.02) vs placebo. At 1 year, 77%, 81%, and 83% of placebo, 10-μg, and 30-μg patients retained SP. The risk of SP loss was nonsignificantly reduced for 10 μg (HR, 0.79; P =.61) and 30 μg (HR, 0.76; P =.55) vs placebo. In the subset with RCFs, 65%, 82%, and 90% of placebo, 10-μg, and 30-μg patients retained SP at 1 year. The risk of RCF SP loss was nonsignificantly reduced for 10 μg (HR, 0.45; P =.19) and 30 μg (HR, 0.27; P =.08) vs placebo. At month 3, 67%, 87% (P =.03), and 92% (P <.01) of the placebo, 10-μg, and 30-μg group fistulas had unassisted maturation by ultrasound interrogation. At month 3 in the subset with an RCF, 47%, 74% (P =.17), and 93% (P <.01) of placebo, 10-μg, and 30-μg group fistulas had unassisted maturation by ultrasound interrogation. Adverse event reports were not meaningfully different between groups. Conclusions PRT-201 appeared safe. The primary efficacy end point was not met. However, both PRT-201 doses were associated with improved unassisted maturation. The 30-μg dose was associated with increased PP in the subset with RCF. Copyright © 2014 by the Society for Vascular Surgery. Source


Patent
Proteon Therapeutics Inc. | Date: 2013-08-02

The present invention relates to methods for the manufacture, purification, formulation, and use of biologically active recombinant elastase proteins. Described are recombinant methods for producing therapeutically useful elastase proteins, as are pharmaceutical compositions comprising said elastase proteins. Novel recombinant elastase proteins and protein preparations are also disclosed. Methods are described for treating and preventing diseases of biological conduits using pharmaceutical compositions containing the elastase proteins of the invention.


Patent
Proteon Therapeutics Inc. | Date: 2010-04-21

Methods are described for dilating biological conduits by removing elastin and remodeling collagens in the wall of the conduit. Methods include the use of agents that increase the release of endogenous elastase and collagenase in the wall of the conduit, either by cells that are normally present in the wall of the conduit or by inflammatory cells that are attracted to the conduit, thereby providing additional conduit dilation. Methods also include the use of agents that increase conduit wall permeability and expose elastin and collagen fibers. Methods also include removing components of the extracellular matrix of arteries and veins leading to an inhibition of intimal hyperplasia in the wall of the vessels by decreasing biomechanical stimuli directed toward the cells in the wall of the vessel. Methods further include the use of agent that degrade microfibers, in addition to elastin, in order to decrease the resynthesis of elastin. Methods also include the use of agent that stabilize the diameter of aneurysmal arteries by blocking cell surface receptors in the wall of the aneurysmal artery that are important in the recruitment of inflammatory cells.


Patent
Proteon Therapeutics Inc. | Date: 2013-08-30

The invention provides methods to for treating an obstructed biological conduit that include administering to the conduit an agent that can degrade extracellular matrix of obstructing tissue. Particular methods include delivery of an enzyme or a mixture of several enzymes to the area or region of obstruction wherein the enzyme(s) have the capability to degrade extracellular matrix components within the obstruction thereby restoring the normal flow of transported fluid through the conduit. The invention also includes prophylactically dilating a section of conduit to minimize the risk of obstruction formation.


Patent
Proteon Therapeutics Inc. | Date: 2014-08-21

The present invention relates to methods for the manufacture, purification, formulation, and use of biologically active recombinant elastase proteins. Described are recombinant methods for producing therapeutically useful elastase proteins, as are pharmaceutical compositions comprising said elastase proteins. Novel recombinant elastase proteins and protein preparations are also disclosed. Methods are described for treating and preventing diseases of biological conduits using pharmaceutical compositions containing the elastase proteins of the invention.

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