A Phase 2, Single-blind, Randomized, Controlled, Multi-center Study to Evaluate the Efficacy and Safety of SRM003 (Vascugel®) in the Treatment of Subjects With Vascular Injury Resulting From Arteriovenous Graft Surgery for Hemodialysis Access

A study to evaluate the efficacy of SRM003 treatment versus participating sites' standard practice treatment in extending the duration of primary patency after arteriovenous graft surgery in subjects with end-stage renal disease.
It is hypothesized that when placed outside the blood vessel, the seeded SRM003 gelatin matrix containing endothelial cells can provide a continuous supply of multiple growth regulatory compounds to the underlying cells within the blood vessel, while being protected from the effects of blood flow in the vessel(s) or complications resulting from being in direct contact with the point of injury.

开始日期2013-03-28

申办/合作机构

Shire Plc

NCT01806545

/ Completed临床2期

A Phase 2, Single-blind, Randomized, Controlled, Multi-center Study to Evaluate the Efficacy and Safety of SRM003 (Vascugel®) in Improving the Rate of Arteriovenous Fistula Maturation and Use in Subjects Undergoing Surgery for Creation of an Arteriovenous Fistula for Hemodialysis Access

A study to evaluate the efficacy of SRM003 treatment versus participating sites' standard practice treatment in improving the rate of AVF maturation and use in subjects with end-stage renal disease undergoing surgery for creation of an AVF to facilitate hemodialysis access.
It is hypothesized that when placed outside the blood vessel, the seeded SRM003 gelatin matrix containing endothelial cells can provide a continuous supply of multiple growth regulatory compounds to the underlying cells within the blood vessel, while being protected from the effects of blood flow in the vessel(s) or complications resulting from being in direct contact with the point of injury.

开始日期2013-03-26

申办/合作机构

Shire Plc

NCT00479180

/ Completed临床1/2期

Safety of Vascugel Treatment After Creation of Arteriovenous Access for Hemodialysis Use

Vascugel™ is safe when placed at the anastomotic site at the time of surgery during creation of an AV graft or fistula for hemodialysis access.

开始日期2006-07-01

申办/合作机构

Pervasis Therapeutics, Inc.

100 项与 SRM-003 相关的临床结果

登录后查看更多信息

100 项与 SRM-003 相关的转化医学

登录后查看更多信息

100 项与 SRM-003 相关的专利（医药）

登录后查看更多信息

项与 SRM-003 相关的文献（医药）

2011-11-01·Journal of vascular surgery2区 · 医学

Influence of diabetes and perivascular allogeneic endothelial cell implants on arteriovenous fistula remodeling

2区 · 医学

Article

作者: Prabir Roy-Chaudhury ; Peter Gaccione ; Helen M. Nugent ; Jeffrey H. Lawson ; Michael S. Conte

OBJECTIVES:

Arteriovenous fistula (AVF) is the preferred type of vascular access for hemodialysis to treat end-stage renal disease. A high proportion of AVF are never used for dialysis because the vein fails to mature adequately. We have previously described the safety and feasibility of Vascugel (Genzyme BioSurgery, Cambridge, Mass) (allogeneic aortic endothelial cells in a gelatin matrix) when placed around the anastomotic and venous outflow sites of AVFs (Vascular intimal Hyperplasia: Extending Arterial and venous patency, Limiting vascular Trauma, and inhibiting Hyperplasia while re-establishing vascular health [V-HEALTH] clinical study). In this retrospective analysis, we investigated factors that influenced AVF remodeling in patients from the V-HEALTH study. We hypothesized that providing healthy endothelial cells and their secreted factors immediately after surgery could enhance venous remodeling in the setting of vascular injury.

METHODS:

Thirty-one AVF patients from the V-HEALTH study were randomized 2:1 to receive either Vascugel or control matrices (placebo) at surgery and were followed for 24 weeks. Venous lumen diameter was measured by ultrasound at 1, 3, and 5 cm from the anastomosis. Vein remodeling (change in lumen diameter at 4, 12, and 24 weeks compared with baseline diameter at 2 weeks) was analyzed using a multiple regression mixed model.

RESULTS:

The results indicated that diabetes was a significant, negative predictor of venous remodeling over the 24-week study (P = .02). The model-predicted change in lumen diameter from 2 to 24 weeks was -0.7 mm in diabetic patients (n = 11) and +2.4 mm in nondiabetic patients (n = 15), a difference of 3.1 mm, 95% confidence interval [CI] (1.4-4.9), P = .0014. Patient race, baseline vein diameter, and time post-AVF creation were also significant factors that affected remodeling (P < .05). Compared with placebo, there was a strong suggestion that Vascugel treatment improved the rate of venous enlargement in diabetic patients (P = .05). The model-predicted change in lumen diameter at 24 weeks was -1.9 mm for placebo-treated diabetic patients and +0.4 mm for Vascugel-treated diabetic patients, a difference of 2.3 mm, 95% CI (-0.1-4.8), P = .06, suggesting that treatment with Vascugel may mitigate the negative influence of diabetes on AVF remodeling.

CONCLUSIONS:

Diabetes negatively impacts AVF remodeling and targeted local therapy with perivascular, allogeneic endothelial cells may ameliorate this effect. A phase II trial designed specifically to evaluate AVF remodeling is needed to determine if Vascugel can increase AVF maturation and use and to support larger randomized trials.

2009-12-01·Journal of vascular surgery2区 · 医学

Multicenter phase I/II trial of the safety of allogeneic endothelial cell implants after the creation of arteriovenous access for hemodialysis use: The V-HEALTH study

2区 · 医学

Article

作者: Peter Gaccione ; Prabir Roy-Chaudhury ; Helen M. Nugent ; Indira Guleria ; Jeffrey H. Lawson ; Michael S. Conte

OBJECTIVES:

Vascular access dysfunction is the major cause of morbidity in patients on hemodialysis to treat end stage renal disease. Preclinical studies have demonstrated that the perivascular placement of implants containing allogeneic aortic endothelial cells (Vascugel) reduces thrombosis, inflammation, stenosis and increases lumen diameter in porcine models of arteriovenous fistulae (AVF) and arteriovenous grafts (AVG). We conducted a phase I/II clinical study to investigate the safety of Vascugel placement around the surgical anastomotic sites of newly constructed dialysis accesses.

METHODS:

From July 2006 to August 2006, eight patients (4 AVG, 4 AVF) were treated with two Vascugel sponges at the venous anastomosis in the open-label phase I trial. From January 2007 to August 2007 57 patients (30 AVG and 27 AVF) were randomized in a 2:1 fashion to receive either Vascugel or control matrices (placebo) at surgery. The phase II AVG patients had sponges placed at both the venous and arterial anastomoses. All patients were followed for 24 weeks. The primary objective of the study was to demonstrate the safety (incidence of infection, intervention, and thrombosis) of Vascugel compared with placebo within 30 days post-surgery. Secondary endpoints included assessments of patency, lumen diameter, and immunologic sensitization to human leukocyte antigens (HLA) determined by measurement of panel reactive antibodies (PRA).

RESULTS:

There was no difference in early complication rates between the Vascugel and placebo groups at 4 weeks (10.9% vs 21.1%, respectively). There were no statistically significant differences in primary or assisted primary patency between the intent to treat groups at 24 weeks. Vascugel treated AVG had a primary patency rate of 38% and an assisted primary patency rate of 72% (vs 23% and 58%, respectively, for placebo). Vascugel treated AVF had a primary patency rate of 60% at 24 weeks and an assisted primary patency rate of 96% (vs 62% and 88%, respectively, for placebo). A greater than 30% increase in PRA was detected in 9 of the 46 (19.5%) Vascugel treated patients and one of the 19 (5.2%) placebo patients (P = .26) and was not associated with any evidence of local or systemic complications.

CONCLUSIONS:

Targeted local therapy with perivascular, allogeneic endothelial cells is a safe and novel therapeutic approach that may be ideally suited to control the response to injury at surgical anastomoses. Larger randomized trials are needed to determine if Vascugel can prolong AVG or AVF patency.

1988-12-01·Infection and immunity2区 · 医学

Resistance of mucoid Pseudomonas aeruginosa to nonopsonic phagocytosis by alveolar macrophages in vitro

2区 · 医学

Article

作者: Helmke, R J ; Krieg, D P ; German, V F ; Mangos, J A

A unique, recently described rat alveolar macrophage cell line (NR8383) was used to study the interaction of the pulmonary immune system with a mucoid cystic fibrosis isolate of Pseudomonas aeruginosa (SRM-3), its nonmucoid revertant (SRM-3R), and a non-cystic fibrosis isolate (PAO-1). Strain SRM-3 was cultivated in a chemostat system to allow maintenance of an entirely mucoid population. The alveolar macrophage response to the mucoid and nonmucoid strains of P. aeruginosa was determined by visually quantitating phagocytosis in acridine orange-stained monolayers and measuring the induction of an oxidative burst as indicated by chemiluminescence and H2O2 production. In all experiments, fewer than 2% of the NR8383 cells engulfed the mucoid SRM-3 isolate, while SRM-3R and PAO-1 were phagocytized by 15 and 41%, respectively. Opsonization by normal serum (complement) provided minimal phagocytic enhancement of these strains, whereas specific anti-P. aeruginosa antibody slightly elevated phagocytic responses to strains with nonmucoid phenotypes while providing a sevenfold increase in uptake of SRM-3. Chemiluminescent and H2O2 responses were comparable with the levels of phagocytosis observed, with very little or no response to the mucoid strain SRM-3. The data indicate that the strains with mucoid phenotypes are refractile to ingestion and that studies which describe ingestion of mucoid strains were likely measuring ingestion of revertants. Alginic acid (2 mg/ml) was found to inhibit stimulation of macrophage response to the opsonized and unopsonized nonmucoid strain PAO-1.

项与 SRM-003 相关的新闻（医药）

2012-04-12

·Mass Device

Shire adds Pervasive Therapeutics to regenerative portfolio | Wall Street Beat

Shire (NSDQ:SHPGY) said it agreed to acquire Pervasis Therapeutics and its endothelial cell technology for an undisclosed amount. The deal adds to the regenerative medicine portfolio Shire started with its May 2011 buyout of Advanced BioHealing. Shire, based in Dublin and Lexington, Mass., shelled out $750 million for the company and its DermaGraft skin substitute for diabetic foot ulcers, becoming one of the first large biopharms to get into the regenerative medicine game. But the much-ballyhooed transformative value of the Advanced BioHealing buyout took a hit when Shire abandoned its pursuit of a leg ulcer indication for DermaGraft shortly after closing the acquisition. That decision was prompted by the failure of a Phase III clinical trial examining DermaGraft in treating venous leg ulcers failed to meet its primary endpoint of complete healing after 16 weeks. Shire said it plans to focus on a Phase II trial of Pervasive’s Vascugel for arteriovenous access for hemodialysis patients. "There are currently no approved therapies that directly target the underlying physiological processes associated with the creation of AV access sites in hemodialysis patients, including inflammation, thrombosis, and restenosis. As a result, there remains a significant unmet need for technologies that improve hemodialysis access for patients with ESRD," Kevin Rakin, president of Shire’s regenerative medicine division, said in prepared remarks. We believe Vascugel has the potential to enhance the rate of blood vessel repair while also providing for increased maintenance of the access site for a prolonged period of time as compared to current treatments. This acquisition marks a very important step for Shire in building a Regenerative Medicine business focused on tissue repair and regeneration." Orthopedic bellwether Biomet’s Q3 results signal sector growth Orthopedic device maker Biomet Inc.‘s 3rd-quarter results could be a bellwether of better things to come for the larger orthopedics sector, according to Leerink Swann analysts Richard Newitter and Rick Wise. "All else equal, we’re inclined to think ortho stocks (Zimmer (NYSE:ZMH), Stryker (NYSE:SYK), NuVasive Inc.(NSDQ:NUVA), Wright Medical (NSDQ:WMGI)) will react positively to the y/y growth acceleration Biomet posted in its U.S. recon division. We note that Biomet (and the rest of the hip/knee industry) is up against easier y/y U.S. recon growth comparisons this quarter, especially in knees, which likely contributed – at least to some extent – to the growth pick-up this quarter," the analysts wrote in a note to investors earlier this week. "Overall, Biomet’s hip performance seems to suggest basically stable hip market growth trends this quarter. U.S. spine growth accelerated for the 3rd quarter in a row, which may suggest key industry pressures (e.g., insurer pushback and ASP declines) are at least not getting worse, which could have positive implications for NUVA. Biomet’s extremities division continues to chug along at a double-digit clip and points to a still strong growth environment for this ortho category. McKesson beats out rivals for $32B VA deal McKesson (NYSE:MCK) won out over rivals Cardinal Health (NYSE:CAH) and Amerisource Bergen (NYSE:ABC) for a U.S. Dept. of Veterans Affairs drug distribution contract worth $32 billion over 8 years. Insulet expands OUS distribution deal Insulet (NSDQ:PODD) enlarged its 5-year, $100 million distribution deal with Ypsomed (FRA:OWX), making the Swiss firm its exclusive distributor in 22 countries in Europe, the Middle East, and Asia and adding at least a year to the agreement. Revolutions Medical inks Korean distribution deal Revolutions Medical (PINK:RMCP) inked a marketing and distribution agreement with Sungwon Medical Co. Ltd. to distribute its RevVac auto-retractable vacuum safety syringe. Pluromed pays back $500k Mass. loan Recent Sanofi (NYSE:SNY) purchase Pluromed Inc. paid back its $500,000 loan from the Mass. Life Sciences Center, with interest, for a total repayment of $654,228. Funding Roundup Tearlab inks $10M private placement Analysts’ ups and downs C.R. Bard (NYSE:BCR): J.P. Morgan increases price target from $92 to $97, maintains "neutral" rating. ICU Medical (NSDQ:ICUI): Benchmark initiates coverage with "buy" rating, a $60 price target.

并购临床3期引进/卖出

100 项与 SRM-003 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
血管系统损伤	临床2期	美国	Shire Plc	2013-03-28
动静脉瘘	临床2期	美国	Shire Plc	2013-03-26

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01806584 (CTgov)	临床2期	血管系统损伤	32	Participating Site's standard practice (Participating Site's Standard Practice)	遞製廠襯範遞醖顧齋膚 = 願糧鬱齋積淵憲襯壓獵齋窪鏇鹽憲餘淵艱鑰膚 (製獵鬱範膚獵顧獵遞構, 觸衊鹹淵壓遞鏇簾夢餘 ~ 齋齋糧鏇選積遞憲鏇餘) 更多	-	2015-12-31
				SRM003 (SRM003)	遞製廠襯範遞醖顧齋膚 = 窪繭艱範齋壓廠網襯夢齋窪鏇鹽憲餘淵艱鑰膚 (製獵鬱範膚獵顧獵遞構, 窪膚糧膚築艱廠獵廠製 ~ 廠觸齋築齋獵鏇鑰願窪) 更多
NCT01806545 (CTgov)	临床2期	动静脉瘘	64	Participating Site's standard practice (Participating Site's Standard Practice)	衊醖廠淵簾淵衊獵獵衊 = 獵鏇積觸壓鑰構齋構鹹齋夢窪獵積簾製簾鏇簾 (餘醖壓製壓膚鬱醖衊壓, 顧膚觸顧廠膚獵膚願齋 ~ 窪網簾膚構襯選齋衊襯) 更多	-	2015-12-24
				SRM003 (SRM003)	衊醖廠淵簾淵衊獵獵衊 = 夢顧鏇醖鹹夢糧網鬱觸齋夢窪獵積簾製簾鏇簾 (餘醖壓製壓膚鬱醖衊壓, 網壓鏇鬱製簾窪窪醖糧 ~ 壓衊鑰淵顧鹽願鹽鬱膚) 更多
V-HEALTH (ASN2010)	临床1/2期	动静脉瘘 diabetes (DM)	-	Vascugel	鹹淵糧衊膚鏇醖醖襯憲(襯範齋製淵壓蓋選網糧) = 積構齋夢築襯簾衊糧膚襯膚膚齋艱繭壓膚齋鹽 (襯壓衊範網憲夢蓋獵餘 )	积极	2010-11-16
				Placebo	鹹淵糧衊膚鏇醖醖襯憲(襯範齋製淵壓蓋選網糧) = 鏇鑰襯鬱壓廠衊襯顧蓋襯膚膚齋艱繭壓膚齋鹽 (襯壓衊範網憲夢蓋獵餘 )