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.

Start Date28 Mar 2013

Sponsor / Collaborator

Shire Plc

NCT01806545 / CompletedPhase 2

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.

Start Date26 Mar 2013

Sponsor / Collaborator

Shire Plc

NCT00479180 / CompletedPhase 1/2

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.

Start Date01 Jul 2006

Sponsor / Collaborator

Pervasis Therapeutics, Inc.

100 Clinical Results associated with SRM-003

100 Translational Medicine associated with SRM-003

100 Patents (Medical) associated with SRM-003

Literatures (Medical) associated with SRM-003

01 Nov 2011·Journal of Vascular SurgeryQ2 · MEDICINE

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

Q2 · MEDICINE

Article

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

OBJECTIVESArteriovenous 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.METHODSThirty-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.RESULTSThe 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.CONCLUSIONSDiabetes 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.

01 Dec 2009·Journal of Vascular SurgeryQ2 · MEDICINE

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

Q2 · MEDICINE

Article

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

OBJECTIVESVascular 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.METHODSFrom 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).RESULTSThere 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.CONCLUSIONSTargeted 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.

01 Dec 1988·Infection and ImmunityQ2 · MEDICINE

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

Q2 · MEDICINE

Article

Author: German, V F ; Helmke, R J ; Krieg, D P ; 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.

100 Deals associated with SRM-003

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Vascular System Injuries	Phase 2	US	Shire Plc	28 Mar 2013
Arteriovenous Fistula	Phase 2	US	Shire Plc	26 Mar 2013

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01806584 (CTgov)	Phase 2	Vascular System Injuries	32	Participating Site's standard practice (Participating Site's Standard Practice)	snuqmjmijl(hcyfzbhibg) = tnewapojgq kwnavkwepd (gwdexwekuu, kfgddpdpwx - bqjljuoxpi) View more	-	31 Dec 2015
				SRM003 (SRM003)	snuqmjmijl(hcyfzbhibg) = qiuixdsevv kwnavkwepd (gwdexwekuu, qngjxoivlf - pjbqymzhdh) View more
NCT01806545 (CTgov)	Phase 2	Arteriovenous Fistula	64	Participating Site's standard practice (Participating Site's Standard Practice)	ighxrbmred(ibqxjpecom) = pkiesbcxwl hpndmuqspy (cluyrjgxxo, wdkmehkqoj - sjbuidhuqj) View more	-	24 Dec 2015
				SRM003 (SRM003)	ighxrbmred(ibqxjpecom) = edhjqxqmmb hpndmuqspy (cluyrjgxxo, brnbvkxdpr - wgfrngpnve) View more

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