An Efficacy and Safety Study of SRM003 in the Treatment of Subjects Undergoing Creation of an Arteriovenous Fistula to Facilitate Hemodialysis Access

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Arteriovenous Fistula

Intervention / Treatment
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* Biological: SRM003
* Other: Participating Site's standard practice


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must be 18 years of age or older at the time of signing and dating informed consent (no upper age limit), can be male or female. Subject who is of child bearing potential must agree to use adequate contraception for 6 months after randomization. Subject must be currently undergoing hemodialysis or anticipating the start of hemodialysis and must require a new permanent, suitable access for the AVF creation in the upper extremity. Subject must have a life expectancy of at least 26 weeks after randomization. Subject must be able to understand and be willing to complete all study requirements. Exclusion Criteria: Subject is currently on an active organ transplant list from a deceased donor or is undergoing assessment and expects to be placed on the active organ or bone marrow transplant list within the next 26 weeks from surgery, or expects to receive a living donor organ or bone marrow within the next 26 weeks and is unwilling to change transplant list status to hold for 3 months after randomization. Subject has had more than 1 access placement surgery (defined as a new access, not a revision) in the target limb. Subject has medical conditions and diseases that may cause non-compliance with the protocol Subject has a known allergy to bovine/porcine products or collagen/gelatin products. Subject has a history of intravenous drug use within 6 months prior to screening Subject is morbidly obese, defined as having a body mass index >40. Pregnant or nursing woman, or plans to become pregnant during the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: SRM003<br>One time implant (2 SRM003 pieces) on surgery day. Post-surgery, up to 26 weeks follow-up for assessment of efficacy/safety. | Biological: SRM003<br>* One time implant (2 SRM003 pieces) on surgery day.<br>* Other names: Allogeneic human aortic endothelial cells cultured in a gelatin matrix (Gelfoam®).;|
| Other: Participating Site's standard practice<br>Subjects will receive sites' standard practice treatment during the surgical procedure. | Other: Participating Site's standard practice<br>* Subjects will receive sites' standard practice treatment during the surgical procedure.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Arteriovenous Fistula (AVF) Maturation by Week 12 Visit Based on Hemodialysis or Color-flow Doppler Ultrasound (CDUS) And Vascular Access Examination | Maturation based on CDUS was assessed in a continuous fashion and was defined by the following criteria: presence of bruit throughout systole and diastole at least 8 centimeters (cm) proximal to the venous anastomosis, blood flow through the outflow vein of at least 500 milliliters (ml) per minute, and a lumen diameter of the outflow vein at least 4 mm. Maturation was determined by CDUS and vascular access examination or by first use of the AVF for hemodialysis based on investigator-reported use. Participants who discontinued prior to the Week 12 visit without assessment of maturity were considered treatment failures. | 12 weeks after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With AVF Maturation by Week 26 Visit Based on Hemodialysis or CDUS And Vascular Access Examination | Maturation based on CDUS was assessed in a continuous fashion and was defined by the following criteria: presence of bruit throughout systole and diastole at least 8 centimeters (cm) proximal to the venous anastomosis, blood flow through the outflow vein of at least 500 milliliters (ml) per minute, and a lumen diameter of the outflow vein at least 4 mm. Maturation was determined by CDUS and vascular access examination or by first use of the AVF for hemodialysis based on investigator-reported use. Participants who discontinued prior to the Week 26 visit without assessment of maturity were considered treatment failures. | 26 weeks after surgery | 
| Time to AVF Maturation Based on Hemodialysis or CDUS and Vascular Access Examination | Time to AVF maturation was defined as the duration of time (in days) from the date of randomization (AVF creation) to the date of maturation, where the date of maturation corresponds to the earlier of either the date of the first use of the study AVF for hemodialysis as determined by the investigator following discussion with the participant, or the date the AVF meets all of the following 3 criteria as determined through CDUS and vascular access examination: presence of bruit throughout systole and diastole at least 8 centimeters proximal to the venous anastomosis, blood flow through the outflow vein of at least 500 milliliters (ml) per minute, and a lumen diameter of the outflow vein at least 4 mm. Participants who died, underwent a kidney transplant, or were either lost to follow-up or did not mature during the study follow-up were censored at the time of death, time of transplant, or time of last visit, respectively. | Up to 26 weeks after surgery | 
| Percentage of Participants With Loss of Unassisted Primary Patency | The time to loss of unassisted primary patency (intervention--free access survival) was defined as the duration of time in days from the date of randomization (AVF creation) until the first date of (a) any intervention designed to establish, maintain, or restore patency; (b) occlusion (commonly due to thrombosis); or (c) access abandonment. | Up to 26 weeks after surgery | 
| Percentage of Participants With Loss of Assisted Primary Patency | The time to loss of assisted primary patency (thrombosis--free access survival) was defined as the duration of time in days from the date of randomization (AVF creation) until the first date of (a) occlusion (commonly due to thrombosis) or (b) access abandonment. | Up to 26 weeks after surgery | 
| Percentage of Participants With Loss of Secondary Patency | The time to loss of secondary patency (access survival until abandonment) was defined as the duration of time in days from the date of randomization (AVF creation) until the date of access abandonment. | Up to 26 weeks after surgery | 
| Change From Week 1 in Average Vascular Access Lumen Diameter Using CDUS | B-mode lumen diameter measurements were obtained in the outflow vein as 3 separate images for each location: at 1, 3, and 5 centimeter into the vein and from the toe of the venous anastomosis. The average of lumen diameter measurements obtained at 1, 3, and 5 cm from the anastomosis was used for this endpoint. | 1, 12, and 26 weeks after surgery | 
| Percentage of Participants With Clinical Success Based on First Use of The Study AVF For Hemodialysis | Clinical success was defined as the ability to undergo hemodialysis using the AVF. The date of clinical success corresponded to the date of the first use of the study AVF for hemodialysis as determined by the investigator, following discussion with the subject. Clinical success was assessed in a continuous fashion and, once achieved, the AVF was considered a clinical success at that and all subsequent time points. The date of clinical success based on the first use of the AVF for hemodialysis was compared with the dates of each study visit (Week 12 and Week 26); for study visits occurring prior to the date of clinical success based on the first use of the AVF for hemodialysis, the subject was counted as a nonsuccess and for study visits occurring on or after the date of maturation based on the first use of the AVF for hemodialysis, the subject was counted as a success. | 12 and 26 weeks after surgery | 
| Number of Interventions to Establish, Maintain, or Restore Patency | The total number of interventions to establish, maintain, or restore patency was recorded for each participant. | 12 and 26 weeks after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Arteriovenous Fistula Surgery, Vascular Injury, Hemodialysis Access