A multi-center Phase 4 observational cohort study to compare AlloSure (ddcfDNA) with standard patient care in Kidney transplant recipients.

 Target population: Patients who are the recipient of the transplanted kidney.

 The problem: In patients with kidney transplant rejection, by the time the clinical diagnosis is confirmed histologically by biopsy, the renal scarring incurred is often too advanced to make delayed treatment.

 Why problem exist:  Following kidney transplant, clinicians face vast array of differentials when graft dysfunction is observed, like drug toxicity, opportunistic infection, primary disease recurrence, and implant rejection. Histologic analysis of the allograft biopsy specimen remains the standard method used to differentiate and classify rejection from other injury in kidney transplants. Invasiveness of renal biopsy may create challenges for clinicians in optimizing the timing for biopsy which leads to delay in injury detection and on time treatment intervention.

 New approach to solve the problem: There is a huge need of a non-invasive technique for early detection of transplanted kidney rejections and injuries. Minimally invasive strategies like donor-derived cell-free DNA (dd-cfDNA) has been used to detect cellular injuries in fetal genetic screening, prenatal trisomy diagnosis as well as pre-clinical neoplasia detection.

 Study: A multi-center Phase 4 observational cohort study to compare AlloSure (ddcfDNA) with standard patient care in Kidney transplant recipients.

 Study duration: Event-driven, estimated 5 years with 1 year follow up study.

 New intervention: In transplantation, there is now a growing body of evidence (109 papers from 55 studies) demonstrating a correlation between dd-cfDNA and clinical outcomes, thus, showing the promise of this tool for the early and accurate detection of allograft injury and rejection.

 Study purpose: 5-year assessment of overall return to dialysis, re-transplant, death due to allograft failure, or death with functioning allograft (infections, malignancies, and cardiovascular death) in groups monitored using AlloSure compared to matched control group on standard of care.

 Sponsor Name: CareDx, Inc.

A Phase 3 Study to Compare the Efficacy and Safety of Humacyte's Human Acellular Vessel with Arteriovenous Fistula in Subjects with End-Stage Renal Disease.

 Target population: Patients with end-stage renal disease (ESRD), who currently receiving hemodialysis (HD) via dialysis catheter (DC).

 The problem: Unfortunately, HD access data indicates that the Fistula First Breakthrough Initiative has not resulted in a dramatic improvement in the percentage of patients that start HD with the desired form of access like Arterio-Venous Fistula (AVF) as originally intended.

Why problem exist: An important contributor to the low prevalence of AVF use is the failure of a large percentage (~60%) of newly created AVF to mature adequately. Hemodialysis Fistula Maturation (HFM) study did not show a statistically relevant association between clinical factors (older age, female gender, black race, vascular morbidity and forearm location) and fistula non-maturation.

 New approach to solve the problem: There is a need of a tissue-engineered vascular conduit which possesses the advantages of an AVF or synthetic grafts, including low infection rate and access longevity; without the significant drawback of non-maturation. A tissue-engineered vascular conduit mimics native vessel, it does not have the compliance mismatch associated with synthetic alternatives. In addition, pre-clinical studies in pigs, canines and primates have shown that the engineered vascular accesses resist intimal hyperplasia at the anastomoses.

 Study: Prospective, multicenter, open-label, randomized, two-arm, comparative phase 3 study.

 Study duration: Between 24-84 months based on the patient’s outcome.

 New intervention: This investigational product is Humacyte’s Human Acellular Vessel (HAV), which is a tissue-engineered vascular conduit developed by 8-week period culturing from human aortic vascular smooth muscle cells, in a bioreactor that imparts arterial-like strain conditions on the growing cells. This is a sterile, non-pyrogenic acellular tubular vessel composed, primarily, of human collagen types I and III plus other extracellular matrix (ECM) proteins, including fibronectin and vitronectin. The HAV is 6 mm in diameter and approximately 42 cm in length (~40 cm usable length once removed from bioreactor bag).

 Study purpose: To collect exploratory data on the efficiency and quality of HD between the HAV and AVF treatment groups as assessed by values available over the course of the study.

 Sponsor Name: Humacyte, Inc.

A Study to Evaluate the Safety and Effectiveness of the InnAVasc Arteriovenous Graft for Hemodialysis Access in Patients with End-Stage Renal Disease.

 Target population: Patients with ESRD who needs Arterio-Venous fistula or Graft (AVF/AVG) for hemodialysis.

 The problem: AVF needs time to get ready for dialysis. The chance that AV fistula or Graft fails due to complications or infection is high.

 Why problem exists: Currently, no available grafts offer protection from needle access injury, and no FDA- approved HD grafts offer immediate cannulation. Only 2 grafts are FDA cleared for early access: 1-(24-72 hours post-implant [Vectra], CR Bard, and 2-[Acuseal], W.L. Gore]), but outcomes data for these devices are lacking.

 New approach to solve the problem: To mitigate dialysis access graft cannulation complications, there is a need to modify AVG and incorporate two multilayer cannulation chambers with potentially improved low bleed technology that are resistant to frequent needle penetration/injury. There is a need to reduce many of the current complications and costs associated with AVG failure and infection. These features could relieve patient-associated pain and suffering and would potentially lead to a significant reduction in health care costs related to chronic dialysis graft injury and the reduction of in-center HD treatment.

 Study: Prospective, multi-center, single-arm study to evaluate the safety and effectiveness of the InnAVasc Arteriovenous Graft for hemodialysis access in patients with end-stage renal disease (ESRD). Initial study enrollment will be limited to a Roll-in cohort of 10 subjects at 2-3 sites.

 Study duration: Approximately 9-12 months.

 New intervention: InnAVasc has developed an AVG modification that incorporates two multilayer cannulation chambers with potentially improved low bleed technology that are resistant to posterior and sidewall needle injury.

 Study purpose: This device has the potential to eliminate current complications and costs associated with AVG failure and infection and could facilitate the transition to home hemodialysis for thousands of patients. It also could relieve patient-associated pain and suffering and may lead to a significant reduction in health care costs related to chronic dialysis graft injury.

 Sponsor Name: InnAVasc Medical, Inc.