Comparison of the Human Acellular Vessel (HAV) With Fistulas as Conduits for Hemodialysis

End Stage Renal Disease Clinical Trial

Official title:

A Phase 3 Study to Compare the Efficacy and Safety of Humacyte's Human Acellular Vessel With That of an Autologous Arteriovenous Fistula in Subjects With End Stage Renal Disease

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03183245
• Other study ID #: CLN-PRO-V007
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: September 29, 2017
• Est. completion date: September 2029

Study information

• Verified date: September 2023
• Source: Humacyte, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main purpose of this study is to compare the Human Acellular Vessel (HAV) with arteriovenous fistula (AVF) when used for hemodialysis access

Description:

This is a Phase 3, prospective, multicenter, open-label, randomized, two-arm, comparative study. Subjects who sign informed consent will undergo study-specific screening assessments within 45 days from the day of informed consent.

Eligible study subjects will be randomized to receive either an HAV or AVF. The randomization will be stratified by upper arm or forearm placement based on the investigator's determination of where the study access (SA) should be located. Subjects will be followed to 24 months post SA creation at routine study visits regardless of patency status. After 24 months, AVF subjects with a patent SA will be followed (while the SA remains patent) for up to 5 years (60 months) post SA creation at routine study visits. After 24 months, HAV subjects will be followed (regardless of SA patency) for 5 years (60 months) post SA creation at routine study visits.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 240
• Est. completion date: September 2029
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Subjects with end-stage renal disease (ESRD), receiving HD via DC and are suitable for the creation of an AVF or implantation of AVG for HD access.

2. Subjects who plan to undergo HD at a dialysis unit of a participating dialysis provider for at least the first 6 months after SA creation.

3. Subjects aged at least 18 years at Screening.

4. Suitable anatomy for creation of a forearm or upper arm AVF and for implantation of straight or looped HAV in either the forearm or upper arm.

5. Hemoglobin =8 g/dL and platelet count =100,000 /mm3.

6. International Normalized Ratio (INR) = 1.5.

7. Female subjects must be either:

1. Of non-childbearing potential, which is defined as post-menopausal (at least 1 year without menses prior to Screening) or documented surgically sterile or post hysterectomy (at least 1 month prior to Screening).

2. Or, of childbearing potential, in which case:

i. Must have a negative urine or serum pregnancy test at Screening, and ii. Must agree to use at least one form of the following birth control methods for the duration of the study:

• Established use of oral, injectable or implanted hormonal methods of contraception.

• Placement of an intrauterine device or intrauterine system.

• Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/ gel/ film/ cream/ suppository.

8. Subject, or legal representative, able to communicate effectively with investigative staff, competent and willing to give written informed consent, and able to comply with entire study procedures including all scheduled follow-up visits.

9. Life expectancy of at least 2 years.

Exclusion Criteria:

1. Subjects who are optimal candidates for radiocephalic AVF as indicated by meeting ALL of the following criteria:

1. No previous failed AVF.

2. Cephalic vein diameter on ultrasound of more than 3.5mm.

3. Radial artery diameter on ultrasound of more than 3mm.

4. Vein depth of less than 0.5cm from the skin.

5. Normal Allen's test indicating that ulnar artery flow to the hand is sufficient.

6. No calcification in the wall of the distal radial artery.

7. Sufficient length of the proposed fistula outflow vein to provide an adequate (at least 6 cm) cannulation segment.

8. No evidence of iatrogenic injury to target artery or vein.

2. Uncontrolled diabetes;

a. HbA1c >10% (at Screening).

3. History or evidence of severe peripheral arterial disease in the extremity selected for implant.

4. Known or suspected central vein stenosis or obstruction on the side of planned SA creation, unless corrected prior to randomization.

5. Planned AVF creation that requires more than one stage to complete. (e.g. basilic vein transposition AVF performed in 2 stages).

6. Planned AVF creation by means other than suture or vascular anastomotic clips (e.g. endovascular surgery or other anastomotic creation devices).

7. Treatment with any investigational drug or device within 60 days prior to study entry (Day 0) or ongoing participation in a clinical trial of an investigational product.

8. Cancer that is actively being treated with a cytotoxic agent.

9. Documented hyper-coagulable state.

10. Bleeding diathesis.

11. Active clinically significant immune-mediated disease, not controlled by maintenance immunosuppression.

1. Low dose glucocorticoid therapy (e.g. 5-10mg prednisone [Deltason]) is acceptable.

2. High dose glucocorticoid therapy for treatment of autoimmune flare, or other inflammatory diseases is excluded.

3. Patients using glucocorticoids for immunosuppression post-transplant to prevent against transplanted allograft rejection in the period post allograft failure are excluded.

4. The following examples of immunosuppressive agents (or the like) are exclusionary for enrollment in this clinical trial:

• tacrolimus or FK506 [Prograf]

• mycophenolate mofetil [Cellcept],

• cyclosporine [Sandimmune or Gengraf]

• sirolimus [Rapamune] (this only includes systemically administered, drug eluting stents are acceptable)

12. Anticipated renal transplant within 6 months.

13. History of heparin-induced thrombocytopenia.

14. Venous outflow from SA cannot be located more centrally than the venous outflow of any previous failed access in that extremity.

15. Active local or systemic infection (white blood cells [WBC] > 15,000 cells/mm3 at Screening). If the infection resolves, the subject must be at least one week post resolution of that infection before SA creation.

16. Known serious allergy or intolerance to aspirin and alternative antiplatelet therapy.

17. Pregnant women, or women intending to become pregnant during the course of the trial.

18. Any other condition which in the judgment of the investigator would preclude adequate evaluation of the safety and efficacy of the SA.

19. Previous enrollment in this study or any other study with HAV.

20. Employees of Humacyte and employees or relatives of an investigator.

Related Conditions & MeSH terms

• End Stage Renal Disease
• Fistula
• Hemodialysis
• Kidney Diseases
• Kidney Failure, Chronic
• Renal Failure
• Vascular Access

Intervention

Biological:
• Human Acellular Vessel (HAV)
Surgical implantation of the HAV and subsequent use of the implanted vascular conduit for hemodialysis vascular access.

Procedure:
• Arteriovenous fistula (AVF)
Surgical creation of an autologous arteriovenous fistula and subsequent use of the implanted vascular conduit for hemodialysis vascular access.

Locations

Country	Name	City	State
United States	Grady Memorial Hospital	Atlanta	Georgia
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Surgical Specialists of Charlotte	Charlotte	North Carolina
United States	The Vascular Experts	Darien	Connecticut
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Denver Health Medical Center	Denver	Colorado
United States	University of California, Irvine	Irvine	California
United States	University of Tennessee Knoxville	Knoxville	Tennessee
United States	University of CA, San Diego - LaJolla VA Hospital	La Jolla	California
United States	University of California San Diego, Jacobs Medical Center	La Jolla	California
United States	Alliance Research	Laguna Hills	California
United States	United Surgical Associates	Lexington	Kentucky
United States	VA Long Beach Healthcare System	Long Beach	California
United States	University of Southern California	Los Angeles	California
United States	South Plains Surgery Center	Lubbock	Texas
United States	Rutgers University	Newark	New Jersey
United States	The Regional Medical Center	Orangeburg	South Carolina
United States	Huntington Hospital	Pasadena	California
United States	Memorial Healthcare System	Pembroke Pines	Florida
United States	Coastal Vascular & Interventional, PLLC	Pensacola	Florida
United States	Arizona Kidney Disease and Hypertension Center (AKDHC)	Phoenix	Arizona
United States	VA Pittsburgh	Pittsburgh	Pennsylvania
United States	Kaiser Permanente Sunnsyide	Portland	Oregon
United States	UC Davis	Sacramento	California
United States	Balboa Nephrology	San Diego	California
United States	Mills Peninsula Hospital	San Mateo	California
United States	Overlook Medical Center	Summit	New Jersey
United States	Olive View- UCLA Medical Center	Sylmar	California
United States	Tampa General Hospital	Tampa	Florida
United States	University of Arizona	Tucson	Arizona
United States	Kidney Care & Transplant Services of New England	West Springfield	Massachusetts

Sponsors (3)

Lead Sponsor	Collaborator
Humacyte, Inc.	California Institute for Regenerative Medicine (CIRM), CTI Clinical Trial and Consulting Services

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of subjects with functional patency at 6 months post study access (SA) creation	Co-primary endpoint #1: Proportion of subjects with functional patency at 6 months post study access (SA) creation; The definition of "functional patency" is: Dialysis with "2 needles for =75% of dialysis sessions over a continuous 4-week period and either: (1) 4 consecutive sessions during the 4-week period in which 2 needles are used and the mean dialysis machine blood pump speed is =300 mL/min, or (2) a measured spKt/Vurea is = 1.4 or urea reduction ratio >70% during any session in which 2 needles are used within the 4-week period. SpKt/Vurea is calculated from pre and post-treatment serum urea nitrogen concentrations, body weight, and dialysis session duration."; The functional patency ascertainment period will take place between the 1st day of Week 21 (Day 140) and the last day of Week 26 (Day 181) after AVF creation or HAV placement. The endpoint is met when the functional patency criteria are satisfied within any consecutive 4 week period within this ascertainment period.	6 months post SA creation
Primary	Proportion of subjects with secondary patency of SA at 12 months post SA creation.	Co-primary endpoint #2: Proportion of subjects with secondary patency of SA at 12 months post SA creation.; The SA maintains secondary patency until it is abandoned, irrespective of interventions to maintain or restore patency.; Abandonment is defined as AVF or HAV that can no longer be used for 2-needle, prescribed dialysis as it may be unable to provide adequate flows and/or is deemed unsafe for the subject, and the associated problem cannot be corrected by any intervention, including medical, surgical, or radiological interventions or rest.	12 months post SA creation
Secondary	Time to loss of secondary patency (abandonment).		12, 24, and 60 months post SA creation
Secondary	Incidence rate of HD access related interventions over the period from SA creation until SA abandonment or 12 months post SA creation		12 months post SA creation
Secondary	Incidence rate of infections related to any HD access in situ over the period from SA creation until 12 months post SA creation, irrespective of SA abandonment.		12 months post SA creation
Secondary	Proportion of subjects with unassisted functional patency at 6 months post SA creation.		6 months post SA creation
Secondary	Incidence rate of HD access-related interventions over the period from SA creation until SA abandonment or the conclusion of the suitability ascertainment period (6 months).		6 months post SA creation
Secondary	Time to loss of primary unassisted patency		12, 24, and 60 months post SA creation
Secondary	Proportion of HD sessions completed via DC (1 or 2 lines) over the period from SA creation until 12 months post SA creation, irrespective of SA abandonment.		12 months post SA creation
Secondary	Number of days with DC in situ "catheter contact time" over the period from SA creation until 12 months post SA creation, irrespective of SA abandonment		12 months post SA creation
Secondary	Histopathological remodeling of HAV and AVF - based on histological examination of SA samples explanted for clinical reasons		12, 24, and 60 months post SA creation
Secondary	Incidence rate of HD access-related infections over the period from SA creation until SA abandonment.		12, 24, and 60 months post SA creation
Secondary	Incidence rate of clinically significant aneurysm or pseudoaneurysm over the period from SA creation until SA abandonment		12, 24, and 60 months post SA creation
Secondary	Incidence rate of SA site infections (CDC definition) over the period from SA creation until SA abandonment.		12, 24, and 60 months post SA creation
Secondary	Frequency and severity of AEs.		12, 24, and 60 months post SA creation