Clinical trial NCT03183245: Comparison of the Human Acellular Vessel (HAV) With Fistulas as Conduits for Hemodialysis
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Renal Failure
End Stage Renal Disease
Hemodialysis
Vascular Access
Lead sponsor: Humacyte, Inc.
Sponsor class: INDUSTRY
Collaborators: name: CTI Clinical Trial and Consulting Services
name: California Institute for Regenerative Medicine (CIRM)
First posted: 2017-06-12
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of subjects with functional patency at 6 months post study access (SA) creation
timeFrame: 6 months post SA creation
measure: Proportion of subjects with secondary patency of SA at 12 months post SA creation.
timeFrame: 12 months post SA creation
Secondary outcomes:
measure: Time to loss of secondary patency (abandonment).
timeFrame: 12, 24, and 60 months post SA creation
measure: Incidence rate of HD access related interventions over the period from SA creation until SA abandonment or 12 months post SA creation
timeFrame: 12 months post SA creation
measure: 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.
timeFrame: 12 months post SA creation
measure: Proportion of subjects with unassisted functional patency at 6 months post SA creation.
timeFrame: 6 months post SA creation
measure: 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).
timeFrame: 6 months post SA creation
measure: Time to loss of primary unassisted patency
timeFrame: 12, 24, and 60 months post SA creation
measure: 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.
timeFrame: 12 months post SA creation
measure: 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
timeFrame: 12 months post SA creation
measure: Histopathological remodeling of HAV and AVF - based on histological examination of SA samples explanted for clinical reasons
timeFrame: 12, 24, and 60 months post SA creation
measure: Incidence rate of HD access-related infections over the period from SA creation until SA abandonment.
timeFrame: 12, 24, and 60 months post SA creation
measure: Incidence rate of clinically significant aneurysm or pseudoaneurysm over the period from SA creation until SA abandonment
timeFrame: 12, 24, and 60 months post SA creation
measure: Incidence rate of SA site infections (CDC definition) over the period from SA creation until SA abandonment.
timeFrame: 12, 24, and 60 months post SA creation
measure: Frequency and severity of AEs.
timeFrame: 12, 24, and 60 months post SA creation
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Arizona Kidney Disease and Hypertension Center (AKDHC)
state: Arizona
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Irvine
country: United States
facility: University of California, Irvine
state: California
city: La Jolla
country: United States
facility: University of California San Diego, Jacobs Medical Center
state: California
city: La Jolla
country: United States
facility: University of CA, San Diego - LaJolla VA Hospital
state: California
city: Laguna Hills
country: United States
facility: Alliance Research
state: California
city: Long Beach
country: United States
facility: VA Long Beach Healthcare System
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Pasadena
country: United States
facility: Huntington Hospital
state: California
city: Sacramento
country: United States
facility: UC Davis
state: California
city: San Diego
country: United States
facility: Balboa Nephrology
state: California
city: San Mateo
country: United States
facility: Mills Peninsula Hospital
state: California
city: Sylmar
country: United States
facility: Olive View- UCLA Medical Center
state: California
city: Denver
country: United States
facility: Denver Health Medical Center
state: Colorado
city: Darien
country: United States
facility: The Vascular Experts
state: Connecticut
city: Pembroke Pines
country: United States
facility: Memorial Healthcare System
state: Florida
city: Pensacola
country: United States
facility: Coastal Vascular & Interventional, PLLC
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Atlanta
country: United States
facility: Grady Memorial Hospital
state: Georgia
city: Decatur
country: United States
facility: Decatur Memorial Hospital
state: Illinois
city: Lexington
country: United States
facility: United Surgical Associates
state: Kentucky
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: West Springfield
country: United States
facility: Kidney Care & Transplant Services of New England
state: Massachusetts
city: Newark
country: United States
facility: Rutgers University
state: New Jersey
city: Summit
country: United States
facility: Overlook Medical Center
state: New Jersey
city: Charlotte
country: United States
facility: Surgical Specialists of Charlotte
state: North Carolina
city: Portland
country: United States
facility: Kaiser Permanente Sunnsyide
state: Oregon
city: Pittsburgh
country: United States
facility: VA Pittsburgh
state: Pennsylvania
city: Orangeburg
country: United States
facility: The Regional Medical Center
state: South Carolina
city: Knoxville
country: United States
facility: University of Tennessee Knoxville
state: Tennessee
city: Lubbock
country: United States
facility: South Plains Surgery Center
state: Texas
Study officials:
affiliation: Humacyte, Inc.
name: Shamik Parikh, MD
role: STUDY_DIRECTOR
References: