E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
End-stage renal disease (ESRD) requiring placement of an arteriovenous (AV) graft in the arm (upper- or forearm) for dialysis access. |
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E.1.1.1 | Medical condition in easily understood language |
An advanced kidney disease requiring placement of a tube in the arm (upper- or forearm) into which needles for dialysis can be inserted. |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Surgical Procedures, Operative [E04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10042613 |
E.1.2 | Term | Surgical and medical procedures |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066772 |
E.1.2 | Term | Vascular access operation |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the safety, efficacy and immunogenicity over 3 months after implantation of HAVs manufactured using the commercial manufacturing system (Luna). |
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E.2.2 | Secondary objectives of the trial |
To evaluate the long-term safety and efficacy of the HAV (manufactured with the Luna system) over a period of up to 36 months after implantation. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subjects with ESRD who are not, or who are no longer candidates for creation of an autologous AV fistula and therefore need placement of an AV graft in the arm (upper- or forearm) for hemodialysis therapy. 2. Already established on hemodialysis 3. At least 18 years of age at Screening. 4. Suitable arterial and venous anatomy for implantation of straight or looped conduits in either the forearm or upper arm (not crossing the elbow). 5. Hemoglobin ≥ 8 g/dL and platelet count ≥ 100,000 cells/mm3 prior to Day 0 (within 45 days). 6. Other hematological and biochemical parameters within a range consistent with ESRD prior to Day 0 (within 45 days). 7. Normal clotting (international normalized ration [INR] ≤ 1.5 or prothrombin time ≤ 18 sec unless the patient is taking an anticoagulant for an approved indication at the time of HAV implantation. 8. Female subjects must be either: a. 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) b. Or, of childbearing potential, in which case: i. Must have a negative serum or urine 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 9. 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. 10. Life expectancy of at least 1 year. |
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E.4 | Principal exclusion criteria |
1. History or evidence of severe peripheral vascular disease in the intended arm for implantation. 2. Known or suspected central vein stenosis or conduit occlusion on the ipsilateral side of the planned implantation, unless the stenosis is corrected prior to HAV implantation. 3. 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. 4. Cancer that is actively being treated with a cytotoxic agent. 5. Documented hyper-coagulable state as defined as either: a. a biochemical diagnosis (e.g. Factor V Leiden, Protein C deficiency, etc.) - OR – b. a clinical history of thrombophilia as diagnosed by 2 or more spontaneous intravascular thrombotic events (e.g deep vein thrombosis, pulmonary embolism, etc.) within the 5 previous years. 6. Spontaneous or unexplained bleeding diathesis clinically documented within the last 5 years or a biochemical diagnosis (e.g. von Willebrand disease, etc.). 7. Active clinically significant immune-mediated disease, not controlled by maintenance immunosuppression. a. Low dose glucocorticoid therapy (e.g. up to 10 mg a day prednisone or prednisolone) is acceptable. b. High dose glucocorticoid therapy for treatment of autoimmune flare, or other inflammatory diseases is excluded. c. Patients using glucocorticoids for immunosuppression post-transplant to prevent against transplanted allograft rejection in the period post allograft failure are excluded. d. The following examples of immunosuppressive agents (or the like) are exclusionary for enrollment in this clinical trial: i. tacrolimus or FK506 [Prograf] ii. mycophenolate mofetil [Cellcept], iii. cyclosporine [Sandimmune or Gengraf] iv. Sirolimus administered systemically (Sirolimus in drug eluting stents is NOT an exclusion) 8. Anticipated renal transplant within 6 months. 9. Venous outflow from HAV cannot be placed more centrally than the venous outflow of any previous failed access on that extremity. 10. 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 1 week post resolution of that infection before implantation. 11. Known serious allergy to planned antiplatelet agent. 12. Pregnant women, or women intending to become pregnant during the course of the trial. 13. Any other condition which in the judgment of the investigator would preclude adequate evaluation of the safety and efficacy of the HAV. 14. Previous enrollment in this study or any other study with HAV. 15. Employees of Humacyte and employees or relatives of the investigator. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Safety Endpoints: • Adverse events indicating possible mechanical failure or weakness of the HAV: anastomotic rupture, anastomotic bleeding, spontaneous HAV rupture, aneurysm, pseudoaneurysm, abnormal post cannulation hemostasis; • HAV infections; • Change from baseline of PRA and anti-HAV IgG levels (at 2 months); • All AEs/SAEs and adverse events of special interest.
Primary Efficacy Endpoints: • Primary patency- defined as being maintained until any intervention designed to maintain or reestablish patency, access thrombosis or the measurement of patency’, i.e., patent without interventions; • Primary assisted patency- defined as being maintained until access thrombosis or the time of measurement of patency, including intervening manipulations (surgical or endovascular interventions) designed to maintain the functionality of patent access’ i.e., patent without an intervention to clear a thrombus; • Secondary patency- defined as being maintained until access abandonment. Access abandonment defined as no remaining segment of the study conduit is incorporated into the vascular access circuit used for dialysis. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
3 months post implantation |
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E.5.2 | Secondary end point(s) |
Secondary Safety Endpoints: • Adverse events indicating possible mechanical failure or weakness of the HAV: anastomotic rupture, anastomotic bleeding, spontaneous HAV rupture, aneurysm, pseudoaneurysm, abnormal post cannulation hemostasis; • HAV infections; • Change from baseline of PRA and anti-HAV IgG levels (at 12 months); • All AEs/SAEs until 12 months post implant, after that only SAEs associated with the HAV and adverse events of special interest.
Secondary Efficacy Endpoints: • Primary patency; • Primary assisted patency; • Secondary patency; • Interventions required to achieve/maintain secondary patency; • Histopathological remodeling of any HAV (based on any samples collected). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
36 month post implantation |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the trial occurs when the last subject remaining on study has reached Month 36 follow up. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |