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ATTENTION:
All statements, other than statements of historical fact, included in this and the accompanying oral presentations are forward-looking statements reflecting management’s current beliefs and expectations. In some cases, you can identify forward-looking statements by terminology such as “will,” “anticipate,” “expect,” “believe,” “intend” and “should” or the negative of these terms or other comparable terminology. Forward-looking statements in these slides and the accompanying oral presentations include, but are not limited to, statements about the our plans and ability to execute product development, process development and preclinical development efforts successfully and on our anticipated timelines; our plans and ability to obtain marketing approval from the U.S. Food and Drug Administration and other regulatory authorities, including the European Medicines Agency, for our bioengineered Human Acellular Vessel™ (HAV™) and other product candidates; our ability to design, initiate and successfully complete clinical trials and other studies for our product candidates and our plans and expectations regarding our ongoing or planned clinical trials, including the V007 Phase III clinical trial; our anticipated growth rate and market opportunities; our ability to use our proprietary scientific technology platform to build a pipeline of additional product candidates; the characteristics and performance of our HAVs; our plans and ability to commercialize our HAVs and other product candidates, if approved by regulatory authorities; the expected size of the target populations for our product candidates; the anticipated benefits of our HAVs relative to existing alternatives; our assessment of the competitive landscape; the degree of market acceptance of HAVs, if approved, and the availability of third-party coverage and reimbursement; our ability to manufacture HAVs and other product candidates in sufficient quantities to satisfy our clinical trial and commercial needs; the performance of other third parties on which we rely, including our third-party manufacturers, our licensors, our suppliers and the organizations conducting our clinical trials; and our future financial performance and capital requirements. These statements relate to future events or to our future financial performance and involve known and unknown risks, uncertainties and other factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by these forward-looking statements. Any forward-looking statements contained herein are based on assumptions that we believe to be reasonable as of the date hereof. Except as required by law, we assume no obligation to update these forward-looking statements, even if new information becomes available in the future.
Be advised, balloon for angioplasty or thrombectomy procedures SHOULD NOT EXCEED 6MM in diameter within the HAV as disruption or tearing of HAV may occur if a balloon larger than 6MM is used. A non-compliant balloon is recommended to ensure maintaining a 6 MM diameter and preventing disruption of the HAV.
Humacyte's HUMAXX Phase III Clinical Trial
STUDY POPULATION:
Female ESRD patients who are currently receiving hemodialysis (HD) via a central venous dialysis catheter (e.g. Permcath™) and who are suitable candidates for placement of a dialysis graft or creation of a dialysis fistula
STUDY SITES:
Approximately 20 Sites in the United States
ENROLLMENT:
At least 150 female patients
RANDOMIZATION:
1:1 AVF: HAV
ENROLLMENT PERIOD:
Approximately 14 months
EXPECTED START DATE:
September 2023
FOLLOW UP PERIOD:
Up to 1 year
SPONSOR:
Humacyte, Inc.
CONTACT:
TBD
Clinical Trial Synopsis - HUMAXX
Official Title of the Clinical Trial:
A Phase 3 Randomized Study to Compare the Efficacy and Safety of the Humacyte Human Acellular Vessel (HAV) with that of an Autogenous Arteriovenous Fistula (AVF) in Female Patients with End-Stage Renal Disease
Female subjects with end-stage renal disease (ESRD) who are currently receiving clinically successful hemodialysis via a central venous dialysis catheter (e.g. Permcath™) and who are suitable candidates for placement of a dialysis graft or creation of a dialysis fistula will be considered for participation in this prospective, multicenter, randomized, two-arm comparative study.
Approximately 150 female patients will be randomized 1:1 to either the HAV or the AVF treatment arm. Patients will be implanted with either a HAV or will have an AVF created in the forearm or upper arm using standard vascular surgical techniques. The randomization will occur in the operating room, but prior to skin incision, and will be stratified by location of the vascular access (upper arm versus forearm) and by type of AVF creation procedure planned by surgeon at randomization (1-stage AVF versus 2-stage AVF). Study Access (SA) placement is based on the Investigator’s determination of where the SA should be located. All subjects will be required to take daily aspirin (81-325 mg) unless they are already taking another antiplatelet agent. Subjects who are known to be aspirin-sensitive should take another antiplatelet agent at the discretion of the Investigator.
During the Primary Study each all patients will be followed through the Month 12 visit without regard of SA patency status, suitability of the SA or HD use, or abandonment of SA. All patients completing the Primary Study with a patent SA will be followed during the Long-term Extension for 12 additional months for a total of 24 months.
Patients whose SA is abandoned during the Long-Term Extension (Year 2) will be terminated from study at the time of abandonment.
Primary Endpoints:
Primary Efficacy Endpoint: Time (total days) free from indwelling catheter (catheter-free days) since randomization to 365 days (Month 12), or until SA abandonment, whichever occurs first.
Primary Safety Endpoint: Infections related to any HD access over the period from SA creation (Day 1) until 12 months (365 days) after SA placement, without regard to SA abandonment.
Secondary Endpoints (Efficacy)
- Time (total days) free from indwelling catheter (catheter-free days) from randomization to 183 days (Month 6), or until SA abandonment, whichever occurs first.
- Duration (total days) of functional patency of the SA over 12 months from randomization.
- Secondary patency of the SA at 6 and 12 months from randomization.
- Time from maturation to SA abandonment.
Secondary Endpoints (Safety)
Complications related to any HD access during the 12 months after SA creation, without regard to SA abandonment. For the purposes of this endpoint, HD access refers to any surgically created access or device to provide a route for HD after randomization (e.g., SA, new AVF or AVG, or catheter).
Study Product: The Investigational Medicinal Product is Humacyte’s HAV, which is a tissue-engineered vascular conduit intended for hemodialysis (HD) access from the upper extremity.
The comparator is an upper extremity arterio-venous fistula (AVF) for HD access surgically created per the institution’s Standard of Care (SoC).
Intervention Guidelines
In the event of study access (SA) occlusion or poor performance, established vascular access revision procedures should be considered. Appropriate revision procedure selection should be determined by the surgical team based on the specific case requirements, and whether the SA is an AVF, AVG, or HAV. Thrombectomy of any of these SAs may be performed in an open or percutaneous fashion depending on the technical faculties available or that may be required, and primary surgical revision may be performed whenever deemed appropriate.
- Prior to interventions a contrast study should be performed and documented.
- If a clinically significant stenosis based on imaging and clinical symptoms is detected, balloon angioplasty or other appropriate surgical or endovascular procedures can be performed at the same session.
- Interventions should be driven by clinical symptoms not by study mandated imaging. If clinically significant stenosis is noted, then intervention is warranted if symptomatic
- Balloons (angioplasty or thrombectomy) should not exceed 6mm in diameter within the body of the HAV.
- Non-compliant angioplasty balloons are recommended for use within the HAV body.
- Cutting balloons should not be used within the body of the HAV, however, use at the anastomoses is permitted.
- The use of long balloons (e.g. > 6cm in length) within looped configurations of the HAV, or near tight curves may result in damage to the vessel as the “shoulders” of the balloon expand to a linear conformation.
- Vascular sheaths used for direct access into the HAV should remain as small as feasible, preferably no larger than 7F.
- For surgical revision cases, please remember to save a tissue specimen for the study sponsor, if medically appropriate
Thrombectomy Procedures
OPEN THROMBECTOMY
- Standard open thrombectomy techniques.
- For open procedures, we recommend gaining adequate control of inflow and outflow prior to incising the SA.
- Recommend using a #11 blade knife to create a vessel or graft-otomy on the anterior half of the access.
- Maximum inflated embolectomy balloon SHOULD NOT EXCEED 6mm IN DIAMETER within the HAV.
- Any balloon that is inflated beyond 6mm within the HAV may lead to disruption or tearing of the HAV and thus, we recommend congruent balloon thrombectomy practices.
PERCUTANEOUS THROMBECTOMY
- Standard percutaneous thrombectomy techniques.
- Maintain small sheath access when possible.
- Maximum inflated embolectomy balloon should not exceed 6mm in diameter within the HAV.
- Any balloon that is inflated beyond 6mm within the HAV may lead to disruption or tearing of the HAV and thus, we recommend congruent balloon thrombectomy practices.
CAUTION: Mechanical, suction, or rotational thrombectomy devices (i.e. Angiojet, Arrow-Trerotola, Amplatz, Trellis, Ekos, etc.) have not been rigorously tested for safety or efficacy within the HAV. We cannot recommend use of these devices for thrombectomy procedures within the HAV until adequate safety testing has been performed. These devices and methods ARE ACCEPTABLE to use within the comparator AVF during this clinical trial.
Angioplasty Procedures
- Standard percutaneous thrombectomy techniques are acceptable.
- Maintain small sheath access when possible.
- Recommend 5Fr vascular sheath, but no larger than 7Fr sheath access.
- Recommend the use of a non-compliant angioplasty balloon.
- Balloon should not exceed 6mm in diameter within the body of the HAV.
- If a venous anastomotic stenosis becomes refractory to treatment with a 6mm balloon, it is permissible to use a 7mm balloon to treat residual stenosis in that area only.
- Balloon length should remain as short as possible to avoid over dilating areas outside of the stenosis.
- Balloons > 6mm in diameter may be used at the anastomoses as long as the body of the balloon remains outside of the HAV.
CAUTION:
- Any balloon that is inflated beyond 6mm within the HAV may lead to disruption or tearing of the HAV.
- The use of long balloons (e.g. > 6cm in length) within looped configurations of the HAV, or near tight curves may result in damage to the vessel as the “shoulders” of the balloon expand to a linear conformation.
- Cutting balloons should not be used within the body of the HAV, however, use at the anastomoses is permitted.
- Drug coated balloons (DCBs) have not been rigorously tested for safety or efficacy within the HAV. We cannot recommend the use of DCBs within the HAV until adequate safety testing has been performed.
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Venous anastomotic stenosis should be managed using a 6 mm balloon initially. If the result is inadequate, serial angioplasty with a 6mm or 7 mm balloon may be used on the residual stenosis. A balloon larger than 7mm should not be used since this may disrupt the HAV. If the stenosis is not adequately resolved, covered stent placement or surgical revision should be considered.
Stenting Procedures
- Use of stents in the HAV are allowed and should be consistent with standard AVF and AVG access management practices.
- Intravascular stents may be used in cases where an adequate result is not obtained by angioplasty alone.
- At the anastomoses, a covered stent is preferable to minimize the risk of in-stent restenosis.
- Placement of a stent of any type within the cannulation zone of an AVF, AVG, or HAV to treat stenosis or pseudoaneurysm should be avoided because of the increased risk of complications such as an infection.
- Stent-graft placement within the SA to treat acute hemorrhage is acceptable, but eventual revision by surgical reconstruction is recommended. Following any angioplasty or stenting procedure, post-intervention images (completion) should be obtained
CAUTION: Drug eluting stents (DESs) have not been rigorously tested for safety or efficacy within the HAV. We cannot recommend the use of DESs within the HAV until adequate safety testing has been performed.
Surgical Interventions
- Surgical interventions or revisions are permitted and should be performed at the discretion of the surgical team
- Any method is permissible
- Any material is permissible
- Additional HAV material is not available for use for surgical revision
- PLEASE REMEMBER TO SAVE A TISSUE SPECIMEN (if appropriate) FOR THE STUDY SPONSOR
Guidelines For Arteriovenous Access Intervention, Management, And Abandonment
The Clinical Events Committee (CEC) has developed a detailed set of access management guidelines for the AV access studies (HUMANITY and HAV ACCESS).
Content approved by WIRB 16 March, 2020
HAV Intervention Procedure Guidelines
Humacyte's 'ACCESS' Phase III Clinical Trial-CLOSED TO ENROLLMENT
STUDY POPULATION:
ESRD patients who are currently receiving hemodialysis with a catheter (e.g. Permcath™) and who are suitable candidates for placement of a dialysis graft or creation of a dialysis fistula
STUDY SITES:
Approximately 35 Sites in the United States
ENROLLMENT: CLOSED TO ENROLLMENT
At least 240 patients
RANDOMIZATION:
1:1 AVF:HAV
ENROLLMENT PERIOD: CLOSED TO ENROLLMENT
Approximately 12 months
EXPECTED START DATE:
August 2017
FOLLOW UP PERIOD:
Up to 5 years
SPONSOR:
Humacyte, Inc.
CONTACT:
Medical Monitor by Region
US: 1-800-723-2890
The HAV-ACCESS Phase III clinical trial will compare the HAV with a current standard of care AVF when used for hemodialysis access in the above study population. Below you will find intervention guidelines, cannulation guidelines, and more information about the Humacyte technology, including the HAV-ACCESS clinical trial, and results from the Phase II study.
Clinical Trial Synopsis - ACCESS
Official Title of the Clinical Trial:
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.
Subjects with end-stage renal disease (ESRD) who are currently receiving hemodialysis with a catheter (e.g. Permcath™) and who are suitable candidates for placement of a dialysis graft or creation of a dialysis fistula will be considered for participation in this prospective, multicenter, randomized, comparative study. Subjects will be implanted with either a HAV or will have an AVF created in the forearm or upper arm using standard vascular surgical techniques. The 1:1 randomization will occur in the operating room, but prior to skin incision, and will be stratified by upper arm or forearm placement based on the Investigator’s determination of where the Study Access (SA) should be located. All subjects will be required to take daily aspirin (81-325 mg) unless they are already taking another antiplatelet agent. Subjects who are known to be aspirin-sensitive should take another antiplatelet agent at the discretion of the Investigator.
Each subject will be followed by study specific visits until the patient completes 2 years (24 months) of follow-up after implantation (irrespective of patency status). After 2 years, subjects with a HAV (irrespective of patency) and subjects with a patent AVF will be followed (while the study access remains patent) for up to 5 years (60 months) post-implantation at routine study visits. The expected duration of the clinical investigation is about 75 m
Primary Endpoints:
Co-primary Endpoint #1:
Proportion of subjects with functional patency at 6 months post SA creation.
- The definition of “functional patency” is that which Dember, et al, of the Hemodialysis Fistula Maturation Study Group described as “clinical maturation.” (Dember 2014)
• 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/V urea is ≥ 1.4 or urea reduction ratio >70% during any session in which 2 needles are used within the 4-week period. SpKt/V urea 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 180) after SA creation. The endpoint is met when the functional patency criteria are satisfied within any consecutive 4 week period within this 6-week ascertainment period. Regular use of the SA for functional hemodialysis (HD) prior to the ascertainment period does not count towards achievement of this endpoint. If a subject has not begun dialysis with 2 needles by Week 23, he or she will not achieve functional patency as defined for this co-primary endpoint.
Co-primary Endpoint #2:
Proportion of subjects with secondary patency 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. (Lee 2011)
Secondary Endpoints:
Efficacy
- Time to loss of secondary patency (abandonment).
• Defined as the time from SA creation until SA abandonment. - Incidence rate of HD access related interventions over the period from SA creation until SA abandonment or 12 months post SA creation.
• For purposes of this study, HD access refers to any surgically created permanent access or device to provide a route for HD (e.g. SA, previous AVF or AVG, dialysis catheter [DC]).
Safety
- 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.
Study Product: The Investigational Medicinal Product is Humacyte’s HAV, a human tissue-engineered vascular conduit for hemodialysis access.
The comparator will be creation of autologous AV.
