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Tissue Engineered Veins in Patients With Chronic Venous Insufficiency (TECVI-1)

Primary Purpose

Chronic Venous Insufficiency

Status

Recruiting

Phase

Phase 1

Locations

Spain

Study Type

Interventional

Intervention

P-TEV

About this trial

This is an interventional treatment trial for Chronic Venous Insufficiency focused on measuring CVI, Leg Ulcer, Tissue Engineering, Personalized Vascular Graft, Chronic Venous Insufficiency, ATMP

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients aged between 18 and 65 years (inclusive)
CVI patients with skin changes and/or recurrent leg ulcer despite optimal conservative treatment for a period of time according to the investigator's judgement
Patients with deep venous reflux (grade 4)
Anesthesiologically cleared and meeting ASA (American Society of Anesthesiologists Classification) class 1 or 2
Laboratory values
- INR <1.7 (in case the patient uses Orfarin, the test might be repeated after the anticoagulant change)
- Platelets ≥ 100 x 10 9 /L
- Hemoglobin ≥ 100 g/L
- Total bilirubin ≤ 1.5 × upper limit of normal (ULN)
- ASAT ≤ 2.5 × ULN
- ALAT ≤ 2.5 × ULN
- Lipid profile within acceptable range according to investigator's opinion
- Clinical chemistries (K, Ca) within acceptable range according to Investigator's opinion
Ability to understand the requirements of the study, provide written informed consent, and comply with the study procedures

Exclusion Criteria:

Patients incapable to give written informed consent
Patients unlikely to cooperate fully in the study and/or with an anticipated poor compliance
Non-walking patients or patients with lost ankle joint function
Patients previously organ-transplanted
Patients with cancer except in-situ stage cancer (basal-cell carcinomas and/or cervix cancer) and five year recurrence free period after treatment
Patients with autoimmune diseases including rheumatoid arthritis, SLE and MS
Pregnant or breast feeding women
Patients with ongoing estrogen treatment/contraception. (intrauterine device, bilateral tubal occlusion, vasectomized partner, sexual abstinence should be used for contraception by women of childbearing period).
BMI ≥ 35
Patients who participate in other clinical trials
Patients with artery pathology (ankle-brachial pressure index < 0,9 or > 1,3)
Patients with thrombophilia according to the laboratory results at inclusion visit. One of the following criteria is needed for thrombophilia: Protein C < 40% or Protein S < 40 % or Leiden factor mutation or Antithrombin III < 40 % or present Lupus anticoagulant or Homocysteine > 1.5 ULN
Patients with an active infection requiring systemic antibiotic treatment
Patients with clinically significant cardiac disease (New York Heart Association, Class III or IV) or measured LVEF 40%
Patients with uncontrolled hypertension
Patients with renal dysfunction eGFR < 45 ml/min (according to the MDRD calculation)
Patients with moderate or severe hepatic impairment (Child Pugh ≥ 7 points, i.e. class B or C)
Patients with ongoing immunosuppression, Cortisol treatment etc.
Less than 3 months since previous ipsilateral venous intervention (e.g. Iliac recanalization)
Clinically significant outflow disease
Heavy smoker: Has smoked 20 cigarettes or more per day for at least past 5 years
Other uncontrolled intercurrent illness that would jeopardize the patient's safety, interfere with the objectives of the protocol, or limit the patient's compliance with study requirements, as determined by the investigator in consultation with the sponsor

Sites / Locations

Junta de AndalusiaRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Personalized Tissue Engineered Vein

Arm Description

P-TEV

Outcomes

Primary Outcome Measures

Thrombosis leading to occlusion of the graft measured by Color Duplex Ultrasound

Ultrasonographic evaluation of occlusions of the graft.

Infection leading to surgical excision of the graft measured by blood samples

White blood cells count: >10 x10E9/L, C- Reactive Protein (CRP): >4 mg/L, sedimentation rate: >12mm).

Infection leading to surgical excision of the graft measured by Color Duplex Ultrasound

Ultrasonographic examination to assess infection of the graft

Infection leading to surgical excision of the graft measured by Computer Tomography

Infection of the graft assessed by Computer Tomography

Reporting of surgical complications

Perioperative surgical complications related to the implanted graft (technical failure leading to surgical failure).

Secondary Outcome Measures

Change in symptoms assessed according to VCSS (Venous Clinical Severity Score)

The VCSS includes 9 hallmarks of venous disease, each scored on a severity scale from 0 (absent) to 3 (severe), plus a category for compression with higher scores representing greater compliance (still scale 0-3).

Change in symptoms assessed according to CEAP classification (clinical, etiologic, anatomic, pathophysiologic)

CEAP classification is assessed on scale from C0 (No visible or palpable signs of venous disease) to C6 (Active venous ulcer).

Health Related Quality of Life assessed by VEINES questionnaire

Responses are made on a 2- to 7-point scale that rates intensity, frequency, and agreement. Higher scores are associated with better quality-of-life.The focus of VEINES is on physical symptoms as opposed to psychological or social aspects.

Health Related Quality of Life assessed by EQ-5D-5L questionnaire

EQ-5D-5L is a standardized self-assessment instrument for health status.It has two components; health state description and evaluation. The first part contains 5 items with five levels of response regarding five dimensions (mobility, hygiene, activities, pain and anxiety).The five questions are compounded into a health index according to a mathematical formula validated against the population in several countries.The second part of the questionnaire comprises a standard vertical 20-cm VAS that is calibrated from 'the worst health you can imagine' (scored 0) at its base to 'the best health you can imagine' (scored 100) at its apex. Respondents are asked to 'mark an X on the scale to indicate how your health is TODAY' and to write the number in an adjoining box.

Durability of the P-TEV assessed by Color Duplex Ultrasound

The time period in which the valve contained in the implant retains its function verified by ultrasonographic examination.

Vessel dilatation in the implant assessed by Duplex Color Ultrasound

Ultrasonographic examination of vessel dilatation

Flow abnormalities in the implant assessed by Duplex Color Ultrasound

Ultrasonographic examination of flow abnormalities

Wall degeneration in the implant assessed by Duplex Color Ultrasound

Ultrasonographic examination of wall degeneration

Full Information

NCT ID

NCT03784131

First Posted

November 16, 2018

Last Updated

September 29, 2023

Sponsor

Verigraft AB

1. Study Identification

Unique Protocol Identification Number

NCT03784131

Brief Title

Tissue Engineered Veins in Patients With Chronic Venous Insufficiency

Acronym

TECVI-1

Official Title

Phase I Open-label, First-in-human Study to Evaluate Feasibility and Safety of Tissue Engineered Veins in Patients With Chronic Venous Insufficiency

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Recruiting

Study Start Date

December 15, 2021 (Actual)

Primary Completion Date

June 2025 (Anticipated)

Study Completion Date

June 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Verigraft AB

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

This study aims to evaluate the safety (incidence of adverse events including serious adverse events and clinical significant laboratory abnormalities) of personalized tissue engineered veins (P-TEV) with valves implanted in patients with severe chronic venous insufficiency (CVI). For each patient a segment of the femoral vein containing the non-functioning valve will be surgically replaced with a single P-TEV containing a functioning valve.

Detailed Description

The advanced therapy medicinal product (ATMP) described herein is a personalized tissue- engineered vein (P-TEV) graft for use in surgical implantation to replace a defective or missing part of a patient's vein. In this specific application a P-TEV graft with a functioning venous bicuspid valve is implanted to replace a nonfunctioning venous valve in the femoral vein of a patient suffering from severe CVI. The P-TEV graft for surgical implantation is 4-6 cm in length. The P-TEV drug substance consists of an extracellular matrix (ECM) scaffold in the form of a decellularized (DC) allogeneic vein scaffold which is populated with autologous components from the patient's own peripheral whole blood (PWB) in an ATMP manufacturing process performed under GMP. As the allogeneic immunogenic material has been removed from the donated vein segment by DC and as the perfusion uses autologous PWB, no immunosuppression is required. Successful implantation and treatment should prevent the reverse blood flow, decrease blood pooling in the lower leg, and thereby alleviate symptoms such as swelling, pain, and ulcers.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Venous Insufficiency

Keywords

CVI, Leg Ulcer, Tissue Engineering, Personalized Vascular Graft, Chronic Venous Insufficiency, ATMP

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

15 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Personalized Tissue Engineered Vein

Arm Type

Experimental

Arm Description

P-TEV

Intervention Type

Drug

Intervention Name(s)

P-TEV

Intervention Description

Replacement of vein with failing valves with personalized tissue engineering vein containing functional valves

Primary Outcome Measure Information:

Title

Thrombosis leading to occlusion of the graft measured by Color Duplex Ultrasound

Description

Ultrasonographic evaluation of occlusions of the graft.

Time Frame

12 months

Title

Infection leading to surgical excision of the graft measured by blood samples

Description

White blood cells count: >10 x10E9/L, C- Reactive Protein (CRP): >4 mg/L, sedimentation rate: >12mm).

Time Frame

12 months

Title

Infection leading to surgical excision of the graft measured by Color Duplex Ultrasound

Description

Ultrasonographic examination to assess infection of the graft

Time Frame

12 months

Title

Infection leading to surgical excision of the graft measured by Computer Tomography

Description

Infection of the graft assessed by Computer Tomography

Time Frame

12 months

Title

Reporting of surgical complications

Description

Perioperative surgical complications related to the implanted graft (technical failure leading to surgical failure).

Time Frame

12 months

Secondary Outcome Measure Information:

Title

Change in symptoms assessed according to VCSS (Venous Clinical Severity Score)

Description

Time Frame

12 months

Title

Change in symptoms assessed according to CEAP classification (clinical, etiologic, anatomic, pathophysiologic)

Description

CEAP classification is assessed on scale from C0 (No visible or palpable signs of venous disease) to C6 (Active venous ulcer).

Time Frame

12 months

Title

Health Related Quality of Life assessed by VEINES questionnaire

Description

Time Frame

12 months

Title

Health Related Quality of Life assessed by EQ-5D-5L questionnaire

Description

Time Frame

12 months

Title

Durability of the P-TEV assessed by Color Duplex Ultrasound

Description

The time period in which the valve contained in the implant retains its function verified by ultrasonographic examination.

Time Frame

12 months

Title

Vessel dilatation in the implant assessed by Duplex Color Ultrasound

Description

Ultrasonographic examination of vessel dilatation

Time Frame

12 months

Title

Flow abnormalities in the implant assessed by Duplex Color Ultrasound

Description

Ultrasonographic examination of flow abnormalities

Time Frame

12 months

Title

Wall degeneration in the implant assessed by Duplex Color Ultrasound

Description

Ultrasonographic examination of wall degeneration

Time Frame

12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients aged between 18 and 75 years (inclusive) CVI patients with painful swelling and/or skin changes and/or recurrent leg ulcer despite optimal conservative treatment for a period of time according to the investigator's judgement Patients with deep venous reflux (grade 3 and above) Meeting ASA (American Society of Anesthesiologists Classification) class 1 or 2 according to the PIs criteria Laboratory values INR <1.7 (in case the patient uses Warfarin, the test might be repeated after the anticoagulant change) Platelets ≥ 100 x 10 9 /L Hemoglobin ≥ 100 g/L Total bilirubin ≤ 1.5 × upper limit of normal (ULN) ASAT ≤ 2.5 × ULN ALAT ≤ 2.5 × ULN Ability to understand the requirements of the study, give direct or representative written informed consent, and comply with the study procedures Exclusion Criteria: Patients incapable to give direct or representative written informed consent Patients unlikely to cooperate fully in the study and/or with an anticipated poor compliance Non-walking patients or patients with lost ankle joint function Patients previously organ-transplanted Patients with cancer except in-situ stage cancer (basal-cell carcinomas and/or cervix cancer) and five year recurrence free period after treatment Patients with autoimmune diseases including rheumatoid arthritis, SLE and MS Pregnant or breast feeding women Patients with ongoing estrogen treatment for example for contraception. Alternative contraceptive methods (e.g. intrauterine device, bilateral tubal occlusion, vasectomized partner, sexual abstinence) should be used by women of reproductive age (defined as pre-menopausal female capable of becoming pregnant). BMI ≥ 35 Patients who have participated in other clinical trials during the last 12 months Patients with artery pathology (ankle-brachial pressure index < 0,9 or > 1,3) Patients with thrombophilia according to the laboratory results at inclusion visit. One of the following criteria is needed for thrombophilia: Protein C < 40% or Protein S < 40 % or Leiden factor mutation or Antithrombin III < 40 % or present Lupus anticoagulant or Homocysteine > 1.5 ULN Patients with an active infection requiring systemic antibiotic treatment Patients with clinically significant cardiac disease (New York Heart Association, Class III or IV) or measured LVEF 40% Patients with uncontrolled hypertension Patients with renal dysfunction eGFR < 45 ml/min (according to the MDRD calculation) Patients with moderate or severe hepatic impairment (Child Pugh ≥ 7 points, i.e. class B or C) Patients with ongoing immunosuppression, systemic Cortisol treatment etc. Less than 3 months since previous ipsilateral venous intervention (e.g. Iliac recanalization) Clinically significant iliocaval stenosis or occlusion Current smoker of more than 20 cigarettes per day Other uncontrolled intercurrent illness that would jeopardize the patient's safety, interfere with the objectives of the protocol, or limit the patient's compliance with study requirements, as determined by the Investigator in consultation with the Sponsor Patients with severe SARSCoV-2 virus infection requiring hospitalization in the past 6 months

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Björquist

Phone

+46705979296

Ext

+46705979296

info@verigraft.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Björquist

Organizational Affiliation

Verigraft AB

Official's Role

Study Director

Facility Information:

Facility Name

Junta de Andalusia

City

Sevilla

Country

Spain

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Petter Björquist, Dr

12. IPD Sharing Statement

Learn more about this trial

Tissue Engineered Veins in Patients With Chronic Venous Insufficiency

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