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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Chronic Venous Insufficiency
• Intervention / Treatment: Drug: P-TEV

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.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Björquist; Phone Number: +46705979296 +46705979296; Email: info@verigraft.com

Study Locations

• Spain
  • Sevilla, Spain
    • Recruiting
    • Junta de Andalusia
    • Contact: Petter Björquist, Dr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Personalized Tissue Engineered Vein; P-TEV	Drug: P-TEV; Replacement of vein with failing valves with personalized tissue engineering vein containing functional valves

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Thrombosis leading to occlusion of the graft measured by Color Duplex Ultrasound	Ultrasonographic evaluation of occlusions of the graft.	12 months
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).	12 months
Infection leading to surgical excision of the graft measured by Color Duplex Ultrasound	Ultrasonographic examination to assess infection of the graft	12 months
Infection leading to surgical excision of the graft measured by Computer Tomography	Infection of the graft assessed by Computer Tomography	12 months
Reporting of surgical complications	Perioperative surgical complications related to the implanted graft (technical failure leading to surgical failure).	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	12 months
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).	12 months
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.	12 months
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.	12 months
Vessel dilatation in the implant assessed by Duplex Color Ultrasound	Ultrasonographic examination of vessel dilatation	12 months
Flow abnormalities in the implant assessed by Duplex Color Ultrasound	Ultrasonographic examination of flow abnormalities	12 months
Wall degeneration in the implant assessed by Duplex Color Ultrasound	Ultrasonographic examination of wall degeneration	12 months
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.	12 months

Collaborators and Investigators

• Sponsor: Verigraft AB
• Investigators: Study Director: Björquist, Verigraft AB

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2021
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: November 16, 2018
• First Submitted That Met QC Criteria: December 20, 2018
• First Posted (Actual): December 21, 2018

Study Record Updates

• Last Update Posted (Actual): October 4, 2023
• Last Update Submitted That Met QC Criteria: September 29, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: ATMP; Chronic Venous Insufficiency; Leg Ulcer; Tissue Engineering; CVI; Personalized Vascular Graft
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Venous Insufficiency
• Other Study ID Numbers: 2015-004021-13

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No