Clinical Trial to Investigate Efficacy and Safety of the IMP in Patients With Non Healing Wounds Originating From Ulcers
Primary Purpose
Skin Ulcer Venous Stasis Chronic
Status
Terminated
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
APZ2 application
Sponsored by
About this trial
This is an interventional treatment trial for Skin Ulcer Venous Stasis Chronic focused on measuring phase I/IIa, mesenchymal stem cells, ABCB5+, APZ2, chronic venous ulcer, varicose ulcer, skin ulcer, advanced therapy medicinal product, APZ2-II-01, autologous use, somatic cell therapy
Eligibility Criteria
Inclusion Criteria:
- Male or female patients aged 18 to 85 years;
- Chronic venous leg ulcer (as defined by the current AWMF guidelines: therapy resistant ulcer that shows no improvement within 3 months despite of optimal phlebological therapies or is not healed within 12 months) for at least 6 weeks but shorter than 3 years diagnosed by doppler ultrasonography (DUS), ankle brachial index (ABI, 0.9-1.3), physical examination and dermatological review;
- Wound size between 5 and 50 square cm measured by a standardized photography at the screening visit;
- Wound location between knee and ankle;
- Patients suffering from 2 ulcers at the same extremity, as long as these ulcers are separated by a minimum bridge of 1 cm of epithelialized skin;
- Patients must agree to have at least one biopsy performed before treatment. In case IMP production from the first biopsy is not successful, a second biopsy will be taken;
- Body mass index (BMI) between 20 and 40 kg/m²;
- Patients understand the nature of the procedure and are providing written informed consent prior to any clinical trial procedure;
- Women of childbearing potential must have a negative blood pregnancy test at Screening and at Visit 5 before the IMP application;
- Women of childbearing potential and their partner must be willing to use highly effective contraceptive methods during the course of the clinical trial.
Exclusion Criteria:
General exclusion criteria
- Evidence of the ulcer extending to the underlying muscle, tendon, or bone;
- Current long-term use (more than 14 days) of steroid medication above Cushing-threshold dose (>7.5 mg/d prednisone or equivalent);
- Diabetes mellitus that has to be evaluated by blood test (Hemoglobin A1c [HbA1c] > 7.5%);
- Peripheral Artery Disease (PAD) including claudication with need of treatment;
- Acute deep vein thrombosis (maximum 30 days from diagnosis) or a still untreated deep vein thrombosis;
- Unable to tolerate leg ulcer compression bandage;
- Infection of the target ulcer requiring treatment as judged clinically;
- Wound size <1.5 cm² measured by a standardized photography at Visit 5;
- Any chronic dermatological disorders diagnosed at the investigator's discretion;
- Skin disorders, unrelated to the ulcer, that are present adjacent to the target wound;
- Current use of medications that influence wound healing: systemic immunosuppressives, cytotoxic medicinal products, and systemic steroids (above Cushing-threshold level);
- Known abuse of alcohol, drugs, or medicinal products;
- Cancerous or pre-cancerous lesions adjacent to the target wound;
- Patients anticipated to be unwilling or unable to comply with the requirements of the protocol;
- Pregnant or lactating women;
- Systemic infectious disease diagnosed by serology testing for syphilis (acute), human immunodeficiency virus (HIV˗1, HIV-2), hepatitis B (acute) or C infection at Screening or at Visit 2;
- Any known allergies to components of the IMP;
- Prior surgical procedures such as bypass or mesh-graft treatment within 2 months prior to IMP application;
- Treatment with active wound care agents (e.g. Iruxol, local antibiotics or silver dressings), which have not been paused 14 days before IMP application;
- Current or previous (within 30 days of enrollment) treatment with another IMP, or participation and/or under follow-up in another clinical trial;
- Previous participation in this clinical trial;
- Evidence of any other medical conditions (such as psychiatric illness, physical examination, or laboratory findings) that may interfere with the planned treatment, affect the patient's compliance, or place the patient at high risk of complications related to the treatment;
- Employees of the sponsor, or employees or relatives of the investigator.
Exclusion criteria for efficacy assessments
- A wound size enlargement of more than 25% between the wound assessment at the screening visit and the wound assessment at Visit 5;
- A wound size reduction of more than 50% between the wound assessment at the screening visit and wound assessment at Visit 5.
Sites / Locations
- Venenzentrum der Dermatologischen und Gefäßchirurgischen Kliniken, Kliniken der Ruhr-Universität Bochum im St. Maria-Hilf-Krankenhaus
- Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie Universitätsklinikum Würzburg
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
APZ2 application
Arm Description
Topical, single application of APZ2; 500000 cells per square cm;
Outcomes
Primary Outcome Measures
Percentage of wound size reduction
Percentage of wound size reduction at Week 12, or last available post-baseline measurement if the Week 12 measurement is missing (last observation carried forward [LOCF])
Assessment of adverse event (AE) occurrence
All during the clinical trial occurring AEs will be registered, documented and evaluated.
Secondary Outcome Measures
Percentage of wound size reduction
Percentage of wound size reduction at Weeks 2, 3, 4, 6, 8, 10 and 12 (without LOCF)
Absolute wound size reduction
Proportion of patients achieving complete wound closure
Time to first complete wound closure
A priori specification not possible
Proportion of patients achieving 30% wound closure
Time to first 30% wound closure
A priori specification not possible
Percentage of wound epithelialization
Amount of wound epithelialization in % of wound area will be assessed by the investigator based on image analysis of images taken from the wound.
Formation of granulation tissue and wound exudation
Formation of granulation tissue in % of wound area will be assessed by the investigator based on image analysis of images taken from the wound.
Wound exudation will be classified by the investigator using following scores:
High: Small amounts of fluid or free fluids are visible when the dressing is removed; dressing is extensively marked or wet
Moderate: Small amounts of fluid are visible when dressing is removed; wound bed may appear glossy; Primary dressing may be lightly marked
Low: Wound bed is dry; there is no visible moisture; Primary dressing is unmarked; dressing may be adherent to wound
Pain assessment as per numerical rating scale (NRS)
Quality of life (QoL) assessment using the SF-36 questionnaire
Dermatologic quality of life assessment using the DLQI questionnaire
Physical examination and vital parameters
Full Information
NCT ID
NCT02742844
First Posted
April 7, 2016
Last Updated
July 1, 2020
Sponsor
RHEACELL GmbH & Co. KG
Collaborators
Ticeba GmbH, FGK Clinical Research GmbH, Granzer Regulatory Consulting & Services
1. Study Identification
Unique Protocol Identification Number
NCT02742844
Brief Title
Clinical Trial to Investigate Efficacy and Safety of the IMP in Patients With Non Healing Wounds Originating From Ulcers
Official Title
An Interventional, Single Arm, Phase I/IIa Clinical Trial to Investigate the Efficacy and Safety of APZ2 on Wound Healing of Chronic Venous Ulcer (CVU)
Study Type
Interventional
2. Study Status
Record Verification Date
February 2020
Overall Recruitment Status
Terminated
Why Stopped
COVID-19 pandemic and patient recruitment issues
Study Start Date
August 2016 (Actual)
Primary Completion Date
January 15, 2019 (Actual)
Study Completion Date
January 15, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
RHEACELL GmbH & Co. KG
Collaborators
Ticeba GmbH, FGK Clinical Research GmbH, Granzer Regulatory Consulting & Services
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The aim of this clinical trial is to investigate the efficacy (by monitoring the wound size reduction) and safety (by monitoring occurring adverse events) of the investigational medicinal product APZ2 after one single application on chronic venous leg ulcer wounds.
Detailed Description
This is an interventional, single arm, phase I/IIa clinical trial to investigate the efficacy and safety of ABCB5+ mesenchymal stem cells (MSCs) on wound healing in patients with chronic venous ulcer (CVU). Autologous MSCs will be isolated ex vivo from a small skin biopsy and will be expanded in vitro. The IMP APZ2 containing the ABCB5+ cells will then be applied on the wound surface of CVU under local anesthesia.
Patients are followed up for efficacy for 3 months which allows to distinguish actual wound healing from transient wound coverage.
The wound healing process will be documented by standardized photography. The wound size evaluation will start on the day of the first change of wound dressing. The quality of the wound healing process will be assessed on the basis of formation of granulation tissue, epithelialization and wound exudation.
Pain will be assessed using a numerical rating scale and quality of life will be investigated with standardized and validated questionnaires. To assess long-term safety of APZ2 an additional follow-up visit at Month 12 post IMP application is included.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Skin Ulcer Venous Stasis Chronic
Keywords
phase I/IIa, mesenchymal stem cells, ABCB5+, APZ2, chronic venous ulcer, varicose ulcer, skin ulcer, advanced therapy medicinal product, APZ2-II-01, autologous use, somatic cell therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
13 (Actual)
8. Arms, Groups, and Interventions
Arm Title
APZ2 application
Arm Type
Experimental
Arm Description
Topical, single application of APZ2; 500000 cells per square cm;
Intervention Type
Biological
Intervention Name(s)
APZ2 application
Intervention Description
Application of IMP on patients wound.
Primary Outcome Measure Information:
Title
Percentage of wound size reduction
Description
Percentage of wound size reduction at Week 12, or last available post-baseline measurement if the Week 12 measurement is missing (last observation carried forward [LOCF])
Time Frame
Week 12 post baseline, or last available post-baseline measurement if the Week 12 measurement is missing
Title
Assessment of adverse event (AE) occurrence
Description
All during the clinical trial occurring AEs will be registered, documented and evaluated.
Time Frame
At biopsy removal, 1-3 days post biopsy, 7-10 days post biopsy, 6-12 weeks post biopsy; at baseline and days 3, 8 and weeks 2, 3, 4, 6, 8, 10, 12 and month 12 post baseline
Secondary Outcome Measure Information:
Title
Percentage of wound size reduction
Description
Percentage of wound size reduction at Weeks 2, 3, 4, 6, 8, 10 and 12 (without LOCF)
Time Frame
Weeks 2, 3, 4, 6, 8, 10 and 12 post baseline
Title
Absolute wound size reduction
Time Frame
Weeks 2, 3, 4, 6, 8, 10, and 12 post baseline
Title
Proportion of patients achieving complete wound closure
Time Frame
Weeks 2, 3, 4, 6, 8, 10, and 12 post baseline and at any time point up to week 12
Title
Time to first complete wound closure
Description
A priori specification not possible
Time Frame
Between baseline and week 12 post baseline
Title
Proportion of patients achieving 30% wound closure
Time Frame
Weeks 2, 3, 4, 6, 8, 10, 12 post baseline and at any time point up to week 12
Title
Time to first 30% wound closure
Description
A priori specification not possible
Time Frame
Between baseline and week 12 post baseline
Title
Percentage of wound epithelialization
Description
Amount of wound epithelialization in % of wound area will be assessed by the investigator based on image analysis of images taken from the wound.
Time Frame
At baseline and days 3, 8 and weeks 2, 3, 4, 6, 8, 10, 12 post baseline
Title
Formation of granulation tissue and wound exudation
Description
Formation of granulation tissue in % of wound area will be assessed by the investigator based on image analysis of images taken from the wound.
Wound exudation will be classified by the investigator using following scores:
High: Small amounts of fluid or free fluids are visible when the dressing is removed; dressing is extensively marked or wet
Moderate: Small amounts of fluid are visible when dressing is removed; wound bed may appear glossy; Primary dressing may be lightly marked
Low: Wound bed is dry; there is no visible moisture; Primary dressing is unmarked; dressing may be adherent to wound
Time Frame
At baseline and days 3, 8 and weeks 2, 3, 4, 6, 8, 10, 12 post baseline
Title
Pain assessment as per numerical rating scale (NRS)
Time Frame
At baseline and days 1-3, 8 and weeks 2, 3, 4, 6, 8, 10, 12 post baseline
Title
Quality of life (QoL) assessment using the SF-36 questionnaire
Time Frame
At baseline and weeks 4, 8, 12 post baseline
Title
Dermatologic quality of life assessment using the DLQI questionnaire
Time Frame
At baseline and weeks 4, 8, 12 post baseline
Title
Physical examination and vital parameters
Time Frame
At Screening, baseline, week 12, month 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female patients aged 18 to 85 years;
Chronic venous leg ulcer (as defined by the current AWMF guidelines: therapy resistant ulcer that shows no improvement within 3 months despite of optimal phlebological therapies or is not healed within 12 months) for at least 6 weeks but shorter than 3 years diagnosed by doppler ultrasonography (DUS), ankle brachial index (ABI, 0.9-1.3), physical examination and dermatological review;
Wound size between 5 and 50 square cm measured by a standardized photography at the screening visit;
Wound location between knee and ankle;
Patients suffering from 2 ulcers at the same extremity, as long as these ulcers are separated by a minimum bridge of 1 cm of epithelialized skin;
Patients must agree to have at least one biopsy performed before treatment. In case IMP production from the first biopsy is not successful, a second biopsy will be taken;
Body mass index (BMI) between 20 and 40 kg/m²;
Patients understand the nature of the procedure and are providing written informed consent prior to any clinical trial procedure;
Women of childbearing potential must have a negative blood pregnancy test at Screening and at Visit 5 before the IMP application;
Women of childbearing potential and their partner must be willing to use highly effective contraceptive methods during the course of the clinical trial.
Exclusion Criteria:
General exclusion criteria
Evidence of the ulcer extending to the underlying muscle, tendon, or bone;
Current long-term use (more than 14 days) of steroid medication above Cushing-threshold dose (>7.5 mg/d prednisone or equivalent);
Diabetes mellitus that has to be evaluated by blood test (Hemoglobin A1c [HbA1c] > 7.5%);
Peripheral Artery Disease (PAD) including claudication with need of treatment;
Acute deep vein thrombosis (maximum 30 days from diagnosis) or a still untreated deep vein thrombosis;
Unable to tolerate leg ulcer compression bandage;
Infection of the target ulcer requiring treatment as judged clinically;
Wound size <1.5 cm² measured by a standardized photography at Visit 5;
Any chronic dermatological disorders diagnosed at the investigator's discretion;
Skin disorders, unrelated to the ulcer, that are present adjacent to the target wound;
Current use of medications that influence wound healing: systemic immunosuppressives, cytotoxic medicinal products, and systemic steroids (above Cushing-threshold level);
Known abuse of alcohol, drugs, or medicinal products;
Cancerous or pre-cancerous lesions adjacent to the target wound;
Patients anticipated to be unwilling or unable to comply with the requirements of the protocol;
Pregnant or lactating women;
Systemic infectious disease diagnosed by serology testing for syphilis (acute), human immunodeficiency virus (HIV˗1, HIV-2), hepatitis B (acute) or C infection at Screening or at Visit 2;
Any known allergies to components of the IMP;
Prior surgical procedures such as bypass or mesh-graft treatment within 2 months prior to IMP application;
Treatment with active wound care agents (e.g. Iruxol, local antibiotics or silver dressings), which have not been paused 14 days before IMP application;
Current or previous (within 30 days of enrollment) treatment with another IMP, or participation and/or under follow-up in another clinical trial;
Previous participation in this clinical trial;
Evidence of any other medical conditions (such as psychiatric illness, physical examination, or laboratory findings) that may interfere with the planned treatment, affect the patient's compliance, or place the patient at high risk of complications related to the treatment;
Employees of the sponsor, or employees or relatives of the investigator.
Exclusion criteria for efficacy assessments
A wound size enlargement of more than 25% between the wound assessment at the screening visit and the wound assessment at Visit 5;
A wound size reduction of more than 50% between the wound assessment at the screening visit and wound assessment at Visit 5.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andreas Kerstan, PD Dr.med.
Organizational Affiliation
Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie Universitätsklinikum Würzburg
Official's Role
Principal Investigator
Facility Information:
Facility Name
Venenzentrum der Dermatologischen und Gefäßchirurgischen Kliniken, Kliniken der Ruhr-Universität Bochum im St. Maria-Hilf-Krankenhaus
City
Bochum
ZIP/Postal Code
44805
Country
Germany
Facility Name
Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie Universitätsklinikum Würzburg
City
Würzburg
ZIP/Postal Code
97080
Country
Germany
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Clinical Trial to Investigate Efficacy and Safety of the IMP in Patients With Non Healing Wounds Originating From Ulcers
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