Clinical trial NCT02742844: 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
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: 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
Lead sponsor: RHEACELL GmbH & Co. KG
Sponsor class: INDUSTRY
Collaborators: name: Ticeba GmbH
name: FGK Clinical Research GmbH
name: Granzer Regulatory Consulting & Services
First posted: 2016-04-19
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Male or female patients aged 18 to 85 years;
2. 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;
3. Wound size between 5 and 50 square cm measured by a standardized photography at the screening visit;
4. Wound location between knee and ankle;
5. 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;
6. 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;
7. Body mass index (BMI) between 20 and 40 kg/m²;
8. Patients understand the nature of the procedure and are providing written informed consent prior to any clinical trial procedure;
9. Women of childbearing potential must have a negative blood pregnancy test at Screening and at Visit 5 before the IMP application;
10. 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

1. Evidence of the ulcer extending to the underlying muscle, tendon, or bone;
2. Current long-term use (more than 14 days) of steroid medication above Cushing-threshold dose (\>7.5 mg/d prednisone or equivalent);
3. Diabetes mellitus that has to be evaluated by blood test (Hemoglobin A1c \[HbA1c\] \> 7.5%);
4. Peripheral Artery Disease (PAD) including claudication with need of treatment;
5. Acute deep vein thrombosis (maximum 30 days from diagnosis) or a still untreated deep vein thrombosis;
6. Unable to tolerate leg ulcer compression bandage;
7. Infection of the target ulcer requiring treatment as judged clinically;
8. Wound size \<1.5 cm² measured by a standardized photography at Visit 5;
9. Any chronic dermatological disorders diagnosed at the investigator's discretion;
10. Skin disorders, unrelated to the ulcer, that are present adjacent to the target wound;
11. Current use of medications that influence wound healing: systemic immunosuppressives, cytotoxic medicinal products, and systemic steroids (above Cushing-threshold level);
12. Known abuse of alcohol, drugs, or medicinal products;
13. Cancerous or pre-cancerous lesions adjacent to the target wound;
14. Patients anticipated to be unwilling or unable to comply with the requirements of the protocol;
15. Pregnant or lactating women;
16. 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;
17. Any known allergies to components of the IMP;
18. Prior surgical procedures such as bypass or mesh-graft treatment within 2 months prior to IMP application;
19. Treatment with active wound care agents (e.g. Iruxol, local antibiotics or silver dressings), which have not been paused 14 days before IMP application;
20. Current or previous (within 30 days of enrollment) treatment with another IMP, or participation and/or under follow-up in another clinical trial;
21. Previous participation in this clinical trial;
22. 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;
23. Employees of the sponsor, or employees or relatives of the investigator.

Exclusion criteria for efficacy assessments

1. A wound size enlargement of more than 25% between the wound assessment at the screening visit and the wound assessment at Visit 5;
2. A wound size reduction of more than 50% between the wound assessment at the screening visit and wound assessment at Visit 5.

Primary outcomes:
measure: Percentage of wound size reduction
timeFrame: Week 12 post baseline, or last available post-baseline measurement if the Week 12 measurement is missing
measure: Assessment of adverse event (AE) occurrence
timeFrame: 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 outcomes:
measure: Percentage of wound size reduction
timeFrame: Weeks 2, 3, 4, 6, 8, 10 and 12 post baseline
measure: Absolute wound size reduction
timeFrame: Weeks 2, 3, 4, 6, 8, 10, and 12 post baseline
measure: Proportion of patients achieving complete wound closure
timeFrame: Weeks 2, 3, 4, 6, 8, 10, and 12 post baseline and at any time point up to week 12
measure: Time to first complete wound closure
timeFrame: Between baseline and week 12 post baseline
measure: Proportion of patients achieving 30% wound closure
timeFrame: Weeks 2, 3, 4, 6, 8, 10, 12 post baseline and at any time point up to week 12
measure: Time to first 30% wound closure
timeFrame: Between baseline and week 12 post baseline
measure: Percentage of wound epithelialization
timeFrame: At baseline and days 3, 8 and weeks 2, 3, 4, 6, 8, 10, 12 post baseline
measure: Formation of granulation tissue and wound exudation
timeFrame: At baseline and days 3, 8 and weeks 2, 3, 4, 6, 8, 10, 12 post baseline
measure: Pain assessment as per numerical rating scale (NRS)
timeFrame: At baseline and days 1-3, 8 and weeks 2, 3, 4, 6, 8, 10, 12 post baseline
measure: Quality of life (QoL) assessment using the SF-36 questionnaire
timeFrame: At baseline and weeks 4, 8, 12 post baseline
measure: Dermatologic quality of life assessment using the DLQI questionnaire
timeFrame: At baseline and weeks 4, 8, 12 post baseline
measure: Physical examination and vital parameters
timeFrame: At Screening, baseline, week 12, month 12
Other outcomes:
Locations:
city: Bochum
country: Germany
facility: Venenzentrum der Dermatologischen und Gefäßchirurgischen Kliniken, Kliniken der Ruhr-Universität Bochum im St. Maria-Hilf-Krankenhaus
city: Würzburg
country: Germany
facility: Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie Universitätsklinikum Würzburg
Study officials:
affiliation: Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie Universitätsklinikum Würzburg
name: Andreas Kerstan, PD Dr.med.
role: PRINCIPAL_INVESTIGATOR
References: