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Allogeneic ABCB5-positive Stem Cells for Treatment of CVU

Primary Purpose

Skin Ulcer Venous Stasis Chronic

Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
allo-APZ2-CVU
Sponsored by
RHEACELL GmbH & Co. KG
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Skin Ulcer Venous Stasis Chronic focused on measuring Chronic Venous Ulcer, ABCB5, Allogeneic, Mesenchymal stem cells, varicose ulcer, skin ulcer, advanced therapy medicinal product, somatic cell therapy, phase I/IIa

Eligibility Criteria

35 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Male or female patients aged 35 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) diagnosed by doppler ultrasonography (DUS), ankle brachial index (ABI, 0.9-1.3), physical examination and dermatological review;
  3. Wound size of target ulcer between 1.5 and 100 cm2 measured by a standardized photography at the screening visits (Visit 1 and Visit 2);
  4. Wound location below knee;
  5. If patients are suffering from 2 or more ulcers at the same extremity, the target ulcer has to be separated by a minimum bridge of 1 cm of epithelialized skin from other ulcers (the largest ulcer should be the target ulcer, if not decided otherwise at discretion of the investigator; the target ulcer is defined at Visit 1);
  6. Body mass index (BMI) between 20 and 45 kg/m²;
  7. Patients understand the nature of the procedure and are providing written informed consent prior to any clinical trial procedure;
  8. Women of childbearing potential must have a negative blood pregnancy test at Visit 1
  9. 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:

  1. Evidence of the ulcer extending to the underlying muscle, tendon, or bone;
  2. Current use of systemic steroid medication above Cushing threshold dose (>7.5 mg/d prednisone or equivalent);
  3. Diabetes mellitus that has to be evaluated by blood test (Haemoglobin 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. Any chronic dermatological disorders diagnosed at the investigator's discretion;
  9. Skin disorders, unrelated to the ulcer, that are present adjacent to the target wound;
  10. Current use of medications that influence wound healing: systemic immunosuppressives, cytotoxic medicinal products, and systemic steroids (above Cushing-threshold level);
  11. Known abuse of alcohol, drugs, or medicinal products;
  12. Cancerous or pre-cancerous lesions adjacent to the target wound;
  13. Patients anticipated to be unwilling or unable to comply with the requirements of the protocol;
  14. Pregnant or lactating women;
  15. Systemic infectious disease diagnosed by serology testing human immunodeficiency virus (HIV˗1, HIV-2);
  16. Any known allergies to components of the IMP;
  17. Prior surgical procedures such as bypass or mesh-graft treatment within 2 months prior to Visit 1;
  18. Patients with significant ulcer healing or wound size enlargement of more than 25% at Visit 2 compared to Visit 1;
  19. Treatment of target ulcer 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 (except for screening failures due to an inclusion or exclusion criterion);
  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.

Sites / Locations

  • Venenzentrum der Dermatologischen und Gefäßchirurgischen Kliniken, Kliniken der Ruhr-Universität Bochum im St. Maria Hilf Krankenhaus
  • Universitätsklinikum Erlangen, Hautklinik
  • Klinik und Poliklinik für Hautkrankheiten, Universitätsmedizin Greifswald
  • Klinische Forschung Hamburg GmbH, Dermatologie / Allergologie
  • pro scientia med im Mare Klinikum; Department Klinische Forschung und Entwicklung
  • Universitätsklinikum Münster, Klinik für Hautkrankheiten, Allgemeine Dermatologie und Venerologie
  • Klinische Forschung Schwerin GmbH
  • Universitätsklinikum Ulm, Klinik für Dermatologie und Allergologie
  • Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Würzburg

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

allo-APZ2-CVU

Arm Description

Application of IMP on patients wound

Outcomes

Primary Outcome Measures

Percentage of wound size reduction
Percentage of wound size reduction at Week 12, or last available post-baseline measurement of Weeks 6, 8 or 10 if the Week 12 measurement is missing (last observation carried forward [LOCF]).
Assessment of adverse event (AE) occurrence
All AEs occurring during the clinical trial will be registered, documented and evaluated.

Secondary Outcome Measures

Percentage of wound size reduction
Absolute wound size reduction
Proportion of patients achieving complete wound closure
Time to first complete wound closure
Proportion of patients achieving 30% wound closure
Time to first 30% wound closure
Epithelialization
Assessment of further wound healing parameters: formation of granulation tissue and wound exudation
Pain assessment as per numerical rating scale (NRS)
Assessment of quality of life (QoL) using the short form 36 (SF-36) questionnaire
Assessment of dermatology-specific quality of life based on the Dermatology Life Quality Index (DLQI) questionnaire
Physical examination and vital signs at Week 6.1 and Week 12

Full Information

First Posted
August 17, 2017
Last Updated
September 9, 2020
Sponsor
RHEACELL GmbH & Co. KG
Collaborators
FGK Clinical Research GmbH, Ticeba GmbH, Granzer Regulatory Consulting & Services
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1. Study Identification

Unique Protocol Identification Number
NCT03257098
Brief Title
Allogeneic ABCB5-positive Stem Cells for Treatment of CVU
Official Title
An Interventional, Single Arm, Multicenter, Phase I/IIa Clinical Trial to Investigate the Efficacy and Safety of Allo-APZ2-CVU on Wound Healing of Chronic Venous Ulcer (CVU)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2020
Overall Recruitment Status
Completed
Study Start Date
November 16, 2017 (Actual)
Primary Completion Date
June 25, 2020 (Actual)
Study Completion Date
June 25, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
RHEACELL GmbH & Co. KG
Collaborators
FGK Clinical Research GmbH, Ticeba GmbH, Granzer Regulatory Consulting & Services

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
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 of Chronic Venous Ulcers) and safety (by monitoring adverse events) of the medicinal product to be studied after two applications on the wound surface in patients with Chronic Venous Ulcers.
Detailed Description
This is an interventional, single arm, phase I/IIa clinical trial to investigate the efficacy and safety of allogeneic ABCB5-positive mesenchymal stem cells (MSCs) on wound healing in patients with chronic venous ulcer (CVU). Allogeneic MSCs will be isolated ex vivo and will be expanded in vitro. The IMP incorporating the ABCB5-positive MSCs will then be applied on the wound surface of CVU under local anesthesia (on Day 0 and Week 6.1). Wound measurements from Visit (V) 2 and V9 will be used to determine the cell amount for the IMP treatments on V3 and V10, respectively. 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 allo-APZ2-CVU three follow-up visits at Months 6, 9 and 12 after the first IMP applications are 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
Chronic Venous Ulcer, ABCB5, Allogeneic, Mesenchymal stem cells, varicose ulcer, skin ulcer, advanced therapy medicinal product, somatic cell therapy, phase I/IIa

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Interventional, single arm, multicenter, phase I/IIa clinical trial
Masking
None (Open Label)
Allocation
N/A
Enrollment
31 (Actual)

8. Arms, Groups, and Interventions

Arm Title
allo-APZ2-CVU
Arm Type
Experimental
Arm Description
Application of IMP on patients wound
Intervention Type
Biological
Intervention Name(s)
allo-APZ2-CVU
Intervention Description
Suspension of ABCB5-positive mesenchymal stem cells
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 of Weeks 6, 8 or 10 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 AEs occurring during the clinical trial will be registered, documented and evaluated.
Time Frame
Up to 12 months
Secondary Outcome Measure Information:
Title
Percentage of wound size reduction
Time Frame
Weeks 2, 3, 4, 6, 6.1, 6.2, 8, 10, and 12 (without LOCF);
Title
Absolute wound size reduction
Time Frame
Weeks 2, 3, 4, 6, 6.1, 6.2, 8, 10, and 12
Title
Proportion of patients achieving complete wound closure
Time Frame
Weeks 2, 3, 4, 6, 8, 10, 12, and at any time point
Title
Time to first complete wound closure
Time Frame
A priori specification not possible; between baseline and week 12 post baseline
Title
Proportion of patients achieving 30% wound closure
Time Frame
Weeks 2, 3, 4, 6, 6.1, 6.2, 8, 10, 12, and at any time point
Title
Time to first 30% wound closure
Time Frame
A priori specification not possible; between baseline and week 12 post baseline
Title
Epithelialization
Time Frame
Weeks 2, 3, 4, 6, 6.1, 6.2, 8, 10, and 12
Title
Assessment of further wound healing parameters: formation of granulation tissue and wound exudation
Time Frame
Visit 3 and Visit 10 before IMP application, Days 1 to 3 and 8, Weeks 2, 3, 4, 6, 6.2, 8, 10, and 12
Title
Pain assessment as per numerical rating scale (NRS)
Time Frame
Days 0, 1 to 3 and 8, Weeks 2, 3, 4, 6, 6.1, 6.2, 8, 10, and 12
Title
Assessment of quality of life (QoL) using the short form 36 (SF-36) questionnaire
Time Frame
Day 0 and Weeks 4, 8 and 12
Title
Assessment of dermatology-specific quality of life based on the Dermatology Life Quality Index (DLQI) questionnaire
Time Frame
Day 0 and Weeks 4, 8 and 12
Title
Physical examination and vital signs at Week 6.1 and Week 12
Time Frame
Week 6.1 and Week 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
35 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female patients aged 35 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) diagnosed by doppler ultrasonography (DUS), ankle brachial index (ABI, 0.9-1.3), physical examination and dermatological review; Wound size of target ulcer between 1.5 and 100 cm2 measured by a standardized photography at the screening visits (Visit 1 and Visit 2); Wound location below knee; If patients are suffering from 2 or more ulcers at the same extremity, the target ulcer has to be separated by a minimum bridge of 1 cm of epithelialized skin from other ulcers (the largest ulcer should be the target ulcer, if not decided otherwise at discretion of the investigator; the target ulcer is defined at Visit 1); Body mass index (BMI) between 20 and 45 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 Visit 1 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: Evidence of the ulcer extending to the underlying muscle, tendon, or bone; Current use of systemic steroid medication above Cushing threshold dose (>7.5 mg/d prednisone or equivalent); Diabetes mellitus that has to be evaluated by blood test (Haemoglobin 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; 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 human immunodeficiency virus (HIV˗1, HIV-2); Any known allergies to components of the IMP; Prior surgical procedures such as bypass or mesh-graft treatment within 2 months prior to Visit 1; Patients with significant ulcer healing or wound size enlargement of more than 25% at Visit 2 compared to Visit 1; Treatment of target ulcer 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 (except for screening failures due to an inclusion or exclusion criterion); 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andreas Kerstan, Dr.
Organizational Affiliation
Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie, 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
Universitätsklinikum Erlangen, Hautklinik
City
Erlangen
ZIP/Postal Code
91054
Country
Germany
Facility Name
Klinik und Poliklinik für Hautkrankheiten, Universitätsmedizin Greifswald
City
Greifswald
ZIP/Postal Code
17475
Country
Germany
Facility Name
Klinische Forschung Hamburg GmbH, Dermatologie / Allergologie
City
Hamburg
ZIP/Postal Code
20253
Country
Germany
Facility Name
pro scientia med im Mare Klinikum; Department Klinische Forschung und Entwicklung
City
Kiel
ZIP/Postal Code
24119
Country
Germany
Facility Name
Universitätsklinikum Münster, Klinik für Hautkrankheiten, Allgemeine Dermatologie und Venerologie
City
Münster
ZIP/Postal Code
48149
Country
Germany
Facility Name
Klinische Forschung Schwerin GmbH
City
Schwerin
ZIP/Postal Code
19055
Country
Germany
Facility Name
Universitätsklinikum Ulm, Klinik für Dermatologie und Allergologie
City
Ulm
ZIP/Postal Code
89081
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
No
Citations:
PubMed Identifier
33011075
Citation
Kerstan A, Niebergall-Roth E, Esterlechner J, Schroder HM, Gasser M, Waaga-Gasser AM, Goebeler M, Rak K, Schrufer P, Endres S, Hagenbusch P, Kraft K, Dieter K, Ballikaya S, Stemler N, Sadeghi S, Tappenbeck N, Murphy GF, Orgill DP, Frank NY, Ganss C, Scharffetter-Kochanek K, Frank MH, Kluth MA. Ex vivo-expanded highly pure ABCB5+ mesenchymal stromal cells as Good Manufacturing Practice-compliant autologous advanced therapy medicinal product for clinical use: process validation and first in-human data. Cytotherapy. 2021 Feb;23(2):165-175. doi: 10.1016/j.jcyt.2020.08.012. Epub 2020 Oct 1.
Results Reference
derived

Learn more about this trial

Allogeneic ABCB5-positive Stem Cells for Treatment of CVU

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