Skin Ulcer Venous Stasis ChronicPhase 1/2NCT03257098
Allogeneic ABCB5-positive Stem Cells for Treatment of CVU
A Phase 1/2 study testing allo-APZ2-CVU in people with Skin Ulcer Venous Stasis Chronic, run by RHEACELL GmbH & Co. KG at 9 sites in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 35 to 85 years
- Conditions the study is for
- Skin Ulcer Venous Stasis Chronic
- What is being tested?
- allo-APZ2-CVU
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 9 sitesGermany
- Study dates
- 16 Nov 2017to 25 Jun 2020
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
Germany9 sites
Venenzentrum der Dermatologischen und Gefäßchirurgischen Kliniken, Kliniken der Ruhr-Universität Bochum im St. Maria Hilf Krankenhaus
Bochum, 44805
Universitätsklinikum Erlangen, Hautklinik
Erlangen, 91054
Klinik und Poliklinik für Hautkrankheiten, Universitätsmedizin Greifswald
Greifswald, 17475
Klinische Forschung Hamburg GmbH, Dermatologie / Allergologie
Hamburg, 20253
pro scientia med im Mare Klinikum; Department Klinische Forschung und Entwicklung
Kiel, 24119
Universitätsklinikum Münster, Klinik für Hautkrankheiten, Allgemeine Dermatologie und Venerologie
Münster, 48149
Klinische Forschung Schwerin GmbH
Schwerin, 19055
Universitätsklinikum Ulm, Klinik für Dermatologie und Allergologie
Ulm, 89081
Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Würzburg
Würzburg, 97080
About this study
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)
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.
Read the 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.
- Conditions
- Skin Ulcer Venous Stasis Chronic
- Being tested
- allo-APZ2-CVU
- Keywords
- Chronic Venous Ulcer, ABCB5, Allogeneic, Mesenchymal stem cells, varicose ulcer, skin ulcer, advanced therapy medicinal product, somatic cell therapy, phase I/IIa
- Medical subject headings
- Varicose Ulcer, Skin Ulcer
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
allo-APZ2-CVUBiological
Suspension of ABCB5-positive mesenchymal stem cells
| Study group | Role | What they receive |
|---|---|---|
| allo-APZ2-CVU | Experimental | Application of IMP on patients wound Receives: Biological: allo-APZ2-CVU |
What is being measured
The primary outcome is the main question the study is designed to answer.
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]).
Measured: Week 12 post baseline, or last available post-baseline measurement if the Week 12 measurement is missing
Assessment of adverse event (AE) occurrence
All AEs occurring during the clinical trial will be registered, documented and evaluated.
Measured: Up to 12 months
Secondary outcomes (12)
Percentage of wound size reduction
Measured: Weeks 2, 3, 4, 6, 6.1, 6.2, 8, 10, and 12 (without LOCF);
Absolute wound size reduction
Measured: Weeks 2, 3, 4, 6, 6.1, 6.2, 8, 10, and 12
Proportion of patients achieving complete wound closure
Measured: Weeks 2, 3, 4, 6, 8, 10, 12, and at any time point
Time to first complete wound closure
Measured: A priori specification not possible; between baseline and week 12 post baseline
Proportion of patients achieving 30% wound closure
Measured: Weeks 2, 3, 4, 6, 6.1, 6.2, 8, 10, 12, and at any time point
Time to first 30% wound closure
Measured: A priori specification not possible; between baseline and week 12 post baseline
Epithelialization
Measured: Weeks 2, 3, 4, 6, 6.1, 6.2, 8, 10, and 12
Assessment of further wound healing parameters: formation of granulation tissue and wound exudation
Measured: 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
Pain assessment as per numerical rating scale (NRS)
Measured: Days 0, 1 to 3 and 8, Weeks 2, 3, 4, 6, 6.1, 6.2, 8, 10, and 12
Assessment of quality of life (QoL) using the short form 36 (SF-36) questionnaire
Measured: Day 0 and Weeks 4, 8 and 12
Assessment of dermatology-specific quality of life based on the Dermatology Life Quality Index (DLQI) questionnaire
Measured: Day 0 and Weeks 4, 8 and 12
Physical examination and vital signs at Week 6.1 and Week 12
Measured: Week 6.1 and Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2017
- Study start16 Nov 2017
- Primary completion25 Jun 2020
- Study completion25 Jun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Skin Ulcer Venous Stasis ChronicStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Interventional, single arm, multicenter, phase I/IIa clinical trial
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- RHEACELL GmbH & Co. KG
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- FGK Clinical Research GmbH, Ticeba GmbH, Granzer Regulatory Consulting & Services
- Responsible party
- Sponsor
- Investigators
- Andreas Kerstan, Dr., Principal investigator, Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie, Würzburg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03257098
- Sponsor's protocol ID
- allo-APZ2-CVU-II-01
- Status last verified
- Sep 2020
- First submitted
- 17 Aug 2017
- Last updated
- 10 Sep 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 33011075
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT03257098
- Acronym / sponsor ID
- allo-APZ2-CVU-II-01
- Conditions
- 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
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- RHEACELL GmbH & Co. KGIndustry (pharma, biotech, devices)
- Collaborators
- FGK Clinical Research GmbH, Ticeba GmbH, Granzer Regulatory Consulting & Services
- Study start
- 16 Nov 2017 (actual)
- Primary completion
- 25 Jun 2020 (actual)
- Study completion
- 25 Jun 2020 (actual)
- First posted
- 22 Aug 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Interventional, single arm, multicenter, phase I/IIa clinical trial
| Arm | Type | Receives |
|---|---|---|
| allo-APZ2-CVU | Experimental | Biological: allo-APZ2-CVUApplication of IMP on patients wound |
Who may qualify
- Ages
- 35 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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);
Key exclusion criteria (23 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| allo-APZ2-CVUSuspension of ABCB5-positive mesenchymal stem cells | Biological | allo-APZ2-CVU |
Primary outcome
Percentage of wound size reduction
Time frame: Week 12 post baseline, or last available post-baseline measurement if the Week 12 measurement is missing
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
Time frame: Up to 12 months
All AEs occurring during the clinical trial will be registered, documented and evaluated.
12 secondary outcomes
Percentage of wound size reduction
Time frame: Weeks 2, 3, 4, 6, 6.1, 6.2, 8, 10, and 12 (without LOCF);
Absolute wound size reduction
Time frame: Weeks 2, 3, 4, 6, 6.1, 6.2, 8, 10, and 12
Proportion of patients achieving complete wound closure
Time frame: Weeks 2, 3, 4, 6, 8, 10, 12, and at any time point
Time to first complete wound closure
Time frame: A priori specification not possible; between baseline and week 12 post baseline
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
Time to first 30% wound closure
Time frame: A priori specification not possible; between baseline and week 12 post baseline
Epithelialization
Time frame: Weeks 2, 3, 4, 6, 6.1, 6.2, 8, 10, and 12
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
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
Assessment of quality of life (QoL) using the short form 36 (SF-36) questionnaire
Time frame: Day 0 and Weeks 4, 8 and 12
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
Physical examination and vital signs at Week 6.1 and Week 12
Time frame: Week 6.1 and Week 12
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2020.
- Derived from this study: PubMed 33011075Kerstan 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andreas Kerstan, Dr. principal investigator
Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie, Würzburg
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing allo-APZ2-CVU in people with Skin Ulcer Venous Stasis Chronic, run by RHEACELL GmbH & Co. KG at 9 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of wound size reduction (time frame: Week 12 post baseline, or last available post-baseline measurement if the Week 12 measurement is missing). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03257098, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2020.