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Diabetic Neuropathic UlcerPhase 1/2NCT03267784

Allogeneic ABCB5-positive Stem Cells for Treatment of DFU "Malum Perforans"

A Phase 1/2 study testing allo-APZ2-DFU in people with Diabetic Neuropathic Ulcer, run by RHEACELL GmbH & Co. KG at 7 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The aim of this clinical trial is to investigate the efficacy (by monitoring the wound surface area reduction of Diabetic Foot Ulcers) and safety (by monitoring adverse events) of two doses of the allogeneic investigational medicinal product "allo-APZ2-DFU" topically administered to the wound matrix of patients with… Read more about this study

Who is it for?
Ages 18 to 85 years
Conditions the study is for
Diabetic Neuropathic Ulcer
What is being tested?
allo-APZ2-DFU
Could I receive a placebo?
No, everyone receives an active treatment
How many people
23 participants
Where
7 sitesGermany
Study dates
21 Nov 2017to 29 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 18 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female patients aged 18 to 85 years;
  • Patients with an existing diagnosis of diabetic mellitus Type 2, evaluated by blood test [HbA1c] < 11%) at the Screening visit (Visit 1). The HbA1c value at visit 1 should not vary more than 1.5% (absolute range) compared to a HbA1c value that was previously measured 1 to 6 months before visit 1;
  • The presence of diabetic neuropathic ulcers "malum perforans" (Grade I and II according to Wagner) at plantar site of the foot diagnosed by ABI ≥0.7, without claudication, or TcPO2 >40 mmHg or doppler ultrasonography (at the discretion of the investigator) to exclude significant arterial diseases and critical limb ischemia, and a diabetic neuropathy test using a 128 Hz vibration tuning fork according to Rydel-Seiffer (as described by Guideline "Nationale Versorgungsleitlinie - Neuropathie bei Diabetes im Erwachsenenalter"). If the ABI is >1.3, an additional doppler ultrasonography must be performed to exclude a PAOD masked by media sclerosis;
  • At Screening Visit 1 and 2 the wound surface area of the target ulcer should be between 1 and 50 cm2 measured by using a scaled measuring sensor in combination with digital image analysis;
  • The ulcer's surface area should be (mostly) free from callus or necrotic tissue;
  • If patients are suffering from two or more ulcers at the same extremity, the target ulcer has to be separated by a minimum bridge of 1 cm of healthy tissue from other ulcers;
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  • Patients are willing and able to wear therapeutic shoes that are especially designed for patients with a diabetic neuropathic foot;
  • 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 must be willing to use highly effective contraceptive methods during the course of the clinical trial.

Who cannot join

  • Presence of acute Charcot foot;
  • Clinical signs of active osteomyelitis in the last three months;
  • Active wet gangrenous tissue;
  • Infection of the target ulcer requiring treatment as judged clinically;
  • Presence of an ulcer Grade ≥3 according to Wagner on the same foot as target ulcer;
  • Patients who are currently receiving dialysis;
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  • Peripheral arterial occlusive disease (PAOD) including claudication with need of treatment;
  • Ulcers due to non-diabetic etiology;
  • Prior surgical procedures such as bypass or mesh-graft treatment within 2 months prior to IMP application;
  • Acute deep vein thrombosis (maximum 30 days from diagnosis) or a still untreated deep vein thrombosis;
  • Any chronic dermatological disorders diagnosed at the investigator's discretion;
  • Skin disorders, unrelated to the ulcer, that are present adjacent to the target wound;
  • Treatment of target wound with active wound care agents (e.g. iruxol, local antibiotics or silver dressings), which have not been stopped 14 days before IMP application;
  • Any malignancy within the past 5 years, excluding successfully treated carcinoma in situ, basal cell carcinoma or squamous cell carcinoma of the skin without evidence of metastases;
  • Current use of steroid medication above Cushing threshold dose (>7.5 mg/d prednisone or equivalent);
  • Known abuse of alcohol, drugs, or medicinal products;
  • Patients anticipated to be unwilling or unable to comply with the requirements of the protocol;
  • Pregnant or lactating women;
  • Patients infected with the human immunodeficiency virus (HIV 1\&2);
  • Any known allergies to components of the IMP or concomitant medication;
  • Current or previous (within 30 days of enrollment) treatment with another IMP, or participation and/or under follow-up in another 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.

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

Germany7 sites

  • Universitätsmedizin Greifswald; Klinik und Poliklinik für Hautkrankheiten

    Greifswald, 17475

  • St. Josefskrankenhaus Heidelberg GmbH; Klinische Studienabteilung

    Heidelberg, 69115

  • Diabetologikum Raab, Privatärztliche Facharztpraxis

    Kassel, 34131

  • pro scientia med im Mare Klinikum, Department Klinische Forschung und Entwicklung

    Kronshagen, 24119

  • Studienambulanz Leipzig, medamed GmbH

    Leipzig, 04107

  • Diabetologikum Ludwigshafen, Gemeinschaftspraxis

    Ludwigshafen, 67059

  • Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Würzburg

    Würzburg, 97080

Other trials in Germany

About this study

Official title: An Interventional, Multicenter, Single Arm, Phase I/IIa Clinical Trial to Investigate the Efficacy and Safety of Allo-APZ2-DFU on Wound Healing of Diabetic Neuropathic Ulcer (DFU)

The aim of this clinical trial is to investigate the efficacy (by monitoring the wound surface area reduction of Diabetic Foot Ulcers) and safety (by monitoring adverse events) of two doses of the allogeneic investigational medicinal product "allo-APZ2-DFU" topically administered to the wound matrix of patients with diabetic neuropathic ulcer.

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 diabetic neuropathic ulcer. Allogeneic MSCs will be isolated ex vivo and will be expanded in vitro. The Investigational medicinal product (IMP) containing the ABCB5-positive MSCs will then be applied two times (at Visit 3 and six weeks later, at Visit 10) on the wound surface of DFU.

Patients are followed up for efficacy for a period of three months starting after the first IMP application which allows to distinguish actual wound healing from transient wound coverage.

The wound healing process will be documented by standardized photography. The wound size reduction evaluation will start two weeks after the first IMP application. 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-DFU three follow-up visits at Months 6, 9 and 12 after the first IMP application are included.

Being tested
allo-APZ2-DFU
Keywords
diabetic neuropathic ulcer, ABCB5, allogeneic, mesenchymal stem cells, skin ulcer, advanced therapy medicinal product, somatic cell therapy, phase I/IIa, Diabetic Foot Ulcer
Medical subject headings
Skin Ulcer, Diabetic Foot

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • allo-APZ2-DFUBiological

    Suspension of ABCB5-positive mesenchymal stem cells

Study groups in NCT03267784
Study groupRoleWhat they receive
Experimental: allo-APZ2-DFUExperimentalApplication of IMP on patients wound
Receives: Biological: allo-APZ2-DFU

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of wound surface area reduction

    Percentage of wound surface area reduction at Week 12, or last available post-baseline measurement of weeks 4, 6 or 8, if the Week 12 measurement is missing (last observation carried forward [LOCF]).

    Measured: Week 12, or last available post-baseline measurement of weeks 4, 6 or 8 if the Week 12 measurement is missing.

  2. 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 (16)

  1. Percentage of wound surface area reduction

    Percentage of wound surface area reduction will be evaluated.

    Measured: Weeks 2, 4, 6, 8 and 12 (without LOCF)

  2. Percentage of invisible and visible wound surface area reduction

    Percentage of invisible and visible wound surface area reduction will be evaluated.

    Measured: Weeks 2, 4, 6, 8 and 12 (without LOCF)

  3. Absolute wound surface area reduction

    Absolute wound surface area reduction will be evaluated.

    Measured: Weeks 2, 4, 6, 8 and 12 (without LOCF)

  4. Absolute invisible and visible wound surface area reduction

    Absolute invisible and visible wound surface area reduction will be evaluated.

    Measured: Weeks 2, 4, 6, 8 and 12 (without LOCF)

  5. Assessment of wound infection

    Wound infection will be evaluated.

    Measured: Days 1 and 2, Weeks 1, 2, 4, 6, 6.1, 6.2, 6.3, 8 and 12

  6. Time to first complete wound closure

    Time to first complete wound closure will be evaluated.

    Measured: A priori specification not possible; between baseline and week 12 post baseline

  7. Proportion of patients achieving complete wound closure

    Proportion of patients achieving complete wound closure will be evaluated.

    Measured: Weeks 2, 4, 6, 8 and 12

  8. Time to first 30% reduction of wound surface area

    Time to first 30% reduction of wound surface area will be evaluated.

    Measured: A priori specification not possible; between baseline and week 12 post baseline

  9. Proportion of patients achieving 30% reduction of wound surface area

    Proportion of patients achieving 30% reduction of wound surface area will be evaluated.

    Measured: Weeks 2, 4, 6, 8 and 12

  10. Assessment of wound exudation, epithelialization and formation of granulation tissue

    Wound exudation, epithelialization and formation of granulation tissue will be evaluated.

    Measured: Day 0 and Week 6.1 prior IMP-application, at Weeks 1, 2, 4, 6, 8 and 12

  11. Time to amputation at target leg until Week 12

    Time to amputation at target leg until week 12 will be evaluated.

    Measured: A priori specification not possible; between baseline and week 12 post baseline

  12. Pain assessment as per numerical rating scale (NRS)

    Pain assessment as per numerical rating scale (NRS) will be evaluated.

    Measured: At both Screening Visits, at Days 0, 1 and 2 and at Weeks 1, 2, 4, 6, 6.1, 6.2, 6.3, 8 and 12

  13. Assessment of Quality of life (QoL) using the short form 36 (SF-36) questionnaire

    Quality of life (QoL) using the short form 36 (SF-36) questionnaire will be evaluated.

    Measured: Screening Visit 1, Visit 3, at Weeks 4 and 12

  14. Assessment of Dermatology-specific QoL based on the Dermatology Life Quality Index (DLQI) questionnaire

    Dermatology-specific QoL based on the Dermatology Life Quality Index (DLQI) questionnaire will be evaluated.

    Measured: Screening Visit 1, Visit 3, at Weeks 4 and 12

  15. Physical examination and vital signs

    Physical examination and vital signs will be evaluated.

    Measured: Week 6.1 and Week 12

  16. Time to amputation of target leg until month 12

    Time to amputation of target leg until month 12 will be evaluated.

    Measured: A priori specification not possible; between baseline and month 12 post baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Aug 2017
  2. Study start21 Nov 2017
  3. Primary completion29 Jun 2020
  4. Study completion29 Jun 2020

Resources

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
Single Group Assignment Interventional, single arm, multicenter, phase I/IIa clinical trial
Masking
None (open label)
Enrolment
23 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03267784
Sponsor's protocol ID
allo-APZ2-DFU-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, Dieter K, Niebergall-Roth E, Klingele S, Junger M, Hasslacher C, Daeschlein G, Stemler L, Meyer-Pannwitt U, Schubert K, Klausmann G, Raab T, Goebeler M, Kraft K, Esterlechner J, Schroder HM, Sadeghi S, Ballikaya S, Gasser M, Waaga-Gasser AM, Murphy GF, Orgill DP, Frank NY, Ganss C, Scharffetter-Kochanek K, Frank MH, Kluth MA. Translational development of ABCB5+ dermal mesenchymal stem cells for therapeutic induction of angiogenesis in non-healing diabetic foot ulcers. Stem Cell Res Ther. 2022 Sep 5;13(1):455. doi: 10.1186/s13287-022-03156-9.

    PubMed 36064604

  • 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

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing allo-APZ2-DFU in people with Diabetic Neuropathic Ulcer, run by RHEACELL GmbH & Co. KG at 7 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 11 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 7 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 surface area reduction (time frame: Week 12, or last available post-baseline measurement of weeks 4, 6 or 8 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 NCT03267784, which also lists 2 linked publications.

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.

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