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

This study is currently recruiting participants.
Verified November 2017 by RHEACELL GmbH & Co. KG
Sponsor:
ClinicalTrials.gov Identifier:
NCT03267784
First Posted: August 30, 2017
Last Update Posted: November 17, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
FGK Clinical Research GmbH
TICEBA GmbH
Granzer Regulatory Consulting & Services
Information provided by (Responsible Party):
RHEACELL GmbH & Co. KG
  Purpose
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 the medicinal product to be studied after one single application on the wound surface of patients with diabetic neuropathic ulcer.

Condition Intervention Phase
Diabetic Neuropathic Ulcer Biological: allo-APZ2-DFU Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Intervention Model Description:
Single Group Assignment Interventional, single arm, multicenter, phase I/IIa clinical trial
Masking: None (Open Label)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by RHEACELL GmbH & Co. KG:

Primary Outcome Measures:
  • Percentage of wound surface area reduction [ Time Frame: Week 12, or last available post-baseline measurement of weeks 4 or 8 if the Week 12 measurement is missing. ]
    Percentage of wound surface area reduction at Week 12, or last available post-baseline measurement of weeks 4 or 8 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.


Secondary Outcome Measures:
  • Percentage of wound surface area reduction [ Time Frame: Weeks 2, 4, 8 and 12 (without LOCF) ]
    Percentage of wound surface area reduction will be evaluated.

  • Percentage of invisible and visible wound surface area reduction [ Time Frame: Weeks 2, 4, 8 and 12 (without LOCF) ]
    Percentage of invisible and visible wound surface area reduction will be evaluated.

  • Absolute wound surface area reduction [ Time Frame: Weeks 2, 4, 8 and 12 (without LOCF) ]
    Absolute wound surface area reduction will be evaluated.

  • Absolute invisible and visible wound surface area reduction [ Time Frame: Weeks 2, 4, 8 and 12 (without LOCF) ]
    Absolute invisible and visible wound surface area reduction will be evaluated.

  • Assessment of wound infection [ Time Frame: Days 1 and 2, Weeks 1, 2, 4, 8 and 12 ]
    Wound infection will be evaluated.

  • Time to first complete wound closure [ Time Frame: A priori specification not possible; between baseline and week 12 post baseline ]
    Time to first complete wound closure will be evaluated.

  • Proportion of patients achieving complete wound closure [ Time Frame: Weeks 2, 4, 8 and 12 ]
    Proportion of patients achieving complete wound closure will be evaluated.

  • Time to first 30% reduction of wound surface area [ Time Frame: A priori specification not possible; between baseline and week 12 post baseline ]
    Time to first 30% reduction of wound surface area will be evaluated.

  • Proportion of patients achieving 30% reduction of wound surface area [ Time Frame: Weeks 2, 4, 8 and 12 ]
    Proportion of patients achieving 30% reduction of wound surface area will be evaluated.

  • Assessment of wound exudation, epithelialization and formation of granulation tissue [ Time Frame: Day 0 prior IMP-application, at Weeks 1, 2, 4, 8 and 12 ]
    Wound exudation, epithelialization and formation of granulation tissue will be evaluated.

  • Time to amputation at target leg until week 12 [ Time Frame: A priori specification not possible; between baseline and week 12 post baseline ]
    Time to amputation at target leg until week 12 will be evaluated.

  • Pain assessment as per numerical rating scale (NRS) [ Time Frame: At both Screening Visits, at Days 0, 1 and 2 and at Weeks 1, 2, 4, 8 and 12 ]
    Pain assessment as per numerical rating scale (NRS) will be evaluated.

  • Assessment of Quality of life (QoL) using the short form 36 (SF-36) questionnaire [ Time Frame: Screening Visit 1, Visit 3, at Weeks 4 and 12 ]
    Quality of life (QoL) using the short form 36 (SF-36) questionnaire will be evaluated.

  • Assessment of Dermatology-specific QoL based on the Dermatology Life Quality Index (DLQI) questionnaire [ Time Frame: Screening Visit 1, Visit 3, at Weeks 4 and 12 ]
    Dermatology-specific QoL based on the Dermatology Life Quality Index (DLQI) questionnaire will be evaluated.

  • Physical examination and vital signs [ Time Frame: Week 12 ]
    Physical examination and vital signs will be evaluated.

  • Time to amputation of target leg until month 12 [ Time Frame: A priori specification not possible; between baseline and month 12 post baseline ]
    Time to amputation of target leg until month 12 will be evaluated.


Estimated Enrollment: 37
Anticipated Study Start Date: November 2017
Estimated Study Completion Date: April 2019
Estimated Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Experimental: allo-APZ2-DFU
Application of IMP on patients wound
Biological: allo-APZ2-DFU
Suspension of ABCB5-positive mesenchymal stem cells

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 IMP incorporating the ABCB5-positive MSCs will then be applied on the wound surface of DFU.

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 two weeks after 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 post IMP applications are included.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female patients aged 18 to 85 years;
  2. 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 3 months before visit 1;
  3. The presence of diabetic neuropathic ulcers "malum perforans" not involving subcutis (Grade I according to Wagner) at plantar site of the foot diagnosed by ABI ≥0.8, 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;
  4. At Screening Visit 1 and 2 the wound surface area should be between 1 and 50 cm² measured by using a scaled measuring sensor in combination with digital image analysis;
  5. The ulcer's surface area should be (mostly) free from callus or necrotic tissue;
  6. Patients suffering from two or more ulcers at the same extremity, as long as these ulcers are separated by a minimum bridge of 1 cm of healthy tissue;
  7. Patients are willing and able to wear therapeutic shoes that are especially designed for patients with a diabetic neuropathic foot;
  8. Body mass index (BMI) between 20 and 40 kg/m²;
  9. Patients understand the nature of the procedure and are providing written informed consent prior to any clinical trial procedure;
  10. Women of childbearing potential must have a negative blood pregnancy test at Visit 1;
  11. Women of childbearing potential must be willing to use highly effective contraceptive methods during the course of the clinical trial.

Exclusion Criteria:

  1. Presence of Charcot foot;
  2. Clinical signs of active osteomyelitis in the last three months;
  3. Active wet gangrenous tissue;
  4. Infection of the target ulcer requiring treatment as judged clinically;
  5. Presence of an ulcer Grade ≥3 according to Wagner on the same foot as target ulcer;
  6. Patients who are currently receiving dialysis;
  7. Peripheral arterial occlusive disease (PAOD) including claudication with need of treatment;
  8. Ulcers due to non-diabetic etiology;
  9. Prior surgical procedures such as bypass or mesh-graft treatment within 2 months prior to IMP application;
  10. Acute deep vein thrombosis (maximum 30 days from diagnosis) or a still untreated deep vein thrombosis;
  11. Any chronic dermatological disorders diagnosed at the investigator's discretion;
  12. Skin disorders, unrelated to the ulcer, that are present adjacent to the target wound;
  13. 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;
  14. 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;
  15. Current use of steroid medication above Cushing threshold dose (>7.5 mg/d prednisone or equivalent);
  16. Known abuse of alcohol, drugs, or medicinal products;
  17. Patients anticipated to be unwilling or unable to comply with the requirements of the protocol;
  18. Pregnant or lactating women;
  19. Patients infected with the human immunodeficiency virus (HIV 1&2);
  20. Any known allergies to components of the IMP or concomitant medication;
  21. Current or previous (within 30 days of enrollment) treatment with another IMP, or participation and/or under follow-up in another 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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03267784


Contacts
Contact: Christoph Ganss, Dr. med. +49 6221 71833 ext 0 office@rheacell.com
Contact: Kathrin Dieter +49 6221 71833 ext 0 kathrin.dieter@rheacell.com

Locations
Germany
Universitätsmedizin Greifswald; Klinik und Poliklinik für Hautkrankheiten Recruiting
Greifswald, Germany, 17475
Principal Investigator: Georg Daeschlein, Dr. med.         
St. Josefskrankenhaus Heidelberg GmbH; Klinische Studienabteilung Recruiting
Heidelberg, Germany, 69115
Principal Investigator: Christoph Hasslacher, Dr. med.         
Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Würzburg Recruiting
Würzburg, Germany, 97080
Contact: Andreas Kerstan, Dr. med.         
Sponsors and Collaborators
RHEACELL GmbH & Co. KG
FGK Clinical Research GmbH
TICEBA GmbH
Granzer Regulatory Consulting & Services
Investigators
Principal Investigator: Andreas Kerstan, Dr. Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie, Würzburg, Germany
  More Information

Responsible Party: RHEACELL GmbH & Co. KG
ClinicalTrials.gov Identifier: NCT03267784     History of Changes
Other Study ID Numbers: allo-APZ2-DFU-II-01
First Submitted: August 17, 2017
First Posted: August 30, 2017
Last Update Posted: November 17, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by RHEACELL GmbH & Co. KG:
diabetic neuropathic ulcer
ABCB5
allogeneic
mesenchymal stem cells
skin ulcer
advanced therapy medicinal product
somatic cell therapy
phase I/IIa
Diabetic Foot Ulcer

Additional relevant MeSH terms:
Ulcer
Pathologic Processes