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

NCT03267784 | Completed Phase 1

• 1 other identifier: allo-APZ2-DFU-II-01
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 7

Brief 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 diabetic neuropathic ulcer.

Conditions

Diabetic Neuropathic Ulcer

Keywords

diabetic neuropathic ulcer; ABCB5; allogeneic; mesenchymal stem cells; skin ulcer; advanced therapy medicinal product; somatic cell therapy; phase I/IIa; Diabetic Foot Ulcer

Outcome Measures

Primary Outcomes (2)

• 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 \[LOCF\]).

  Week 12, or last available post-baseline measurement of weeks 4, 6 or 8 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.

  Up to 12 months

Secondary Outcomes (16)

• Percentage of wound surface area reduction

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

• Percentage of invisible and visible wound surface area reduction

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

• Absolute wound surface area reduction

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

• Absolute invisible and visible wound surface area reduction

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

• Assessment of wound infection

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

Study Arms (1)

Experimental: allo-APZ2-DFU

EXPERIMENTAL

Application of IMP on patients wound

Biological: allo-APZ2-DFU

Interventions

allo-APZ2-DFU BIOLOGICAL

Suspension of ABCB5-positive mesenchymal stem cells

Experimental: allo-APZ2-DFU

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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.

You may not qualify if:

• 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;
• 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);

Sponsors & Collaborators

• RHEACELL GmbH & Co. KG: lead
• FGK Clinical Research GmbH: collaborator
• Ticeba GmbH: collaborator
• Granzer Regulatory Consulting & Services: collaborator

Study Sites (7)

Universitätsmedizin Greifswald; Klinik und Poliklinik für Hautkrankheiten

Greifswald, 17475, Germany

Location

St. Josefskrankenhaus Heidelberg GmbH; Klinische Studienabteilung

Heidelberg, 69115, Germany

Location

Diabetologikum Raab, Privatärztliche Facharztpraxis

Kassel, 34131, Germany

Location

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

Kronshagen, 24119, Germany

Location

Studienambulanz Leipzig, medamed GmbH

Leipzig, 04107, Germany

Location

Diabetologikum Ludwigshafen, Gemeinschaftspraxis

Ludwigshafen, 67059, Germany

Location

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

Würzburg, 97080, Germany

Location

Related Publications (2)

• 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.

  PMID: 36064604 DERIVED

• 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.

  PMID: 33011075 DERIVED

MeSH Terms

Conditions

Skin Ulcer; Diabetic Foot

Condition Hierarchy (Ancestors)

Skin Diseases; Skin and Connective Tissue Diseases; Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Foot Ulcer; Leg Ulcer; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Diabetic Neuropathies

Study Officials

• Andreas Kerstan, Dr.

  Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie, Würzburg, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single Group Assignment Interventional, single arm, multicenter, phase I/IIa clinical trial

Study Record Dates

• First Submitted: August 17, 2017
• First Posted: August 30, 2017
• Study Start: November 21, 2017
• Primary Completion: June 29, 2020
• Study Completion: June 29, 2020
• Last Updated: September 10, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

DE (7)