Allogeneic ABCB5-positive Stem Cells for Treatment of CVU

NCT03257098 | Completed Phase 1

• 1 other identifier: allo-APZ2-CVU-II-01
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 9

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.

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 I/IIa

Outcome Measures

Primary Outcomes (2)

• 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 \[LOCF\]).

  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.

  Up to 12 months

Secondary Outcomes (12)

• Percentage of wound size reduction

  Weeks 2, 3, 4, 6, 6.1, 6.2, 8, 10, and 12 (without LOCF);

• Absolute wound size reduction

  Weeks 2, 3, 4, 6, 6.1, 6.2, 8, 10, and 12

• Proportion of patients achieving complete wound closure

  Weeks 2, 3, 4, 6, 8, 10, 12, and at any time point

• Time to first complete wound closure

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

• Proportion of patients achieving 30% wound closure

  Weeks 2, 3, 4, 6, 6.1, 6.2, 8, 10, 12, and at any time point

Study Arms (1)

allo-APZ2-CVU

EXPERIMENTAL

Application of IMP on patients wound

Biological: allo-APZ2-CVU

Interventions

allo-APZ2-CVU BIOLOGICAL

Suspension of ABCB5-positive mesenchymal stem cells

allo-APZ2-CVU

Eligibility Criteria

• Age: 35 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 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.

You may not qualify if:

• 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);

Sponsors & Collaborators

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

Study Sites (9)

Venenzentrum der Dermatologischen und Gefäßchirurgischen Kliniken, Kliniken der Ruhr-Universität Bochum im St. Maria Hilf Krankenhaus

Bochum, 44805, Germany

Location

Universitätsklinikum Erlangen, Hautklinik

Erlangen, 91054, Germany

Location

Klinik und Poliklinik für Hautkrankheiten, Universitätsmedizin Greifswald

Greifswald, 17475, Germany

Location

Klinische Forschung Hamburg GmbH, Dermatologie / Allergologie

Hamburg, 20253, Germany

Location

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

Kiel, 24119, Germany

Location

Universitätsklinikum Münster, Klinik für Hautkrankheiten, Allgemeine Dermatologie und Venerologie

Münster, 48149, Germany

Location

Klinische Forschung Schwerin GmbH

Schwerin, 19055, Germany

Location

Universitätsklinikum Ulm, Klinik für Dermatologie und Allergologie

Ulm, 89081, Germany

Location

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

Würzburg, 97080, Germany

Location

Related Publications (1)

• 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

Varicose Ulcer; Skin Ulcer

Condition Hierarchy (Ancestors)

Varicose Veins; Vascular Diseases; Cardiovascular Diseases; Leg Ulcer; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Andreas Kerstan, Dr.

  Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie, Würzburg

  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: Interventional, single arm, multicenter, phase I/IIa clinical trial

Study Record Dates

• First Submitted: August 17, 2017
• First Posted: August 22, 2017
• Study Start: November 16, 2017
• Primary Completion: June 25, 2020
• Study Completion: June 25, 2020
• Last Updated: September 10, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

DE (9)