Allogeneic ABCB5-positive Stem Cells for Treatment of PAOD

NCT03339973 | Terminated Phase 1 DMC

• 1 other identifier: allo-APZ2-PAOD-II-01
• Study Type: interventional
• Target: 24
• Locations: 5 countries
• Sites: 18

Brief Summary

The aim of this clinical trial is to investigate the efficacy (by monitoring the wound size reduction of Peripheral Arterial Occlusive Disease-related clinically relevant ulcers) and safety (by monitoring adverse events) of one dose of allo-APZ2-PAOD administered intramuscularly into an affected lower leg of patients with Peripheral Arterial Occlusive Disease.

Conditions

Peripheral Arterial Occlusive Disease

Keywords

Peripheral Arterial Occlusive Disease; ABCB5; allogeneic; mesenchymal stem cells; advanced therapy medicinal product; somatic cell therapy; phase I/IIa; non-healing ulcers

Outcome Measures

Primary Outcomes (2)

• Percent change from baseline to week 12 in total wound size of the target leg

  Percent change from baseline to week 12 in total wound size of the target leg will be evaluated. The total wound size of the target leg is calculated as sum of the wound sizes of all relevant ulcers of the target leg.

  Week 12, 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 (17)

• Time to total healing of all relevant ulcers at target leg

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

• Percent change in total wound size of the target leg

  Baseline, week 1, 2, 4, 6, and 8.

• Absolute change in total wound size of the target leg

  Baseline, week 1, 2, 4, 6, 8 and 12.

• Ankle-brachial index (ABI) of target leg;

  Screening Visit, Baseline, Week 2, 4, 8 and 12.

• Number of amputated toes at target leg

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

Study Arms (2)

allo-APZ2-PAOD

EXPERIMENTAL

20-30 intramuscular injections, single dose of allo-APZ2-PAOD, 150 - 225 x 10\^6 cells per patient (depending on length of lower leg)

Biological: allo-APZ2-PAOD

Placebo

PLACEBO COMPARATOR

20-30 intramuscular injections, vehicle solution (depending on length of lower leg)

Drug: Placebo

Interventions

allo-APZ2-PAOD BIOLOGICAL

Suspension of ABCB5-positive mesenchymal stem cells in pre-filled syringe

allo-APZ2-PAOD

Placebo DRUG

Solution for injection in pre-filled syringe

Placebo

Eligibility Criteria

• Age: 45 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 45 to 85 years;
• Patients having PAOD clinically confirmed (maximal systolic ankle pressures ≤ 70 mmHg or systolic toe pressures ≤ 50 mmHg or transcutaneous partial oxygen pressures (tcp02) ≤ 30 mmHg in supine position) as Rutherford category 5 in at least one lower extremity;
• Angiography results (DSA, CTA or MRA) for the localization of the high-grade obstruction of an artery of the affected leg (≥ 70 %) that is the leading cause for the ulceration are present and not older than 3 months;
• One or more clinically relevant and quantifiable ulcer(s) below the ankle with a minimum size of 0.5 cm² per ulcer and a maximum wound size of 20 cm² for all ulcers together;
• Positive vote of the Advisory Board on the suitability of the wound(s) for enrolment, based on the wound photographs;
• Patients not eligible for surgical/interventional reconstruction due to technical limitations or comorbidity;
• No evidence of wound healing after standard of care treatment for at least 1 week before screening;
• In Patients suffering from 2 or more ulcers at the same extremity, these ulcers must be separated by a minimum bridge of 1 cm of epithelialized skin;
• If patients are hypertensive, they have to be treated with anti-hypertensive medication according to the applicable guideline;
• Body mass index (BMI) between 20 and 40 kg/m²;
• Women of childbearing potential must have a negative blood pregnancy test at screening;
• Women of childbearing potential and their partner must be willing to use highly effective contraceptive methods during the course of the clinical trial;
• Patients must be able to consent, have been informed of the nature, the scope and the relevance of the study, voluntarily agree to participation and the study's provisions, and have duly signed the ICF. Subject agrees to comply with the protocol-mandated procedures and visits.

You may not qualify if:

• Patients with skin lesions of leading venous origin or patients suffering from a vasculitis;
• Patients with thrombangiitis obliterans;
• Diabetic patients in whom the leading cause for lesions is microangiopathy or neuropathy;
• Patients with high grade obstruction (≥ 70 %) in the aorto-iliac segment or the common femoral artery as leading cause for skin lesions;
• Patients with ulcers at the heel due to immobility;
• Patients with osteomyelitis at ulceration;
• Patients medicated with vitamin K antagonist, if treatment cannot be stopped before injection or bridged according to applicable guidelines;
• Patients medicated with DOACs, if they cannot be withheld for 24 hours before injection;
• Surgical/interventional reconstruction during 1 week before screening (not applicable if it becomes evident during reconstruction that revascularization is not successful: these patients can be included immediately);
• Patients for whom major amputation is scheduled on target leg;
• Patients who had a myocardial infarction during 3 months before screening;
• Patients with uncontrolled infection at any of the relevant ulcers;
• Patients with uncontrolled acute or chronic infection with systemic symptoms;
• Known serious disease with life expectancy of less than 1 year;
• Any chronic dermatological disorders diagnosed at the investigator's discretion;

Sponsors & Collaborators

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

Study Sites (18)

LKH-Univ. Klinikum Graz

Graz, 8036, Austria

Location

Konventhospital der Barmherzigen Brüder Linz

Linz, 4021, Austria

Location

Hanusch-Krankenhaus Wien

Vienna, 1140, Austria

Location

Krajská zdravotní a.s. - Masarykova nemocnice v Ústí nad Labem, o.z.

Ústí nad Labem, 401 13, Czechia

Location

Franziskus-Krankenhaus Berlin

Berlin, 10787, Germany

Location

Universitätsklinikum "Carl Gustav Carus" der TU Dresden

Dresden, 01307, Germany

Location

Helios Weißeritztal-Kliniken Klinikum Freital

Freital, 01705, Germany

Location

Universitäres Herzzentrum Hamburg GmbH (UHZ)

Hamburg, 20246, Germany

Location

Asklepios Klinikum Harburg

Hamburg, 21075, Germany

Location

St. Josefskrankenhaus Heidelberg GmbH

Heidelberg, 69115, Germany

Location

Universitätsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

SRH Klinikum Karlsbad-Langensteinbach GmbH

Karlsbad, 76307, Germany

Location

Universitätsklinikum Schleswig-Holstein, Campus Kiel

Kiel, 24105, Germany

Location

Universitätsklinikum Mannheim

Mannheim, 68167, Germany

Location

Klinikum der Universität München, Campus Innenstadt

München, 80336, Germany

Location

Medizinisches Versorgungszentrum der Barmherzigen Brüder Trier

Trier, 54292, Germany

Location

Szpital Kliniczny Przemienienia Pańskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu

Poznan, 48-848, Poland

Location

East Surrey Hospital, Surrey and Sussex Healthcare NHS Trust

Redhill, RH1 5RH, United Kingdom

Location

MeSH Terms

Conditions

Peripheral Arterial Occlusive Disease 1

Study Officials

• Oliver Müller, Prof. Dr.

  Christian-Albrechts-Universität zu Kiel, Klinik für Innere Medizin III Kardiologie, Angiologie und internistische Intensivmedizin, Kiel, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, placebo-controlled, double-blind, interventional, multicenter, phase I/IIa clinical trial

Study Record Dates

• First Submitted: October 11, 2017
• First Posted: November 13, 2017
• Study Start: March 5, 2018
• Primary Completion: May 15, 2020
• Study Completion: May 15, 2020
• Last Updated: June 29, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

PL (1); AU (3); DE (12); GB (1); CZ (1)