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Peripheral Arterial Occlusive DiseasePhase 1/2NCT03339973

Allogeneic ABCB5-positive Stem Cells for Treatment of PAOD

A Phase 1/2 study testing allo-APZ2-PAOD in people with Peripheral Arterial Occlusive Disease, run by RHEACELL GmbH & Co. KG at 18 sites in 5 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 45 to 85 years
Conditions the study is for
Peripheral Arterial Occlusive Disease
What is being tested?
allo-APZ2-PAOD
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
24 participants
Where
18 sitesin 5 countries
Study dates
5 Mar 2018to 15 May 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 45 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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;
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  • 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.

Who cannot join

  • 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;
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  • 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 with uncontrolled hypertension defined as systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg; For these patients a re-screening and inclusion into the study will be possible after blood pressure is controlled;
  • 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;
  • Skin disorders, unrelated to the ulcer, that are present adjacent to any of the relevant ulcers;
  • Active malignancy or history of malignancy within 5 years prior to study entry;
  • Patients tested positive for human immunodeficiency virus (HIV˗1, HIV-2), Hepatitis B or Hepatitis C;
  • Any known allergies to components of the IMP;
  • Current or previous (within 30 days of enrolment) treatment with another IMP, or participation and/or under follow-up in another clinical trial;
  • Current use of glucocorticoid-medication above Cushing threshold dose (>7.5 mg/d prednisone or equivalent) or any other prohibited medication or therapy;
  • Known abuse of alcohol, drugs, or medicinal products;
  • Patients anticipated to be unwilling or unable to comply with the requirements of the protocol;
  • 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;
  • Pregnant or lactating woman;
  • Employees of the sponsor, or employees or relatives of the investigator.

Trial locations and contacts

18 sites in 5 countries.

18 sites in 5 countries

Germany12 sites
  • Franziskus-Krankenhaus Berlin

    Berlin, 10787

  • Universitätsklinikum "Carl Gustav Carus" der TU Dresden

    Dresden, 01307

  • Helios Weißeritztal-Kliniken Klinikum Freital

    Freital, 01705

  • Universitäres Herzzentrum Hamburg GmbH (UHZ)

    Hamburg, 20246

  • Asklepios Klinikum Harburg

    Hamburg, 21075

  • St. Josefskrankenhaus Heidelberg GmbH

    Heidelberg, 69115

  • Universitätsklinikum Heidelberg

    Heidelberg, 69120

  • SRH Klinikum Karlsbad-Langensteinbach GmbH

    Karlsbad, 76307

  • Universitätsklinikum Schleswig-Holstein, Campus Kiel

    Kiel, 24105

  • Universitätsklinikum Mannheim

    Mannheim, 68167

  • Klinikum der Universität München, Campus Innenstadt

    München, 80336

  • Medizinisches Versorgungszentrum der Barmherzigen Brüder Trier

    Trier, 54292

Other trials in Germany

Austria3 sites
  • LKH-Univ. Klinikum Graz

    Graz, 8036

  • Konventhospital der Barmherzigen Brüder Linz

    Linz, 4021

  • Hanusch-Krankenhaus Wien

    Vienna, 1140

Other trials in Austria

Czechia1 site
  • Krajská zdravotní a.s. - Masarykova nemocnice v Ústí nad Labem, o.z.

    Ústí nad Labem, 401 13

Other trials in Czechia

Poland1 site
  • Szpital Kliniczny Przemienienia Pańskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu

    Poznan, 48-848

Other trials in Poland

United Kingdom1 site
  • East Surrey Hospital, Surrey and Sussex Healthcare NHS Trust

    Redhill, RH1 5RH

Other trials in United Kingdom

About this study

Official title: A Randomised, Placebo-controlled, Double-blind, Interventional, Multicenter, Phase I/IIa Clinical Trial to Investigate the Efficacy and Safety of Allo-APZ2-PAOD for the Treatment of Peripheral Arterial Occlusive Disease (PAOD)

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.

Read the detailed description

This is an interventional, randomised, placebo-controlled, double-blind phase I/IIa clinical trial to investigate the efficacy and safety of allo-APZ2-PAOD for the treatment of Peripheral Arterial Occlusive Disease patients with non-healing ulcers. The allogeneic investigational product allo-APZ2-PAOD contains skin-derived ABCB5-positive mesenchymal stem cells isolated from skin tissue of healthy donors and stored in a donor cell bank.

Patients are followed up for efficacy for 12 weeks by clinical visits at the clinical trial sites to monitor wound healing. The wound healing process of all relevant ulcers will be documented by standardized photography and the quality of the wound healing process will be assessed.

Pain will be assessed using a numerical rating scale and quality of life will be investigated with a standardized and validated questionnaire. To assess long-term safety of allo-APZ2-PAOD three follow-up visits at Months 6, 9 and 12 post IMP applications are included. An unblinded external Independent Data Monitoring Committee (IDMC) will continuously monitor safety throughout the study.

Being tested
allo-APZ2-PAOD, Placebo
Keywords
Peripheral Arterial Occlusive Disease, ABCB5, allogeneic, mesenchymal stem cells, advanced therapy medicinal product, somatic cell therapy, phase I/IIa, non-healing ulcers
Medical subject headings
Peripheral Arterial Occlusive Disease 1

What participants receive

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

  • allo-APZ2-PAODBiological

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

  • PlaceboDrug

    Solution for injection in pre-filled syringe

Study groups in NCT03339973
Study groupRoleWhat they receive
allo-APZ2-PAODExperimental20-30 intramuscular injections, single dose of allo-APZ2-PAOD, 150 - 225 x 10^6 cells per patient (depending on length of lower leg)
Receives: Biological: allo-APZ2-PAOD
PlaceboPlacebo comparator20-30 intramuscular injections, vehicle solution (depending on length of lower leg)
Receives: Drug: Placebo

What is being measured

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

  1. 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.

    Measured: Week 12, or last available post-baseline measurement 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 (17)
  1. Time to total healing of all relevant ulcers at target leg

    Time to total healing of all relevant ulcers at target leg will be evaluated.

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

  2. Percent change in total wound size of the target leg

    Percent change in total wound size of the target leg will be evaluated.

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

  3. Absolute change in total wound size of the target leg

    Absolute change in total wound size of the target leg will be evaluated.

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

  4. Ankle-brachial index (ABI) of target leg;

    Ankle-brachial index (ABI) of target leg will be evaluated.

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

  5. Number of amputated toes at target leg

    Number of amputated toes at target leg will be registered, documented and evaluated.

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

  6. Time to major amputation at target leg until week 12;

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

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

  7. Assessment of epithelialization in % of wound area of all relevant ulcers of the target leg

    Epithelialization of all relevant ulcers of the target leg will be evaluated by the investigator based on image analysis for each ulcer individually.

    Measured: Day 0 prior IMP-application, week 2, 4, 8 and 12.

  8. Assessment of further wound healing parameters: formation of granulation tissue in % of wound area and wound exudation of all relevant ulcers of the target leg

    Formation of granulation tissue in % of wound area will be assessed by the investigator based on image analysis for each ulcer individually.

    Wound exudation of all relevant ulcers of the target leg will be evaluated as high-moderate-low based on amounts of fluid on the wound.

    Measured: Day 0 prior IMP-application, week 2, 4, 8 and 12.

  9. 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.

    The SF-36 questionnaire is a self-administered questionnaire containing 36 items.

    It measures health on eight multi-item dimensions, covering functional status, well being, and overall evaluation of health.

    Measured: Day 0 prior IMP-application, week 2, 8 and 12.

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

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

    Measured: Day 0 prior IMP-application, week 2, 4, 8 and 12.

  11. Physical examination at week 12;

    A full physical examination will be performed at week 12 and abnormal physical examination results will be evaluated and reported as AEs.

    Measured: Week 12.

  12. Vital signs: Body temperature at week 12;

    Body temperature at week 12 will be evaluated.

    Measured: Week 12.

  13. Vital signs: Blood pressure at week 12;

    Blood pressure at week 12 will be evaluated.

    Measured: Week 12.

  14. Vital signs: Heart rate at week 12;

    Heart rate at week 12 will be evaluated.

    Measured: Week 12.

  15. Assessment of Laboratory values (Hematology) at Week 12:

    The Hematology values will be measured and evaluated at Week 12

    Measured: Week 12.

  16. Assessment of Laboratory values (Clinical chemistry) at Week 12

    The clinical chemistry values will be measured and evaluated at Week 12.

    Measured: Week 12.

  17. Time to major amputation

    Time to major amputation 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 posted13 Nov 2017
  2. Study start5 Mar 2018
  3. Primary completion15 May 2020
  4. Study completion15 May 2020

Why it stopped: Very slow recruitment of patients and the current COVID-19 pandemic situation.

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
Randomised
Intervention model
Parallel groups
Model description
Randomized, placebo-controlled, double-blind, interventional, multicenter, phase I/IIa clinical trial
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03339973
Sponsor's protocol ID
allo-APZ2-PAOD-II-01
Status last verified
Jun 2020
First submitted
11 Oct 2017
Last updated
29 Jun 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing allo-APZ2-PAOD in people with Peripheral Arterial Occlusive Disease, run by RHEACELL GmbH & Co. KG at 18 sites in 5 countries.

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 13 inclusion and 27 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: stopped early, as of the sponsor's last update on 29 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in Germany, Austria, Czechia, Poland, United Kingdom. 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. Some participants in this study may receive a placebo. 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 was stopped early (reason given: Very slow recruitment of patients and the current COVID-19 pandemic situation.). Results are not available in the source record.

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?

Percent change from baseline to week 12 in total wound size of the target leg (time frame: Week 12, or last available post-baseline measurement 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?
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 29 Jun 2020.

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