peripheral arterial occlusive disease MedDRA version: 21.1 Level: PT Classification code 10062585 Term: Peripheral arterial occlusive disease System Organ Class: 10047065 - Vascular disorders
Conditions
Interventions
Product Name: allo-APZ2-PAOD
Product Code: allo-APZ2-PAOD
Pharmaceutical Form: Suspension for injection in pre-filled syringe
Current Sponsor code: T202-3
Other descriptive name: Allogeneic skin-deriv
Sponsors
RHEACELL GmbH & Co. KG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patients aged 45 to 85 years; 2. 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; 3. 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 6 months; 4. 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; 5. Positive vote of the Advisory Board on the suitability of the wound(s) for enrolment, based on the wound photographs; 6. Patients not eligible for surgical/interventional reconstruction due to technical limitations or comorbidity; 7. No evidence of wound healing after standard of care treatment for at least 1 week before screening; 8. 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; 9. If patients are hypertensive, they have to be treated with anti-hypertensive medication according to the applicable guideline; 10. Body mass index (BMI) between 20 and 40 kg/m²; 11. Women of childbearing potential must have a negative blood pregnancy test at screening; 12. Women of childbearing potential and their partner must be willing to use highly effective contraceptive methods during the course of the clinical trial; 13. 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 informed consent form (ICF). Subject agrees to comply with the protocol-mandated procedures and visits. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 56
Exclusion criteria
Exclusion criteria: 1. Patients with skin lesions of leading venous origin or patients suffering from a vasculitis; 2. Patients with thrombangiitis obliterans; 3. Diabetic patients in whom the leading cause for lesions is microangiopathy or neuropathy; 4. Patients with high grade obstruction (= 70 %) in the aorto-iliac segment or the common femoral artery as leading cause for skin lesions; 5. Patients with ulcers at the heel due to immobility; 6. Patients with osteomyelitis at ulceration; 7. Patients medicated with vitamin K antagonist, if treatment cannot be stopped before injection or bridged according to applicable guidelines; 8. Patients medicated with DOACs, if they cannot be withheld for 24 hours before injection; 9. 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); 10. Patients for whom major amputation is scheduled on target leg; 11. 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; 12. Patients who had a myocardial infarction during 3 months before screening; 13. Patients with uncontrolled infection at any of the relevant ulcers; 14. Patients with uncontrolled acute or chronic infection with systemic symptoms; 15. Known serious disease with life expectancy of less than 1 year; 16. Any chronic dermatological disorders diagnosed at the investigator’s discretion; 17. Skin disorders, unrelated to the ulcer, that are present adjacent to any of the relevant ulcers; 18. Active malignancy or history of malignancy within 5 years prior to study entry; 19. Patients tested positive for human immunodeficiency virus (HIV-1, HIV-2), Hepatitis B or Hepatitis C; 20. Any known allergies to components of the IMP; 21. Current or previous (within 30 days of enrolment) treatment with another IMP, or participation and/or under follow-up in another clinical trial; 22. Current use of glucocorticoid-medication above Cushing threshold dose (>7.5 mg/d prednisone or equivalent) or any other prohibited medication or therapy; 23. Known abuse of alcohol, drugs, or medicinal products; 24. Patients anticipated to be unwilling or unable to comply with the requirements of the protocol; 25. 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; 26. Pregnant or lactating woman; 27. Employees of the sponsor, or employees or relatives of the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The aim of this clinical trial is to investigate the efficacy (by monitoring the wound size reduction of PAOD-related clinically relevant ulcers) and safety (by monitoring adverse events [AEs]) of one dose of allo-APZ2-PAOD administered intramuscularly into an affected lower leg of patients with PAOD. ;Secondary Objective: Not applicable;Primary end point(s): 1. Primary efficacy endpoint: Percent change from baseline to week 12 in total wound size of the target leg. The total wound size of the target leg is calculated as sum of the wound sizes of all relevant ulcers of the target leg. 2. Primary safety endpoint: Adverse events.;Timepoint(s) of evaluation of this end point: 1. Week 12, or last available post-baseline measurement of weeks 6 or 8 if the Week 12 measurement is missing. 2. During all patient visits except screening. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoints: 1. Time to total healing of all relevant ulcers at target leg; 2. Percent change in total wound size of the target leg; 3. Absolute change in total wound size of the target leg; 4. Ankle-brachial index (ABI) of target leg; 5. Number of amputated toes at target leg; 6. Time to major amputation at target leg until week 12; 7. Epithelialization assessment of all relevant ulcers of the target leg; 8. Assessment of formation of granulation tissue and wound exudation of all relevant ulcers of the target leg; 9. Assessment of quality of life (QoL) using the short form 36 (SF-36) questionnaire; 10. Pain assessment as per numerical rating scale (NRS). Secondary safety endpoints: 11. Physical examination and vital signs at week 12; 12. Laboratory assessments at Week 12 13. Time to major amputation.;Timepoint(s) of evaluation of this end point: Secondary efficacy endpoints: 1. A priori specification not possible; between baseline and week 12 post baseline; 2. Baseline, week 1, 2, 4, 6, and 8; 3. Baseline, week 1, 2, 4, 6, 8 and 12; 4. Screening Visit, Baseline, Week 2, 4, 8 and 12; 5. A priori specification not possible; between baseline and week 12 post baseline. 6. A priori specification not possible; between baseline and week 12 post baseline. 7. Day 0 prior IMP-application, week 2, 4, 8 and 12; 8. Day 0 prior IMP-application, week 2, 4, 8 and 12; 9. Day 0 prior IMP-application, week 2, 8 and 12; 10. Day 0 prior IMP-application, week 2, 4, 8 and 12; Secondary safety endpoints: 11. Week 12; 12. Week 12; 13. A priori specification not possible; between baseline and month 12 post baseline. | — |
Countries
Austria, Czech Republic, Germany, Poland, United Kingdom
Contacts
Public ContactInformation Office
RHEACELL GmbH & Co. KG
Outcome results
None listed