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)
Overview
- Phase
- Phase 1
- Intervention
- allo-APZ2-PAOD
- Conditions
- Peripheral Arterial Occlusive Disease
- Sponsor
- RHEACELL GmbH & Co. KG
- Enrollment
- 24
- Locations
- 18
- Primary Endpoint
- Percent change from baseline to week 12 in total wound size of the target leg
- Status
- Terminated
- Last Updated
- 5 years ago
Overview
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.
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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;
Exclusion Criteria
- •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;
Arms & Interventions
allo-APZ2-PAOD
20-30 intramuscular injections, single dose of allo-APZ2-PAOD, 150 - 225 x 10\^6 cells per patient (depending on length of lower leg)
Intervention: allo-APZ2-PAOD
Placebo
20-30 intramuscular injections, vehicle solution (depending on length of lower leg)
Intervention: Placebo
Outcomes
Primary Outcomes
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.
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.
Assessment of adverse event (AE) occurrence
Time Frame: Up to 12 months.
All AEs occurring during the clinical trial will be registered, documented and evaluated.
Secondary Outcomes
- Vital signs: Heart rate at week 12;(Week 12.)
- 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.)
- Number of amputated toes at target leg(A priori specification not possible; between baseline and week 12 post baseline.)
- Time to major amputation at target leg until week 12;(A priori specification not possible; between baseline and week 12 post baseline.)
- Assessment of epithelialization in % of wound area of all relevant ulcers of the target leg(Day 0 prior IMP-application, week 2, 4, 8 and 12.)
- Vital signs: Blood pressure at week 12;(Week 12.)
- Absolute change in total wound size of the target leg(Baseline, week 1, 2, 4, 6, 8 and 12.)
- Assessment of Laboratory values (Hematology) at Week 12:(Week 12.)
- Time to major amputation(A priori specification not possible; between baseline and month 12 post baseline.)
- Ankle-brachial index (ABI) of target leg;(Screening Visit, Baseline, Week 2, 4, 8 and 12.)
- 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(Day 0 prior IMP-application, week 2, 4, 8 and 12.)
- Assessment of quality of life (QoL) using the short form 36 (SF-36) questionnaire(Day 0 prior IMP-application, week 2, 8 and 12.)
- Pain assessment as per numerical rating scale (NRS).(Day 0 prior IMP-application, week 2, 4, 8 and 12.)
- Physical examination at week 12;(Week 12.)
- Vital signs: Body temperature at week 12;(Week 12.)
- Assessment of Laboratory values (Clinical chemistry) at Week 12(Week 12.)