An Interventional, Multicenter, Single Arm, Phase I/IIa Clinical Trial to Investigate the Efficacy and Safety of Allo-APZ2-DFU on Wound Healing of Diabetic Neuropathic Ulcer (DFU)
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Diabetic Neuropathic Ulcer
- Sponsor
- RHEACELL GmbH & Co. KG
- Enrollment
- 23
- Locations
- 7
- Primary Endpoint
- Percentage of wound surface area reduction
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
The aim of this clinical trial is to investigate the efficacy (by monitoring the wound surface area reduction of Diabetic Foot Ulcers) and safety (by monitoring adverse events) of two doses of the allogeneic investigational medicinal product "allo-APZ2-DFU" topically administered to the wound matrix of patients with diabetic neuropathic ulcer.
Detailed Description
This is an interventional, single arm, phase I/IIa clinical trial to investigate the efficacy and safety of allogeneic ABCB5-positive mesenchymal stem cells (MSCs) on wound healing in patients with diabetic neuropathic ulcer. Allogeneic MSCs will be isolated ex vivo and will be expanded in vitro. The Investigational medicinal product (IMP) containing the ABCB5-positive MSCs will then be applied two times (at Visit 3 and six weeks later, at Visit 10) on the wound surface of DFU. Patients are followed up for efficacy for a period of three months starting after the first IMP application which allows to distinguish actual wound healing from transient wound coverage. The wound healing process will be documented by standardized photography. The wound size reduction evaluation will start two weeks after the first IMP application. The quality of the wound healing process will be assessed on the basis of formation of granulation tissue, epithelialization and wound exudation. Pain will be assessed using a numerical rating scale and quality of life will be investigated with standardized and validated questionnaires. To assess long-term safety of allo-APZ2-DFU three follow-up visits at Months 6, 9 and 12 after the first IMP application are included.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female patients aged 18 to 85 years;
- •Patients with an existing diagnosis of diabetic mellitus Type 2, evaluated by blood test \[HbA1c\] \< 11%) at the Screening visit (Visit 1). The HbA1c value at visit 1 should not vary more than 1.5% (absolute range) compared to a HbA1c value that was previously measured 1 to 6 months before visit 1;
- •The presence of diabetic neuropathic ulcers "malum perforans" (Grade I and II according to Wagner) at plantar site of the foot diagnosed by ABI ≥0.7, without claudication, or TcPO2 \>40 mmHg or doppler ultrasonography (at the discretion of the investigator) to exclude significant arterial diseases and critical limb ischemia, and a diabetic neuropathy test using a 128 Hz vibration tuning fork according to Rydel-Seiffer (as described by Guideline "Nationale Versorgungsleitlinie - Neuropathie bei Diabetes im Erwachsenenalter"). If the ABI is \>1.3, an additional doppler ultrasonography must be performed to exclude a PAOD masked by media sclerosis;
- •At Screening Visit 1 and 2 the wound surface area of the target ulcer should be between 1 and 50 cm2 measured by using a scaled measuring sensor in combination with digital image analysis;
- •The ulcer's surface area should be (mostly) free from callus or necrotic tissue;
- •If patients are suffering from two or more ulcers at the same extremity, the target ulcer has to be separated by a minimum bridge of 1 cm of healthy tissue from other ulcers;
- •Patients are willing and able to wear therapeutic shoes that are especially designed for patients with a diabetic neuropathic foot;
- •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;
Exclusion Criteria
- •Presence of acute Charcot foot;
- •Clinical signs of active osteomyelitis in the last three months;
- •Active wet gangrenous tissue;
- •Infection of the target ulcer requiring treatment as judged clinically;
- •Presence of an ulcer Grade ≥3 according to Wagner on the same foot as target ulcer;
- •Patients who are currently receiving dialysis;
- •Peripheral arterial occlusive disease (PAOD) including claudication with need of treatment;
- •Ulcers due to non-diabetic etiology;
- •Prior surgical procedures such as bypass or mesh-graft treatment within 2 months prior to IMP application;
- •Acute deep vein thrombosis (maximum 30 days from diagnosis) or a still untreated deep vein thrombosis;
Outcomes
Primary Outcomes
Percentage of wound surface area reduction
Time Frame: Week 12, or last available post-baseline measurement of weeks 4, 6 or 8 if the Week 12 measurement is missing.
Percentage of wound surface area reduction at Week 12, or last available post-baseline measurement of weeks 4, 6 or 8, if the Week 12 measurement is missing (last observation carried forward \[LOCF\]).
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
- Time to first 30% reduction of wound surface area(A priori specification not possible; between baseline and week 12 post baseline)
- Assessment of Dermatology-specific QoL based on the Dermatology Life Quality Index (DLQI) questionnaire(Screening Visit 1, Visit 3, at Weeks 4 and 12)
- Absolute wound surface area reduction(Weeks 2, 4, 6, 8 and 12 (without LOCF))
- Assessment of wound exudation, epithelialization and formation of granulation tissue(Day 0 and Week 6.1 prior IMP-application, at Weeks 1, 2, 4, 6, 8 and 12)
- Pain assessment as per numerical rating scale (NRS)(At both Screening Visits, at Days 0, 1 and 2 and at Weeks 1, 2, 4, 6, 6.1, 6.2, 6.3, 8 and 12)
- Absolute invisible and visible wound surface area reduction(Weeks 2, 4, 6, 8 and 12 (without LOCF))
- Time to amputation at target leg until Week 12(A priori specification not possible; between baseline and week 12 post baseline)
- Assessment of Quality of life (QoL) using the short form 36 (SF-36) questionnaire(Screening Visit 1, Visit 3, at Weeks 4 and 12)
- Physical examination and vital signs(Week 6.1 and Week 12)
- Time to amputation of target leg until month 12(A priori specification not possible; between baseline and month 12 post baseline)
- Percentage of wound surface area reduction(Weeks 2, 4, 6, 8 and 12 (without LOCF))
- Percentage of invisible and visible wound surface area reduction(Weeks 2, 4, 6, 8 and 12 (without LOCF))
- Assessment of wound infection(Days 1 and 2, Weeks 1, 2, 4, 6, 6.1, 6.2, 6.3, 8 and 12)
- Proportion of patients achieving complete wound closure(Weeks 2, 4, 6, 8 and 12)
- Proportion of patients achieving 30% reduction of wound surface area(Weeks 2, 4, 6, 8 and 12)
- Time to first complete wound closure(A priori specification not possible; between baseline and week 12 post baseline)