Evaluation of AUP1602-C in Combination with Foam Dressing for Non-Healing Neuroischemic Diabetic Foot Ulcers: A Phase 2A Open-Label Study
- Trial ID
- 2024-519317-66-00
- Protocol
- AT-W-CLI-2024-10
- Sponsor
- Aurealis Oy
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** and **safety** of AUP1602-C, a cell suspension for topical administration, in the treatment of non-healing, neuroischemic **diabetic foot ulcers** (DFU). Specifically, the study aims to assess the proportion of patients achieving complete wound closure at 20 weeks after starting treatment with AUP1602-C plus standard of care (SoC). This is clinically relevant as achieving complete wound closure is a critical endpoint in the management of DFU, potentially reducing the risk of complications such as infections and amputations. Additionally, the study will assess the local and systemic safety and tolerability of the dose of 2.5 x 108 CFU/cm2 ulcer size of AUP1602-C plus SoC up to 20 weeks from the first administration.
The secondary objectives include:
- Assessing the time to wound closure with AUP1602-C plus SoC treatment.
- Evaluating the proportion of patients achieving complete wound closure after starting treatment with AUP1602-C.
- Assessing the proportion of patients achieving 40% or more wound area reduction (WAR).
- Evaluating the effect of AUP1602-C plus SoC on the proportion of WAR.
- Assessing the effect of AUP1602-C plus SoC on wound area, volume, depth reduction, time to complete wound closure, wound healing rate, quality of ulcer healing, long-term healing (durability), and local ulcer recurrence.
- Describing the impact of AUP1602-C plus SoC on pain perception in DFU patients.
- Assessing local and systemic safety of AUP1602-C during the long-term safety follow-up period in patients with non-healing, neuroischemic DFU.
- Evaluating the impact of AUP1602-C plus SoC on target ulcer-related peri-wound skin maceration, local wound infections, local surgical procedures, and amputations in DFU patients.
- Describing the effect of AUP1602-C plus SoC on the number of target ulcer-related hospital visits, patient-days of antibiotic therapy, and patient-days of hospitalization in DFU patients.
Participants
The clinical trial focuses on patients with **Diabetic Foot Ulcer**. The study population includes both male and female participants aged 18 years and above. Participants are required to have a general health status that allows them to comply with study procedures, as assessed by the Investigator. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants are selected based on specific criteria, including having type 1 or type 2 diabetes with an HbA1c of ≤ 11.0% and possessing at least one non-healing ulcer that meets detailed inclusion criteria. Lifestyle considerations include the requirement for participants to use effective contraceptive measures if they are women of childbearing potential or men capable of fathering children. Additionally, participants must be willing to wear off-loading footwear as directed by the Investigator. The trial does not include individuals with active wound infections or clinical evidence of osteomyelitis at the screening visit.
Plans and Procedures
The clinical trial is a **Phase IIa** exploratory study designed to evaluate the safety and efficacy of **AUP1602-C**, a **cell suspension for topical administration**, in treating non-healing neuroischemic **diabetic foot ulcers**. This single-center, prospective, uncontrolled, open-label, single-arm study aims to assess the proportion of patients achieving complete wound closure at 20 weeks post-treatment initiation. The trial will also evaluate the local and systemic safety and tolerability of the treatment, with a dose of 2.5 billion CFU/cm² ulcer size, over a period of up to 20 weeks.
Participants will be involved in the study for a maximum of 20 weeks, with the trial estimated to conclude by September 30, 2026. The study will commence with a screening visit to confirm eligibility based on specific inclusion criteria, such as age, diabetes management, and ulcer characteristics. Following the screening, eligible participants will undergo a run-in period to establish a baseline for the non-healing status of the target ulcer. The investigational treatment will then be administered, and participants will be monitored through a series of follow-up visits at weeks 4, 8, 12, 16, and 20 to assess wound healing progress and any adverse events.
The primary endpoints include the proportion of patients achieving complete wound closure and the incidence of adverse events up to 20 weeks. Secondary endpoints focus on the time to achieve various degrees of wound closure, recurrence rates, and changes in pain intensity. Participants may be withdrawn from the study if they achieve complete wound closure within 12 weeks or if they experience significant adverse events. The study's design ensures rigorous monitoring and data collection to evaluate the potential of AUP1602-C as a treatment for diabetic foot ulcers.
Treatment
The clinical trial involves the use of an **experimental medication** known as AUP1602-C, which is a **cell suspension for topical administration**. This investigational product is developed by AUREALIS OY and is intended for the treatment of non-healing neuroischemic diabetic foot ulcers. The pharmaceutical form of AUP1602-C is a cell suspension, and it is applied topically to the ulcer site. The dosage is specified as 2.5 billion colony forming units (CFU) per square centimeter of ulcer size, with a maximum daily dose of 2.5 billion CFU. The total maximum dose over the treatment period is 65 billion CFU. The treatment duration is up to 12 weeks, with the frequency of administration determined by the study protocol. The active substance, AUP1602-C, is classified as a structurally diverse substance, and it is not a pediatric formulation.
In addition to the experimental treatment, the study includes the use of **standard-of-care (SoC) therapy** as a non-experimental treatment. The SoC therapy is administered alongside AUP1602-C to evaluate the combined efficacy and safety in achieving complete wound closure. The study is designed to assess both local and systemic safety and tolerability of the treatment regimen over a period of up to 20 weeks from the first administration. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the treatment protocol.
Efficacy
The efficacy of the investigational treatment AUP1602-C for non-healing neuroischemic diabetic foot ulcers will be assessed through several primary and secondary endpoints. The primary efficacy endpoint is the proportion of patients achieving complete wound closure at 20 weeks after the initiation of treatment with AUP1602-C. Secondary endpoints include the time to achieve complete wound closure within 12 and 20 weeks, the time to achieve greater than 75% and 50% wound closure within the same timeframes, and the proportion of patients achieving complete wound closure at specific timepoints: weeks 4, 8, 12, 16, and 20.
Additional secondary endpoints involve the assessment of wound area reduction (WAR) at various intervals, the proportion of patients with target ulcer recurrence, and the time to ulcer recurrence. The study will also evaluate changes in patient-reported pain intensity using a numerical rating scale, the incidence of peri-wound skin maceration, local wound infection events, and surgical procedures related to the target ulcer. The incidence of target ulcer-related amputation events and the number of hospital visits and days of antibiotic therapy related to the target ulcer will also be recorded.
These efficacy parameters will be measured and collected at specified timepoints throughout the study, including during the run-in period and at weeks 4, 8, 12, 16, and 20 after the first administration of AUP1602-C. The analysis will utilize validated methods such as planimetry for measuring ulcer area and progression towards healing. The study aims to provide comprehensive data on the efficacy of AUP1602-C in promoting wound healing in the specified patient population.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Male or female patients aged 18 years and above, depending on the Investigator’s assessment of physical and psychological wellbeing of the patient to comply with study procedures and FU.
- Patients with DM of type 1 or 2 having an HbA1c of ≤ 11.0% OR 97.0 mmol/mol OR 14.9 mmol/L at the screening visit S-V1(results up to 3 months prior to signing ICF accepted) undergoing therapy for glycaemic control using available diabetes drugs including insulin
- Patients with at least one DFU that fulfils all of the following criteria: • Non-healing target ulcer defined as ≤ 20.0% reduction in area in response to SoC during the 2-weeks run-in period, • Duration: ≥ 3 months and ≤ 12 months at screening visit 1 (S-V1), • Located either in the plantar or on the dorsum of foot, or at or below the ankle, • Ulcer is accessible for administration of AUP1602-C and can be completely covered by the primary and secondary dressings, • Full-thickness, not involving bone or joints (i.e., University of Texas classification Grade 1A, 1C, 2A, 2C)(2) , • No clinical signs of active wound infection defined by IDSA/IWGDF criteria(3) or clinical evidence of osteomyelitis at screening visit 1 (S-V1), • Area of the target ulcer between 1.0-10.0 cm2 after debridement at screening visit 1 (S-V1) • Ulcer and peri-wound tissue suitable for application of foam dressings (i.e., no contraindications and sufficient peri-wound space to hold the dressing). • Ulcer area can be reliably measured by the planimetry method for determining treatment volume and assessing progression towards healing
- Patients with more than one ulcer will be included if ulcers are separated by a minimum of 2.0 cm healthy tissue. The largest ulcer fulfilling the inclusion criteria will be selected for the investigational treatment.
- Patients with either an ABI ≥ 0.7 OR a TBI ≥ 0.5, AND a toe systolic pressure of at least 50.0 mmHg (or ankle systolic pressure of at least 70.0 mmHg if toe-pressure is not measured) on the foot with the target ulcer
- Revascularized patients with an ulcer fulfilling the inclusion criteria can be included 3 months after the procedure.
- Patients with an assessment of the baseline level of neuropathy in the lower limb where the target ulcer is located.
- Patients must be willing to wear off-loading footwear, while ambulating, for the period requested by the Investigator
- A WOCBP must have a negative serum pregnancy test at the time of screening after signing the ICF and a negative pregnancy dip-stick test at baseline (before starting treatment)
- WOCBP must agree to use a highly effective contraceptive measure (methods that can achieve a failure rate of less than 1% per year when used consistently and correctly)2 , throughout the study. Male patients who are biologically capable of having children must agree to apply at least two methods of contraception including male barrier protection throughout the study.
- Patients who understand and are willing to comply with study procedures and give written informed consent prior to enrolment in the study or initiation of study procedures.
Exclusion Criteria
- Current or previous (within 2 weeks prior to start of run-in period) treatment with another investigational drug and/or medical device or participation in another clinical study.
- Target ulcers requiring urgent vascular surgical interventions.
- Target ulcer other than non-healing DFU fulfilling inclusion criteria (e.g., including, but not limited to, pressure ulcers, burn wounds).
- Serum creatinine level of > 3.0 x ULN.
- Prior radiation therapy (within 6 weeks prior to first AUP1602-C dosing) of any part of the foot/leg bearing the target ulcer under study or total body irradiation.
- Sickle-cell diseases, Reynaud’s, or other peripheral vascular disease including venous leg ulcers or any vasculitic ulcer irrespective of the cause will be excluded.
- Active or unstable Charcot deformity of the study foot (i.e., foot is erythematous, warm, oedematous, and is actively remodelling).
- Patients with other reasons for wound healing disturbances: e.g., bleeding disorders, vitamin K deficiency, hypocalcaemia, major immune deficiencies
- Active malignant disease of any kind except for basal cell carcinoma (of the skin) not colocated with the target ulcer. A patient, who has had a malignant disease in the past, completed treatment and is currently disease-free and not on active treatment for at least 3 months, may be considered for study entry. Cancer therapies with known therapeutic effects longer than 3 months may be considered as exclusion and should be consulted with Medical Monitor/Sponsor.
- Haemoglobin of less than 8.5 g/dL.
- Liver transaminase and total bilirubin levels > 3 x ULN
- Current or previous (within 30 days prior to start of run-in period) treatment of target ulcer with a treatment that could interfere with wound healing/IMP such as biological agents, growth factors, skin equivalents/substitutes (e.g., Regranex®, Apligraf®, or Dermagraft®), keratinocytes, platelet-rich-plasma or other cell therapies, collagen products, blood products, placental products, oxygen therapy, topical steroids or cold plasma.
- Patients receiving haemodialysis or CAPD therapy.
- Positive for HBV, HCV, or HIV (serology test results up to 3 months prior signing ICF accepted).
- Patients with confirmed active infection with SARS-CoV-2 and related disease (COVID19) at Baseline (V1) prior to first administration of trial medication
- Planned major surgery during the run-in, treatment and efficacy and FU period of the study
- Known abuse of alcohol, drugs, or medical products. Tobacco use will be allowed.
- Previous treatment with AUP1602-C.
- Any diagnosed unstable psychological or physical condition including major organ failure that could interfere with compliance.
- Myocardial infarction diagnosed within 1 month prior to start of run-in period.
- WBC < 3.0 x 109 cells/L; > 12.0 x 109 cells/L
- Albumin < 2.5 g/dL (or total protein < 4.0 g/dL).
- Current or previous (within 1 week prior to first AUP1602-C dosing) treatment with active wound care agents (e.g., local/topical antibiotics OR antibacterials such as silver, iodine, chlorhexidine) OR systemic antibiotics for any indication unless the duration of activity for the treatment extends beyond this period
- The patient has any other factor/reason which may, in the opinion of the Investigator, compromise participation and/or FU in the study.
- Pregnant or lactating woman at the time of signing the ICF and prior to first AUP1602-C dosing.
- Close affiliation with the Investigator (e.g., a close relative, financially dependent on the investigational site) or patient who is an employee of the Sponsor’s company
- Patients who are institutionalized because of legal or regulatory order.
- Current or previous (within 2 weeks prior to first AUP1602-C dosing) use of corticosteroids and immunosuppressants. Treatment with immunosuppressive agents with known therapeutic effects longer than 2 weeks may be considered as exclusion and should be consulted with Medical Monitor/Sponsor.
- Known hypersensitivity to any of the components of AUP1602-C
- Ulcer of University of Texas Grade ≥ 3, with deep abscess, sinus track, necrosis or gangrene that cannot be removed by debridement.
- Target ulcers with excessive exudation requiring more than one dressing change within 24 hrs at 1 st treatment visit (V1).
- Target ulcers with clinically significant peri-wound skin maceration.
- Target ulcer with known or suspected active infection, which requires antimicrobials
- Women whose postmenopausal status has not been confirmed and last menstrual cycle was less than 12 months ago
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Italy | Not Yet Recruiting | 15 Apr 2025 | 12 |