Diabetic foot ulcers MedDRA version: 21.1 Level: LLT Classification code 10012664 Term: Diabetic foot ulcer System Organ Class: 100000004858
Conditions
Interventions
Product Name: AUP1602-C
Product Code: AUP1602-C
Pharmaceutical Form: Cutaneous suspension
INN or Proposed INN: AUP1602-C
Current Sponsor code: AUP1602-C
Other descriptive name: AUP1602-C
Concentration
Sponsors
Aurealis Oy
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: The study population are patients with chronic, non-healing DFU in phase 1, and DFU and optionally VLU for phase 2A part. The protocol will be amended in such case. The patients have to meet all of the following criteria to be eligible to enter the study: 1. Male or female patients aged 18 to 80 years 2. Patients with DM of type 1 or 2 having glycosylated haemoglobin (HbA1c) of =11% and a serum creatinine level of =1.5 times the upper limit of normal (ULN) 3. Patients with at least one ulcer that fulfills all of the following criteria at screening and at baseline (prior to treatment start) -Present for =1 month -Located either in the plantar or on the dorsum of foot, or in the distal part of the leg, around the malleolar area to be accessible for administration of AUP1602-C/placebo and to be completely covered by the primary and secondary dressings -Partial- or full-thickness, not involving bone, tendon, or joints, i.e. University of Texas classification Grade 1A, 1C, 2A or 2C -No clinical signs of active infection or osteomyelitis -Size of the target ulcer for DFU must be between 1-9 cm2 after debridement -Chronic target ulcer, defined as =65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: Patients meeting any of the following criteria will not be permitted to enter the study: 2. Current or previous (within 2 weeks prior to start of screening/run-in period) treatment with another investigational drug and/or medical device or participation in another clinical study 3. Current or previous (within 30 days prior to start of screening/run-in period) treatment with a biologic agent, growth factors or skin equivalents (e.g. Regranex®, Apligraf®, or Dermagraft®) 4. Current or previous (within 1 week prior to first study drug dosing) treatment with active wound care agents (e.g. local and systemic antibiotics or silver dressings) 5. Current or previous (within 2 weeks prior to first study drug dosing) use of corticosteroids and immunosuppressants 6. Known hypersensitivity to any of the investigational drug or vehicle components 7. Ulcer of University of Texas Grade =3, with deep abscess, or gangrene 8. Target ulcer with known or suspected active infection which requires antimicrobials. Any antibiotic therapy must be completed or discontinued within 1 week prior to first study drug dosing 9. Target ulcer positive for MRSA 10. Target ulcer other than chronic non-healing DFU (e.g. pressure ulcers, burn wounds) 11. Prior radiation therapy (within 6 weeks prior to first study drug dosing) of any part of the foot/leg bearing the target ulcer under study 12. Sickle-cell anemia, Reynaud’s, or other peripheral vascular disease including venous leg ulcers 13. Infective endocarditis or increased risk for infective endocarditis, which includes, but is not limited to, prosthetic cardiac valve or prosthetic material used for cardiac valve repair, previous infective endocarditis, congenital heart disease, and cardiac transplantation recipients who develop clinically significant cardiac valvulopathy, history of rheumatic fever or rheumatic heart disease diagnosed by echocardiogram, or history (within 10 years prior to enrollment) of IV drug abuse 14. Active Charcot deformity of the study foot (i.e. foot is erythematous, warm, edematous, and is actively remodeling) 15. Patients with other reasons for wound healing disturbances: e.g. bleeding disorders, vitamin K deficiency, hypocalcemia, major immune deficiencies 16. Active malignant disease of any kind except for basal cell carcinoma (of the skin) not co-located with the target ulcer. A patient, who has had a malignant disease in the past, was treated and is currently disease-free and not on active treatment with an immune-suppressive therapy at least for 3 months, may be considered for study entry 17. Pregnant or lactating woman 18. Haemoglobin of less than 8.5 g/dL 19. Transaminase levels greater than 3 times ULN 20. Patients receiving haemodialysis or chronic ambulatory peritoneal dialysis (CAPD) therapy 21. Positive for hepatitis B or C virus (HBV, HCV), or human immunodeficiency virus (HIV); serology test results not older than 3 months are accepted 22. Planned surgery during the study period 23. Known abuse of alcohol, drugs, or medical products. Tobacco use will be allowed 24. Previous participation in this clinical study 25. Any diagnosed unstable condition that could interfere with compliance, such as psychiatric disorder 26. Myocardial infarction diagnosed within last 3 months prior to start of screening/run-in period 27. Confirmed or suspected COVID-19 infection
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: PHASE 1 PRIMARY OBJECTIVES ?-To determine local and systemic safety and tolerability of single and repeated topical administrations of AUP1602-C of safety (2.5 x 105 colony-forming unit [CFU]/cm2 ulcer size), low (2.5 x 106 CFU/cm2 ulcer size), medium (2.5 x 107 CFU/cm2 ulcer size), and high dose (2.5 x 108 CFU/cm2 ulcer size) in patients with chronic DFUs ?-To determine the recommended phase 2 dose (RP2D) of AUP1602-C and the treatment schedule to be applied in phase 2A of the study PHASE 2A PRIMARY OBJECTIVES -To confirm local and systemic safety and tolerability of the RP2D and selected treatment schedule of AUP1602-C in DFU patients -To assess the efficacy of the RP2D and selected treatment schedule of AUP1602-C in DFU patients compared to a placebo control arm;Secondary Objective: PHASE 1 & 2A SECONDARY OBJECTIVES -To assess the efficacy of multiple administrations of AUP1602-C in DFU patients (for phase 1 only as being primary objective in phase 2A) -To determine the effect of AUP1602-C treatment on wound volume and depth reduction, time to complete wound closure, long-term healing and ulcer recurrence -To determine the effect of AUP1602-C treatment on local wound infections, local surgical procedures, and amputation rate -To determine the effect of AUP1602-C treatment on patient’s quality of life and pain perception -To determine the effect of AUP1602-C treatment on vital signs, electrocardiography (ECG), echocardiogram, ophthalmoscopy, physical examination, and clinical laboratory -To determine the presence of AUP1602-C (plasmid) in the systemic circulation, urine and faeces;Primary end point(s): PHASE 1 PRIMARY ENDPOINTS -Incidence of adverse events (AEs) and potential dose-limiting toxicities (DLTs) for safety, low, medium, and high dose cohorts of single and repeatedly administered AUP1602-C PHASE 2A PRIMARY ENDPOINTS -Incidence of AEs in each treatment arm (including overall AEs, AEs of special interest (local tolerability), AEs related | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): PHASE 1 & 2A SECONDARY ENDPOINTS -Percentage of wound size reduction during the treatment period and at Weeks 1, 2, 3, 4, 6, 8, 12 (Month 3), and 24 (Month 6) after last study drug administration (phase 1 only) -Proportion of patients with a target ulcer achieving complete wound closure during the treatment period and up to 1, 2, 3, 4, 6, 8, and 12 weeks (3 months) after last study drug administration (phase 1 only) -Percentage of wound volume and depth reduction during the treatment period and at Weeks 1, 2, 3, 4, 6, 8, 12 (Month 3), and 24 (Month 6) after last study drug administration -Time to complete wound closure -Percentage of patients with complete wound closure at Week 24 (Month 6) after last study drug administration -Proportion of patients with ulcer recurrence after 6, 12 (Month 3), and 24 (Month 6) weeks post wound closure -Proportion of patients with local wound infections related to the target ulcer during the treatment period and at Weeks 6, 12 (Month 3) and 24 (Month 6) after last study drug administration -Proportion of patients with local surgical procedures during the treatment period and at Weeks 6, 12 (Month 3) and 24 (Month 6) after last study drug administration -Proportion of patients with amputations (minor or major) related to the target ulcer during the treatment period and at Weeks 6, 12 (Month 3) and 24 (Month 6) after last study drug administration -Change from baseline in health-related quality of life using EuroQol-5D (EQ-5D) visual analog scale (VAS), EQ-5D utility index, and Dermatology Life Quality Index (DLQI) score -Change from baseline in patient’s pain intensity using a numerical rating scale (ranging from 0 = no pain to 10 = worst imaginable pain) -Incidence of abnormal vital signs values, ECG data, echocardiogram data, ophthalmoscopy data, physical examination findings, laboratory data -Assessment of biodistribution of AUP1602-C (plasmid) in the blood by AUP- quantitative polymerase chain reaction (qP | — |
Countries
Germany, Poland
Contacts
Public ContactThomas Wirth
Aurealis Oy
Outcome results
None listed