Phase 2A–Evaluation of AUP1602-C with foam dressing as a new treatment for diabetic foot ulcers

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Aurealis Oy

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Decision date (initial)

2025-05-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

Efficacy:
To assess the proportion of patients achieving complete wound closure at 20 weeks after starting treatment with AUP1602-C plus SoC in patients with non-healing, neuroischaemic o assess the proportion of patients achieving complete wound closure at 20 eeks after starting treatment with AUP1602-C plus SoC in patients with non-healing, neuroischaemic DFU, fulfilling inclusion criteria DFU, fulfilling inclusion criteria

Safety and Tolerability:
To assess local and systemic safety and tolerability of the dose 2.5 x 108 CFU/cm2 ulcer size of AUP1602-C plus SoC up to 20 weeks from the first administration of AUP1602-C in patients with non-healing, neuroischaemic DFU, fulfilling inclusion
criteria

Secondary objectives 9

1. To assess the time to wound closure with AUP1602-C plus SoC treatment
2. To assess the proportion of patients achieving complete wound closure after starting treatment with AUP1602-C
3. To assess the proportion of patients achieving 40% or more WAR
4. To assess the effect of AUP1602-C plus SoC on proportion of WAR
5. To assess the effect of AUP1602-C plus SoC on wound area, wound volume and wound depth reduction, time to complete wound closure, wound healing rate, quality of ulcer healing, long-term healing (durability) and local ulcer recurrence
6. To describe the impact of AUP1602-C plus SoC on pain perception in DFU patients
7. To assess local and systemic safety of AUP1602-C during the long-term safety FU period in patients with non-healing, neuroischaemic DFU
8. To assess 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
9. To describe the effect of AUP1602-C plus SoC on number of target ulcer related hospital visits, patient-days of antibiotic therapy, and patient-days of hospitalisation, in DFU patients

Conditions and MedDRA coding

Diabetic Foot Ulcer

Regulatory references

Scientific advice from competent authorities

Medicines And Healthcare Products Regulatory Agency, Finnish Medicines Agency, Food And Drug Administration, Paul-Ehrlich-Institut, European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. 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.
2. 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
3. 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
4. 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.
5. 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
6. Revascularized patients with an ulcer fulfilling the inclusion criteria can be included 3 months after the procedure.
7. Patients with an assessment of the baseline level of neuropathy in the lower limb where the target ulcer is located.
8. Patients must be willing to wear off-loading footwear, while ambulating, for the period requested by the Investigator
9. 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)
10. 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.
11. 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 34

1. 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.
2. Target ulcers requiring urgent vascular surgical interventions.
3. Target ulcer other than non-healing DFU fulfilling inclusion criteria (e.g., including, but not limited to, pressure ulcers, burn wounds).
4. Serum creatinine level of > 3.0 x ULN.
5. 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.
6. 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.
7. Active or unstable Charcot deformity of the study foot (i.e., foot is erythematous, warm, oedematous, and is actively remodelling).
8. Patients with other reasons for wound healing disturbances: e.g., bleeding disorders, vitamin K deficiency, hypocalcaemia, major immune deficiencies
9. 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.
10. Haemoglobin of less than 8.5 g/dL.
11. Liver transaminase and total bilirubin levels > 3 x ULN
12. 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.
13. Patients receiving haemodialysis or CAPD therapy.
14. Positive for HBV, HCV, or HIV (serology test results up to 3 months prior signing ICF accepted).
15. Patients with confirmed active infection with SARS-CoV-2 and related disease (COVID19) at Baseline (V1) prior to first administration of trial medication
16. Planned major surgery during the run-in, treatment and efficacy and FU period of the study
17. Known abuse of alcohol, drugs, or medical products. Tobacco use will be allowed.
18. Previous treatment with AUP1602-C.
19. Any diagnosed unstable psychological or physical condition including major organ failure that could interfere with compliance.
20. Myocardial infarction diagnosed within 1 month prior to start of run-in period.
21. WBC < 3.0 x 109 cells/L; > 12.0 x 109 cells/L
22. Albumin < 2.5 g/dL (or total protein < 4.0 g/dL).
23. 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
24. The patient has any other factor/reason which may, in the opinion of the Investigator, compromise participation and/or FU in the study.
25. Pregnant or lactating woman at the time of signing the ICF and prior to first AUP1602-C dosing.
26. 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
27. Patients who are institutionalized because of legal or regulatory order.
28. 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.
29. Known hypersensitivity to any of the components of AUP1602-C
30. Ulcer of University of Texas Grade ≥ 3, with deep abscess, sinus track, necrosis or gangrene that cannot be removed by debridement.
31. Target ulcers with excessive exudation requiring more than one dressing change within 24 hrs at 1 st treatment visit (V1).
32. Target ulcers with clinically significant peri-wound skin maceration.
33. Target ulcer with known or suspected active infection, which requires antimicrobials
34. Women whose postmenopausal status has not been confirmed and last menstrual cycle was less than 12 months ago

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Proportion of patients (incidence of) achieving complete wound closure at 20 weeks after starting AUP1602-C treatment.
2. Incidence of local and systemic AEs up to 20 weeks after starting AUP1602-C treatmen
3. Time to AUP1602-C discontinuation
4. Proportion of patients withdrawn from AUP1602-C within 12 weeks for reasons other than complete wound closure

Secondary endpoints 22

1. Time to achieve complete wound closure within 12 and 20 weeks after starting AUP1602-C treatment
2. Time to >75% wound closure within 12 and 20 weeks after starting AUP1602-C treatment
3. Time to > 50% wound closure within 12 and 20 weeks after starting AUP1602-C treatment
4. Proportion of patients achieving complete wound closure (Timeframe: Weeks 4, 8, 12, 16 and 20 after starting AUP1602-C treatment )
5. Proportion of patients achieving ≥ 40% WAR at 4 weeks after starting AUP1602-C treatment (at FU-V1)
6. Proportion of WAR at 4, 8, 12, 16 and 20 weeks after first AUP1602-C treatment
7. Proportion of patients with > 75% WAR (Timeframe: Weeks 4, 8, 12, 16 and 20 after first AUP1602-C treatment)
8. Proportion of patients with > 50% WAR (Timeframe: Weeks 4, 8, 12, 16 and 20 after first AUP1602-C treatment)
9. Proportion of wound volume and depth reduction (Timeframe: Weeks 4, 8, 12, 16 and 20 after first AUP1602-C treatment)
10. Proportion of patients with target ulcer recurrence (Timeframe: Weeks 8, 12, 16 and 20 after first AUP1602-C administration, and 6 and 12 months after last AUP1602-C administration)
11. Time to ulcer recurrence (Timeframe: 12 and 20 weeks after starting AUP1602-C, and at 6 and 12 months after last AUP1602-C treatment)
12. Wound healing rate (WAR per week and proportion WAR per week) (Timeframe: Weeks 4, 8, 12, 16 and 20 after first AUP1602-C administration)
13. Proportion of patients with scaring, hypertrophic scaring (keloid) of the wound, and pigmentation of peri-wound skin (Timeframe: Weeks 4, 8, 12, 16 and 20 after first AUP1602-C administration, and 6 and 12 months after last AUP1602-C treatment)
14. Change from baseline in patient’s pain intensity using a numerical rating scale (NRS, ranging from 0 = no pain to 10 = worst imaginable pain) (Timeframe: Weeks 4, 8, 12, 16 and 20 after first AUP1602-C administration)
15. Incidence and prevalence of target ulcer related peri-wound skin maceration events (Timeframe: during run-in period, and Weeks 4, 8, 12, 16 and 20 after first AUP1602-C administration)
16. Incidence and prevalence of target ulcer related local wound infection events (Timeframe: during run-in period, Weeks 4, 8, 12, 16 and 20 after first AUP1602-C administration, and 6 and 12 months after last AUP1602-C administration)
17. Incidence of surgical procedures related to the target ulcer (Timeframe: during run-in period, Weeks 4, 8, 12, 16 and 20 after first AUP1602-C administration, and 6 and 12 months after last AUP1602-C administration
18. Incidence of target ulcer related amputation events (Timeframe: during run-in period, Weeks 4, 8, 12, 16 and 20 after first AUP1602-C administration, and 6 and 12 months after last AUP1602-C administration)
19. Incidence of local and systemic AEs occuring during the long-term safety FU period
20. Number of target ulcer related hospital visits during run-in, treatment and efficacy FU periods
21. Number of patient-days of target ulcer related antibiotic therapy during run-in, treatment and efficacy FU periods
22. Number of patient-days of hospitalization due to complications related to target ulcer during run-in, treatment and efficacy FU periods

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Aurealis Oy

Sponsor organisation

Aurealis Oy

Address

Microkatu 1

City

Kuopio

Postcode

70210

Country

Finland

Scientific contact point

Organisation

Aurealis Oy

Contact name

CMO

Public contact point

Organisation

Aurealis Oy

Contact name

CMO

Third parties 11

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 23 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications