AUP1602-C for Diabetic foot ulcer

Inclusion criteria

• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Revascularized patients with an ulcer fulfilling the inclusion criteria can be included 3 months after the procedure."}
• {"criterion_text":"- Patients with an assessment of the baseline level of neuropathy in the lower limb where the target ulcer is located."}
• {"criterion_text":"- Patients must be willing to wear off-loading footwear, while ambulating, for the period requested by the Investigator"}
• {"criterion_text":"- 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)"}

Exclusion criteria

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

Primary endpoints

• {"endpoint_text":"- Proportion of patients (incidence of) achieving complete wound closure at 20 weeks after starting AUP1602-C treatment.","definition_or_measurement_approach":"Measured as proportion of patients achieving complete wound closure at 20 weeks after starting treatment."}
• {"endpoint_text":"- Incidence of local and systemic AEs up to 20 weeks after starting AUP1602-C treatmen","definition_or_measurement_approach":"Incidence of adverse events assessed up to 20 weeks after starting treatment (local and systemic)."}
• {"endpoint_text":"- Time to AUP1602-C discontinuation","definition_or_measurement_approach":"Time from first administration to discontinuation of AUP1602-C."}
• {"endpoint_text":"- Proportion of patients withdrawn from AUP1602-C within 12 weeks for reasons other than complete wound closure","definition_or_measurement_approach":"Proportion of patients withdrawn within 12 weeks for reasons other than complete wound closure."}

Secondary endpoints

• {"endpoint_text":"- Time to achieve complete wound closure within 12 and 20 weeks after starting AUP1602-C treatment","definition_or_measurement_approach":"Time-to-event assessed at 12 and 20 weeks after starting treatment."}
• {"endpoint_text":"- Time to >75% wound closure within 12 and 20 weeks after starting AUP1602-C treatment","definition_or_measurement_approach":"Time to achieve >75% wound closure assessed at 12 and 20 weeks."}
• {"endpoint_text":"- Time to > 50% wound closure within 12 and 20 weeks after starting AUP1602-C treatment","definition_or_measurement_approach":"Time to achieve >50% wound closure assessed at 12 and 20 weeks."}
• {"endpoint_text":"- Proportion of patients achieving complete wound closure (Timeframe: Weeks 4, 8, 12, 16 and 20 after starting AUP1602-C treatment )","definition_or_measurement_approach":"Proportion assessed at Weeks 4, 8, 12, 16 and 20."}
• {"endpoint_text":"- Proportion of patients achieving ≥ 40% WAR at 4 weeks after starting AUP1602-C treatment (at FU-V1)","definition_or_measurement_approach":"Proportion achieving ≥40% wound area reduction (WAR) at 4 weeks (FU-V1)."}
• {"endpoint_text":"- Proportion of WAR at 4, 8, 12, 16 and 20 weeks after first AUP1602-C treatment","definition_or_measurement_approach":"Proportion of wound area reduction assessed at Weeks 4,8,12,16,20."}
• {"endpoint_text":"- Proportion of patients with > 75% WAR (Timeframe: Weeks 4, 8, 12, 16 and 20 after first AUP1602-C treatment)","definition_or_measurement_approach":"Proportion with >75% WAR at specified timepoints."}
• {"endpoint_text":"- Proportion of patients with > 50% WAR (Timeframe: Weeks 4, 8, 12, 16 and 20 after first AUP1602-C treatment)","definition_or_measurement_approach":"Proportion with >50% WAR at specified timepoints."}
• {"endpoint_text":"- Proportion of wound volume and depth reduction (Timeframe: Weeks 4, 8, 12, 16 and 20 after first AUP1602-C treatment)","definition_or_measurement_approach":"Proportion of wound volume and depth reduction assessed at Weeks 4,8,12,16,20."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Proportion with ulcer recurrence assessed at Weeks 8,12,16,20 and at 6 and 12 months after last administration."}
• {"endpoint_text":"- Time to ulcer recurrence (Timeframe: 12 and 20 weeks after starting AUP1602-C, and at 6 and 12 months after last AUP1602-C treatment)","definition_or_measurement_approach":"Time-to-event for ulcer recurrence measured at specified timeframes."}
• {"endpoint_text":"- Wound healing rate (WAR per week and proportion WAR per week) (Timeframe: Weeks 4, 8, 12, 16 and 20 after first AUP1602-C administration)","definition_or_measurement_approach":"WAR per week and proportion WAR per week assessed at Weeks 4,8,12,16,20."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Proportion with scarring/pigmentation events assessed at Weeks 4,8,12,16,20 and at 6 and 12 months."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Change from baseline in NRS pain score assessed at Weeks 4,8,12,16,20."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Incidence/prevalence of peri-wound maceration assessed during run-in and at Weeks 4,8,12,16,20."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Incidence/prevalence of local wound infections assessed during run-in, Weeks 4-20 and at 6 and 12 months after last administration."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Incidence of surgical procedures related to target ulcer assessed during run-in, Weeks 4-20 and at 6 and 12 months after last administration."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Incidence of amputation events assessed during run-in, Weeks 4-20 and at 6 and 12 months after last administration."}
• {"endpoint_text":"- Incidence of local and systemic AEs occuring during the long-term safety FU period","definition_or_measurement_approach":"Incidence of local and systemic adverse events during long-term safety follow-up."}
• {"endpoint_text":"- Number of target ulcer related hospital visits during run-in, treatment and efficacy FU periods","definition_or_measurement_approach":"Count of target ulcer related hospital visits during run-in, treatment and efficacy follow-up periods."}
• {"endpoint_text":"- Number of patient-days of target ulcer related antibiotic therapy during run-in, treatment and efficacy FU periods","definition_or_measurement_approach":"Number of patient-days on antibiotic therapy related to target ulcer during specified periods."}
• {"endpoint_text":"- Number of patient-days of hospitalization due to complications related to target ulcer during run-in, treatment and efficacy FU periods","definition_or_measurement_approach":"Number of patient-days of hospitalization due to complications related to target ulcer during specified periods."}

Methods

• K2_ESMERALD__Referral Letter EN (document available in CTIS document list)
• K2_ESMERALD__Referral Letter_IT (document available in CTIS document list)
• K2_ESMERALD_Recruitment Material Poster FlyerWording (recruitment poster/flyer material document)
• K2_ICF_Patientrecruitment procedure_en (patient recruitment procedure document)

Italy

Earliest CTIS Part Ii Submission Date

16-12-2024

Latest Decision Or Authorization Date

16-05-2025

Processing Time Days

151

Number Of Sites

1

Number Of Participants

12

Primary sponsor

Full Name

Aurealis Oy

Organisation Type

Pharmaceutical company

Country Of Registered Address

Finland

Third parties

• {"country":"Netherlands","full_name":"BaseClear B.V.","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Labor Dr. Spranger","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"Biotec Distribution Wales Limited","duties_or_roles":"sponsorDuties codes: 14","organisation_type":"Industry"}
• {"country":"Sweden","full_name":"BC Platforms AB","duties_or_roles":"sponsorDuties codes: 10, 6, 7","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Millmount Healthcare Limited","duties_or_roles":"sponsorDuties codes: 14","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Productlife Limited","duties_or_roles":"sponsorDuties codes: 13, 8","organisation_type":"Pharmaceutical company"}
• {"country":"Denmark","full_name":"Cap Partner LLC","duties_or_roles":"sponsorDuties codes: 15 (Independent evaluation of Images)","organisation_type":"Industry"}
• {"country":"Germany","full_name":"PCI Pharma Services Germany GmbH","duties_or_roles":"sponsorDuties codes: 14","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Proinnovera GmbH","duties_or_roles":"sponsorDuties codes: 1, 11, 12, 5","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Biotec Distribution Wales Limited","duties_or_roles":"sponsorDuties codes: 14","organisation_type":"Industry"}
• {"country":"United States","full_name":"Ekare Inc.","duties_or_roles":"sponsorDuties codes: 15 (Imaging)","organisation_type":"Non-Pharmaceutical company"}