Evaluation of AUP12602-C as New Topical Treatment for DFUs (DIAMEND STUDY)
Study Details
Study Description
Brief Summary
This is a phase 2 study performed in diabetic foot ulcer (DFU) patients with chronic non-healing, neuro-ischemic wounds to investigate the safety, tolerability and efficacy of AUP1602-C.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
This is a phase 2 multi-centre, parallel arm, patient and central evaluator-blinded, randomized, SoC plus placebo-controlled study of the RP2D of AUP1602-C performed in DFU patients with non-healing wounds. The RP2D of AUP1602-C derived from phase 1 study is 2.5 x 10E8 CFU/cm2 ulcer area and is used in this study.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: AUP1602-C AUP1602-C is administered topically during the treatment period. |
Biological: AUP1602-C
AUP1602-C is topically applied on chronic wounds and covered by wound dressing.
|
| Placebo Comparator: Placebo Placebo is administered topically during the treatment period. |
Other: Placebo
Placebo is topically applied on chronic wounds and covered by wound dressing.
|
Outcome Measures
Primary Outcome Measures
- Incidence of local and systematic adverse events (AEs) [6 weeks]
Incidence of local and systematic adverse events (AEs) for repeatedly administered AUP1602-C and of the placebo control arm.
- Incidence of Wound Closure [20 weeks]
Proportion of patients with a target ulcer achieving complete wound closure
Secondary Outcome Measures
- To evaluate the effect size of the efficacy parameters for AUP1602-C and placebo control arm in DFU patients [20 weeks]
Percentage of wound area reduction Percentage of wound volume and depth reduction
- To evaluate the effect size of the efficacy parameters for AUP1602-C and placebo control arm in DFU patients [20 weeks]
Time to complete wound closure Time to >50% wound area reduction Time to >75% wound area reduction
- To evaluate the effect size of the efficacy parameters for AUP1602-C and placebo control arm in DFU patients [20 weeks]
Proportion of patients with complete wound closure Proportion of patients with a >50% wound area reduction Proportion of patients with a >75% wound area reduction Proportion of patients with a target ulcer recurrence
- To evaluate the effect of the RP2D and selected treatment schedules on the percentage of wound area reduction in DFU patients [20 weeks]
• Percentage of wound area reduction
- To evaluate the effect of the RP2D and selected treatment schedules on the percentage of wound area reduction in DFU patients [20 weeks]
Time to complete wound closure Time to >50% wound area reduction Time to >75% wound area reduction
- To evaluate the effect of the RP2D and selected treatment schedules on the percentage of wound area reduction in DFU patients [20 weeks]
Proportion of patients with complete wound closure Proportion of patients with a >50% wound area reduction Proportion of patients with a >75% wound area reduction
- To evaluate the effect of the RP2D and selected treatment schedules long-term healing in DFU patients [20 weeks]
• Proportion of patients with complete wound closure
- To evaluate the effect of the RP2D and selected treatment schedules ulcer recurrence in DFU patients [20 weeks]
• Proportion of patients with a target ulcer recurrence
- Changes in Quality of Life according to EQ-5D-5L [20 weeks]
Change from baseline in health-related quality is assessed according to EuroQoL-5 Dimensions (EQ-5D-5L) patient quesionnaire. Five single-item dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) are assessed. Result of the questionnaire is scored from 0 (worst health imaginable) to 100 (best health imaginable).
- Changes in Quality of Life according to DLQI [20 weeks]
Change from baseline in health-related quality is assessed according to Dermatology Life Quality Index (DLQI). It consists of 10 questions, where each question is scored from 0 (not affected at all) to 3 (very much affected). The DLQI score will be calculated as the sum of the 10 individual question scores and ranges from 0 to 30, with lower scores indicating better quality of life.
- Changes in pain assessment according to VAS [20 weeks]
Change from baseline in patient's pain intensity according to a numerical Visual Analog Scale (VAS) ranging from 0 = no pain to 10= worst imaginable pain.
- Incidence of target ulcer related hospital visits [20 weeks]
Number of target ulcer related hospital visits Number of patient-days of hospitalization due to complications related to target ulcer Number of patient-days of target ulcer related antibiotic therapy
Eligibility Criteria
Criteria
Inclusion Criteria:
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Male or female patients aged 18 and above
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Patients with DM of type 1 or 2 having a glycosylated haemoglobin (HbA1c) of ≤ 11.0% OR 97.0 mmol/mol OR 14.9 mmol/l at randomization undergoing therapy for glycaemic control using available diabetes drugs including insulin
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Patients with at least one DFU that fulfils all the following criteria:
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Non-healing target ulcer defined as ≤ 20.0% reduction in area in response to SoC during the 2-weeks run-in period,
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Duration: ≥ 4 weeks and ≤ 12 months at screening visit 1,
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Located either in the plantar or on the dorsum of foot, or at or below the ankle,
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Ulcer is accessible for administration of IMP and can be completely covered by the primary and secondary dressings,
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Full-thickness, not involving bone or joints (i.e., University of Texas classification Grade 1A, 1C, 2A, 2C)(5),
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No clinical signs of active wound infection defined by IDSA/IWGDF criteria(6) or clinical evidence osteomyelitis at randomization (V1),
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Area of the target ulcer between 1.0-10.0 cm2 after debridement at randomization (V1)
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Ulcer and periwound tissue suitable for application of film dressings (i.e., no contraindications and sufficient periwound space to hold the dressing).
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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.
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Patients with either an ankle brachial index (ABI) ≥ 0.7 OR a toe-brachial index (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.
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Revascularized patients with an ulcer fulfilling the inclusion criteria can be included 3.0 months after the procedure.
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Patients with an assessment of the baseline level of neuropathy in the lower limb where the target ulcer is located.
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Patients must be willing to wear off-loading footwear, while ambulating, for the period requested by the Investigator.
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A woman of childbearing potential (WOCBP) must have a negative serum pregnancy test at the time of screening after sign the informed consent and a negative pregnancy dip-stick test at baseline (before starting treatment).
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Females of childbearing potential 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) , 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.
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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:
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Participating in another clinical study or treatment with another investigational product and/or medical device in the 30 days prior to inclusion in the study or within the 5 half-lives of the investigational product, whichever is longer.
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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, collagen products, blood products, placental products, oxygen therapy, topical steroids.
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Current or previous (within 1 week prior to first IMP (AUP1602-C or placebo) 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.
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Current or previous (within 2 weeks prior to first IMP (AUP1602-C or placebo) 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.
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Known hypersensitivity to any of the components of AUP1602-C or placebo
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Ulcer of University of Texas Grade ≥ 3, with deep abscess, sinus track, necrosis or gangrene that cannot be removed by debridement.
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Target ulcers with excessive exudation requiring more than one dressing change within 24-hrs.
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Target ulcers with clinically significant periwound skin maceration.
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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 IMP (AUP1602-C or placebo) dosing.
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Target ulcers requiring urgent vascular surgical interventions.
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Target ulcer other than non-healing DFU fulfilling inclusion criteria (e.g., including, but not limited to, pressure ulcers, burn wounds).
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Serum creatinine level of > 3.0 times the upper limit of normal (ULN).
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Prior radiation therapy (within 6 weeks prior to first IMP (AUP1602-C or placebo) dosing) of any part of the foot/leg bearing the target ulcer under study or total body irradiation.
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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.
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Active or unstable Charcot deformity of the study foot (i.e., foot is erythematous, warm, oedematous, and is actively remodelling).
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Patients with other reasons for wound healing disturbances: e.g., bleeding disorders, vitamin K deficiency, hypocalcaemia, major immune deficiencies.
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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, 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.
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Haemoglobin of less than 8.5 g/dL
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Liver transaminase & total bilirubin levels greater than 3 times ULN.
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Patients receiving haemodialysis or continuous ambulatory peritoneal dialysis (CAPD) therapy.
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Positive for hepatitis B or C virus (HBV, HCV), or human immunodeficiency virus (HIV) (serology test results up to 3 months prior signing ICF accepted).
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Patients with confirmed active infection with SARS-CoV-2 and related disease (COVID-19) at Baseline (V1) prior to first administration of trial medication.
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Planned major surgery during the run-in, treatment and post-treatment efficacy and safety follow-up period of the study.
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Known abuse of alcohol, drugs, or medical products. Tobacco use will be allowed.
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Previous treatment with AUP1602-C.
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Any diagnosed unstable psychological or physical condition including major organ failure that could interfere with compliance.
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Myocardial infarction diagnosed within 1 month prior to start of run-in period.
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White Blood Cells (WBC) < 3.0 X 109 cells/L；> 12.0 X 109 cells/L
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Albumin < 2.5 g/dL (or total protein < 4.0 g/dl).
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The patient has any other factor/reason which may, in the opinion of the Investigator, compromise participation and/or follow-up in the study.
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Pregnant or lactating woman at the time of signing the informed consent and prior to first IMP (AUP1602-C or placebo) dosing.
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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.
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Patients who are institutionalized because of legal or regulatory order.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Institut für Diabetesforschung Muenster GmbH | Münster | Germany | ||
| 2 | Hauärztliche und Diabetologische Praxis | Pirna | Germany | ||
| 3 | Ospedale San Donato | Arezzo | Italy | ||
| 4 | Azienda Ospedaliero-Universitaria Careggi | Firenze | Italy | ||
| 5 | AOU Pisana - Ospedale S. Chiara | Pisa | Italy | ||
| 6 | Ospedale S. Jacopo Pistoia, Diabetologia e Diabetic foot unit Aziendale | Pistoia | Italy | ||
| 7 | Med-Polonia SP. Z O.O. | Poznan | Poland | ||
| 8 | PODOS Klinika Leczenia Ran Podema sp. z o.o. | Warsaw | Poland | ||
| 9 | Lecran Centrum Opieki Nad Ranami | Wrocław | Poland | ||
| 10 | Mikomed | Łódź | Poland |
Sponsors and Collaborators
- Aurealis Oy
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- AT-W-CLI-2022-04