Treatment of Diabetic Foot Ulcers With AUP1602-C

NCT04281992 | Completed Phase 1

• 2 other identifiers: AP-W-CLI-2018-82018-003415-22
• Study Type: interventional
• Target: 26
• Locations: 2 countries
• Sites: 2

Brief Summary

This is a two-part phase 1/2A study performed in diabetic foot ulcer (DFU) patients with chronic non-healing wounds to investigate the safety and efficacy of AUP1602-C.

Conditions

Diabetic Foot Ulcer

Outcome Measures

Primary Outcomes (3)

• Incidence of adverse events (AEs) and potential dose-limiting toxicities (DLTs)

  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

  4 weeks

• Incidence of Treatment-Emergent Adverse Events

  • Incidence of AEs

  6 months

• Incidence of Wound Closure

  * Percentage (%) of patients with a target ulcer achieving complete wound closure * Percentage (%) of wound size reduction (wound area measurements in cm\^2)

  6 months

Secondary Outcomes (9)

• Incidence of Wound Closure

  6 months

• Incidence of ulcer recurrence

  6 months

• Incidence of Wound Infections

  6 months

• Incidence of surgical procedures

  6 months

• Changes in Quality of Life according to EQ-5D-5L

  6 months

Study Arms (1)

AUP1602-C

EXPERIMENTAL

AUP1602-C will be administered topically once or repeatedly three times per week during the treatment period.

Biological: AUP1602-C

Interventions

AUP1602-C BIOLOGICAL

AUP1602-C is topically applied on chronic wounds and covered by wound dressing.

AUP1602-C

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients aged 18 to 80 years
• Patients with DM of type 1 or 2 having a glycosylated haemoglobin (HbA1c) of ≤11% and a serum creatinine level of ≤1.5 times the upper limit of normal (ULN)
• 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 areato 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 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 \<30% reduction in size in response to SoC during the 2-week screening period
• Target ulcer appropriately debrided (\<10% black and at least 50% of red/pink on a colorimetric scale)
• Ulcer and periwound tissue suitable to using film dressings (i.e. no contraindications \[e.g.: excessive exudation, maceration\] and sufficient periwound space to hold the dressing)
• Patients with more than one ulcer will be included if ulcers are separated by a minimum of 5 cm healthy tissue but only one target ulcer will be selected for the investigational treatment (based on investigator decision)
• Patients with an ankle brachial index (ABI) ≥0.7 on the foot with the target ulcer
• Patients with an assessment of the baseline level of neuropathy of the foot using Semmes-Weinstein monofilaments
• Patients must adhere to wear therapeutic shoes or off-loading footwear if indicated

You may not qualify if:

• 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
• 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®)
• Current or previous (within 2 weeks prior to first study drug dosing) treatment with active wound care agents (e.g. local and systemic antibiotics or silver dressings)
• Current or previous (within 2 weeks prior to first study drug dosing) use of corticosteroids and immunosuppressants
• Known hypersensitivity to any of the investigational drug or vehicle components
• Ulcer of University of Texas Grade ≥2, with deep abscess, or gangrene
• Target ulcer with known or suspected active infection which requires antimicrobials. Any antibiotic therapy must be completed or discontinued within 2 weeks prior to first study drug dosing
• Target ulcer positive for MRSA
• Target ulcer other than chronic non-healing DFU (e.g. pressure ulcers, burn wounds)
• 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
• Sickle-cell anemia, Reynaud's, or other peripheral vascular disease including venous leg ulcers
• 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 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
• Active Charcot deformity of the study foot (i.e. foot is erythematous, warm, edematous, and is actively remodeling)
• Patients with other reasons for wound healing disturbances: e.g. bleeding disorders, vitamin K deficiency, hypocalcemia, major immune deficiencies
• 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

Sponsors & Collaborators

• Aurealis Oy: lead

Study Sites (2)

Medizinische Hochschule Hannover (MHH) CRC Core Facility

Hanover, Germany

Location

Mikomed

Lodz, Poland

Location

Related Publications (1)

• Schindler C, Mikosinski J, Mikosinski P, Karkkainen HR, Sanio M, Kurkipuro J, Mierau I, Smith W, Vartiainen A, Decory L, Weber D, Wirth T, Yrjanheikki J, Schellong S, Samaranayake H. Multi-target gene therapy AUP1602-C to improve healing and quality of life for diabetic foot ulcer patients: a phase I, open-label, dose-finding study. Ther Adv Endocrinol Metab. 2024 Nov 4;15:20420188241294134. doi: 10.1177/20420188241294134. eCollection 2024.

  PMID: 39838970 DERIVED

MeSH Terms

Conditions

Diabetic Foot

Condition Hierarchy (Ancestors)

Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Foot Ulcer; Leg Ulcer; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Diabetic Neuropathies

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Analyses for phase 1 part will be done by cohort and analyses for phase 2A part will be done by treatment arms.

Study Record Dates

• First Submitted: February 14, 2020
• First Posted: February 24, 2020
• Study Start: January 28, 2020
• Primary Completion: March 20, 2023
• Study Completion: March 20, 2023
• Last Updated: September 28, 2023

Record last verified: 2023-09

Locations

PL (1); DE (1)