Clinical Trial Enzyme Application Targeting Venous Leg Ulcers (CLEANVLU)

An Open Label, Multiple Ascending Dose Study of the Safety, Tolerability and Bio-effect of Aurase for Wound Debridement in Patients With Venous Leg Ulcers.

This is an adaptive open-label, first-in-human (Phase IIa) study designed to assess the safety (and efficacy) of Aurase Wound Gel, an enzymatic debridement product, intended for topical application to sloughy venous leg ulcers (VLU)

Study Overview

• Status: Completed
• Conditions: Venous Leg Ulcer; Leg Injuries and Disorders
• Intervention / Treatment: Drug: Aurase Wound gel

Detailed Description

The study has been designed as a dose escalation study, and will serially explore increasing concentrations of the Aurase enzyme in a relevant patient population. Five cohorts (of 10 patients each, except cohort 1 with 5 patients), will receive standard of care supplemented with increasing concentrations of Aurase and will be assessed for clinical tolerability at the wound site, systemic safety and efficacy (extent of wound debridement) over a period of 4 weeks. Patients will receive a total of 12 doses of Aurase Wound Gel. At the end of the study, patients will revert to standard of care only.

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 2

Contacts and Locations

Study Locations

• Hungary
  • Budapest, Hungary, 1036
    • Obudai Egeszsegugyi Centrum Kft.
  • Budapest, Hungary
    • Uno Medical Trials
• United Kingdom
  • Hull, United Kingdom, HU32JZ
    • Hull Royal Infirmary
• United States
  • California
    • San Francisco, California, United States, 94117
      • Center for Clinical Research
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Jacksonville
    • Miami, Florida, United States, 33146
      • University of Miami
    • Miami, Florida, United States, 33143
      • Doctors Research Network
  • Virginia
    • Salem, Virginia, United States, 24153
      • FASMA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female patients aged 18 years and older at screening
• Patients with at least one defined Venous Leg Ulcer (VLU) suitable for treatment that is no smaller than 2cm2 but no larger than 50cm2
• Presence of devitalised tissue within the reference ulcer suitable for debridement therapy
• Confirmed, clinically diagnosed VLU (30 days or more) which has been present for less than 2 years
• Willing and able to attend and comply with study visits and study related activities

Exclusion Criteria:

• Diabetic Foot Ulcer
• A clinical history of a bleeding disorder including haemophilia, purpura, or thrombocytopenia
• Current or history of use of anti-thrombotic therapy less than 7 days prior to screening.
• Stage 4 or 5 chronic kidney disease, defined as estimated glomerular filtration rate (eGFR) less than or equal to 30 mL/min
• Reference ulcer has active infection or florid oedema at screening
• Oral or intravenous antibiotics for any indication within 72 hours of screening
• Reference ulcer has exposed tendons, ligaments, muscle, or bone
• Active osteomyelitis, cellulitis or gangrene in either leg
• Patients with amputation above a trans metatarsal amputation (TMA) in the target leg
• Planned vascular surgery, angioplasty, or thrombolysis procedures within the study period, or 4 weeks before screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aurase wound gel X0; Cohort 1: Aurase wound gel x0 dose concentration	Drug: Aurase Wound gel; Aurase Wound Gel is reconstituted from Aurase Component A (a hydrogel) and Aurase Component B (stabilised solutions of Aurase enzyme). By diluting different strengths of Aurase Component B with Component A, specific concentrations of Aurase Wound Gels with differing Aurase contents are yielded.
Experimental: Aurase wound gel X1; Cohort 2: Aurase wound gel x1 dose concentration	Drug: Aurase Wound gel; Aurase Wound Gel is reconstituted from Aurase Component A (a hydrogel) and Aurase Component B (stabilised solutions of Aurase enzyme). By diluting different strengths of Aurase Component B with Component A, specific concentrations of Aurase Wound Gels with differing Aurase contents are yielded.
Experimental: Aurase wound gel X1.8; Cohort 3: Aurase wound gel X1.8 dose concentration	Drug: Aurase Wound gel; Aurase Wound Gel is reconstituted from Aurase Component A (a hydrogel) and Aurase Component B (stabilised solutions of Aurase enzyme). By diluting different strengths of Aurase Component B with Component A, specific concentrations of Aurase Wound Gels with differing Aurase contents are yielded.
Experimental: Aurase wound gel X5; Cohort 4: Aurase wound gel X5 dose concentration	Drug: Aurase Wound gel; Aurase Wound Gel is reconstituted from Aurase Component A (a hydrogel) and Aurase Component B (stabilised solutions of Aurase enzyme). By diluting different strengths of Aurase Component B with Component A, specific concentrations of Aurase Wound Gels with differing Aurase contents are yielded.
Experimental: Aurase wound gel X9; Cohort 5: Aurase wound gel X9 dose concentration	Drug: Aurase Wound gel; Aurase Wound Gel is reconstituted from Aurase Component A (a hydrogel) and Aurase Component B (stabilised solutions of Aurase enzyme). By diluting different strengths of Aurase Component B with Component A, specific concentrations of Aurase Wound Gels with differing Aurase contents are yielded.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)		From the time of signing informed consent up to the last visit (Day 29)
Change in study wound pain burden from baseline measured by Numerical Rating Scale (NRS)	Subject will be asked to describe the level of wound pain on a scale of 0-10: 0 being no pain, 10 being worst imaginable pain	Pre-dosing and post-dose at day 1 (baseline) through to day 29 (end of study)
Change in study wound itch burden from baseline measured by Numerical Rating Scale (NRS)	Subject will be asked to describe the level of wound itch on a scale of 0-10: 0 being no itch, 10 being worst imaginable itch	Pre-dose at day 1 (baseline) through to day 29 (end of study)
Grading of clinical signs of wound inflammation	5-point ordinal grading scale (1 [none] to 5 [severe] ) of wound erythema, oedema made by clinical assessor by Visual Assessment (VA)	Pre-dosing and Post-dose at day 1 (baseline) through to day 29 (end of study)
Grading of clinical signs of wound infection	5-point ordinal grading scale (1 [none] to 5 [severe] ) of wound exudate and induration or grading of presence/absence of wound bleeding and infection made by clinical assessor by Visual Assessment (VA)	Day 1 (baseline) through to day 29 (end of study)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in surface area of wound compared to baseline		Day 1 (baseline), day 5, day 12, day 19, day 29 (end of study)
Change in surface area of devitalised tissue (slough, eschar) compared to baseline		Day 1 (baseline), day 5, day 12, day 19, day 29 (end of study)
Change in surface area of granulation tissue from baseline		Day 1 (baseline) , day 5, day 12, day 19, day 29 (end of study)
Number of patients achieving 100% debridement	Determination of 100% debridement made by clinical assessor upon assessment of wound at each study visit	Day 1 (baseline), day 5, day 12, day 19, day 29 (end of study)
Systemic absorption of Aurase enzyme assessed through pharmacokinetic profiling of blood samples		Pre-dose and Post dose at day 1 (baseline) and day 29 (end of study) or early termination visit (if applicable)
Assessment of the presence of antibodies to Aurase in plasma (Anti-Drug Antibody [ADA] activity) through applicable laboratory analysis of blood samples		Day 1 (Baseline) and day 29 (end of study) or early termination visit (if applicable)
Assessment of systemic clotting factors in plasma	Activated partial thromboplastin time (APTT)/ prothrombin time (PT)/Fibrinogen plasma concentrations determined through laboratory analysis of blood samples	Day 0 (Screening), day 1 (Baseline), day 8 and day 29 (end of study) or early termination visit (if applicable)

Collaborators and Investigators

• Sponsor: SolasCure Limited

Study record dates

Study Major Dates

• Study Start (Actual): August 9, 2021
• Primary Completion (Actual): February 6, 2023
• Study Completion (Actual): February 6, 2023

Study Registration Dates

• First Submitted: June 25, 2021
• First Submitted That Met QC Criteria: July 1, 2021
• First Posted (Actual): July 9, 2021

Study Record Updates

• Last Update Posted (Actual): February 15, 2023
• Last Update Submitted That Met QC Criteria: February 14, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Wounds; Leg Ulcer; Venous Leg Ulcer; Chronic Leg Ulcer
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Wounds and Injuries; Skin Ulcer; Varicose Veins; Ulcer; Leg Ulcer; Varicose Ulcer; Leg Injuries
• Other Study ID Numbers: SC-VLU-001; 2020-001392-32 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No