Clinical Trial Enzyme Application Targeting Venous Leg Ulcers (CLEANVLU)
Primary Purpose
Venous Leg Ulcer, Leg Injuries and Disorders
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Aurase Wound gel
Sponsored by
About this trial
This is an interventional treatment trial for Venous Leg Ulcer focused on measuring Wounds, Chronic Leg Ulcer, Leg Ulcer, Venous Leg Ulcer
Eligibility Criteria
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 slough 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
Sites / Locations
- Center for Clinical Research
- Mayo Clinic Jacksonville
- Doctors Research Network
- University of Miami
- FASMA
- Óbudai Egészségügyi Centrum Kft.
- Uno Medical Trials
- Hull Royal Infirmary
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Aurase wound gel X0
Aurase wound gel X1
Aurase wound gel X1.8
Aurase wound gel X5
Aurase wound gel X9
Arm Description
Cohort 1: Aurase wound gel x0 dose concentration
Cohort 2: Aurase wound gel x1 dose concentration
Cohort 3: Aurase wound gel X1.8 dose concentration
Cohort 4: Aurase wound gel X5 dose concentration
Cohort 5: Aurase wound gel X9 dose concentration
Outcomes
Primary Outcome Measures
Incidence of treatment emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
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
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
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)
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)
Secondary Outcome Measures
Change in surface area of wound compared to baseline
Change in surface area of devitalised tissue (slough, eschar) compared to baseline
Change in surface area of granulation tissue from baseline
Number of patients achieving 100% debridement
Determination of 100% debridement made by clinical assessor upon assessment of wound at each study visit
Systemic absorption of Aurase enzyme assessed through pharmacokinetic profiling of blood samples
Assessment of the presence of antibodies to Aurase in plasma (Anti-Drug Antibody [ADA] activity) through applicable laboratory analysis of blood samples
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04956900
Brief Title
Clinical Trial Enzyme Application Targeting Venous Leg Ulcers
Acronym
CLEANVLU
Official Title
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.
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Completed
Study Start Date
August 9, 2021 (Actual)
Primary Completion Date
February 6, 2023 (Actual)
Study Completion Date
February 6, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
SolasCure Limited
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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)
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Venous Leg Ulcer, Leg Injuries and Disorders
Keywords
Wounds, Chronic Leg Ulcer, Leg Ulcer, Venous Leg Ulcer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Model Description
Cohort study design with each cohort having an ascending dose of Aurase wound gel. At the time of initiation, 5 sequential cohorts are planned.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
43 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Aurase wound gel X0
Arm Type
Experimental
Arm Description
Cohort 1: Aurase wound gel x0 dose concentration
Arm Title
Aurase wound gel X1
Arm Type
Experimental
Arm Description
Cohort 2: Aurase wound gel x1 dose concentration
Arm Title
Aurase wound gel X1.8
Arm Type
Experimental
Arm Description
Cohort 3: Aurase wound gel X1.8 dose concentration
Arm Title
Aurase wound gel X5
Arm Type
Experimental
Arm Description
Cohort 4: Aurase wound gel X5 dose concentration
Arm Title
Aurase wound gel X9
Arm Type
Experimental
Arm Description
Cohort 5: Aurase wound gel X9 dose concentration
Intervention Type
Drug
Intervention Name(s)
Aurase Wound gel
Intervention Description
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.
Primary Outcome Measure Information:
Title
Incidence of treatment emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame
From the time of signing informed consent up to the last visit (Day 29)
Title
Change in study wound pain burden from baseline measured by Numerical Rating Scale (NRS)
Description
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
Time Frame
Pre-dosing and post-dose at day 1 (baseline) through to day 29 (end of study)
Title
Change in study wound itch burden from baseline measured by Numerical Rating Scale (NRS)
Description
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
Time Frame
Pre-dose at day 1 (baseline) through to day 29 (end of study)
Title
Grading of clinical signs of wound inflammation
Description
5-point ordinal grading scale (1 [none] to 5 [severe] ) of wound erythema, oedema made by clinical assessor by Visual Assessment (VA)
Time Frame
Pre-dosing and Post-dose at day 1 (baseline) through to day 29 (end of study)
Title
Grading of clinical signs of wound infection
Description
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)
Time Frame
Day 1 (baseline) through to day 29 (end of study)
Secondary Outcome Measure Information:
Title
Change in surface area of wound compared to baseline
Time Frame
Day 1 (baseline), day 5, day 12, day 19, day 29 (end of study)
Title
Change in surface area of devitalised tissue (slough, eschar) compared to baseline
Time Frame
Day 1 (baseline), day 5, day 12, day 19, day 29 (end of study)
Title
Change in surface area of granulation tissue from baseline
Time Frame
Day 1 (baseline) , day 5, day 12, day 19, day 29 (end of study)
Title
Number of patients achieving 100% debridement
Description
Determination of 100% debridement made by clinical assessor upon assessment of wound at each study visit
Time Frame
Day 1 (baseline), day 5, day 12, day 19, day 29 (end of study)
Title
Systemic absorption of Aurase enzyme assessed through pharmacokinetic profiling of blood samples
Time Frame
Pre-dose and Post dose at day 1 (baseline) and day 29 (end of study) or early termination visit (if applicable)
Title
Assessment of the presence of antibodies to Aurase in plasma (Anti-Drug Antibody [ADA] activity) through applicable laboratory analysis of blood samples
Time Frame
Day 1 (Baseline) and day 29 (end of study) or early termination visit (if applicable)
Title
Assessment of systemic clotting factors in plasma
Description
Activated partial thromboplastin time (APTT)/ prothrombin time (PT)/Fibrinogen plasma concentrations determined through laboratory analysis of blood samples
Time Frame
Day 0 (Screening), day 1 (Baseline), day 8 and day 29 (end of study) or early termination visit (if applicable)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Center for Clinical Research
City
San Francisco
State/Province
California
ZIP/Postal Code
94117
Country
United States
Facility Name
Mayo Clinic Jacksonville
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
Doctors Research Network
City
Miami
State/Province
Florida
ZIP/Postal Code
33143
Country
United States
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33146
Country
United States
Facility Name
FASMA
City
Salem
State/Province
Virginia
ZIP/Postal Code
24153
Country
United States
Facility Name
Óbudai Egészségügyi Centrum Kft.
City
Budapest
ZIP/Postal Code
1036
Country
Hungary
Facility Name
Uno Medical Trials
City
Budapest
Country
Hungary
Facility Name
Hull Royal Infirmary
City
Hull
ZIP/Postal Code
HU32JZ
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
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Clinical Trial Enzyme Application Targeting Venous Leg Ulcers
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