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.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 43
- 试验地点
- 8
- 主要终点
- Grading of clinical signs of wound inflammation
研究概览
简要总结
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)
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Aurase wound gel X0
Cohort 1: Aurase wound gel x0 dose concentration
干预措施: Aurase Wound gel (Drug)
Aurase wound gel X1
Cohort 2: Aurase wound gel x1 dose concentration
干预措施: Aurase Wound gel (Drug)
Aurase wound gel X1.8
Cohort 3: Aurase wound gel X1.8 dose concentration
干预措施: Aurase Wound gel (Drug)
Aurase wound gel X5
Cohort 4: Aurase wound gel X5 dose concentration
干预措施: Aurase Wound gel (Drug)
Aurase wound gel X9
Cohort 5: Aurase wound gel X9 dose concentration
干预措施: Aurase Wound gel (Drug)
结局指标
主要结局
Grading of clinical signs of wound inflammation
时间窗: Pre-dosing and Post-dose at day 1 (baseline) through to day 29 (end of study)
5-point ordinal grading scale (1 \[none\] to 5 \[severe\] ) of wound erythema, oedema made by clinical assessor by Visual Assessment (VA)
Incidence of treatment emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: From the time of signing informed consent up to the last visit (Day 29)
Change in study wound itch burden from baseline measured by Numerical Rating Scale (NRS)
时间窗: Pre-dose at day 1 (baseline) through to day 29 (end of study)
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
Change in study wound pain burden from baseline measured by Numerical Rating Scale (NRS)
时间窗: Pre-dosing and post-dose at day 1 (baseline) through to day 29 (end of study)
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
Grading of clinical signs of wound infection
时间窗: Day 1 (baseline) through to day 29 (end of study)
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)
次要结局
- 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 wound compared to baseline(Day 1 (baseline), day 5, day 12, day 19, day 29 (end of study))
- Assessment of systemic clotting factors in plasma(Day 0 (Screening), day 1 (Baseline), day 8 and day 29 (end of study) or early termination visit (if applicable))
- 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(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))