A Prospective Randomized Double-Blinded Placebo Controlled, Explorative Phase I Trial to Investigate the Safety and Tolerability of Two Different Doses of Topically Administered APOSEC™ in Healthy Male Subjects With Artificial Dermal Wounds
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- - The number of subjects experiencing Adverse Events, Serious Adverse Events, Dose-limiting toxicities or local tolerability issues as a measure of Safety and Tolerability will be assessed throughout the study period.
研究概览
简要总结
This is a prospective, single center, randomized, double-blinded, placebo-controlled, exploratory phase I clinical trial in healthy male subjects to investigate the safety and tolerability of the cytokine based gel APOSEC™. The proof of safety and tolerability of APOSEC™ is the primary objective. The secondary objective is to measure the extent of wound healing of APOSEC™.
详细描述
APOSEC™ is a human product derived from lyophilized conditional medium of peripheral blood mononuclear cells (PBMC) following 24 hours cultivation after irradiation with 60Gy. The soluble factors produced by these factors (secretome) have regenerative functions and enhance wound healing due to the activation of signaling cascades involved in the cell migration, proliferation and cell survival. The product also possesses strong angiogenic properties as well in vivo and in vitro. APOSEC™ is intended for topical use only, to promote healing of wounds in association with standard wound care. Standard wound care includes initial debridement, avoidance and treatment of wound related infections and a non-weight-bearing regime to decrease the pressure on the wound.
The verum APOSEC™ is processed as lyophilisate and resuspended in Nugel for the final formulation. It will be compared with a placebo, a cell-free parallel produced cell-free control lyophilisate that is finally formulated in Nugel as well.
10 eligible healthy volunteers will consecutively be allocated to 2 different dose groups of APOSEC™ in a dose escalation scheme. The first 5 subjects in group A receive the low dose of APOSEC™ (12.5*10^6 lyophilized PBMC/mL), the subsequent 5 subjects in group B will receive the high dose of APOSEC™ (25*10^6 lyophilized PBMC/mL). Each volunteer will receive both Verum and Placebo on two artificial wounds on the inner upper non-dominant arm. The location of application of the Verum and Placebo (proximal or distal) is subjected to randomization.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy male subjects with 18-50 years of age at the day of inclusion
- •Written informed consent will be obtained prior to screening examination
- •BMI of 19-27 (extremes included)
- •Subjects are in good clinical and mental health as established by medical history, physical examination, vital signs, electrocardiogram, results of biochemistry, hematology, virology and urine analysis at the Screening Visit
排除标准
- •Lack of willingness or capacity to co-operate appropriately
- •Regular use of medications
- •History of malignancies
- •History of wound healing abnormalities
- •Chronic dermatological disease
- •History of chronic autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease, diabetes mellitus, Lupus erythematodus
- •Tattoos in the region of planned punch biopsy
- •Positive HIV serology or evidence of active hepatitis
- •Allergy requiring medical treatment within 4 weeks before study initiation
- •Active infection of fever > 38°C within 7 days prior randomisation
- •Blood donation within 4 weeks before study initiation
- •Clinically relevant abnormalities in the laboratory testing, vital signs, ECG or physical examination
- •Participation in another clinical trial with an investigational day within 4 weeks before study participation
研究组 & 干预措施
Group A: Low dose
Each volunteer in group A will receive both Verum and Placebo.
The Verum lyophilized APOSEC™ is derived from 12.5*10^6 cells/ml irradiated lyophilized PBMC. The lyophilizate will be resuspended in 0.9% 200 µL NaCl and finally formulated in 800 µL Nugel.
As Placebo a cell-free control lyophilisate resuspended in 0.9% 200 µL NaCl and finally formulated with 800 µL Nugel is used. The location of application on the inner upper arm (proximal or distal) of Verum and Placebo will be randomized.
干预措施: APOSEC™ for cutaneous use (Drug)
Group B: High dose
Each volunteer in group B will receive both Verum and Placebo.
The Verum lyophilized APOSEC™ is derived from 25*10^6 cells/ml irradiated lyophilized PBMC. The lyophilizate will be resuspended in 0.9% 200 µL NaCl and finally formulated in 800 µL Nugel.
As Placebo a cell-free control lyophilisate resuspended in 0.9% 200 µL NaCl and finally formulated with 800 µL Nugel is used. The location of application on the inner upper arm (proximal or distal) of Verum and Placebo will be randomized.
干预措施: APOSEC™ for cutaneous use (Drug)
结局指标
主要结局
- The number of subjects experiencing Adverse Events, Serious Adverse Events, Dose-limiting toxicities or local tolerability issues as a measure of Safety and Tolerability will be assessed throughout the study period.
时间窗: day 0 to day 17
The primary objective is to investigate safety and tolerability of two different doses of APOSEC™ during the treatment and follow-up period of the study. Correspondingly, the primary endpoints are Adverse Events, Serious Adverse Events and Dose-limiting toxicities. Assessment of local tolerability or any adverse events will be accomplished by a score (expanding from no visible reaction to severe erythema with induration, vesicles / bullae / pustles / erosion / ulceration). Presence of local pain will be assessed by a Visual Analogue Scale (VAS).
次要结局
- - Scarring formation with respect to induration of palpable scar tissue.(day 7)
- Presence or absence of complete wound closure at End of Treatment (EOT) after Verum vs. Placebo administration.(day 7)
- - Changes in wound size between baseline and End of Treatment (EOT) assessed by photographic analysis.(day 1 to day 7)
- Presence or absence of re-epithelization and angiogenesis assessed by the markers CD31 and vWF.(day 1 / day 7)
- Investigator satisfaction assessment on applicability of the gel(day 0 - day 6)
研究者
Michael Wolzt
Univ.-Prof. Dr.med.univ. Michael Wolzt
Medical University of Vienna