A Prospective, Double-Blind, Cross-Over, Pilot Study to Assess Safety and Efficacy of Topical Sirolimus 2% in the Treatment of Plantar Blistering in Patients With Epidermolysis Bullous Simplex (EBS)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Foot Health Status Questionnaire, Physical Activity Domain Score
研究概览
简要总结
Epidermolysis bullosa (EB) simplex is a rare orphan disease caused by a mutation in DNA leading to abnormal dominant keratins in the skin. Patients with EB simplex develop lifelong painful thick soles on their feet, and current standard of care is supportive. This pilot study will target the dominant mutant keratin proteins in the skin to ameliorate the severity of EB simplex. The purpose is to improve the function of EB simplex feet with an application of topical sirolimus, 2%. The investigators plan on inhibiting the mTOR pathway to down regulate the translation of defective keratin proteins and work through anti proliferative pathways.
详细描述
The proposed 40 week pilot study being conducted is a prospective, double-blind, randomized, placebo-controlled crossover study. Participants will be assigned to treat both feet with either topical sirolimus, 2% cream daily or placebo (vehicle-control) for 12 weeks, followed by a 4 week washout period, then re-treatment to both feet will occur by the cross-over intervention.
These studies will exploit the naturally occurring transcriptional regulation of keratin sequences, the known gene aberration causing EB simplex, and assess the potential for mTOR pathway inhibition in treatment of the patient's plantar lesions. The objective of this study is to assess (1) the safety of topical rapamycin for plantar lesions for the treatment of EB simplex, and 2) test if topical rapamycin to improves the clinical severity of lesional skin, including pain and itch, in subjects with EB simplex at the end of treatment versus baseline and compared to an intrasubject placebo treated control. Wound size measurement, quality of life evaluation will be assessed using epidermolysis bullosa (QOLEB), and EB disease activity and Scarring Index (EBDASI). With the results of this pilot study, physicians would be able to transition from supportive care (the current state of the art for EB simplex) to targeted molecular therapeutics, leading to improved mobility and quality of life for patients with EB simplex.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 4 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must:
- •Be capable of understanding the purpose and risks of the study and sign a written Informed Consent Form (ICF); Legally authorized representative of subjects willing and able to give consent for children 4-18 yo.
- •Be male or female with a diagnosis of EBS
- •Minimum EBDASI feet activity score of 2/10
- •Age - 4 years or older
- •Ability to complete 12 study visits within a 40-week period, each for approximately 30-60 minutes.
- •Anticipated life expectancy ≥52 weeks.
- •Males and females of childbearing potential should be using an effective means of contraception.
- •Laboratory values within the range of normal for the participating institution unless the PI feels they are not clinically relevant
- •Be able to comply with all study requirements
排除标准
- •Allergy to sirolimus or components of the vehicle ointment
- •Pregnancy, breast feeding
- •Prior history of liver disease
- •Serious known concurrent medical illness or infection, which could potentially present a safety risk and/or prevent compliance with the requirements of the treatment program.
- •Known immunodeficiency virus or syndrome including those with:
- •Acquired Immunodeficiency Syndrome (AIDS)
- •Human Immunodeficiency Virus (HIV)
- •Hepatitis B
- •Prior history of grafting surgeries or other surgeries in the dermatologic treatment area
- •History of significant condition in the dermatologic treatment area such as trauma, which could impair evaluation for the treatment of EBS or non-healing chronic wound.
- •Use of other investigational drugs within 30 days of the screening visit and/or has not recovered from any side effects of prior investigational drugs or procedure in the affected area (e.g., a biopsy).
- •Use of acitretin within the last 1 month
- •Use of Roaccutane within last 3 months
- •Botox injections to the feet within the last 6 months.
- •Participant is planning extra physical activities within the next 3 months.
- •Amputated foot
研究组 & 干预措施
Sirolimus, then Placebo
Participants will receive Sirolimus, 2% topical ointment for 12 weeks followed by placebo to match sirolimus for 12 weeks.
干预措施: Sirolimus, 2% (Drug)
Sirolimus, then Placebo
Participants will receive Sirolimus, 2% topical ointment for 12 weeks followed by placebo to match sirolimus for 12 weeks.
干预措施: Vehicle (Drug)
Placebo, then Sirolimus
Participants will receive placebo to match sirolimus for 12 weeks followed by Sirolimus, 2% topical ointment for 12 weeks.
干预措施: Sirolimus, 2% (Drug)
Placebo, then Sirolimus
Participants will receive placebo to match sirolimus for 12 weeks followed by Sirolimus, 2% topical ointment for 12 weeks.
干预措施: Vehicle (Drug)
结局指标
主要结局
Foot Health Status Questionnaire, Physical Activity Domain Score
时间窗: Week 0 and week 12 of the respective treatment period
Physical Activity was assessed utilizing the validated Foot Health Status Questionnaire (FHSQ). Low Score (0) means severely limited in performing a broad range of physical activities. High Score (100) means can perform all desired physical activities. Data are reported per intervention.
Trough Concentration of Sirolimus
时间窗: Week 12
Trough measurements were taken prior to topical sirolimus administration at the week 12 study visit.
Foot Health Status Questionnaire, Foot Function Domain Score
时间窗: Week 0 and week 12 of the respective treatment period
Foot function was assessed utilizing the validated Foot Health Status Questionnaire (FHSQ). Low Score (0) means severely limited in performing a broad range of physical activities. High Score (100) means can perform all desired physical activities. Data are reported per intervention.
次要结局
- Child Dermatological Quality of Life Questionnaire Score(Week 0 and week 12 of the respective treatment period)
- Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) Disease Severity Scale Score(Week 0 and week 12 of the respective treatment period)
- Average Steps Per Day Assessed by FitBit® / Pedometer(12 weeks)
- Foot Plantar Pressure Measurements(Baseline, week 12)
- 5-D Pruritus Scale Score(Week 0 and week 12 of the respective treatment period)
- Plantar Defect Size Using 3D Photography(Baseline, week 12)
- Change in mTOR Pathway Inhibition(Baseline, week 12)
研究者
Joyce Teng
Director of Pediatric Dermatology
Stanford University