SCARFREE-001: A Phase 2 Dose-Finding and Proof-of-Concept Study of Intradermal Verteporfin for Scar Prevention in Open and Closed Surgical Wounds
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- POSAS (Patient and Observer Scar Assessment Scale)
研究概览
简要总结
The purpose of this clinical trial is to investigate whether the drug verteporfin can reduce the formation of scars in adult patients undergoing a tummy tuck procedure (abdominoplasty).
The main questions the study aims to answer are:
- Whether treatment with verteporfin can reduce scar formation in surgical wounds that are closed with sutures, compared with placebo (saline). This will be assessed based on how the scars look after 3 months using a standardized scar assessment questionnaire (Patient and Observer Scar Assessment Scale).
- Whether treatment with verteporfin can reduce scar formation in small open wounds created after taking small tissue samples (4 mm), compared with placebo. This will also be assessed after 3 months using the same questionnaire.
The researchers will compare three different doses of verteporfin (0.5 mg/mL, 1.0 mg/mL, and 2.0 mg/mL) with placebo. Each participant will receive all three doses as well as placebo, but in different areas of the surgical wound and in different small wounds, allowing comparisons to be made within the same person.
Participants will:
- Undergo a planned abdominoplasty procedure
- During surgery, receive small injections in the skin with either verteporfin or placebo in different parts of the surgical wound.
- Have four small wounds (4 mm) created from tissue samples, which will also be treated with verteporfin or placebo.
- Attend follow-up visits after 1 week, 1 month, and 3 months, where the scars will be examined.
- Have photographs and ultrasound measurements taken of the scars.
- Complete questionnaires about their own assessment of the appearance of the scars.
详细描述
Introduction and Background:
Scar formation after skin injury represents a significant medical challenge with both physical and psychosocial consequences. Scars can cause pain, pruritus, restricted movement, and substantial psychological distress.
While adult wound healing typically results in scar formation, fetal wounds heal with minimal or no scarring, suggesting that regenerative, scarless healing is biologically possible under specific conditions. Recent research has identified the Yes-Associated Protein (YAP)/ Transcriptional Co-Activator with PDZ-binding motif (TAZ) signaling pathway as central to fibrosis development. Inhibition of this pathway has shown promising results in experimental fibrosis models.
YAP is a mechano-sensitive transcription coactivator regulated by the Hippo pathway. Its activity has emerged as a key determinant of whether injured tissues undergo regenerative healing (restoring normal structure) or fibrotic repair (scar formation). Recent studies across multiple organs indicate that the timing and duration of YAP activity is critical: Transient or timely YAP modulation can promote regeneration, whereas sustained YAP activation or complete loss of YAP often skews healing toward fibrosis.
Verteporfin is a Food and Drug Administration (FDA)-approved benzoporphyrin derivative used for treating macular degeneration that also inhibits the YAP/TAZ pathway. Animal studies have demonstrated that verteporfin reduces extracellular matrix deposition in liver, kidney, and retinal fibrosis. Most notably, Mascharak et al. recently showed that a single dose of verteporfin induced scarless wound healing in the Duroc pig, a model with skin healing characteristics closely resembling those of humans. The results were further validated using a human foreskin graft model in nude mice. Despite these promising preclinical results, human evidence for verteporfin's potential as a scar-preventing treatment is lacking. This study represents the first attempt to translate these findings into clinical practice.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
The study is conducted as a partially blinded trial. The operating surgeon administering the intradermal verteporfin is unblinded to ensure correct dose preparation and accurate placement of the IMP. Participants and outcome assessors remain blinded to treatment allocation throughout the study.
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
- •Age ≥ 18 years old
- •Scheduled to undergo elective abdominoplasty amenable to primary closure
- •ASA class I-II
- •Fitzpatrick skin type I-IV
- •Ability to provide written and informed consent and willing to comply with study procedures
排除标准
- •Pregnancy or planned pregnancy within the next 6 months at the time of inclusion
- •Breastfeeding
- •Smoking within the previous 6 months
- •Excessive alcohol intake (>10 units/week for women, >14 units/week for men)
- •Participants who are unable to read, understand and communicate in Danish sufficiently to provide informed consent and comply with study procedures
- •Known conditions of pathological scarring or other conditions affecting wound healing
- •Known hypersensitivity to verteporfin or any excipients
- •Porphyria or other photosensitivity disorders
- •Moderate hepatic dysfunction, defined as:
- •AST or ALT >1.2 × ULN
- •Hypoalbuminemia or prolonged PT
- •Biliary obstruction, defined as:
- •ALP or GGT >1.2 × ULN
- •Abnormal bilirubin
- •Autoimmune or fibrotic skin conditions including (but not limited to):
- •1. Keloids or hypertrophic scars, scleroderma, lupus, GVD, morphea, lichen sclerosus, Ehlers-Danlos syndrome, cutis laxa, Marfan syndrome
- •Current use of photosensitizing medications (e.g. tetracyclines, thiazides, phenothiazines)
- •Any medical condition deemed by the investigator to pose a risk to safety or data integrity
结局指标
主要结局
POSAS (Patient and Observer Scar Assessment Scale)
时间窗: Month 3
Closed wound endpoint: Difference in scar quality between three verteporfin doses (0.5, 1.0, 2.0 mg/mL) and placebo, assessed in sutured incision segments using the Observer component of the POSAS 3.0. Open wound endpoint: Difference in scar quality between three verteporfin doses (0.5, 1.0, 2.0 mg/mL) and placebo, assessed in punch biopsy wounds using the Observer component of the POSAS 3.0. POSAS Observer scores range from 10 (normal skin) to 50 (worst imaginable scar) and includes ten items assessing clinically relevant scar characteristics and overall scar quality. Each wound type (closed and open) will be evaluated independently.
次要结局
- Safety and Tolerability(Day 7, month 1 and month 3)
- MSS (Manchester Scar Scale)(Month 3)
- Ultrasound Assessment of Scar Thickness(Month 1 and 3)
- Photographic Documentation(Day 7, month 1 and 3)
- Patient-Reported Scar Outcomes using SCAR-Q Appearance Scale and SCAR-Q Symptom Scale(Month 1 and 3)