Effect of YAP1-inhibition in Surgical Wounds.

Jöri Pünchera

Status and phase: Not yet enrolling; Phase 2; Phase 1

Conditions: Scar Formation

Treatments: Drug: Verteporfin Injection; Drug: NaCl (placebo)

Study type: Interventional

Funder types: Other

Identifiers

NCT06944249

CCER_Etude 2024- 00419

Details and patient eligibility

About

When we get injured, our body naturally tries to heal. In adults, this healing often leads to scars - thick, stiff tissue known as fibrotic tissue. Unlike normal tissue, fibrotic tissue doesn't function properly and can cause serious health problems, depending on the affected organ. Once it forms, fibrosis is usually permanent.

A good example of the fibrosis process is the healing of our skin: after a cut or surgery, the resulting scar is a type of fibrosis. Special cells called fibroblasts are key players in this process.

Our study looks at a drug called verteporfin, which is already approved both in Europe and the U.S. Previous research on mice and human cells suggests it can reduce or even prevent fibrosis.

We are now testing, clinically, histologically and by scRNA-seq, whether injecting verteporfin into the skin during wound healing, specifically after surgical procedures, can prevent thick, rigid scars from forming. Since the skin is easy to observe and sample, it offers a great model for studying this.

Will verteporfin have an impact on how surgical wounds heal? That's what we aim to find out.

Enrollment: 24 estimated patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Willing and able to provide informed consent as documented by signature
• Age is >/= 18 years and < 56 years (differently said: starting from the 18th birthday to completion of their 55 years)
• Indication for a safety margin excision (5 mm laterally) due to melanoma in situ or severe dysplastic nevi previously completely excised
• Length of initial scar from 15 mm to 50 mm
• The initial lesion was excised on the back (to ensure that all patients undergo their safety margin excision within the internationally accepted timeframe, we will also accept patients requiring the procedure at another anatomical site if a particular batch cannot be filled within 4 weeks of its first patient's enrollment)

Exclusion criteria

• Clinical adenopathy (cervical, axillar, inguinal) defined as a lymph node of more than 1 cm diameter
• Melanoma in situ of lentigo maligna or acral lentiginous type
• Head and neck location
• Diameter of initial lesion above or equal to 3 cm
• Known and documented hypersensitivity to Verteporfin or to any of its excipients: lactose monohydrate, egg phosphatidylglycerol (to simplify we will exclude patients with known and documented allergy to egg protein), dimyristoyl phosphatidylcholine, ascorbyl palmitate, butylated hydroxytoluene (E321)
• Porphyria
• Moderate hepatic dysfunction referred to as any of the following: AST >1.2x upper normal range, ALT >1.2x upper normal range, decreased albumin level, prolongation of PT
• Biliary obstruction referred to as any of the following: ALP >1.2x upper normal range, GGT >1.2x upper normal range, anormal bilirubin level
• Pregnancy referred to as: positive beta-hCG blood test
• Breast-feeding
• Planned pregnancy in the next 6 months
• History of either one of the following: keloids, scleroderma, morphea, lupus erythematosus, nephrogenic systemic fibrosis, graft-versus-host disease, lichen sclerosus, eosinophilic fasciitis, Ehlers-Danlos syndrome, cutis laxa, Marfan syndrome, or pseudoxanthoma elasticum

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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24 participants in 2 patient groups, including a placebo group

Study arm (verteporfin)

Experimental group

Treatment:

Drug: Verteporfin Injection

Placebo arm

Placebo Comparator group

Treatment:

Drug: NaCl (placebo)