Effect of YAP1-inhibition in Surgical Wounds.

NCT ID: NCT06944249

Last Updated: 2025-04-25

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-05-08
• Study Completion Date: 2026-07-31

Brief Summary

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.

Conditions

Scar Formation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Study arm (verteporfin)

Group Type: EXPERIMENTAL

Verteporfin Injection

Intervention Type: DRUG

During the safety margin excision, the study drug (Verteporfin) will be injected into the wound before suturing.

Placebo arm

Group Type: PLACEBO_COMPARATOR

NaCl (placebo)

Intervention Type: DRUG

During the safety margin excision, the placebo (NaCl) will be injected into the wound before suturing.

Interventions

NaCl (placebo)

During the safety margin excision, the placebo (NaCl) will be injected into the wound before suturing.

Intervention Type: DRUG

Verteporfin Injection

During the safety margin excision, the study drug (Verteporfin) will be injected into the wound before suturing.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Geneva, Switzerland

OTHER

Sponsor Role: collaborator

University Hospital, Geneva

OTHER

Sponsor Role: collaborator

Jöri Pünchera

OTHER

Sponsor Role: lead

Responsible Party

Jöri Pünchera

attending physician, M.D.

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Jöri Pünchera, M.D.

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Geneva

Central Contacts

Jöri Pünchera, M.D.

Role: CONTACT

jpuc@hug.ch

+41223729450

Michael Mühlstädt, M.D.

Role: CONTACT

mmuh@hug.ch

+41223729450

References

Mascharak S, desJardins-Park HE, Davitt MF, Griffin M, Borrelli MR, Moore AL, Chen K, Duoto B, Chinta M, Foster DS, Shen AH, Januszyk M, Kwon SH, Wernig G, Wan DC, Lorenz HP, Gurtner GC, Longaker MT. Preventing Engrailed-1 activation in fibroblasts yields wound regeneration without scarring. Science. 2021 Apr 23;372(6540):eaba2374. doi: 10.1126/science.aba2374.

Reference Type: BACKGROUND

PMID: 33888614 (View on PubMed)

Jiang D, Correa-Gallegos D, Christ S, Stefanska A, Liu J, Ramesh P, Rajendran V, De Santis MM, Wagner DE, Rinkevich Y. Two succeeding fibroblastic lineages drive dermal development and the transition from regeneration to scarring. Nat Cell Biol. 2018 Apr;20(4):422-431. doi: 10.1038/s41556-018-0073-8. Epub 2018 Mar 28.

Reference Type: BACKGROUND

PMID: 29593327 (View on PubMed)

Jiang D, Rinkevich Y. Converting fibroblastic fates leads to wound healing without scar. Signal Transduct Target Ther. 2021 Sep 1;6(1):332. doi: 10.1038/s41392-021-00738-6. No abstract available.

Reference Type: BACKGROUND

PMID: 34471094 (View on PubMed)

Other Identifiers

CCER_Etude 2024- 00419

Identifier Type: -

Identifier Source: org_study_id