Effect of YAP1-inhibition in Surgical Wounds.

NCT06944249 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: CCER_Etude 2024- 00419
• Study Type: interventional
• Target: 24
• Locations: 0 countries
• Sites: N/A

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

Keywords

YAP1; Verteporfin; Scar; Fibrosis; Wound healing

Outcome Measures

Primary Outcomes (1)

• Quantification of the profibrotic mesenchymal fibroblast subpopulation in the study group compared to the placebo group.

  For comparison between groups, skin samples of the repaired tissue taken at visit 4 (Day 90 +/- 10) will be compared between the patients of both groups.

  There are 90 +/- 10 days between visit 1 and visit 4.

Secondary Outcomes (6)

• The changes of fibroblast subpopulations, clusters, and their different cell-cell interactions in both groups before and after the study intervention.

  There are 90 +/- 10 days between visit 1 and visit 4.

• Quantification of pilosebaceous units and profibrotic activity (quantity of collagen I and III and its ratio, fibronectin, α-SMA, nuclear localization of YAP1 and En1-staining) and its change over time

  There are 90 +/- 10 days between visit 1 and visit 4.

• Quantification of the different fibroblast subpopulations in unwounded, healthy skin.

  The initial excision will take place 21 to 54 days before V1.

• The changes of different fibroblast subpopulations passing from unwounded skin to scarred, to repaired skin.

  There are a maximum of 56 days + 90 +/- 10 days between the inital mole removal and visit 4.

• Comparison of the clinical outcomes of the scars in both groups.

  There are a minimum of 154 and a maximum of 178 days between visit 3 and visit 5.

Study Arms (2)

Study arm (verteporfin)

EXPERIMENTAL

Drug: Verteporfin Injection

Placebo arm

PLACEBO COMPARATOR

Drug: NaCl (placebo)

Interventions

NaCl (placebo) DRUG

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

Placebo arm

Verteporfin Injection DRUG

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

Study arm (verteporfin)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Jöri Pünchera: lead
• University of Geneva, Switzerland: collaborator
• University Hospital, Geneva: collaborator

Related Publications (3)

• 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.

  PMID: 33888614 BACKGROUND

• 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.

  PMID: 29593327 BACKGROUND

• 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.

  PMID: 34471094 BACKGROUND

MeSH Terms

Conditions

Cicatrix; Fibrosis

Interventions

Verteporfin

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Porphyrins; Tetrapyrroles; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Jöri Pünchera, M.D.

  University Hospital, Geneva

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jöri Pünchera, M.D.

CONTACT

+41223729450; jpuc@hug.ch

Michael Mühlstädt, M.D.

CONTACT

+41223729450; mmuh@hug.ch

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: attending physician, M.D.

Study Record Dates

• First Submitted: April 17, 2025
• First Posted: April 25, 2025
• Study Start: May 8, 2025
• Primary Completion: April 30, 2026
• Study Completion (Estimated): July 31, 2026
• Last Updated: April 25, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share