Study of LUT017 Gel to Improve Healing of Skin Wounds After Removal of Benign Lesions in Healthy Adults

A Phase 1, Open-Label Clinical Trial to Assess the Safety, Tolerability, and Preliminary Efficacy Study of a Single Dose of Topically Administered LUT017 Gel for Cutaneous Wound Healing in Volunteers With Healthy Skin

This is a Phase 1 research study evaluating the safety and potential benefits of a topical gel called LUT017 in helping skin wounds heal after minor skin procedures. The study will enroll healthy adults who are already scheduled to have two benign (non-cancerous) skin lesions, such as moles, removed as part of routine care.

When the lesions are removed, two small wounds will be created. One wound will be treated with LUT017 gel, and the other will be treated with a placebo gel that does not contain active medication. This allows each participant to serve as their own comparison. The study team will monitor how the wounds heal over approximately one week using clinical evaluation, photographs, and safety assessments.

LUT017 is a topical medication designed to activate natural skin repair pathways and potentially promote faster healing. The main purpose of this study is to determine whether a single application of LUT017 gel is safe and well tolerated when applied to fresh skin wounds, and to look for early signs that it may improve or speed up wound healing compared to placebo.

The primary question this study aims to answer is: Is LUT017 gel safe when applied to acute skin wounds, and does it show preliminary evidence of improving early wound healing in healthy adults?

Participants will be followed for about one week after treatment, with blood tests and skin evaluations to monitor for any side effects. The information gathered from this study will help determine whether LUT017 should continue to be developed as a potential treatment to support wound healing.

Study Overview and Clinical Context

This is a Phase 1, open-label, ascending-dose clinical study designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary biological activity of LUT017 gel when applied topically to acute, procedure-generated cutaneous wounds in healthy adult subjects. The study represents the first clinical investigation of LUT017 in the setting of acute wound healing in normal skin and is intended to establish an initial safety profile, characterize systemic exposure following single-dose topical administration, and inform dose selection for future controlled trials in impaired wound-healing conditions.

Participants are healthy adults who are already scheduled to undergo elective excision of two or more clinically benign skin lesions. These procedures create standardized acute wounds, allowing controlled evaluation of early healing responses under reproducible conditions. The study uses a paired-wound intra-subject comparison design, in which one wound receives LUT017 gel and the other receives placebo. This approach minimizes inter-subject variability and enhances the interpretability of early biological effects.

The therapeutic hypothesis underlying this study is that localized activation of epidermal regenerative signaling pathways can enhance early re-epithelialization and wound repair without inducing clinically significant systemic exposure or proliferative toxicity.

Mechanistic Rationale

LUT017 is a small-molecule inhibitor of BRAF. Although BRAF inhibitors were initially developed to suppress oncogenic BRAF V600 mutations in melanoma, it has been demonstrated that in cells expressing wild-type BRAF, particularly in the presence of upstream RAS signaling, inhibition of BRAF can induce paradoxical activation of downstream MAPK signaling. This occurs through RAF dimerization and CRAF transactivation, resulting in enhanced ERK phosphorylation.

In epidermal keratinocytes, ERK activation promotes proliferation, cytoskeletal reorganization, migration into the wound bed, and restoration of epithelial barrier integrity. Preclinical wound-healing studies conducted in excisional and diabetic mouse models demonstrated accelerated wound closure following topical administration of a BRAF inhibitor analogue closely related to LUT017. Histologic evaluation showed increased phosphorylated ERK expression at wound margins and earlier onset of re-epithelialization. Molecular analyses also demonstrated activation of Wnt/β-catenin signaling and induction of regenerative phenotypes within wound beds.

Importantly, two-stage carcinogenesis models evaluating topical exposure to regenerative doses of BRAF inhibitors did not demonstrate increased papilloma or squamous cell carcinoma formation, supporting the safety of localized MAPK activation under controlled topical conditions.

Investigational Product

LUT017 is a non-approved investigational BRAF inhibitor with a molecular weight of 546.94 Daltons and molecular formula C27H18ClF3N8. The compound has been optimized for topical administration and formulated as an aqueous-based gel intended to promote dermal penetration while limiting systemic absorption.

The formulation contains polyethylene glycol 400, Transcutol HP, 2-propanol, diisopropyl adipate, benzyl alcohol, Carbopol 980 NF polymer, sodium hydroxide, and purified water. The gel has a pH range of approximately 5 to 7 and is supplied in 50-gram tubes for clinical use. The formulation strategy was designed to balance local pharmacodynamic activity with minimal systemic exposure in order to mitigate class-associated toxicities observed with systemic BRAF inhibitors.

Nonclinical Safety and Toxicology

LUT017 has undergone a comprehensive nonclinical evaluation program including dermal toxicity, repeated-dose systemic toxicology, genotoxicity, phototoxicity, ocular irritation, and cardiovascular safety pharmacology.

Repeated-dose dermal toxicity studies in rodents and minipigs for up to 56 days demonstrated no systemic organ toxicity, no clinically meaningful electrocardiographic abnormalities, and no persistent laboratory abnormalities at exposures exceeding those anticipated clinically. The no observed adverse effect level (NOAEL) for dermal administration was established at 5 mg/kg/day in both species.

Oral repeated-dose studies demonstrated dose-dependent but reversible laboratory findings at high exposures, with a NOAEL of 25 mg/kg/day in female animals. These systemic exposures exceeded projected levels following topical administration in humans.

Genotoxicity testing was negative across bacterial reverse mutation assays, in vitro micronucleus testing, in vivo micronucleus assays, and comet assays. Phototoxicity assessments in vitro and in vivo did not demonstrate photoreactive potential at clinically relevant concentrations. Cardiovascular safety pharmacology studies in telemetry-monitored animals demonstrated no clinically significant QT prolongation or arrhythmogenic signal.

Collectively, these findings support initiation of human clinical evaluation with appropriate safety monitoring and conservative dose escalation.

Study Design

The study uses a sequential cohort, ascending-dose design. Approximately nine subjects will be enrolled across three cohorts of three subjects each. Three topical concentrations of LUT017 gel (0.03%, 0.1%, and 0.25% w/w) will be evaluated.

Immediately following lesion excision and confirmation of hemostasis, one wound will receive a single application of LUT017 gel at the assigned cohort concentration, and the paired wound will receive placebo gel. Assignment follows a predefined anatomical rule to ensure consistency across subjects.

Escalation to the next cohort will occur only after review of safety and tolerability data through the Day 7 visit for all subjects in the preceding cohort. Because this is a single-dose study with short follow-up, formal determination of maximum tolerated dose is not the primary objective; dose progression is guided by clinical safety findings.

Total subject participation is approximately one week, with additional follow-up if clinically indicated.

Safety Monitoring

Safety evaluation is the primary objective of this study. Subjects undergo physical examination, vital sign assessment, clinical laboratory testing (hematology and chemistry panels), and systematic adverse event monitoring from Day 0 through Day 7. Plasma pharmacokinetic sampling is performed to assess potential systemic exposure following topical application.

Given the class effects of BRAF inhibitors, dermatologic monitoring is emphasized. Investigators assess for cutaneous proliferative lesions, photosensitivity reactions, inflammatory eruptions, follicular abnormalities, and other local reactions at treated sites. Any suspicious lesions are evaluated and managed according to standard clinical practice.

Predefined stopping criteria include study suspension in the event of treatment-related death or multiple severe treatment-related adverse events.

Pharmacokinetic Assessment

To characterize systemic exposure following topical administration, plasma samples are collected on Day 0 and Day 7. These data will allow estimation of systemic absorption and confirmation that circulating levels remain minimal, as predicted by nonclinical modeling.

Statistical Considerations

This early-phase study is not powered for confirmatory efficacy testing. Safety data will be summarized descriptively. Exploratory wound-healing parameters, including comparative re-epithelialization and wound appearance between LUT017-treated and placebo-treated sites, will be analyzed descriptively. No formal hypothesis testing is planned.

Risk-Benefit Considerations

Potential risks include localized cutaneous hyperproliferation, inflammatory dermatologic reactions, and theoretically minimal systemic exposure-related effects. These risks are mitigated through conservative dose escalation, intra-subject control design, short exposure duration, predefined stopping rules, and close clinical monitoring.

The anticipated benefit is improved early wound repair through targeted activation of regenerative signaling pathways. The data generated will establish foundational safety and biological activity parameters necessary for subsequent trials in patients with impaired or chronic wound-healing conditions.

Inclusion Criteria

1. Subjects scheduled to undergo excision of two or more clinically benign skin lesions (e.g., melanocytic nevi or seborrheic keratoses) that will result in at least two comparable acute cutaneous wounds suitable for study treatment.
2. Subject must be ≥ 18 years of age.
3. Subjects must be in generally good health, with no dermatologic or systemic condition that may impair normal wound healing, as determined by the Investigator.
4. Lesions selected for excision must be benign, confirmed clinically by the treating dermatologist or surgeon prior to the procedure.
5. Must be able and willing to provide informed consent prior to study participation.
6. Female subjects of childbearing potential must have a negative pregnancy test at day 0. They should agree to use highly effective methods of birth control, defined as those with failure less than 1%, such as implants, injectables, combined oral contraceptives, some intrauterine contraceptive devices (IUD's), sexual abstinence, or a vasectomized partner.

Exclusion Criteria

1. Any lesion scheduled for excision that is suspicious for malignancy or has not been clinically assessed as benign by the treating dermatologist or surgeon.

2. History of abnormal wound healing, including keloid formation, hypertrophic scarring, chronic non-healing wounds, or delayed healing after prior procedures.

3. Target ulcer shows any signs of infection (only non-infected ulcers are eligible).

4. Unable to tolerate multi-layer bandages or compression garments.

5. Decompensated congestive heart failure.

6. Active soft tissue or bone infection requiring antibiotics.

7. Skin cancer on the target limb within the last 24 months.

8. Actively receiving chemotherapy and/or radiation therapy for cancer.

9. Treatment with a serine/threonine-protein kinase BRAF inhibitor, including but not limited to Zelboraf® (vemurafenib), Tafinlar® (dabrafenib), BraftoviTM (encorafenib) or Nexavar® (sorafenib), within 30 days or 5 half-lives of the drug prior to Day 0, whichever is longer.

10. Blood chemistry and complete blood count (CBC) values from the most recent laboratory assessment performed within the past 12 monsth:

    1. White Blood Cells (WBC) < 1.5 x 109/L.
    2. Absolute < 0.9 x 109/L.
    3. Platelet count < 50 x 109/L.
    4. Alanine aminotransferase > 3 x upper limit of normal.
    5. Aspartate aminotransferase > 3 x upper limit of normal.
    6. Serum albumin <2.0 g/dL.

11. Current use of systemic corticosteroids > 5 mg daily or equivalent within 4 weeks.

12. Currently pregnant or trying to become pregnant.

13. Inability or unwillingness to participate in all aspects of study protocol or as determined by the Investigator.

14. Known hypersensitivity to the ingredients of the study drug.

15. No known history of diabetis