A Pilot Study to Examine the Efficacy and Tolerability of Sirolimus on Epidermal Nevi Lesions in Patients 6 Years Old and Above.

We hypothesize that topical sirolimus could suppress the mTOR activation of linear verrucous epidermal nevi, particularly when the variants are involving genes upstream of mTOR and perhaps even those of the RAS pathway through crosstalk and downstream signaling. Indeed, a recent study noted a few cases of epidermal nevi that were improved within 3-4 months by the use of topical sirolimus. We propose to perform a pilot study of epidermal nevi to observe the impact of treatment twice daily of epidermal nevi with serial photography and scoring to capture alterations during the 3 months of the study. We will also grade local tolerance to the topical gel.

Study Overview

• Status: Not yet recruiting
• Conditions: Epidermal Nevi
• Intervention / Treatment: Drug: sirolimus topical gel 0.2%

Detailed Description

Epidermal nevi are skin growths that develop because of a genetic change that occurs after conception, meaning only some skin cells are affected. These growths appear as thickened, often darker areas of skin that form lines or swirls. On the arms and legs, they usually appear as straight streaks, while on the trunk and face they follow curved patterns called the lines of Blaschko, which reflect how skin cells develop before birth.

These skin changes are caused by specific genetic changes that turn on certain cell growth pathways inside skin cells. Most linear verrucous epidermal nevi involve one of two major pathways that control cell growth: the PI3K/AKT/mTOR pathway or the RAS/MAPK pathway. In more than 40% of cases, changes in the FGFR3 or PIK3CA genes cause constant activation of the PI3K/AKT/mTOR pathway, leading to excess skin growth.

Sirolimus (also called rapamycin) is a medication that blocks the mTOR pathway, slowing down cell growth and protein production. Medications like this are already used to treat certain cancers caused by overactive mTOR signaling.

Topical sirolimus is FDA-approved as a 0.2% gel (Hyftor) to treat facial angiofibromas in people with tuberous sclerosis complex (TSC). In TSC, genetic changes cause the mTOR pathway to be overly active, leading to skin growths called angiofibromas. Studies have shown that applying sirolimus to the skin can reduce the size and visibility of these lesions.

• Study Type: Interventional
• Enrollment (Estimated): 14
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Dermatology CTU; Phone Number: 312-503-5944; Email: NUderm-research@northwestern.edu

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University Feinberg School of Medicine, Department of Dermatology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients 6 years of age or above with a non-inflammatory epidermal nevi
• Lesion(s) that have been present for at least 3 years and are relatively stable
• At least 2 cm in length (ideally continuous, but can be cumulatively)
• The lesions is raised, hyperpigmented compared to the surrounding skin, and is noninflammatory with a physician global assessment (PGA) of at least 3 (moderate).
• Agree to avoid emollient use at the nevus site throughout the study
• Agree to not bath or shower 2 hours post-application, knowing that the gel can be applied after bathing or showering.

Exclusion Criteria:

• Patients currently or recently (within past 4 weeks) using a topical keratolytic or topical anti-inflammatory medication at the lesional site (i.e. topical steroid, topical retinoid, alpha-OH acid)
• Pregnant or planning to become pregnant during the course of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients 6 years of age or older with a non-inflammatory epidermal nevi	Drug: sirolimus topical gel 0.2%; Topical sirolimus will be applied twice daily to the nevi with a maximum daily dose of 600 mg for patients 6-11 years of age and 800 mg for patients 12 years and older.; Other Names: Hyftor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement of nevi flattening and normalization of skin color	The extent of nevi improvement will be scored at baseline and week 12 from standardized photographs by two independent asessors with an adjudicator (if needed). The score will be defined as follows: 0 = 100% improvement; = 90-99% improvement; = 69-89% improvement; = 50-69% improvement; = 30-49% improvement; = 10-29% improvement; = 0-9% improvement; = worsening	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Satisfaction scores of treatment	Patients (and parents/LAR) will be asked for their satisfaction of the treatment (not satisfied, satisfied, very satisfied) at week 12	12 weeks
Patient-reported improvement of lesion	Patients (and parents/LAR) will be asked their self-evaluation of lesion improvment from 0-5 (0= cleared, 1= almost cleared, 2= good improvement, 3= slight improvement, 4= no change, 5= worse) at baseline and week 12	12 weeks
Reduction in peak itch score	At least 2-point reduction in peak itch NRS score (on a scale of 0-10, 0=no itch and 10=worse itch) from baseline to week 12	12 weeks

Collaborators and Investigators

• Sponsor: Northwestern University
• Investigators: Principal Investigator: Amy Paller, MD, Northwestern University

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: September 4, 2026
• First Submitted That Met QC Criteria: September 4, 2026
• First Posted (Actual): September 10, 2026

Study Record Updates

• Last Update Posted (Actual): September 10, 2026
• Last Update Submitted That Met QC Criteria: September 4, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: mTOR; epidermal nevi; topical sirolimus; Hyftor
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms; Neoplasms by Histologic Type; Congenital Abnormalities; Abnormalities, Multiple; Neurocutaneous Syndromes; Nevi and Melanomas; Nevus; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nevus, Sebaceous of Jadassohn
• Other Study ID Numbers: STU00224904

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No