Epidermal Growth Factor Receptor Inhibition for Keratinopathies

Part of paid clinical trials in Chicago, Illinois.

Sponsor
Northwestern University
Study ID
NCT06545695
Phase
PHASE1/PHASE2
Status
Not Yet Recruiting

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Conditions

  • Epidermolytic Ichthyosis
  • Pachyonychia Congenita
  • Palmoplantar Keratoderma

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Erlotinib — DRUG
    Part B will be the dose escalation component, in which the subject will initiate 50 mg erlotinib,8 weeks later escalate to 75 mg, and then 8 weeks later to 100 mg erlotinib pending tolerance after each 8-week period.

Study Details

Epidermal growth factor receptor (EGFR) signaling plays a key role in regulating epidermal cell proliferation, survival, and differentiation. Keratins form a scaffold with epidermal desmosomes that involves ErbB/ EGFR signaling and keratin deficiency makes keratinocytes more sensitive to EGFR activation. Erlotinib, an EGFR inhibitor, was approved 20 years ago for cancer treatment and is generally used at 150 mg daily in adults \>50 kg. While gastrointestinal and cutaneous side effects commonly occur at doses of 150 mg, adverse events occur less often at lower doses. We first reported erlotinib as effective for Olmsted syndrome, a rare hereditary EDD with painful PPK that results from variants in TRPV3. Erlotinib is now the treatment of choice for children and adults with Olmsted syndrome. Erlotinib is thought to inhibit formation of a complex that includes TRPV3, EGFR, and its primary skin-based ligand, TGF-a, which in turn regulates keratinocyte proliferation and differentiation. High-throughput screening to identify compounds that stabilize keratin filaments have also pointed to the EGFR pathway for targeting. Reviews and recent case reports have suggested the benefit of erlotinib for PC, Given these preliminary data, we hypothesize that EGFR activation is a characteristic feature of keratinopathies. Further, we expect that oral low-dose erlotinib will improve the scaling and skin thickening of the spectrum of keratinopathies and be tolerated by most patients. For those who experience pain, particularly from plantar involvement, we predict that erlotinib therapy will improve mobility and pain. Finally, we aim to find the mechanism by which erlotinib improves the phenotypes of the various keratinopathies to better understand these disorders and predict response. We will look specifically at the impact on differentiation vs. hyperproliferation and barrier function, as well as the immune modulatory effects of the erlotinib using a multi-omics approach.

Key Dates

Start date
Jul 1, 2027
Status verified
Oct 2025
Primary completion
Jun 30, 2031
Completion
Jun 30, 2031

Study Design

Enrollment
44 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Erlotinib Treatment Arm

Primary Outcome Measure

Reduction in Investigator Global Assessment (IGA) [ Time Frame: 24 weeks ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
Department of Dermatology, Northwestern University Feinberg School of MedicineChicagoIllinois60611-

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By research site
Department of Dermatology, Northwestern University Feinberg School of Medicine· Chicago, IL

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