Epidermolytic IchthyosisPhase 1/2NCT06545695
Epidermal Growth Factor Receptor Inhibition for Keratinopathies
A Phase 1/2 study testing Erlotinib in people with Epidermolytic Ichthyosis and Palmoplantar Keratoderma, run by Northwestern University at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Epidermolytic Ichthyosis, Palmoplantar Keratoderma, Pachyonychia Congenita
- What is being tested?
- Erlotinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jul 2027to 30 Jun 2031
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The participant must be at least 18 years of age.
- The participant must have a clinically and genetically confirmed diagnosis of a keratinopathy (Epidermolytic ichthyosis/EI: KRT 1, 2, or 10 pathogenic variant; Epidermolytic palmoplantar keratoderma/PPK: KRT 9; Pachyonychia congenita/PC form of PPK: KRT 6a, 6b, 6c, 16, 17). A blood or saliva sample will be collected for genetic confirmation if the underlying genetic change has not been confirmed by a CLIA-approved laboratory.
- The participant must have an investigator scored IGA at screening and baseline of at least 2 (moderate) at affected sites.
- The participant must abstain from use of any investigational drug or biologic within 4 weeks or 5 half-lives if longer, oral retinoid or oral steroid for at least 4 weeks, and topical medications (prescription or over-the-counter) in the week before the 8-week observation period. Otherwise stable medications (at least a month before the observation period and continued) will be allowed.
- The participant agrees to use standard of care with respect to bathing and exfoliation/foot care, except in the week before the visits. Moisturizers/ emollients are allowed throughout the treatment period, but use must be consistent and withheld to the designated area of sampling on the arms (EI) or plantar foot (PC/PPK) for 48 hours prior to visits when skin samples are taken.
- The participant is willing to have blood collected for safety and biopsies for investigation of mechanism.
- Participant is in good general health and free of any known disease state or physical condition which, in the investigator's opinion, might impair the evaluation of the EI or PC/PPK.
- Participant is able and willing to follow all study instructions
Who cannot join
- The participant has EI or PC/PPK lesions on the assessment area that are infected or require therapy to treat the infection within 7 days of enrollment.
- The participant has had major surgery during the past 4 weeks.
- Participants have received an investigational drug or biologic within 4 weeks or 5 half-lives, whichever is longer, prior to starting treatment with and during treatment with erlotinib.
- Participants must be off oral retinoid or oral steroid for at least 4 weeks before drug initiation.
- Participants who require medications and OTC supplements that inhibit/ induce CYP3A4 activity to control concurrent medical conditions.
- Participants with known hypersensitivity to any of the ingredients in the study medication formulation.
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- Participants previously treated for invasive cancer within the past 5 years unless the Investigator concludes history of cancer is not confounding to safety.
- Participants who are pregnant, breastfeeding or planning to become pregnant during the study or within a month after the study ends.
- Participants of childbearing potential who are unwilling or unable to comply with contraception measures.
- The participant has any condition or situation which, in the Investigator's opinion, may put the subject at significant risk, could confound the study results, or could interfere significantly with the subject's participation in the study.
- Participants deemed by the investigator as unwilling or unable to remain compliant with all tests and procedures, adherence to the study drug administration regimen and other protocol-required activities.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Department of Dermatology, Northwestern University Feinberg School of Medicine
Chicago, Illinois, 60611
About this study
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.
Read the detailed description
We will conduct the first interventional multi-site Phase 1/2a trial of low-dose erlotinib to test its safety and efficacy as systemic treatment of moderate-to-severe keratinopathies.
The trial will have three parts:
During Part A, the natural history of keratinopathies and baseline for scores will be determined through at least 8 weeks of observation. We will use the mean of scores for our baseline, rather than a static measure at baseline to account for potential variability without the intervention.
Part B will be the dose escalation component, in which the subject will initiate 50 mg erlotinib,8 wks later escalate to 75 mg, and then 8 wks later to 100 mg erlotinib pending tolerance after each 8-week period. During this 24-week period, we will be assessing safety (Phase 1) in comparison to the 8-week baseline observation period (own control) and at ease dosing level. We will also evaluate efficacy based on dosing (Phase 2a) to achieve preliminary data to guide future trials if the use of erlotinib is a "go" based on safety.
Part C is the open-label extension period. Each participant will decide on the continued dosing for the subsequent 6 months in shared decision making with the investigator based on tolerance and effect. In total, the study involves 1 year on the erlotinib treatment, although the primary endpoint is 6 months after initiation. The additional 6 months will allow for further observation for potential toxicity and possible improved effect after additional time on drug. Participants will be eligible to participate in the open-label treatment period only if they have maintained >70% compliance with completion of studies during the initial 6 months.
- Being tested
- Erlotinib
- Medical subject headings
- Hyperkeratosis, Epidermolytic, Keratoderma, Palmoplantar, Pachyonychia Congenita
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ErlotinibDrug
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 group | Role | What they receive |
|---|---|---|
| Erlotinib Treatment Arm | Experimental | Not described Receives: Drug: Erlotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reduction in Investigator Global Assessment (IGA)
Reduction in IGA score from baseline to week 24 of at least 50%. The Investigator Global Assessment/IGA will be the primary efficacy analysis, using the strata of clear 0, mild 1, moderate 2, severe 3, and very severe 4.
Measured: 24 weeks
Percentage of Grade 3 and 4 Adverse Events
The percentage of participants with Grade 3 and 4 events, based on the current Common Toxicity Criteria for Adverse Events (CTCAE) listing
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2024
- Study start1 Jul 2027 (estimated)
- Primary completion30 Jun 2031 (estimated)
- Study completion30 Jun 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Epidermolytic IchthyosisStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 44 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Collaborators
- Yale University
- Responsible party
- Principal investigator, Amy Paller, Northwestern University
- Investigators
- Amy Paller, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06545695
- Sponsor's protocol ID
- AP08062024
- Status last verified
- Jul 2026
- First submitted
- 6 Aug 2024
- Last updated
- 3 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Epidermal Growth Factor Receptor Inhibition for Keratinopathies
- ClinicalTrials.gov ID
- NCT06545695
- Acronym / sponsor ID
- AP08062024
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 44 participants (estimated)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Collaborators
- Yale University
- Study start
- 1 Jul 2027 (estimated)
- Primary completion
- 30 Jun 2031 (estimated)
- Study completion
- 30 Jun 2031 (estimated)
- First posted
- 9 Aug 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
We will conduct the first interventional multi-site Phase 1/2a trial of low-dose erlotinib to test its safety and efficacy as systemic treatment of moderate-to-severe keratinopathies.
The trial will have three parts:
During Part A, the natural history of keratinopathies and baseline for scores will be determined through at least 8 weeks of observation. We will use the mean of scores for our baseline, rather than a static measure at baseline to account for potential variability without the intervention.
Part B will be the dose escalation component, in which the subject will initiate 50 mg erlotinib,8 wks later escalate to 75 mg, and then 8 wks later to 100 mg erlotinib pending tolerance after each 8-week period. During this 24-week period, we will be assessing safety (Phase 1) in comparison to the 8-week baseline observation period (own control) and at ease dosing level. We will also evaluate efficacy based on dosing (Phase 2a) to achieve preliminary data to guide future trials if the use of erlotinib is a "go" based on safety.
Part C is the open-label extension period. Each participant will decide on the continued dosing for the subsequent 6 months in shared decision making with the investigator based on tolerance and effect. In total, the study involves 1 year on the erlotinib treatment, although the primary endpoint is 6 months after initiation. The additional 6 months will allow for further observation for potential toxicity and possible improved effect after additional time on drug. Participants will be eligible to participate in the open-label treatment period only if they have maintained >70% compliance with completion of studies during the initial 6 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Erlotinib Treatment Arm | Experimental | Drug: Erlotinib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- The participant must be at least 18 years of age.
- The participant must have a clinically and genetically confirmed diagnosis of a keratinopathy (Epidermolytic ichthyosis/EI: KRT 1, 2, or 10 pathogenic variant; Epidermolytic palmoplantar keratoderma/PPK: KRT 9; Pachyonychia congenita/PC form of PPK: KRT 6a, 6b, 6c, 16, 17). A blood or saliva sample will be collected for genetic confirmation if the underlying genetic change has not been confirmed by a CLIA-approved laboratory.
- The participant must have an investigator scored IGA at screening and baseline of at least 2 (moderate) at affected sites.
- The participant must abstain from use of any investigational drug or biologic within 4 weeks or 5 half-lives if longer, oral retinoid or oral steroid for at least 4 weeks, and topical medications (prescription or over-the-counter) in the week before the 8-week observation period. Otherwise stable medications (at least a month before the observation period and continued) will be allowed.
- The participant agrees to use standard of care with respect to bathing and exfoliation/foot care, except in the week before the visits. Moisturizers/ emollients are allowed throughout the treatment period, but use must be consistent and withheld to the designated area of sampling on the arms (EI) or plantar foot (PC/PPK) for 48 hours prior to visits when skin samples are taken.
Key exclusion criteria (11 listed)
- The participant has EI or PC/PPK lesions on the assessment area that are infected or require therapy to treat the infection within 7 days of enrollment.
- The participant has had major surgery during the past 4 weeks.
- Participants have received an investigational drug or biologic within 4 weeks or 5 half-lives, whichever is longer, prior to starting treatment with and during treatment with erlotinib.
- Participants must be off oral retinoid or oral steroid for at least 4 weeks before drug initiation.
- Participants who require medications and OTC supplements that inhibit/ induce CYP3A4 activity to control concurrent medical conditions.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ErlotinibPart 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. | Drug | Erlotinib Treatment Arm |
Primary outcome
Reduction in Investigator Global Assessment (IGA)
Time frame: 24 weeks
Reduction in IGA score from baseline to week 24 of at least 50%. The Investigator Global Assessment/IGA will be the primary efficacy analysis, using the strata of clear 0, mild 1, moderate 2, severe 3, and very severe 4.
Percentage of Grade 3 and 4 Adverse Events
Time frame: 24 weeks
The percentage of participants with Grade 3 and 4 events, based on the current Common Toxicity Criteria for Adverse Events (CTCAE) listing
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2026.
- Individual participant dataSharing planned: Undecided
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Amy Paller principal investigator
Northwestern University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Erlotinib in people with Epidermolytic Ichthyosis and Palmoplantar Keratoderma, run by Northwestern University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 3 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Stephanie Rangel (312-503-5942, NUderm-research@northwestern.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Reduction in Investigator Global Assessment (IGA) (time frame: 24 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2026.