Using Dupilumab to Treat Itch in Genetic Skin Disorders

Repurposing Dupilumab for Management of Pruritic Genetic Inflammatory Skin Disorders: a Single-Site Pilot Study

This study is testing if dupilumab can help reduce severe itching and improve quality of life for people with genetic skin disorders.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 6 Months and up
• Sex: All
• Sponsor: Northwestern University (Academic / other)
• Drugs / interventions: dupilumab, methotrexate
• Locations: 1 site (Chicago, Illinois)
• Trial ID: NCT05649098 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the use of dupilumab, a medication typically used for asthma and eczema, to alleviate severe itching associated with various genetic inflammatory skin disorders. The study will include a 16-week open-label treatment phase followed by a 20-month extension for eligible participants. Patients will be monitored for their itch severity and overall response to the treatment, with a focus on those who have genetic confirmation of their skin condition. The goal is to determine if dupilumab can effectively reduce itch and improve quality of life for these patients.

Who should consider this trial

Good fit: Ideal candidates include individuals over 6 months of age with a clinical diagnosis of a genetic skin disorder and significant itch severity.

Not a fit: Patients without a confirmed genetic skin disorder or those with mild itch (NRS < 4) may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve the quality of life for patients suffering from severe itch due to genetic skin disorders.

How similar studies have performed: While dupilumab has been successful in treating other conditions, this specific application for genetic skin disorders is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

1. Male or female \> 6 months of age at screening visit
2. Clinical diagnosis of a genetic skin disorder at the screening visit, ideally with genetic or histological confirmation.
3. Must have had the gene with one or more variants identified by genotyping. If the genotype has not been performed or has not been performed at a CLIA-approved laboratory, be willing to provide a sample (saliva, buccal swab, blood) for genetic testing before starting the dupilumab.
4. Average Itch Numerical Rating Scale (NRS) ≥ 4 and Worst Itch NRS of at least 5 during the previous 7 days (self-reported if \>8 years old; proxy reported if under 8 years)
5. Must be willing to provide information weekly about Average and Worst Itch/self- or proxy-assessed severity and wear the sensor device to track itch and sleep weekly throughout the first 24 weeks of the trial (Parts A and B).
6. Must be willing and able to adhere to the prohibitions and restrictions specified in this protocol.
7. Subject, parent/caregiver or legal guardians, as appropriate, are able to understand and complete the study requirements and study-related questionnaires

Exclusion Criteria:

1. Subjects \< 6 months of age at screening visit.
2. Unable to provide informed consent or assent (or who do not have consent from a Legally Authorized Representative if \< 18 years).
3. Diagnosis of ichthyosis vulgaris as the sole inherited disorder
4. Used of dupilumab within 5 drug half-lives (105 days) of baseline visit
5. Subjects who have used any of the following treatments within 4 weeks, or within a period equal to 5 times the half-life of the drug, before the baseline visit, whichever is longer:

   1. Immunosuppressive/immunomodulating drugs (eg, systemic corticosteroids, cyclosporine, mycophenolate-mofetil, IFN-γ, Janus kinase inhibitors, azathioprine, methotrexate, etc.), systemic anti-inflammatory medication, or phototherapy
   2. Other biologics: within 5 half-lives (if known) or 16 weeks, whichever is longer
6. Initiation of topical or systemic retinoids, topical keratolytics, or topical anti-inflammatory agents within 4 weeks before study start/Part A (systemic retinoids and topical medications/emollients can be used during the trial if started at least 4 wks before the observation period and continued throughout Parts A and B). Note: Rescue therapy for disease flares or local infection will be allowed per investigator discretion but must be for no more than a total of 1 week during any 4-week period and, if topical, involve application to less than 10% BSA.
7. Subjects with active infections or recent history of serious infections, malignancies or history of malignancies, or any severe, progressive, or uncontrolled renal, hepatic, hematologic, endocrine, pulmonary, cardiac, neurologic or psychiatric cerebral disease, or signs or symptoms thereof. It is recognized that patients with ichthyosis may have arthritis, while patients with junctional or dystrophic EB may have a variety of associated issues (eg nutritional, anemia, etc). The decision to include will be based on investigator's discretion but must reflect the likelihood for stable disease and lack of anticipated interference with assessment of itch.
8. Treatment with a live (attenuated) vaccine within 4 weeks before the Week 0 visit when dupilumab is initiated; use of vaccination during the study requires consultation with the study investigator and primary care provider.
9. Active acute or chronic infection requiring treatment with systemic antibiotics/ anti-virals/ anti-fungals within 2 weeks before the initiation of dupilumab (start of dupilumab can be delayed). Delay in initiation because of treatment with a topical antimicrobial to a localized superficial site will be determined by the investigator.

Where this trial is running

Chicago, Illinois

• Ann & Robert H. Lurie Children's Hospital of Chicago — Chicago, Illinois, United States (Recruiting)

Study contacts

• Principal investigator: Amy Paller — Northwestern University
• Study coordinator: Northwestern Dermatology CTU

Conditions Skin Diseases; Itch; Pruritus; epidermolysis bullosa; ichthyosis; genetic skin disorders