Repurposing Dupilumab for Management of Pruritic Genetic Inflammatory Skin Disorders

Launched by NORTHWESTERN UNIVERSITY · Dec 5, 2022

Keywords

ClinConnect Summary

This clinical trial is studying a medication called dupilumab to see if it can help reduce severe itching caused by certain genetic skin disorders. It aims to find out if dupilumab can improve itchiness in patients who struggle with these conditions and if it can be safely used by everyone, regardless of their specific skin disorder. The study is expected to last 26 months, with an initial treatment phase of 16 weeks, followed by a 20-month extension for those who qualify and wish to continue.

To participate, individuals must be at least 6 months old and have a diagnosed genetic skin disorder, ideally confirmed by genetic testing. They should be experiencing significant itchiness, rated at least a 4 out of 10 on a scale. Participants will need to track their itch levels and wear a device that monitors their sleep and itching for the first 24 weeks of the trial. It’s important to note that certain medications and conditions may exclude someone from participating, so potential participants should discuss their medical history with the study team. Overall, this trial aims to find new ways to improve the quality of life for people affected by these challenging skin conditions.

Gender

ALL

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.

Trial Officials