Clinical trial NCT03041038: The Efficacy and Safety of Secukinumab in Patients With Ichthyoses
Official title: A Multicenter Study With a Randomized, Double-Blind, Placebo-Controlled Period, Followed by an Open-Label Maintenance Dosing Period to Evaluate the Efficacy and Safety of Secukinumab in Patients With Ichthyoses
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ichthyosis
Autosomal Recessive Congenital Ichthyosis
Lamellar Ichthyosis
Congenital Ichthyosiform Erythroderma
Epidermolytic Ichthyosis
Netherton Syndrome
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: Icahn School of Medicine at Mount Sinai
First posted: 2017-02-02
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The ichthyoses are a group of lifelong genetic disorders which share characteristics of generalized skin thickening, scaling and underlying cutaneous inflammation. There are no therapies based on growing understanding of what causes the disease. However, there have been recent discoveries of marked elevations in expression of interleukin-17A (IL-17A) and IL-17-related cytokines in the skin of individuals with ichthyosis, which may explain the inflammation. Investigators propose that IL-17-targeting therapeutics will safely suppress the inflammation and possibly the other features of ichthyosis, improving quality of life.

Detailed description: The ichthyoses are a group of lifelong genetic disorders which share characteristics of generalized skin thickening, scaling and underlying cutaneous inflammation. The vast majority are orphan disorders and are associated with extremely poor quality of life related to social ostracism from altered appearance, associated itchiness and discomfort, and functional limitations from the skin disease. Among the most common of these orphan disorders are autosomal recessive congenital ichthyosis (ARCI) with its phenotypic subsets of lamellar ichthyosis (ARCI-LI) and congenital ichthyosiform erythroderma (ARCI-CIE), epidermolytic ichthyosis (EI) and Netherton syndrome (NS). Therapy is time-consuming for patients or parents and is supportive, focusing on clearance of the scaling. There are no therapies based on growing understanding of what causes the disease. There have been recent discoveries of marked elevations in expression of interleukin-17A (IL-17A) and IL-17-related cytokines in the skin of individuals with ichthyosis, which may explain the inflammation. Psoriasis, another inflammatory skin disorder with redness and scaling, has now been shown to result from IL-17 pathway activation and IL-17A inhibition is the most effective therapy known to treat psoriasis. Investigators propose that IL-17-targeting therapeutics will safely suppress the inflammation and possibly the other features of ichthyosis, improving quality of life. In this long-term, open-label extension, Investigators propose to treat adults with ichthyosis and at least moderate erythema with subcutaneously administered anti-IL-17 antibody (secukinumab) and to serially assess clinical response to this therapy and its safety.

Eligibility criteria: Inclusion Criteria:

* Subject has provided informed consent
* Subjects are at least 18 years of age or older at the time of screening
* Female subjects must not be pregnant or breast-feeding
* Female subjects of child-bearing potential with a negative urine pregnancy test and using at least one form of contraception (abstinence allowed)
* Subjects must have a confirmed diagnosis of ARCI (divided phenotypically into ARCI-LI or ARCI-CIE), EI or NS (by genotype or willingness to be genotyped)
* Subjects must be clinically judged to be immunocompetent.
* Subjects will have no allergy to secukinumab or components of the product.
* Subjects will have normal baseline laboratory testing (CMP, CBC, HIV negative, hepatitis B, C negative, QuantiFERON®-TB gold negative)
* Subjects must have an erythema score of at least 18 on IASI and an IASI-E score of 12 (at least moderate severity of erythema) at baseline

Exclusion Criteria:

* Subjects who are unable to give informed consent or assent.
* Subjects without a confirmed diagnosis ARCI, EI, or NS.
* Subjects who have a known allergy to secukinumab.
* Female subjects who are pregnant, considering becoming pregnant, or will breastfeed.
* Subjects who have prior biologic use targeting IL-17A/IL-17 receptor A or IL-12/IL-23 or who have prior use of TNF-alpha blockers.
* Subjects who have used a systemic retinoid within one month prior to initiation.
* Subjects who have used topical retinoids or keratolytics within one week prior to initiation.
* Subjects who have used emollient on the area to be biopsied in the previous 24 hours

Primary outcomes:
measure: Reduction at Week 16 in the Ichthyosis Area Severity Index (IASI)
timeFrame: 16 Weeks
measure: Total Number of Bacterial or Fungal Mucocutaneous Infections Through Week 16
timeFrame: 16 weeks of secukinumab/placebo double blind followed by 32 week open label treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Department of Dermatology, Northwestern University Feinberg School of Medicine
state: Illinois
city: New York
country: United States
facility: Department of Dermatology Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Northwestern University Department of Dermatology
name: Amy Paller, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mt. Sinai Hospital Department of Dermatology
name: Emma Guttman-Yassky, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lefferdink R, Rangel SM, Chima M, Ibler E, Pavel AB, Kim H, Wu B, Abu-Zayed H, Wu J, Jackson K, Singer G, Choate KA, Guttman-Yassky E, Paller AS. Secukinumab responses vary across the spectrum of congenital ichthyosis in adults. Arch Dermatol Res. 2023 Mar;315(2):305-315. doi: 10.1007/s00403-022-02325-3. Epub 2022 Feb 26.