The Efficacy and Safety of Secukinumab in Patients With Ichthyoses

NCT ID: NCT03041038

Last Updated: 2021-08-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-31
• Study Completion Date: 2020-08-31

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.

Conditions

Ichthyosis; Autosomal Recessive Congenital Ichthyosis; Lamellar Ichthyosis; Congenital Ichthyosiform Erythroderma; Epidermolytic Ichthyosis; Netherton Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Secukinumab

Secukinumab 300mg (liquid formation) administered subcutaneously weekly for 5 weeks then monthly until end of trial

Group Type: EXPERIMENTAL

Secukinumab

Intervention Type: DRUG

Anti IL-17A antibody

Placebo

Placebo (sterile saline) 2ml administered subcutaneously weekly for 5 weeks then monthly until end of trial

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

Secukinumab

Anti IL-17A antibody

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Other Intervention Names

Cosentyx; Sterile Saline

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Icahn School of Medicine at Mount Sinai

OTHER

Sponsor Role: collaborator

Northwestern University

OTHER

Sponsor Role: lead

Responsible Party

Amy Paller

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Amy Paller, MD

Role: PRINCIPAL_INVESTIGATOR

Northwestern University Department of Dermatology

Emma Guttman-Yassky, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Mt. Sinai Hospital Department of Dermatology

Locations

Department of Dermatology, Northwestern University Feinberg School of Medicine

Chicago, Illinois, United States

Department of Dermatology Icahn School of Medicine at Mount Sinai

New York, New York, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 35218370 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

CAIN457AUS05T

Identifier Type: -

Identifier Source: org_study_id