The Efficacy and Safety of Secukinumab in Patients With Ichthyoses

August 2, 2021 updated by: Amy Paller, Northwestern University

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Department of Dermatology, Northwestern University Feinberg School of Medicine
    • New York
      • New York, New York, United States, 10029
        • Department of Dermatology Icahn School of Medicine at Mount Sinai

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Secukinumab
Secukinumab 300mg (liquid formation) administered subcutaneously weekly for 5 weeks then monthly until end of trial
Drug: Secukinumab
Anti IL-17A antibody
Other Names:
  • Cosentyx
Placebo Comparator: Placebo
Placebo (sterile saline) 2ml administered subcutaneously weekly for 5 weeks then monthly until end of trial
Drug: Placebo
Other Names:
  • Sterile Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Reduction at Week 16 in the Ichthyosis Area Severity Index (IASI)
Time Frame: 16 Weeks
Primary Efficacy Endpoint. The IASI score was modelled after the Eczema Area and Severity Index (EASI) and Psoriasis Area and Severity Index (PASI), commonly used in clinical trials for atopic dermatitis and psoriasis, respectively. This scale measures erythema and scaling and has a range of 0-48 (sum of a max score of 24 for erythema and 24 for scaling). A higher score means worse clinical severity. Mean difference IASI total score at Baseline was compared to IASI total score at Week 16.
16 Weeks
Total Number of Bacterial or Fungal Mucocutaneous Infections Through Week 16
Time Frame: 16 weeks of secukinumab/placebo double blind followed by 32 week open label treatment
Primary Safety Endpoint
16 weeks of secukinumab/placebo double blind followed by 32 week open label treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Northwestern University

Collaborators

Icahn School of Medicine at Mount Sinai

Investigators

  • Principal Investigator: Amy Paller, MD, Northwestern University Department of Dermatology
  • Principal Investigator: Emma Guttman-Yassky, MD, PhD, Mt. Sinai Hospital Department of Dermatology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2016

Primary Completion (Actual)

August 31, 2020

Study Completion (Actual)

August 31, 2020

Study Registration Dates

First Submitted

January 17, 2017

First Submitted That Met QC Criteria

January 31, 2017

First Posted (Estimate)

February 2, 2017

Study Record Updates

Last Update Posted (Actual)

August 25, 2021

Last Update Submitted That Met QC Criteria

August 2, 2021

Last Verified

August 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CAIN457AUS05T

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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