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The Efficacy and Safety of Secukinumab in Patients With Ichthyoses

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ClinicalTrials.gov Identifier: NCT03041038
Recruitment Status : Active, not recruiting
First Posted : February 2, 2017
Last Update Posted : July 11, 2019
Sponsor:
Collaborator:
Icahn School of Medicine at Mount Sinai
Information provided by (Responsible Party):
Amy Paller, Northwestern University

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.

Condition or disease Intervention/treatment Phase
Ichthyosis Autosomal Recessive Congenital Ichthyosis Lamellar Ichthyosis Congenital Ichthyosiform Erythroderma Epidermolytic Ichthyosis Netherton Syndrome Drug: Secukinumab Drug: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 21 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 Start Date : December 2016
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019


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 Name: Cosentyx

Placebo Comparator: Placebo
Placebo (sterile saline) 2ml administered subcutaneously weekly for 5 weeks then monthly until end of trial
Drug: Placebo
Other Name: Sterile Saline




Primary Outcome Measures :
  1. Reduction at week 16 in the Ichthyosis Area Severity Index (IASI) [ Time Frame: 16 Weeks ]
    Primary Efficacy Endpoint

  2. Occurrence of bacterial or fungal mucocutaneous infection through week 16 [ Time Frame: 16 weeks ]
    Primary Safety Endpoint


Secondary Outcome Measures :
  1. Change in the IASI-E and IASI-S at week 16 [ Time Frame: 16 weeks ]
  2. Change in CISI (Congenital Ichthyosis Severity Index) for skin redness/ erythema as well as skin hyperkeratosis/scaling at week 16 [ Time Frame: Week 16 ]
  3. A 2-point reduction in CISI for redness/erythema as well as skin hyperkeratosis/scaling at week 16 [ Time Frame: Week 16 ]
  4. A 50% reduction in IASI at week 16 [ Time Frame: Week 16 ]
  5. A 75% reduction in composite and individual IASIs at week 16 [ Time Frame: Week 16 ]
  6. Reduction in Bodemer score at week 16 [ Time Frame: Week 16 ]
  7. A 3-point reduction in patient-reported itch and pain at week 16 [ Time Frame: Week 16 ]
  8. Improvement in the 5-D itch score [ Time Frame: Week 16 ]

Other Outcome Measures:
  1. Reduction in transepidermal water loss (TEWL), a functional measure of barrier, at week 16 [ Time Frame: Week 16 ]
  2. Reduction in the Dermatology Life Quality Index (DLQI) at week 16 [ Time Frame: Week 16 ]
  3. Reduction in the iQoL-32 index at week 16 [ Time Frame: Week 16 ]
  4. Occurrence of any AEs by week 16 [ Time Frame: Week 16 ]
  5. Occurrence of infections by week 16 [ Time Frame: Week 16 ]
  6. Occurrence of SAEs by week 16 [ Time Frame: Week 16 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03041038


Locations
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United States, Illinois
Department of Dermatology, Northwestern University Feinberg School of Medicine
Chicago, Illinois, United States, 60611
United States, New York
Department of Dermatology Icahn School of Medicine at Mount Sinai
New York, New York, United States, 10029
Sponsors and Collaborators
Northwestern University
Icahn School of Medicine at Mount Sinai
Investigators
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Principal Investigator: Amy Paller, MD Northwestern University Department of Dermatology
Principal Investigator: Emma Guttman-Yassky, MD, PhD Mt. Sinai Hospital Department of Dermatology

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Responsible Party: Amy Paller, Principal Investigator, Northwestern University
ClinicalTrials.gov Identifier: NCT03041038     History of Changes
Other Study ID Numbers: CAIN457AUS05T
First Posted: February 2, 2017    Key Record Dates
Last Update Posted: July 11, 2019
Last Verified: July 2019
Additional relevant MeSH terms:
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Ichthyosis
Ichthyosis, Lamellar
Netherton Syndrome
Ichthyosiform Erythroderma, Congenital
Hyperkeratosis, Epidermolytic
Dermatitis, Exfoliative
Skin Abnormalities
Congenital Abnormalities
Infant, Newborn, Diseases
Keratosis
Skin Diseases
Skin Diseases, Genetic
Genetic Diseases, Inborn
Abnormalities, Multiple
Dermatitis
Skin Diseases, Eczematous
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs