The Efficacy and Safety of Secukinumab in Patients With Ichthyoses

• Sponsor: Northwestern University (Other)
• Overall Status: Completed
• CT.gov ID: NCT03041038
• Collaborator: Icahn School of Medicine at Mount Sinai (Other)
• Enrollment: 20
• Locations: 2
• Arms: 2
• Duration (Months): 45
• Patients Per Site: 10
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 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: Dec 1, 2016
• Actual Primary Completion Date: Aug 31, 2020
• Actual Study Completion Date: Aug 31, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Reduction at Week 16 in the Ichthyosis Area Severity Index (IASI) [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.

2. Total Number of Bacterial or Fungal Mucocutaneous Infections Through Week 16 [16 weeks of secukinumab/placebo double blind followed by 32 week open label treatment]

   Primary Safety Endpoint

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Dermatology, Northwestern University Feinberg School of Medicine	Chicago	Illinois	United States	60611
2	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

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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 14, 2018

More Information

Publications

None provided.

• Responsible Party: Amy Paller, Principal Investigator, Northwestern University
• ClinicalTrials.gov Identifier: NCT03041038
• Other Study ID Numbers: CAIN457AUS05T
• First Posted: Feb 2, 2017
• Last Update Posted: Aug 25, 2021
• Last Verified: Aug 1, 2021

• Additional relevant MeSH terms: Ichthyosis; Ichthyosis, Lamellar; Netherton Syndrome; Ichthyosiform Erythroderma, Congenital; Hyperkeratosis, Epidermolytic; Dermatitis, Exfoliative

Study Results

Participant Flow

Arm/Group Title	Secukinumab	Placebo
Arm/Group Description	Secukinumab 300mg (liquid formation) administered subcutaneously weekly for 5 weeks then monthly until end of trial Secukinumab: Anti IL-17A antibody	Placebo (sterile saline) 2ml administered subcutaneously weekly for 5 weeks then monthly until end of trial Placebo
Period Title: Overall Study
STARTED	11	9
Week 16	10	8
Week 32	9	8
COMPLETED	5	7
NOT COMPLETED	6	2

Baseline Characteristics

Arm/Group Title	Secukinumab	Placebo	Total
Arm/Group Description	Secukinumab 300mg (liquid formation) administered subcutaneously weekly for 5 weeks then monthly until end of trial Secukinumab: Anti IL-17A antibody	Placebo (sterile saline) 2ml administered subcutaneously weekly for 5 weeks then monthly until end of trial Placebo	Total of all reporting groups
Overall Participants	11	9	20
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	34.2 (11.7)	35.5 (12.7)	34.7 (12.9)
Sex: Female, Male (Count of Participants)
Female	8 72.7%	4 44.4%	12 60%
Male	3 27.3%	5 55.6%	8 40%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 9.1%	1 11.1%	2 10%
Not Hispanic or Latino	10 90.9%	8 88.9%	18 90%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 9.1%	0 0%	1 5%
White	9 81.8%	8 88.9%	17 85%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 9.1%	1 11.1%	2 10%
Ichthyosis Subtype (Count of Participants)
CIE	3 27.3%	2 22.2%	5 25%
EI	2 18.2%	2 22.2%	4 20%
LI	4 36.4%	2 22.2%	6 30%
NS	2 18.2%	3 33.3%	5 25%
Site (Count of Participants)
Mount Sinai	4 36.4%	2 22.2%	6 30%
Northwestern	7 63.6%	7 77.8%	14 70%
Weight (kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms]	69.9 (13.5)	75.5 (30.4)	72.4 (22.0)
Ichthyosis Area Severity Index (IASI) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	33.7 (6.5)	36.2 (4.7)	34.8 (5.9)

Outcome Measures

1. Primary Outcome

Title	Reduction at Week 16 in the Ichthyosis Area Severity Index (IASI)
Description	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.
Time Frame	16 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Secukinumab	Placebo
Arm/Group Description	Secukinumab 300mg (liquid formation) administered subcutaneously weekly for 5 weeks then monthly until end of trial Secukinumab: Anti IL-17A antibody	Placebo (sterile saline) 2ml administered subcutaneously weekly for 5 weeks then monthly until end of trial Placebo
Measure Participants	11	9
Mean (95% Confidence Interval) [units on a scale]	2.4	4.3

2. Primary Outcome

Title	Total Number of Bacterial or Fungal Mucocutaneous Infections Through Week 16
Description	Primary Safety Endpoint
Time Frame	16 weeks of secukinumab/placebo double blind followed by 32 week open label treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Secukinumab	Placebo	Open Label
Arm/Group Description	Secukinumab 300mg (liquid formation) administered subcutaneously weekly for 5 weeks then monthly until end of trial Secukinumab: Anti IL-17A antibody	Placebo (sterile saline) 2ml administered subcutaneously weekly for 5 weeks then monthly until end of trial Placebo	Participants transitioned to open label treatment with Secukinumab300mg monthly after week 16.
Measure Participants	11	9	18
Number [infections]	5	5	10

Adverse Events

Time Frame	56 weeks
Arm/Group Title	Secukinumab		Placebo		Open Label
Arm/Group Description	Secukinumab 300mg (liquid formation) administered subcutaneously weekly for 5 weeks then monthly until end of trial Secukinumab: Anti IL-17A antibody		Placebo (sterile saline) 2ml administered subcutaneously weekly for 5 weeks then monthly until end of trial Placebo		Participants transitioned to open label treatment with Secukinumab300mg monthly after week 16.
All Cause Mortality
	Secukinumab		Placebo		Open Label
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/9 (0%)		0/18 (0%)
Serious Adverse Events
	Secukinumab		Placebo		Open Label
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/11 (9.1%)		0/9 (0%)		1/18 (5.6%)
Gastrointestinal disorders
Hospitalization-GERD	1/11 (9.1%)	1	0/9 (0%)	0	1/18 (5.6%)	1
Infections and infestations
Hospitalization-pyelonephritis	0/11 (0%)	0	0/9 (0%)	0	1/18 (5.6%)	1
Other (Not Including Serious) Adverse Events
	Secukinumab		Placebo		Open Label
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/11 (27.3%)		2/9 (22.2%)		6/18 (33.3%)
Infections and infestations
Bronchial infection	0/11 (0%)	0	1/9 (11.1%)	1	0/18 (0%)	0
Conjunctivitis	1/11 (9.1%)	1	0/9 (0%)	0	0/18 (0%)	0
Flu-like symptoms	1/11 (9.1%)	1	0/9 (0%)	0	1/18 (5.6%)	1
Otitis externa bacterial	0/11 (0%)	0	0/9 (0%)	0	1/18 (5.6%)	1
Skin Infection	0/11 (0%)	0	0/9 (0%)	0	3/18 (16.7%)	3
Upper Respiratory Infection	1/11 (9.1%)	1	1/9 (11.1%)	1	1/18 (5.6%)	1
Urinary tract infection	0/11 (0%)	0	1/9 (11.1%)	1	2/18 (11.1%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.