Clinical trial NCT04488185: An Efficacy Study of Secukinumab in Plaque Psoriasis Patients With Subclinical Psoriatic Arthritis as Measured by Musculoskeletal Ultrasound
Official title: An Exploratory, Randomized, Double-blind, Parallel-group, Multicenter Study to Compare Secukinumab 300 mg With Placebo After 16 Weeks of Treatment in Adults With Moderate to Severe Plaque Psoriasis and Subclinical Enthesitis Measured by Musculoskeletal Ultrasound
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Psoriasis
Keywords: Psoriasis
Subclinical enthesitis
secukinumab
subclinical psoriatic arthritis
Plaque psoriasis
AIN457
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2020-07-27
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Given the role of IL-17 in the development of entheseal-driven pathology, a therapeutic strategy aimed at blocking IL-17 would be a logical option for the treatment of subclinical enthesitis in psoriasis patients. This study will be the first randomized trial of a biologic therapy versus placebo in participants with plaque psoriasis and subclinical psoriatic arthritis, using musculoskeletal ultrasound.

Detailed description: The primary objective of this study is to estimate the difference in effect between secukinumab 300 mg s.c. and placebo, based on change from baseline to Week 16 in the OMERACT ultrasound enthesitis score.

Eligibility criteria: Inclusion Criteria:

* Clinical diagnosis of chronic plaque-type psoriasis confirmed through physical examination by a dermatologist, with at least six months of clinical history prior to the baseline visit
* Moderate to severe plaque psoriasis at baseline as defined as:
* ≥ 10 % Body Surface Area (BSA) involvement, or
* ≥ 3% to \<10% Body Surface Area with involvement of special regions (nails, scalp, or intertriginous skin), or with a history of psoriatic arthritis in a parent

Candidate for systemic therapy, defined as having psoriasis inadequately controlled by current topical and/or systemic treatment(s) (including topical corticosteroids), phototherapy, or previous systemic therapies

Presence of sonographic enthesitis at screening, in at least one enthesis, defined by the presence of at least abnormal thickening and hypoechogenicity of the tendon insertion, with or without presence of Doppler signal (Grade 0-3), or by the presence of grade ≥ 2 Doppler signal, independent of gray scale abnormalities

Exclusion Criteria:

* Diagnosis of PsA as per CASPAR confirmed by a rheumatologist (including the presence of inflammatory pain in entheses or joints), and any other known rheumatological disease affecting the assessed joints
* Exposure to any IL-17 or IL-23(p19) inhibitor for the treatment of psoriasis (approved or investigational) within twelve months prior to screening, or exposure to any inhibitors of TNF-ɑ and IL12/23 within six months prior to screening
* Previous exposure to non-biologic systemic therapy for psoriasis, including methotrexate, PDE-4 inhibitors, or systemic corticosteroids within 12 weeks or 5 half-lives (whichever is longer) prior to screening
* A degree of obesity that impedes proper ultrasound examination of entheses and joints
* Forms of diagnosed psoriasis other than chronic plaque psoriasis (e.g., erythrodermic, generalized or localized pustular psoriasis, or new onset guttate psoriasis)

Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Change from Baseline in the Outcome Measures in Rheumatology (OMERACT) ultrasound enthesitis score
timeFrame: Baseline and Week 16
Secondary outcomes:
measure: Change from Baseline in the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) ultrasound enthesitis score
timeFrame: Baseline and Week 16
measure: Change from Baseline in the PsASon13 unilateral ultrasound composite score of synovitis
timeFrame: Baseline and Week 16
measure: Number of participants who achieve complete resolution of enthesitis based on OMERACT criteria (yes, no)
timeFrame: Baseline and Week 16
measure: Number of participants who achieve Psoriasis Area and Severity Index 90 (PASI 90) (yes, no)
timeFrame: Baseline and Week 16
measure: Number of participants who achieve Psoriasis Area and Severity Index 100 (PASI 100) (yes, no)
timeFrame: Baseline and Week 16
measure: Number of participants who achieve Investigator's Global Assessment modified 2011 (IGA mod 2011) score of 0 or 1 (yes, no)
timeFrame: Baseline and Week 16
measure: Change from Baseline in Body Surface Area (BSA)
timeFrame: Baseline and Week 16
measure: Change from Baseline in Dermatology Life Quality Index (DLQI) score
timeFrame: Baseline and Week 16
measure: Number of participants who achieve Dermatology Life Quality Index (DLQI) score of 0 or 1 (yes, no)
timeFrame: Baseline and Week 16
measure: Change from Baseline in HAQ-DI score
timeFrame: Baseline and Week 16
measure: Number of participants who achieve HAQ-DI change from baseline ≤ -0.35 (yes, no)
timeFrame: Baseline and Week 16
Other outcomes:
Locations:
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
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