Clinical trial NCT02662985: Study of Power Doppler Ultrasound (PDUS) to Measure Response of Secukinumab Treatment in Patients With Active Psoriatic Arthritis (PsA)
Official title: A 52-week, Multicenter Study to Assess the Time Course of Response to Secukinumab on Joint Inflammation Using Power Doppler Ultrasonography in Patients With Active Psoriatic Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Psoriatic Arthritis
Keywords: Power Doppler Ultrasonography
Psoriatic Arthritis
Enthesitis
Synovitis
Outcome Measures in Rheumatology
Spondyloarthritis Research Consortium of Canada
active psoriatic arthritis
secukinumab
Arthritis
GLOESS
monoclonal antibody
PsA
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2016-01-26
Enrollment: 166
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: This study was designed to leverage the sensitivity of ultrasonography available in clinical practice setting to better describe the time course of response to secukinumab (150 mg and 300 mg) on joint synovitis and enthesitis in PsA patients with an inadequate response to non-biologic DMARDs. PDUS changes in joint synovitis will be assessed using the global Outcome Measures in Rheumatology (OMERACT)-European League against Rheumatism (EULAR) synovitis score (GLOESS) and changes in joint enthesitis were assessed using the OMERACT enthesitis score.

Detailed description: This was a 52-week, multicenter, international study consisting of a 2 to 4-week Screening period, a 12-week randomized, placebo-controlled double-blind treatment period (Period 1), a 12-week open-label treatment period (Period 2) and a 6-month open-label extension period (Period 3).

Treatment Period 1 is a 12-week placebo-controlled, randomized period primarily designed to demonstrate the early and optimal efficacy of secukinumab vs placebo on joint synovitis using PDUS via the GLOESS and global entheseal score after 12 weeks of treatment.

The main aim of Period 2 was to assess the maintenance or increased magnitude of treatment response on joint synovitis for patients from the original secukinumab groups and to assess the time course of response with secukinumab on joint synovitis in the original placebo group switched to secukinumab from Week 12.

The main aim of Period 3 (extension period) was to allow patients who respond to secukinumab to extend study treatment up to Week 52 or until commercial drug becomes available, whichever occurs sooner.

Eligibility criteria: Inclusion Criteria:

1. Patient must be able to understand and communicate with the Investigator and comply with the requirements of the study and must provide written, signed and dated informed consent before any study assessment is performed.
2. Male or female patients at least 18 years of age.
3. Diagnosis of PsA as per CASPAR with active PsA for at least 6 months and a TJC ≥ 3 of 78 and SJC ≥ 3 of 76 at Baseline.
4. Patients must have a total synovitis PDUS score ≥ 2 and inflammation related to PD signal ≥ 1 for at least 2 (affected joints as observed via PDUS) of 48 joints at the Screening visit and at the Baseline visit (before infusion).
5. At least 1 clinically-involved enthesitis site at Screening and at the Baseline visit (before infusion) defined by SPARCC index different from 0.

Exclusion Criteria:

1. Chest X-ray or chest MRI with evidence of ongoing infectious or malignant process obtained within 3 months prior to Screening and evaluated by a qualified physician.
2. Previous exposure to secukinumab or other biologic drug directly targeting IL-17 or IL-17 receptor.
3. Any change in the dose of oral corticosteroids in the last 4 weeks prior to the Baseline visit or use of i.v. intramuscular or intra-articular corticosteroid during the last 4 weeks prior to the enrollment visit.
4. Patients who have previously been treated with TNFα inhibitors (investigational or approved).
5. History of hypersensitivity to the study drug or its excipients or to drugs of similar classes.
6. Previous treatment with any cell-depleting therapies including but not limited to anti CD20 investigational agents (e.g. CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti CD19).
7. Prohibited psoriasis treatments/medications with topical corticosteroids in the last 4 weeks prior to randomization.
8. Pregnant or nursing (lactating) women.

Primary outcomes:
measure: Difference Between Secukinumab and Placebo in Terms of Joint Synovitis as Measured by the Power Doppler Ultrasonography (PDUS) Global OMERACT-EULAR Synovitis Score (GLOESS)
timeFrame: 12 weeks
Secondary outcomes:
measure: Proportion of Participants With American College of Rheumatology (ACR)-20 Response
timeFrame: Week 12
measure: Proportion of Participants With American College of Rheumatology (ACR)-50 Response
timeFrame: Week 12
measure: Spondyloarthritis Research Consortium of Canada (SPARCC)
timeFrame: Baseline to Week 12
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Novartis Investigative Site
state: California
city: Los Angeles
country: United States
facility: Novartis Investigative Site
state: California
city: Wheaton
country: United States
facility: Novartis Investigative Site
state: Maryland
city: Salt Lake City
country: United States
facility: Novartis Investigative Site
state: Utah
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Ciudad Autonoma de Bs As
country: Argentina
facility: Novartis Investigative Site
city: Tucuman
country: Argentina
facility: Novartis Investigative Site
city: Vienna
country: Austria
facility: Novartis Investigative Site
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Ghent
country: Belgium
facility: Novartis Investigative Site
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Bogota
country: Colombia
facility: Novartis Investigative Site
state: Cundinamarca
city: Prague 2
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Boulogne Billancourt
country: France
facility: Novartis Investigative Site
city: Montpellier
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Erlangen
country: Germany
facility: Novartis Investigative Site
city: Miskolc
country: Hungary
facility: Novartis Investigative Site
state: Baz
city: Dublin 4
country: Ireland
facility: Novartis Investigative Site
city: Padova
country: Italy
facility: Novartis Investigative Site
state: PD
city: Genova
country: Italy
facility: Novartis Investigative Site
city: Pisa
country: Italy
facility: Novartis Investigative Site
city: Mexico
country: Mexico
facility: Novartis Investigative Site
state: Ciudad De Mexico
city: Guadalajara Jalisco
country: Mexico
facility: Novartis Investigative Site
city: Amsterdam
country: Netherlands
facility: Novartis Investigative Site
city: Oslo
country: Norway
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Leeds
country: United Kingdom
facility: Novartis Investigative Site
state: West Yorkshire
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: D'Agostino MA, Schett G, Lopez-Rdz A, Senolt L, Fazekas K, Burgos-Vargas R, Maldonado-Cocco J, Naredo E, Carron P, Duggan AM, Goyanka P, Boers M, Gaillez C. Response to secukinumab on synovitis using Power Doppler ultrasound in psoriatic arthritis: 12-week results from a phase III study, ULTIMATE. Rheumatology (Oxford). 2022 May 5;61(5):1867-1876. doi: 10.1093/rheumatology/keab628.