Study of Power Doppler Ultrasound (PDUS) to Measure Response of Secukinumab Treatment in Patients With Active Psoriatic Arthritis (PsA)

Psoriatic Arthritis Clinical Trial

— PDUS  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02662985
• Other study ID #: CAIN457F2354
• Secondary ID: 2015-002394-38
• Status: Completed
• Phase: Phase 3
• Start date: August 22, 2016
• Est. completion date: November 10, 2020

Study information

• Verified date: November 2021
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 166
• Est. completion date: November 10, 2020
• Est. primary completion date: November 10, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 TNFa 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.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Psoriatic
• Psoriatic Arthritis

Intervention

Drug:
• AIN457 (secukinumab)
Is a recombinant monoclonal antibody which neutralizes the activity of IL-17A, and has been shown to be effective in treating patients with moderate-to-severe plaque psoriasis. Secukinumab 150 mg provided in 1 mL pre filled syringes (PFS) for s.c. injection. The 300 mg dose was administered as 2 × PFS injections.
• Placebo
Secukinumab placebo was provided in a 1 mL PFS for s.c. injection.

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Ciudad Autonoma de Bs As
Argentina	Novartis Investigative Site	Tucuman
Austria	Novartis Investigative Site	Vienna
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Ghent
Canada	Novartis Investigative Site	Toronto	Ontario
Colombia	Novartis Investigative Site	Bogota	Cundinamarca
Czechia	Novartis Investigative Site	Prague 2	Czech Republic
France	Novartis Investigative Site	Boulogne Billancourt
France	Novartis Investigative Site	Montpellier
France	Novartis Investigative Site	Paris
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Erlangen
Hungary	Novartis Investigative Site	Miskolc	Baz
Ireland	Novartis Investigative Site	Dublin 4
Italy	Novartis Investigative Site	Genova
Italy	Novartis Investigative Site	Padova	PD
Italy	Novartis Investigative Site	Pisa
Mexico	Novartis Investigative Site	Guadalajara Jalisco
Mexico	Novartis Investigative Site	Mexico	Ciudad De Mexico
Netherlands	Novartis Investigative Site	Amsterdam
Norway	Novartis Investigative Site	Oslo
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
United Kingdom	Novartis Investigative Site	Leeds	West Yorkshire
United States	Novartis Investigative Site	Beverly Hills	California
United States	Novartis Investigative Site	Los Angeles	California
United States	Novartis Investigative Site	Salt Lake City	Utah
United States	Novartis Investigative Site	Wheaton	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Austria,  Belgium,  Canada,  Colombia,  Czechia,  France,  Germany,  Hungary,  Ireland,  Italy,  Mexico,  Netherlands,  Norway,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference Between Secukinumab and Placebo in Terms of Joint Synovitis as Measured by the Power Doppler Ultrasonography (PDUS) Global OMERACT-EULAR Synovitis Score (GLOESS)	Mixed model repeated measures (MMRM) analysis of change in Global OMERACT-EULAR Synovitis Score (GLOESS) score at Week 12 (observed data) to compare treatments; The range for the GLOESS score is 0 to 144. GLOESS is the ultrasound scoring system measured for 24 pairs of joints. The scoring is from 0 to 3 for each joint; so the minimum score can be 0 and maximum can be 144.	12 weeks
Secondary	Proportion of Participants With American College of Rheumatology (ACR)-20 Response	ACR 20 responder has = 20% improvement in TJC and SJC and >20% improvement in 3 of the following 5 domains: patient's assessment of disease activity, physician's assessment of disease activity, patient's	Week 12
Secondary	Proportion of Participants With American College of Rheumatology (ACR)-50 Response	ACR 50 responder has = 50% improvement in TJC and SJC and >25% improvement in 3 of the following 5 domains: patient's assessment of disease activity, physician's assessment of disease activity, patient's assessment of PsA pain, HAQ-DI, or hsCRP.	Week 12
Secondary	Spondyloarthritis Research Consortium of Canada (SPARCC)	Repeated measures mixed effect (MMRM) analysis of SPARCC total score change from baseline to Week 12 between the 2 treatment groups.; SPARCC index ranges from 0 to 16.	Baseline to Week 12