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

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

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.

Study Overview

• Status: Completed
• Conditions: Psoriatic Arthritis
• Intervention / Treatment: Drug: AIN457 (secukinumab); Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 166
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Ciudad Autonoma de Bs As, Argentina, C1428AZF
    • Novartis Investigative Site
  • Tucuman, Argentina, 4000
    • Novartis Investigative Site
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1181ACH
      • Novartis Investigative Site
• Austria
  • Vienna, Austria, 1040
    • Novartis Investigative Site
• Belgium
  • Bruxelles, Belgium, 1200
    • Novartis Investigative Site
  • Ghent, Belgium, 9000
    • Novartis Investigative Site
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5T 2S8
      • Novartis Investigative Site
• Colombia
  • Cundinamarca
    • Bogota, Cundinamarca, Colombia
      • Novartis Investigative Site
• Czechia
  • Czech Republic
    • Prague 2, Czech Republic, Czechia, 128 50
      • Novartis Investigative Site
• France
  • Boulogne Billancourt, France, 92104
    • Novartis Investigative Site
  • Montpellier, France, 34295
    • Novartis Investigative Site
  • Paris, France, 75651
    • Novartis Investigative Site
• Germany
  • Berlin, Germany, 13086
    • Novartis Investigative Site
  • Erlangen, Germany, 91054
    • Novartis Investigative Site
• Hungary
  • Baz
    • Miskolc, Baz, Hungary, 3529
      • Novartis Investigative Site
• Ireland
  • Dublin 4, Ireland, 4
    • Novartis Investigative Site
• Italy
  • Genova, Italy, 16132
    • Novartis Investigative Site
  • Pisa, Italy, 56126
    • Novartis Investigative Site
  • PD
    • Padova, PD, Italy, 35128
      • Novartis Investigative Site
• Mexico
  • Guadalajara Jalisco, Mexico, 44610
    • Novartis Investigative Site
  • Ciudad De Mexico
    • Mexico, Ciudad De Mexico, Mexico, 06700
      • Novartis Investigative Site
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • Novartis Investigative Site
• Norway
  • Oslo, Norway, 0319
    • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08022
    • Novartis Investigative Site
  • Madrid, Spain, 28046
    • Novartis Investigative Site
  • Madrid, Spain, 28040
    • Novartis Investigative Site
  • Madrid, Spain, 28009
    • Novartis Investigative Site
  • Madrid, Spain, 28935
    • Novartis Investigative Site
• United Kingdom
  • West Yorkshire
    • Leeds, West Yorkshire, United Kingdom, LS7 4SA
      • Novartis Investigative Site
• United States
  • California
    • Beverly Hills, California, United States, 90211
      • Novartis Investigative Site
    • Los Angeles, California, United States, 90095
      • Novartis Investigative Site
  • Maryland
    • Wheaton, Maryland, United States, 20902
      • Novartis Investigative Site
  • Utah
    • Salt Lake City, Utah, United States, 84102
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group 1; In Treatment Period-1: Patients in this group were administered secukinumab with 12 weeks of treatment from baseline. In Treatment Period-2: Patients continued to receive the same active dose of secukinumab every 4 weeks until Week 24 In Treatment Period 3 (extension period): the extension period allowed responder patients the possibility to continue open-label secukinumab treatment up to Week 52	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.; Other Names: Secukinumab
Placebo Comparator: Group 2; In Treatment Period-1: Patients received placebo at baseline and same time points as secukinumab until Week 8. In Treatment Period-2: Patients commenced open-label secukinumab every 4 weeks from Week 12, as follows, based on their clinical characteristics at Week 12 In Treatment Period-3: Open-label secukinumab continued to be assigned to patients	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.; Other Names: Secukinumab; Drug: Placebo; Secukinumab placebo was provided in a 1 mL PFS for s.c. injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2016
• Primary Completion (Actual): November 10, 2020
• Study Completion (Actual): November 10, 2020

Study Registration Dates

• First Submitted: January 13, 2016
• First Submitted That Met QC Criteria: January 20, 2016
• First Posted (Estimate): January 26, 2016

Study Record Updates

• Last Update Posted (Actual): December 7, 2021
• Last Update Submitted That Met QC Criteria: November 8, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: Arthritis; Psoriatic Arthritis; monoclonal antibody; PsA; Synovitis; secukinumab; Enthesitis; Power Doppler Ultrasonography; Outcome Measures in Rheumatology; Spondyloarthritis Research Consortium of Canada; active psoriatic arthritis; GLOESS
• Additional Relevant MeSH Terms: Skin Diseases; Joint Diseases; Musculoskeletal Diseases; Skin Diseases, Papulosquamous; Spinal Diseases; Bone Diseases; Spondylarthropathies; Spondylarthritis; Spondylitis; Psoriasis; Arthritis; Arthritis, Psoriatic; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: CAIN457F2354; 2015-002394-38 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

IPD Plan Description

Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No