Study of Efficacy and Safety of Secukinumab in Psoriatic Arthritis and Axial Spondyloarthritis Patients With Active Enthesitis Including One Achilles Tendon Site (ACHILLES)

• ClinicalTrials.gov Identifier: NCT02771210
• Recruitment Status: Active, not recruiting
• First Posted: May 13, 2016
• Last Update Posted: June 11, 2019
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

The purpose of this study is to demonstrate efficacy, including effects on inflammation by magnetic resonance imaging (MRI) assessments, of secukinumab on Achilles tendon enthesitis for up to 1 year with a primary focus at Week 24, in patients with active Psoriatic Arthritis and axial Spondyloarthritis despite current or previous non-steroidal anti-inflammatory drugs (NSAID) and/or disease modifying anti-rheumatic drug (DMARD) and/or anti-TNFα therapy.

Condition or disease	Intervention/treatment	Phase
Psoriatic Arthritis; Axial Spondyloarthritis; Enthesitis	Biological: AIN457/Secukinumab; Drug: AIN457/Secukinumab Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 204 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled Multicenter Study of Subcutaneous Secukinumab to Demonstrate Efficacy in the Treatment of Enthesitis at the Achilles Tendon up to 1 Year in Adult Patients With Active Psoriatic Arthritis (PsA) and Axial Spondyloarthritis (axSpA) (ACHILLES)
• Actual Study Start Date: August 30, 2016
• Estimated Primary Completion Date: January 8, 2020
• Estimated Study Completion Date: January 8, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: AIN457/Secukinumab; Secukinumab 150 mg s.c. or Secukinumab 300 mg s.c., respective dose will be assigned according to underlying condition, in case of PsA according to severity of concomitant Psoriasis or pre-exposure to anti-TNFα	Biological: AIN457/Secukinumab; Induction: Week 0,1,2,3 150 mg or 300 mg Secukinumab s.c. Maintenance: 150 mg or 300 mg Secukinumab s.c. every 4 weeks starting at Week 4
Placebo Comparator: AIN457/Secukinumab Placebo; Secukinumab Placebo s.c.	Drug: AIN457/Secukinumab Placebo; Induction: Week 0,1,2,3 Secukinumab Placebo s.c. Maintenance: Secukinumab Placebo s.c. every 4 weeks starting at Week 4 until Week 24 followed by 150 or 300 mg Secukinumab s.c. every 4 weeks

Outcome Measures

Primary Outcome Measures :

1. Percentage of patients with resolution of Achilles tendon enthesitis [ Time Frame: Week 24 ]
   To measure the percentage of patients with resolution of Achilles tendon enthesitis as assessed by the respective subcomponent of the Leeds enthesitis index (LEI).

Secondary Outcome Measures :

1. Heel Pain [ Time Frame: Week 24 ]
   The efficacy of secukinumab is superior to placebo based on the mean change of heel pain measured on a 10-point numerical rating scale.
2. Percentage of patients with an improvement of bone marrow edema [ Time Frame: Week 24 ]
   The efficacy of secukinumab is superior to placebo based on the percentage of patients with an improvement of bone marrow edema as assessed by the respective subcomponent of the Psoriatic Arthritis Magnetic Resonance Imaging Score (PsAMRIS) in the affected foot at Baseline.
3. Percentage of patients with resolution of enthesitis [ Time Frame: Week 24 ]
   The efficacy of secukinumab is superior to placebo based on the percentage of patients with resolution of enthesitis as assessed by the Leeds enthesitis index (LEI).
4. Mean change in Physician's global assessment of disease activity [ Time Frame: Week 24 ]
   The efficacy of secukinumab is superior to placebo based on the mean change in physician's global assessment of disease activity.
5. Mean change in Patient's global assessment of disease activity [ Time Frame: Week 24 ]
   The efficacy of secukinumab is superior to placebo based on the mean change in patient's global assessment of disease activity.
6. Mean change in Physician's global assessment of heel enthesiopathy activity [ Time Frame: Week 24 ]
   The efficacy of secukinumab is superior to placebo based on the mean change in physician's global assessment of heel enthesiopathy activity.
7. Mean change in Patient's global assessment of heel enthesiopathy activity [ Time Frame: Week 24 ]
   The efficacy of secukinumab is superior to placebo based on the mean change in patient's global assessment of heel enthesiopathy activity.
8. Change in Short Form-36 Physical Component Summary (SF-36 PCS) or Short Form-36 (SF-36) v2 [ Time Frame: Week 24 ]
   The improvement in secukinumab is superior to placebo based on the change from Baseline in Short Form-36 Physical Component Summary (SF-36 PCS) or Short Form-36 (SF-36) v2.
9. Increase in percentage of patients with resolution of Achilles tendon enthesitis after switching from placebo [ Time Frame: Week 24 - Week 52 ]
   To measure the increase in percentage of patients with resolution of Achilles tendon enthesitis after switching from placebo to secukinumab.
10. Increase in mean change of Heel Pain in patients after switching from placebo [ Time Frame: Week 24 - Week 52 ]
    To describe the increase in mean change of heel pain in patients after switching from placebo to secukinumab.
11. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: 52 weeks ]
    These assessments will be implemented in terms of physical examination and vital signs outcomes, clinical laboratory results, nature and frequency of the observed adverse events and serious adverse events, frequency and severity of any injection site reactions and ECG outcomes. During the first 24 weeks of the study, comparisons between the secukinumab treatment arm and the placebo treatment arm will also take place.

Eligibility Criteria

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

Criteria

Key Inclusion Criteria:

- Patients with Psoriatic arthritis: Diagnosis of Psoriatic arthritis as per the Classification criteria for Psoriatic Arthritis (CASPAR criteria) with symptoms for at least 6 months and active Psoriatic arthritis as assessed by ≥ 1 tender joints out of 78 and ≥ 1 swollen joints out of 76 at Baseline (dactylitis of a digit counts as one joint each).

- Patients with Axial Spondyloarthritis: Diagnosis of Axial Spondyloarthritis as per the classification of the Assessment of Spondyloarthritis International Society axial Spondyloarthritis (ASAS) criteria and objective signs of inflammation at Screening (magnetic resonance imaging (MRI) or definite radiographic sacroilitis and/or abnormal C-Reactive Protein) and active disease assessed by total Bath ankylosing spondylitis disease activity index (BASDAI) ≥ 4 (0-10) at Baseline.

• Diagnosis of Achilles tendon enthesitis according to swelling and tenderness at the insertional site of the Achilles tendon into the calcaneus.
• Onset of heel pain ≥ 1 month at Baseline.
• Heel enthesitis that is magnetic resonance imaging (MRI)-positive according to the investigator`s judgement.
• Patients who have been exposed to up to two TNFα inhibitors.

Key Exclusion Criteria:

• Chest X-ray or chest magnetic resonance imaging (MRI) with evidence of ongoing infectious or malignant process.
• Previous exposure to secukinumab or other biologic drug directly targeting Interleukin (IL)-17 or Interleukin (IL)-17 receptor.
• Ongoing use of psoriasis treatments / medications (e.g. topical corticosteroids, ultraviolet (UV) therapy) at randomization.
• Patients who have previously been exposed to more than two Tumor necrosis factor (TNF) inhibitors (investigational or approved).
• Patients who have ever received biologic immunomodulating agents (investigational or approved), except those targeting Tumor necrosis factor (TNF) inhibitors.
• Pregnant or nursing (lactating) women.
• History of ongoing, chronic or recurrent infectious disease or evidence of tuberculosis infection.

Other protocol-defined inclusion/exclusion criteria may apply.

Contacts and Locations

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Sponsors and Collaborators

Novartis Pharmaceuticals

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02771210 History of Changes
• Other Study ID Numbers: CAIN457F3301; 2016-000972-91 ( EudraCT Number )
• First Posted: May 13, 2016
• Last Update Posted: June 11, 2019
• Last Verified: June 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect 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

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

Active psoriatic arthritis; Axial spondyloarthritides; Subcutaneous; Secukinumab in prefilled syringe; Enthesitis; Achilles tendon

Additional relevant MeSH terms:

Arthritis; Arthritis, Psoriatic; Spondylarthritis; Enthesopathy; Joint Diseases; Musculoskeletal Diseases; Spondylarthropathies; Spondylitis; Spinal Diseases; Bone Diseases; Psoriasis; Skin Diseases, Papulosquamous; Skin Diseases; Tendinopathy; Muscular Diseases; Tendon Injuries; Wounds and Injuries; Antibodies, Monoclonal; Immunologic Factors; Physiological Effects of Drugs