PsA Secukinumab XCT Structural Progression Study

September 3, 2023 updated by: Lai-Shan Tam, Chinese University of Hong Kong

Prevention of Metacarpophalangeal Joints Structure Damage in Patients With Psoriatic Arthritis Using Secukinumab

Psoriatic arthritis is related with chronic inflammation and progressive radiographic damages, and it in turn lead to disability and loss in function-ability. Recent advance in treatment pathway through anti IL-17 gives promising clinical improvement. Yet, its effect on radiographic progression remains uncertain. This study aimed to ascertain the effect of secukinumab on structural progression in PsA by evaluation through high resolution peripheral quantative computed tomography (HRpqCT).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Psoriatic arthritis (PsA) is a chronic inflammatory joint disease associated with psoriasis. PsA is associated with distinctive clinical features including changes in skin and nails, peripheral arthritis, axial disease, dactylitis and enthesitis. Synovial inflammation in peripheral joints is the most prevalent feature of the disease ranging in severity from mild joint inflammation to disabling peripheral arthritis [1]. Within 2 years of diagnosis, radiological erosions were developed in 47% of the patients [2]. Without proper monitoring and treatment, it will lead to significant structure damage and loss of physical function, and even arthritis mutilans, which is the most severe destructive form of PsA [3]. Prevention of structural damage is one of the primary goals of treating PsA patients to maximise health-related quality of life [4].

Detection of bone erosions in PsA patients is usually achieved by conventional radiographs although the sensitivity is low [5]. High-resolution peripheral quantitative CT (HR-pQCT) is a novel technique for detailed bone microstructure analysis with high reproducibility in assessing bony erosions [6]. With its high spatial resolution of 130 μm, HR-pQCT exhibited a higher sensitivity in detecting erosion compared with radiograph and magnetic resonance imaging (MRI) [7]. Recently, Finzel et al. described an indirect method to assess volume based on measurements of the width and depth of the erosions using HR-pQCT [8]. Quantitative measurement of erosion volume can also be achieved [6]. Using this method, erosion repair under biological disease-modifying antirheumatic drugs (DMARDs) treatment has been demonstrated in patients with rheumatoid arthritis (RA) [8, 9]. Bone apposition at the margin of erosions (osteosclerosis) with the formation of a new cortical lining was associated with a decrease in erosion depth or width, which may indicate either periosteal or endosteal repair processes [8, 9]. Valid measurement of erosion volume using HR-pQCT will facilitate the testing of treatments that may help to heal erosion. Decrease in erosion volume and the presence of osteosclerosis on HR-pQCT could be promising markers for erosion healing.

Interleukin 17 (IL-17) is a proinflammatory cytokine which produced by type 17 helper T cells (Th17). It is now considered to be a key cytokine in the pathogenesis of a number of autoimmune disorders in humans including PsA [10]. IL-17 was also reported to be associated with the presence of joint erosion [11]. Recently, secukinumab, an anti-interleukin-17A monoclonal antibody, was reported to be effective in reducing disease activity and decreased the rate of radiographic joint damage compared with placebo [12]. However, whether healing of erosion could occur in PsA has never been evaluated.

On the other hand, osteophytes formation at the entheseal regions of the joints in PsA is distinctive feature compared with RA [13]. The formation of osteophytes is tightly regulated by anabolic pathways, which resembles the pathogenesis of new bone formation in ankylosing spondylitis (AS). Tumor necrosis factor (TNF) inhibition was unable to halt the structural progression in AS patients [14-16], it also lacked efficacy in stopping the progression of osteophytes in PsA patients [17]. Inhibition of IL-17 by secukinumab was effective in the treatment of both AS [18] and PsA [12]. Secukinumab also decreased the rate of radiographic joint damage regarding to erosion and joint space narrowing [12]. However, it is unknown if it has any effect in the progression of osteophytes. In an animal model, although over-expression of IL-17 alone failed to induce entheseal and periosteal bone formation, inhibition of IL-17 leaded to significant reduction of such bone formation in an IL-23 overexpression model [19]. Moreover, IL-17A accelerates bone formation by stimulating the proliferation and osteoblastic differentiation of mesenchymal progenitor cells after injury [20]. It is worth exploring if secukinumab could prevent the progression of osteophytes in PsA patients.

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Hong Kong
      • Hong Kong, Hong Kong
        • Department of Medicine and Therapeutics

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. ≥18 years old;
  2. without severe deformity in MCP joints which would influence the longitudinal assessment of HR-pQCT;
  3. with active disease, which is defined as three or more than tender joints and three or more than swollen joints, despite previous treatment with nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs.

Exclusion Criteria:

  1. limited in ability to perform usual self-care, vocational, and avocational activities;
  2. pregnancy;
  3. previous therapy with biologic;
  4. the presence of active inflammatory diseases other than PsA;
  5. active infection in 2 weeks before randomization or a history of ongoing, chronic, or recurrent infections including tuberculosis;
  6. history of hepatitis B & C;
  7. history of malignant disease within the past 5 years (excluding basal cell carcinoma or actinic keratosis, in-situ cervical cancer, or non-invasive malignant colon polyps);
  8. contraindications to secukinumab.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Secukinumab
Subject will received secukinumab 150mg at week 0-4, and once monthly till week 48
Drug: Secukinumab
Subject will take secukinumab once weekly in week 0-4, and once monthly till week 48
Other Names:
  • Cosentyx
Placebo Comparator: Placebo
Subject will received placebo 150mg at week 0-4, and once monthly till week 48
Drug: Placebo
Subject will take placebo once weekly in week 0-4, and once monthly till week 48

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Difference in changes in the volume of erosions on metacarpophalangeal joints (MCP) 2-4 measured by HR-pQCT at 24 weeks between secukinumab and placebo group
Time Frame: 24 weeks
The erosion volume will be calculated from HR-pQCT images
24 weeks
Difference in changes in the volume of erosions on metacarpophalangeal joints (MCP) 2-4 measured by HR-pQCT at 48 weeks between secukinumab and placebo group
Time Frame: 48 weeks
The erosion volume will be calculated from HR-pQCT images
48 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The percentage of erosions with healing determined using HR-pQCT on MCP 2-4
Time Frame: 24 weeks
Erosion healing is defined as a decrease in erosion volume of ≥0.4 mm3 from baseline, and the presence of grade 2 osteosclerosis at the margin of erosion
24 weeks
The percentage of erosions with healing determined using HR-pQCT on MCP 2-4
Time Frame: 48 weeks
Erosion healing is defined as a decrease in erosion volume of ≥0.4 mm3 from baseline, and the presence of grade 2 osteosclerosis at the margin of erosion
48 weeks
Changes in depth and width of erosion using HR-pQCT
Time Frame: 24 weeks
The erosion volume will be calculated from HR-pQCT images
24 weeks
Changes in depth and width of erosion using HR-pQCT
Time Frame: 48 weeks
The erosion volume will be calculated from HR-pQCT images
48 weeks
Marginal osteosclerosis using HR-pQCT
Time Frame: 24 weeks
The marginal osteosclerosis will be calculated from HR-pQCT images
24 weeks
Marginal osteosclerosis using HR-pQCT
Time Frame: 48 weeks
The marginal osteosclerosis will be calculated from HR-pQCT images
48 weeks
Changes in the height of osteophytes using HR-pQCT
Time Frame: 24 weeks
The height of osteophytes will be analysed from HR-pQCT images
24 weeks
Changes in the height of osteophytes using HR-pQCT
Time Frame: 48 weeks
The height of osteophytes will be analysed from HR-pQCT images
48 weeks
Changes in joint space volume using HR-pQCT
Time Frame: Week 24
HR-pQCT measures the joint space volume
Week 24
Changes in joint space volume using HR-pQCT
Time Frame: Week 48
HR-pQCT measures the joint space volume
Week 48

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in HAQ (Health Assessment Questionnaire)
Time Frame: Week 24
HAQ (0-3) assessing functional disability, with higher score representing higher functional disability.
Week 24
Changes in HAQ (Health Assessment Questionnaire)
Time Frame: Week 48
HAQ (0-3) assessing functional disability, with higher score representing higher functional disability.
Week 48
Changes in patient reported outcome (SF-36)
Time Frame: Week 48
SF-36 is a questionnaire representing subject's physical & mental well being ranging from 0-100, with 100 representing better outcome.
Week 48
Changes in patient reported outcome (SF-36)
Time Frame: Week 24
SF-36 is a questionnaire representing subject's physical & mental well being ranging from 0-100, with 100 representing better outcome.
Week 24
Changes in Psoriatic Arthritis Impact of Disease (PsAID)
Time Frame: Week 24
PsAID (0-12) measures the impact of PsA in patients with lower score representing better QoL
Week 24
Changes in Psoriatic Arthritis Impact of Disease (PsAID)
Time Frame: Week 48
PsAID (0-12) measures the impact of PsA in patients with lower score representing better QoL
Week 48
Changes in van der Heijde-Sharp score on radiograph at 48 weeks
Time Frame: 48 weeks
The van der Heijde-sharp score assess erosion (0-528) and joint space narrowing (0-208) in x-ray, which higher score represent higher radiographic damages
48 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Chinese University of Hong Kong

Investigators

  • Principal Investigator: Lai Shan Tam, MD, Chinese University of Hong Kong

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 18, 2020

Primary Completion (Actual)

September 30, 2022

Study Completion (Actual)

September 30, 2022

Study Registration Dates

First Submitted

August 2, 2018

First Submitted That Met QC Criteria

August 7, 2018

First Posted (Actual)

August 9, 2018

Study Record Updates

Last Update Posted (Estimated)

September 6, 2023

Last Update Submitted That Met QC Criteria

September 3, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PsA secukinumab XCT study 2018

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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