PsA Secukinumab XCT Structural Progression Study
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|ClinicalTrials.gov Identifier: NCT03623867|
Recruitment Status : Not yet recruiting
First Posted : August 9, 2018
Last Update Posted : January 31, 2019
|Condition or disease||Intervention/treatment||Phase|
|Psoriatic Arthritis||Drug: Secukinumab Drug: Placebo||Phase 4|
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 . Within 2 years of diagnosis, radiological erosions were developed in 47% of the patients . 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 . Prevention of structural damage is one of the primary goals of treating PsA patients to maximise health-related quality of life .
Detection of bone erosions in PsA patients is usually achieved by conventional radiographs although the sensitivity is low . High-resolution peripheral quantitative CT (HR-pQCT) is a novel technique for detailed bone microstructure analysis with high reproducibility in assessing bony erosions . 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) . 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 . Quantitative measurement of erosion volume can also be achieved . 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 . IL-17 was also reported to be associated with the presence of joint erosion . 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 . 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 . 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 . Inhibition of IL-17 by secukinumab was effective in the treatment of both AS  and PsA . Secukinumab also decreased the rate of radiographic joint damage regarding to erosion and joint space narrowing . 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 . Moreover, IL-17A accelerates bone formation by stimulating the proliferation and osteoblastic differentiation of mesenchymal progenitor cells after injury . It is worth exploring if secukinumab could prevent the progression of osteophytes in PsA patients.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Subject will be randomised into secukinumab or placebo group in 1:1 ratio|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Prevention of Metacarpophalangeal Joints Structure Damage in Patients With Psoriatic Arthritis Using Secukinumab|
|Estimated Study Start Date :||April 1, 2019|
|Estimated Primary Completion Date :||September 30, 2020|
|Estimated Study Completion Date :||September 30, 2021|
Subject will received secukinumab 150mg at week 0-4, and once monthly till week 52
Subject will take secukinumab once weekly in week 0-4, and once monthly till week 52
Other Name: Cosentyx
Placebo Comparator: Placebo
Subject will received placebo 150mg at week 0-4, and once monthly till week 52
Subject will take placebo once weekly in week 0-4, and once monthly till week 52
- Difference in changes in the volume of erosions on metacarpophalangeal joints (MCP) 2-4 measured by HR-pQCT at 52 weeks between secukinumab and placebo group [ Time Frame: 52 weeks ]The erosion volume will be calculated from HR-pQCT images
- The percentage of erosions with healing determined using HR-pQCT on MCP 2-4 at 52 weeks [ Time Frame: 52 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
- Changes in depth and width of erosion using HR-pQCT at 52 weeks [ Time Frame: 52 weeks ]The erosion volume will be calculated from HR-pQCT images
- Marginal osteosclerosis using HR-pQCT at 52 weeks [ Time Frame: 52 weeks ]The marginal osteosclerosis will be calculated from HR-pQCT images
- Changes in the height of osteophytes using HR-pQCT at 52 weeks [ Time Frame: 52 weeks ]The height of osteophytes will be analysed from HR-pQCT images
- Changes in van der Heijde-Sharp score on radiograph at 52 weeks [ Time Frame: 52 weeks ]The van der Heijde-sharp score assess erosion and joint space narrowing in x-ray, which higher score represent higher radiographic damages
- Changes in HAQ (Health Assessment Questionnaire) [ Time Frame: Week 28 ]HAQ (0-3) assessing functional disability, with higher score representing higher functional disability.
- Changes in HAQ (Health Assessment Questionnaire) [ Time Frame: Week 52 ]HAQ (0-3) assessing functional disability, with higher score representing higher functional disability.
- Changes in patient reported outcome (SF-36) [ Time Frame: Week 28 ]SF-36 is a questionnaire representing subject's physical & mental well being ranging from 0-100, with 100 representing better outcome.
- Changes in patient reported outcome (SF-36) [ Time Frame: Week 52 ]SF-36 is a questionnaire representing subject's physical & mental well being ranging from 0-100, with 100 representing better outcome.
- Changes in The Dermatology Life Quality Index (DLQI) [ Time Frame: Week 28 ]DLQI assess subjects' QoL base on skin condition. DLQI ranges from 0-30 with higher score representing poorer quality of life
- Changes in The Dermatology Life Quality Index (DLQI) [ Time Frame: Week 52 ]DLQI assess subjects' QoL base on skin condition. DLQI ranges from 0-30 with higher score representing poorer quality of life
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03623867
|Contact: Isaac Cheng, MSc||3505 email@example.com|
|Contact: Lai Shan Tam, MD||3505 firstname.lastname@example.org|
|Department of Medicine and Therapeutics|
|Hong Kong, Hong Kong|
|Principal Investigator:||Lai Shan Tam, MD||Chinese University of Hong Kong|