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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 : October 5, 2018
Sponsor:
Information provided by (Responsible Party):
Lai-Shan Tam, Chinese University of Hong Kong

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Psoriatic Arthritis Drug: Secukinumab Drug: Placebo Phase 4

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  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
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)
Primary Purpose: Treatment
Official Title: Prevention of Metacarpophalangeal Joints Structure Damage in Patients With Psoriatic Arthritis Using Secukinumab
Estimated Study Start Date : October 1, 2018
Estimated Primary Completion Date : September 30, 2020
Estimated Study Completion Date : September 30, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Secukinumab

Arm Intervention/treatment
Experimental: Secukinumab
Subject will received secukinumab 150mg at week 0-4, and once monthly till week 52
Drug: Secukinumab
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
Drug: Placebo
Subject will take placebo once weekly in week 0-4, and once monthly till week 52




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. Marginal osteosclerosis using HR-pQCT at 52 weeks [ Time Frame: 52 weeks ]
    The marginal osteosclerosis will be calculated from HR-pQCT images

  4. 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

  5. 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

  6. Changes in HAQ (Health Assessment Questionnaire) [ Time Frame: Week 28 ]
    HAQ (0-3) assessing functional disability, with higher score representing higher functional disability.

  7. Changes in HAQ (Health Assessment Questionnaire) [ Time Frame: Week 52 ]
    HAQ (0-3) assessing functional disability, with higher score representing higher functional disability.

  8. 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.

  9. 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.

  10. 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

  11. 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



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

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.

Information from the National Library of Medicine

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


Contacts
Contact: Isaac Cheng, MSc 3505 1429 ichength@cuhk.edu.hk
Contact: Lai Shan Tam, MD 3505 3128 lstam@cuhk.edu.hk

Locations
Hong Kong
Department of Medicine and Therapeutics
Hong Kong, Hong Kong
Sponsors and Collaborators
Chinese University of Hong Kong
Investigators
Principal Investigator: Lai Shan Tam, MD Chinese University of Hong Kong
  Study Documents (Full-Text)

Documents provided by Lai-Shan Tam, Chinese University of Hong Kong:
Study Protocol  [PDF] July 27, 2018


Publications:

Responsible Party: Lai-Shan Tam, Professor, Chinese University of Hong Kong
ClinicalTrials.gov Identifier: NCT03623867     History of Changes
Other Study ID Numbers: PsA secukinumab XCT study 2018
First Posted: August 9, 2018    Key Record Dates
Last Update Posted: October 5, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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

Additional relevant MeSH terms:
Arthritis
Arthritis, Psoriatic
Joint Diseases
Musculoskeletal Diseases
Spondylarthropathies
Spondylarthritis
Spondylitis
Spinal Diseases
Bone Diseases
Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs