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low recruitment
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Given the role of IL-17 in the development of entheseal-driven pathology, a therapeutic strategy aimed at blocking IL-17 would be a logical option for the treatment of subclinical enthesitis in psoriasis patients. This study will be the first randomized trial of a biologic therapy versus placebo in participants with plaque psoriasis and subclinical psoriatic arthritis, using musculoskeletal ultrasound.
The primary objective of this study is to estimate the difference in effect between secukinumab 300 mg s.c. and placebo, based on change from baseline to Week 16 in the OMERACT ultrasound enthesitis score.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Secukinumab 300mg | Experimental | Randomized in a 2:1 ratio to secukinumab or placebo |
|
| Placebo | Placebo Comparator | Randomized in a 2:1 ratio to secukinumab or placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Secukinumab 300 mg | Biological | Secukinumab 300 mg administered s.c. (2 single-use prefilled syringes of 150 mg/mL), on Days 1, 8, 15, 22, 29, 57, 85. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change from Baseline in the Outcome Measures in Rheumatology (OMERACT) ultrasound enthesitis score | Twelve (12) entheses (bilateral AT, LE, PP, DP, PA, QT) will be scored in terms of inflammatory and morphological components according to the OMERACT enthesitis composite semi-quantitative scale (0 to 3). The lowest OMERACT score a participant can have at baseline is 2 (based on Inclusion Criterion number 6, which requires at least 2 points in the B-mode or the Doppler mode in at least one enthesis). The highest OMERACT score expected at baseline will be 72, assuming that each of the 12 entheses assessed shows a maximum of 3 points in the gray scale score, and a maximum of 3 points in the Doppler score. The largest change expected from baseline to Week 16 is -60 points (improvement). This assumes that the presence of structural changes (calcifications, enthesophytes and erosions) may add a maximum of 12 points to the score, and it may not be modifiable with study treatment during the study period. | Baseline and Week 16 |
| Measure | Description | Time Frame |
|---|---|---|
| Change from Baseline in the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) ultrasound enthesitis score | Sixteen (16) entheses (bilateral AT, LE, PP, DP, PA, QT, SS, TT) will be scored in terms of inflammatory components according with the GRAPPA ultrasound enthesitis score. The lowest GRAPPA score a participant may have at baseline is 2 (based on Inclusion Criterion number 6, which requires at least 2 points in the B-mode or the Doppler mode in at least 1 enthesis). The highest GRAPPA score expected at baseline is 248, assuming the maximum score that could be assigned to each enthesis. The largest change expected from baseline to Week 16 is -136 points (improvement). This value assumes that the presence of structural changes (calcifications, enthesophytes, and erosions) may add a maximum of 136 points to the score, and it may not be modifiable with study treatment during the study period. |
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Inclusion Criteria:
Candidate for systemic therapy, defined as having psoriasis inadequately controlled by current topical and/or systemic treatment(s) (including topical corticosteroids), phototherapy, or previous systemic therapies
Presence of sonographic enthesitis at screening, in at least one enthesis, defined by the presence of at least abnormal thickening and hypoechogenicity of the tendon insertion, with or without presence of Doppler signal (Grade 0-3), or by the presence of grade ≥ 2 Doppler signal, independent of gray scale abnormalities
Exclusion Criteria:
Other protocol-defined inclusion/exclusion criteria may apply
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27932277 | Background | Acquitter M, Misery L, Saraux A, Bressollette L, Jousse-Joulin S. Detection of subclinical ultrasound enthesopathy and nail disease in patients at risk of psoriatic arthritis. Joint Bone Spine. 2017 Dec;84(6):703-707. doi: 10.1016/j.jbspin.2016.10.005. Epub 2016 Dec 5. | |
| 23945732 | Background | Armstrong AW, Robertson AD, Wu J, Schupp C, Lebwohl MG. Undertreatment, treatment trends, and treatment dissatisfaction among patients with psoriasis and psoriatic arthritis in the United States: findings from the National Psoriasis Foundation surveys, 2003-2011. JAMA Dermatol. 2013 Oct;149(10):1180-5. doi: 10.1001/jamadermatol.2013.5264. |
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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
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| ID | Term |
|---|---|
| D011565 | Psoriasis |
| ID | Term |
|---|---|
| D017444 | Skin Diseases, Papulosquamous |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| C555450 | secukinumab |
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|
| Placebo | Other | Placebo administered s.c. (2 single-use prefilled 1 mL syringes) on Days 1, 8, 15, 22, 29, 57, 85. |
|
| Baseline and Week 16 |
| Change from Baseline in the PsASon13 unilateral ultrasound composite score of synovitis | Joints examined by the PsASon13 unilateral ultrasound composite score: Small finger joints: MCP2, MCP5, H-PIP1, H-PIP2, H-PIP3; Distal interphalangeal finger joints: H-DIP3; Small joints of feet: MTP1, MTP5, F-PIP1; Distal interphalangeal joints of feet: F-DIP2, F-DIP3; Large joints: wrist and knee. Lowest score a participant may have at baseline is 0. Highest score a participant may have at baseline is 184 (5 small finger joints, each ranging from 0 to 18; 1 distal interphalangeal finger joint, each ranging from 0 to 16; 3 small joints of feet, each ranging from 0 to 12; 2 distal interphalangeal joints of feet, each ranging from 0 to 12; 1 wrist ranging from 0 to 12; and 1 knee ranging from 0 to 6). Largest change expected from baseline to Week 16 is -118 points (improvement). This assumes that the presence of structural changes (erosions and osteophytes) may add a maximum of 66 points to the score and it may not be modifiable with study treatment during the study period. | Baseline and Week 16 |
| Number of participants who achieve complete resolution of enthesitis based on OMERACT criteria (yes, no) | Proportion of participants experiencing complete resolution of their enthesitis based on Change from Baseline in the Outcome Measures in Rheumatology (OMERACT) score | Baseline and Week 16 |
| Number of participants who achieve Psoriasis Area and Severity Index 90 (PASI 90) (yes, no) | Psoriasis Area Severity Index 90 Scores range from 0 to 72. A score of more than 10 generally translates to "moderate-to-severe". Usually, the higher your PASI score, the lower the quality of life. A PASI 90 is at least a 90% improvement (reduction) in PASI score. | Baseline and Week 16 |
| Number of participants who achieve Psoriasis Area and Severity Index 100 (PASI 100) (yes, no) | Psoriasis Area Severity Index 100 Scores range from 0 to 72. A score of more than 10 generally translates to "moderate-to-severe". Usually, the higher your PASI score, the lower the quality of life. A PASI 100 is a complete clearing of psoriasis (PASI score = 0). | Baseline and Week 16 |
| Number of participants who achieve Investigator's Global Assessment modified 2011 (IGA mod 2011) score of 0 or 1 (yes, no) | The IGA mod 2011 scale is a visual assessment that consists of a score ranging from 0 (clear) to 4 (severe). Skin rated a 4 is bright red in color with marked plaque elevation and is dominated by thick, non-tenacious scale. For a treatment to be considered successful, the affected area must receive a score of 0 or 1 and experience a two-point improvement from Baseline. | Baseline and Week 16 |
| Change from Baseline in Body Surface Area (BSA) | The total percentage of body surface area affected by psoriasis | Baseline and Week 16 |
| Change from Baseline in Dermatology Life Quality Index (DLQI) score | A 10-item measure to assess health-related quality of life in adults with skin diseases. Scores range from 0-30 with a higher score being less quality of life. | Baseline and Week 16 |
| Number of participants who achieve Dermatology Life Quality Index (DLQI) score of 0 or 1 (yes, no) | A 10-item measure to assess health-related quality of life in adults with skin diseases. Scores range from 0-30 with a higher score being less quality of life. | Baseline and Week 16 |
| Change from Baseline in HAQ-DI score | Health Assessment Questionnaire-Disability Index (HAQ-DI) is a 20-question scale assessing functional ability. The final HAQ-DI score ranges from 0 (no problems functioning) to 3 (not able to function). | Baseline and Week 16 |
| Number of participants who achieve HAQ-DI change from baseline ≤ -0.35 (yes, no) | Health Assessment Questionnaire-Disability Index (HAQ-DI) is a 20-question scale assessing functional ability. The final HAQ-DI score ranges from 0 (no problems functioning) to 3 (not able to function). | Baseline and Week 16 |
| 18795920 | Background | Basra MK, Fenech R, Gatt RM, Salek MS, Finlay AY. The Dermatology Life Quality Index 1994-2007: a comprehensive review of validation data and clinical results. Br J Dermatol. 2008 Nov;159(5):997-1035. doi: 10.1111/j.1365-2133.2008.08832.x. Epub 2008 Sep 15. |
| 17216680 | Background | Cassell SE, Bieber JD, Rich P, Tutuncu ZN, Lee SJ, Kalunian KC, Wu CW, Kavanaugh A. The modified Nail Psoriasis Severity Index: validation of an instrument to assess psoriatic nail involvement in patients with psoriatic arthritis. J Rheumatol. 2007 Jan;34(1):123-9. |
| 12933510 | Background | Chen M, Kianifard F. A nonparametric procedure associated with a clinically meaningful efficacy measure. Biostatistics. 2000 Sep;1(3):293-8. doi: 10.1093/biostatistics/1.3.293. |
| 18485527 | Background | Doherty SD, Van Voorhees A, Lebwohl MG, Korman NJ, Young MS, Hsu S, National Psoriasis Foundation. National Psoriasis Foundation consensus statement on screening for latent tuberculosis infection in patients with psoriasis treated with systemic and biologic agents. J Am Acad Dermatol. 2008 Aug;59(2):209-17. doi: 10.1016/j.jaad.2008.03.023. Epub 2008 May 15. |
| 24794490 | Background | El Miedany Y, El Gaafary M, Youssef S, Ahmed I, Nasr A. Tailored approach to early psoriatic arthritis patients: clinical and ultrasonographic predictors for structural joint damage. Clin Rheumatol. 2015 Feb;34(2):307-13. doi: 10.1007/s10067-014-2630-2. Epub 2014 May 3. |
| 30756253 | Background | Elnady B, El Shaarawy NK, Dawoud NM, Elkhouly T, Desouky DE, ElShafey EN, El Husseiny MS, Rasker JJ. Subclinical synovitis and enthesitis in psoriasis patients and controls by ultrasonography in Saudi Arabia; incidence of psoriatic arthritis during two years. Clin Rheumatol. 2019 Jun;38(6):1627-1635. doi: 10.1007/s10067-019-04445-0. Epub 2019 Feb 12. |
| 26916344 | Background | Faustini F, Simon D, Oliveira I, Kleyer A, Haschka J, Englbrecht M, Cavalcante AR, Kraus S, Tabosa TP, Figueiredo C, Hueber AJ, Kocijan R, Cavallaro A, Schett G, Sticherling M, Rech J. Subclinical joint inflammation in patients with psoriasis without concomitant psoriatic arthritis: a cross-sectional and longitudinal analysis. Ann Rheum Dis. 2016 Dec;75(12):2068-2074. doi: 10.1136/annrheumdis-2015-208821. Epub 2016 Feb 25. |
| 26402388 | Background | Feldman SR, Zhao Y, Shi L, Tran MH. Economic and Comorbidity Burden Among Patients with Moderate-to-Severe Psoriasis. J Manag Care Spec Pharm. 2015 Oct;21(10):874-88. doi: 10.18553/jmcp.2015.21.10.874. |
| 25361855 | Background | Ficjan A, Husic R, Gretler J, Lackner A, Graninger WB, Gutierrez M, Duftner C, Hermann J, Dejaco C. Ultrasound composite scores for the assessment of inflammatory and structural pathologies in Psoriatic Arthritis (PsASon-Score). Arthritis Res Ther. 2014 Oct 31;16(5):476. doi: 10.1186/s13075-014-0476-2. |
| 8033378 | Background | Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI)--a simple practical measure for routine clinical use. Clin Exp Dermatol. 1994 May;19(3):210-6. doi: 10.1111/j.1365-2230.1994.tb01167.x. |
| 357213 | Background | Fredriksson T, Pettersson U. Severe psoriasis--oral therapy with a new retinoid. Dermatologica. 1978;157(4):238-44. doi: 10.1159/000250839. |
| 15708927 | Background | Gladman DD, Antoni C, Mease P, Clegg DO, Nash P. Psoriatic arthritis: epidemiology, clinical features, course, and outcome. Ann Rheum Dis. 2005 Mar;64 Suppl 2(Suppl 2):ii14-7. doi: 10.1136/ard.2004.032482. |
| 15948985 | Background | Gottlieb AB, Griffiths CE, Ho VC, Lahfa M, Mrowietz U, Murrell DF, Ortonne JP, Todd G, Cherill R, Marks I, Emady-Azar S, Paul CF; Multi-Centre Investigator Group. Oral pimecrolimus in the treatment of moderate to severe chronic plaque-type psoriasis: a double-blind, multicentre, randomized, dose-finding trial. Br J Dermatol. 2005 Jun;152(6):1219-27. doi: 10.1111/j.1365-2133.2005.06661.x. |
| 20688358 | Background | Gutierrez M, Filippucci E, De Angelis R, Salaffi F, Filosa G, Ruta S, Bertolazzi C, Grassi W. Subclinical entheseal involvement in patients with psoriasis: an ultrasound study. Semin Arthritis Rheum. 2011 Apr;40(5):407-12. doi: 10.1016/j.semarthrit.2010.05.009. Epub 2010 Aug 5. |
| 30053825 | Background | Kampylafka E, d'Oliveira I, Linz C, Lerchen V, Stemmler F, Simon D, Englbrecht M, Sticherling M, Rech J, Kleyer A, Schett G, Hueber AJ. Resolution of synovitis and arrest of catabolic and anabolic bone changes in patients with psoriatic arthritis by IL-17A blockade with secukinumab: results from the prospective PSARTROS study. Arthritis Res Ther. 2018 Jul 27;20(1):153. doi: 10.1186/s13075-018-1653-5. |
| 18313491 | Background | King MT, Fayers PM. Making quality-of-life results more meaningful for clinicians. Lancet. 2008 Mar 1;371(9614):709-10. doi: 10.1016/S0140-6736(08)60324-4. No abstract available. |
| 18598104 | Background | Manuel O, Kumar D. QuantiFERON-TB Gold assay for the diagnosis of latent tuberculosis infection. Expert Rev Mol Diagn. 2008 May;8(3):247-56. doi: 10.1586/14737159.8.3.247. |
| 29204762 | Background | Mathew AJ, Bird P, Gupta A, George R, Danda D. Magnetic resonance imaging (MRI) of feet demonstrates subclinical inflammatory joint disease in cutaneous psoriasis patients without clinical arthritis. Clin Rheumatol. 2018 Feb;37(2):383-388. doi: 10.1007/s10067-017-3895-z. Epub 2017 Dec 4. |
| 21700682 | Background | Naredo E, Moller I, de Miguel E, Batlle-Gualda E, Acebes C, Brito E, Mayordomo L, Moragues C, Uson J, de Agustin JJ, Martinez A, Rejon E, Rodriguez A, Dauden E; Ultrasound School of the Spanish Society of Rheumatology and Spanish ECO-APs Group. High prevalence of ultrasonographic synovitis and enthesopathy in patients with psoriasis without psoriatic arthritis: a prospective case-control study. Rheumatology (Oxford). 2011 Oct;50(10):1838-48. doi: 10.1093/rheumatology/ker078. Epub 2011 Jun 23. |
| 30468001 | Background | Savage L, Goodfield M, Horton L, Watad A, Hensor E, Emery P, Wakefield R, Wittmann M, McGonagle D. Regression of Peripheral Subclinical Enthesopathy in Therapy-Naive Patients Treated With Ustekinumab for Moderate-to-Severe Chronic Plaque Psoriasis: A Fifty-Two-Week, Prospective, Open-Label Feasibility Study. Arthritis Rheumatol. 2019 Apr;71(4):626-631. doi: 10.1002/art.40778. Epub 2019 Mar 4. |
| 30742092 | Background | Scher JU, Ogdie A, Merola JF, Ritchlin C. Preventing psoriatic arthritis: focusing on patients with psoriasis at increased risk of transition. Nat Rev Rheumatol. 2019 Mar;15(3):153-166. doi: 10.1038/s41584-019-0175-0. |
| 22134799 | Background | Tinazzi I, McGonagle D, Biasi D, Confente S, Caimmi C, Girolomoni G, Gisondi P. Preliminary evidence that subclinical enthesopathy may predict psoriatic arthritis in patients with psoriasis. J Rheumatol. 2011 Dec;38(12):2691-2. doi: 10.3899/jrheum.110505. No abstract available. |
| 26054432 | Background | Villani AP, Rouzaud M, Sevrain M, Barnetche T, Paul C, Richard MA, Beylot-Barry M, Misery L, Joly P, Le Maitre M, Aractingi S, Aubin F, Cantagrel A, Ortonne JP, Jullien D. Prevalence of undiagnosed psoriatic arthritis among psoriasis patients: Systematic review and meta-analysis. J Am Acad Dermatol. 2015 Aug;73(2):242-8. doi: 10.1016/j.jaad.2015.05.001. Epub 2015 Jun 6. |
| 14522626 | Background | Weisman S, Pollack CR, Gottschalk RW. Psoriasis disease severity measures: comparing efficacy of treatments for severe psoriasis. J Dermatolog Treat. 2003 Sep;14(3):158-65. doi: 10.1080/09546630310013360. |
| 31749987 | Background | Zabotti A, McGonagle DG, Giovannini I, Errichetti E, Zuliani F, Zanetti A, Tinazzi I, De Lucia O, Batticciotto A, Idolazzi L, Sakellariou G, Zandonella Callegher S, Sacco S, Quartuccio L, Iagnocco A, De Vita S. Transition phase towards psoriatic arthritis: clinical and ultrasonographic characterisation of psoriatic arthralgia. RMD Open. 2019 Oct 23;5(2):e001067. doi: 10.1136/rmdopen-2019-001067. eCollection 2019. |
| 25881759 | Result | Acquacalda E, Albert C, Montaudie H, Fontas E, Danre A, Roux CH, Breuil V, Lacour JP, Passeron T, Ziegler LE. Ultrasound study of entheses in psoriasis patients with or without musculoskeletal symptoms: A prospective study. Joint Bone Spine. 2015 Jul;82(4):267-71. doi: 10.1016/j.jbspin.2015.01.016. Epub 2015 Apr 13. |