Efficacy at 24 Weeks With Long Term Safety, Tolerability and Efficacy up to 5 Years of Secukinumab in Patients of Active Psoriatic Arthritis

NCT01752634 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: CAIN457F23122012-004439-22
• Study Type: interventional
• Target: 397
• Locations: 11 countries
• Sites: 76

Brief Summary

This study was to provide 24 - 52 week efficacy, safety and tolerability data to support the registration of the secukinumab (AIN457) prefilled syringe (PFS) for subcutaneous self administration in subjects with active PsA despite current or previous NSAID, DMARD and/or anti-TNFα therapy. An additional 4 years of long-term efficacy and safety data were collected during the post Week 52 period of the study.

Conditions

Psoriatic Arthritis

Keywords

Psoriatic arthritis, PsA, ACR, CASPAR, PASDAS

Outcome Measures

Primary Outcomes (1)

• Number of Participants Achieving American College of Rheumatology 20 (ACR20) Response Criteria

  ACR20 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 20% improvement in tender 68-joint count, swollen 66-joint count and at least 3 of the following 5 measures: patient's assessment of RA pain, patient's global assessment of disease activity, physician's global assessment of disease activity, subject self-assessed disability (Health Assessment Questionnaire \[HAQ-DI\] score), and/or acute phase reactant (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR). For subjects with early escape at Week 16 or had missing values at Week 24 or discontinued prior to Week 24, their ACR20 was set to nonresponse at Week 24. This applied for all treatment regimens in order to minimize bias. The Placebo arm was analyzed as one group, irrespective of the re-randomization, as assessments made under the re-randomized active treatment were not included in this analysis.

  Week 24

Secondary Outcomes (8)

• Number of Participants Achieving a PASI75 Response in the Subgroup of Subjects Who Have ≥3% Skin Involvement With Psoriasis

  Week 24

• Number of Participants Achieving a PASI90 Response in the Subgroup of Subjects Who Have ≥3% Skin Involvement With Psoriasis

  Week 24

• Change From Baseline in DAS28-CRP

  Baseline, Week 24

• Change From Baseline in SF36-Physical Component Score

  Baseline, Week 24

• Change From Baseline in Stanford Health Assessment Questionnaire Disability Index (HAQ-DI)

  Baseline, Week 24

Study Arms (4)

Secukinumab (AIN457) 75 mg s.c.

EXPERIMENTAL

Secukinumab 75 mg at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4.

Drug: Secukinumab (AIN457)

Secukinumab (AIN457) 150 mg s.c.

EXPERIMENTAL

Secukinumab 150 mg at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4.

Drug: Secukinumab (AIN457)

Secukinumab (AIN457) 300 mg s.c.

EXPERIMENTAL

Secukinumab 300 mg at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4

Drug: Secukinumab (AIN457)

Placebo s.c.

PLACEBO COMPARATOR

Placebo at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4. Non-responder (assessed at Week 16) were re-randomized to receive AIN457 150mg or AIN457 300 mg starting at Week 16. Responder (assessed at Week 16) were re-randomized to receive AIN457 150mg or AIN457 300 mg starting at Week 24.

Drug: Secukinumab (AIN457); Drug: Placebo

Interventions

Secukinumab (AIN457) DRUG

Secukinumab (AIN457)

Placebo s.c.; Secukinumab (AIN457) 150 mg s.c.; Secukinumab (AIN457) 300 mg s.c.; Secukinumab (AIN457) 75 mg s.c.

Placebo DRUG

Placebo PFS for s.c. administration.

Placebo s.c.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of PsA classified by CASPAR criteria and with symptoms for at least 6 months with moderate to severe PsA who must have at Baseline ≥3 tender joints out of 78 and ≥3 swollen out of 76 (dactylitis of a digit counts as one joint each)
• Rheumatoid factor and anti-CCP antibodies negative at screening
• Diagnosis of active plaque psoriasis or nail changes consistent with psoriasis or documented history of plaque psoriasis
• Subjects with PsA should have taken NSAIDs for at least 4 weeks prior to randomization with inadequate control of symptoms or at least one dose if stopped due to intolerance to NSAIDs
• Subjects taking corticosteroids must be on a stable dose of ≤10 mg/day prednisone or equivalent for at least 2 weeks before randomization and should remain on a stable dose up to Week 24
• Subjects taking MTX (≤ 25 mg/week) are allowed to continue their medication if the dose is stable for at least 4 weeks before randomization and should remain on a stable dose up to Week 52.

You may not qualify if:

• Chest X-ray or chest MRI with evidence of ongoing infectious or malignant process, obtained within 3 months prior to screening and evaluated by a qualified physician
• Subjects taking high potency opioid analgesics (e.g. methadone, hydromorphone, morphine)
• Previous exposure to secukinumab or other biologic drug directly targeting IL-17 or IL-17 receptor
• Ongoing use of prohibited psoriasis treatments / medications (e.g., topical corticosteroids, UV therapy) at randomization. The following wash out periods need to be observed:
• Oral or topical retinoids 4 weeks
• Photochemotherapy (e.g. PUVA) 4 weeks
• Phototherapy (UVA or UVB) 2 weeks
• Topical skin treatments (except in face, scalp and genital area during screening, only corticosteroids with mild to moderate potency) 2 weeks
• Subjects who have ever received biologic immunomodulating agents except for those targeting TNFα, investigational or approved
• Previous treatment with any cell-depleting therapies including but not limited to anti-CD20, investigational agents (e.g., CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19)

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (76)

Novartis Investigative Site

Peoria, Arizona, 85381, United States

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Novartis Investigative Site

Aventura, Florida, 33180, United States

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Novartis Investigative Site

Palm Harbor, Florida, 34684, United States

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Novartis Investigative Site

Sarasota, Florida, 34239, United States

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Novartis Investigative Site

Tamarac, Florida, 33321, United States

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Novartis Investigative Site

Tampa, Florida, 33624, United States

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Novartis Investigative Site

Zephyrhills, Florida, 33542, United States

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Novartis Investigative Site

Lincoln, Nebraska, 68516, United States

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Novartis Investigative Site

Omaha, Nebraska, 68114, United States

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Novartis Investigative Site

Freehold, New Jersey, 07728, United States

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Novartis Investigative Site

Syracuse, New York, 13210, United States

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Novartis Investigative Site

Asheville, North Carolina, 28801, United States

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Novartis Investigative Site

Charlotte, North Carolina, 28210, United States

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Novartis Investigative Site

Oklahoma City, Oklahoma, 73102, United States

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Novartis Investigative Site

Oklahoma City, Oklahoma, 73103, United States

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Novartis Investigative Site

Duncansville, Pennsylvania, 16635, United States

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Novartis Investigative Site

Charleston, South Carolina, 29460, United States

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Novartis Investigative Site

Columbia, South Carolina, 29204, United States

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Novartis Investigative Site

Greenville, South Carolina, 29601, United States

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Novartis Investigative Site

League City, Texas, 77573, United States

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Novartis Investigative Site

Mesquite, Texas, 75150, United States

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Novartis Investigative Site

Kogarah, New South Wales, 2217, Australia

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Novartis Investigative Site

Maroochydore, Queensland, 4558, Australia

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Novartis Investigative Site

Hobart, Tasmania, 7000, Australia

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Novartis Investigative Site

Malvern East, Victoria, 3145, Australia

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Novartis Investigative Site

Genk, 3600, Belgium

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Novartis Investigative Site

Hasselt, 3500, Belgium

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Novartis Investigative Site

Leuven, 3000, Belgium

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Novartis Investigative Site

Winnipeg, Manitoba, R3A 1M3, Canada

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Novartis Investigative Site

Waterloo, Ontario, N2J 1C4, Canada

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Novartis Investigative Site

Pointe-Claire, Quebec, H9R 3J1, Canada

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Novartis Investigative Site

Québec, Quebec, G1W 4R4, Canada

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Novartis Investigative Site

Sainte-Foy, Quebec, G1W 4Y5, Canada

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Novartis Investigative Site

Trois-Rivières, Quebec, G8Z 1Y2, Canada

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Novartis Investigative Site

Bruntál, Czech Republic, 792 01, Czechia

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Novartis Investigative Site

Pardubice, Czech Republic, 53002, Czechia

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Novartis Investigative Site

Prague, 128 50, Czechia

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Novartis Investigative Site

Uherské Hradiště, 686 01, Czechia

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Novartis Investigative Site

Aachen, 52064, Germany

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Novartis Investigative Site

Berlin, 12203, Germany

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Novartis Investigative Site

Erlangen, 91054, Germany

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Novartis Investigative Site

Erlangen, 91056, Germany

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Novartis Investigative Site

Germering, 82110, Germany

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Novartis Investigative Site

Hamburg, 22081, Germany

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Novartis Investigative Site

Herne, 44649, Germany

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Novartis Investigative Site

Würzburg, 97080, Germany

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Novartis Investigative Site

Zerbst, 39261, Germany

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Novartis Investigative Site

Lodz, 90-265, Poland

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Novartis Investigative Site

Poznan, 60 529, Poland

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Novartis Investigative Site

Poznan, 60-218, Poland

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Novartis Investigative Site

Warsaw, 02 691, Poland

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Novartis Investigative Site

Warsaw, 04141, Poland

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Novartis Investigative Site

Wroclaw, 50-368, Poland

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Novartis Investigative Site

Ponce, 00716, Puerto Rico

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Novartis Investigative Site

Chelyabinsk, 454076, Russia

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Novartis Investigative Site

Kazan', 420097, Russia

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Novartis Investigative Site

Moscow, 115522, Russia

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Novartis Investigative Site

Petrozavodsk, 185019, Russia

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Novartis Investigative Site

Rostov-on-Don, 344022, Russia

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Novartis Investigative Site

Saint Petersburg, 190068, Russia

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Novartis Investigative Site

Sestroretsk, 197706, Russia

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Novartis Investigative Site

Yaroslavl, 150003, Russia

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Novartis Investigative Site

Yekaterinburg, 620028, Russia

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Novartis Investigative Site

Bangkok, 10400, Thailand

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Novartis Investigative Site

London, England, E11 1NR, United Kingdom

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Novartis Investigative Site

Salford, Manchester, M6 8HD, United Kingdom

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Novartis Investigative Site

Cannock, Staffordshire, WS11 2XY, United Kingdom

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Novartis Investigative Site

Guildford, Surrey, GU2 7XX, United Kingdom

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Novartis Investigative Site

Dudley, West Midlands, DY1 2HQ, United Kingdom

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Novartis Investigative Site

Leeds, West Yorkshire, LS7 4SA, United Kingdom

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Novartis Investigative Site

Blackpool, FY3 7EN, United Kingdom

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Novartis Investigative Site

Cambridge, CB2 2QQ, United Kingdom

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Novartis Investigative Site

Glasgow, G51 4TF, United Kingdom

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Novartis Investigative Site

London, NW3 2QG, United Kingdom

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Novartis Investigative Site

London, SE1 9RT, United Kingdom

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Novartis Investigative Site

Southampton, SO16 6YD, United Kingdom

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Related Publications (10)

• Mease PJ, Warren RB, Nash P, Grouin JM, Lyris N, Willems D, Taieb V, Eells J, McInnes IB. Comparative Effectiveness of Bimekizumab and Secukinumab in Patients with Psoriatic Arthritis at 52 Weeks Using a Matching-Adjusted Indirect Comparison. Rheumatol Ther. 2024 Jun;11(3):817-828. doi: 10.1007/s40744-024-00652-7. Epub 2024 Mar 6.

  PMID: 38446397 DERIVED

• McInnes IB, Mease PJ, Kivitz AJ, Nash P, Rahman P, Rech J, Conaghan PG, Kirkham B, Navarra S, Belsare AD, Delicha EM, Pricop L. Long-term efficacy and safety of secukinumab in patients with psoriatic arthritis: 5-year (end-of-study) results from the phase 3 FUTURE 2 study. Lancet Rheumatol. 2020 Apr;2(4):e227-e235. doi: 10.1016/S2665-9913(20)30036-9.

  PMID: 38268157 DERIVED

• Pournara E, Kormaksson M, Nash P, Ritchlin CT, Kirkham BW, Ligozio G, Pricop L, Ogdie A, Coates LC, Schett G, McInnes IB. Clinically relevant patient clusters identified by machine learning from the clinical development programme of secukinumab in psoriatic arthritis. RMD Open. 2021 Nov;7(3):e001845. doi: 10.1136/rmdopen-2021-001845.

  PMID: 34795065 DERIVED

• Coates LC, Wallman JK, McGonagle D, Schett GA, McInnes IB, Mease PJ, Rasouliyan L, Quebe-Fehling E, Asquith DL, Fasth AER, Pricop L, Gaillez C. Secukinumab efficacy on resolution of enthesitis in psoriatic arthritis: pooled analysis of two phase 3 studies. Arthritis Res Ther. 2019 Dec 4;21(1):266. doi: 10.1186/s13075-019-2055-z.

  PMID: 31801620 DERIVED

• Deodhar A, Gladman DD, McInnes IB, Spindeldreher S, Martin R, Pricop L, Porter B, Safi J Jr, Shete A, Bruin G. Secukinumab Immunogenicity over 52 Weeks in Patients with Psoriatic Arthritis and Ankylosing Spondylitis. J Rheumatol. 2020 Apr;47(4):539-547. doi: 10.3899/jrheum.190116. Epub 2019 Jun 15.

  PMID: 31203228 DERIVED

• Coates LC, Gladman DD, Nash P, FitzGerald O, Kavanaugh A, Kvien TK, Gossec L, Strand V, Rasouliyan L, Pricop L, Ding K, Jugl SM, Gaillez C; FUTURE 2 study group. Secukinumab provides sustained PASDAS-defined remission in psoriatic arthritis and improves health-related quality of life in patients achieving remission: 2-year results from the phase III FUTURE 2 study. Arthritis Res Ther. 2018 Dec 7;20(1):272. doi: 10.1186/s13075-018-1773-y.

  PMID: 30526678 DERIVED

• McInnes IB, Mease PJ, Schett G, Kirkham B, Strand V, Williams N, Fox T, Pricop L, Jugl SM, Gandhi KK; FUTURE 2 Study Group. Secukinumab provides rapid and sustained pain relief in psoriatic arthritis over 2 years: results from the FUTURE 2 study. Arthritis Res Ther. 2018 Jun 7;20(1):113. doi: 10.1186/s13075-018-1610-3.

  PMID: 29880010 DERIVED

• Coates LC, Mease PJ, Gossec L, Kirkham B, Sherif B, Gaillez C, Mpofu S, Jugl SM, Karyekar C, Gandhi KK. Minimal Disease Activity Among Active Psoriatic Arthritis Patients Treated With Secukinumab: 2-Year Results From a Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Phase III Study. Arthritis Care Res (Hoboken). 2018 Oct;70(10):1529-1535. doi: 10.1002/acr.23537. Epub 2018 Sep 1.

  PMID: 29409133 DERIVED

• McInnes IB, Mease PJ, Ritchlin CT, Rahman P, Gottlieb AB, Kirkham B, Kajekar R, Delicha EM, Pricop L, Mpofu S. Secukinumab sustains improvement in signs and symptoms of psoriatic arthritis: 2 year results from the phase 3 FUTURE 2 study. Rheumatology (Oxford). 2017 Nov 1;56(11):1993-2003. doi: 10.1093/rheumatology/kex301.

  PMID: 28968735 DERIVED

• McInnes IB, Mease PJ, Kirkham B, Kavanaugh A, Ritchlin CT, Rahman P, van der Heijde D, Landewe R, Conaghan PG, Gottlieb AB, Richards H, Pricop L, Ligozio G, Patekar M, Mpofu S; FUTURE 2 Study Group. Secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis (FUTURE 2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015 Sep 19;386(9999):1137-46. doi: 10.1016/S0140-6736(15)61134-5. Epub 2015 Jun 28.

  PMID: 26135703 DERIVED

MeSH Terms

Conditions

Arthritis, Psoriatic; Salivary Gland Adenoma, Pleomorphic

Interventions

secukinumab

Condition Hierarchy (Ancestors)

Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Arthritis; Joint Diseases; Psoriasis; Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2012
• First Posted: December 19, 2012
• Study Start: April 14, 2013
• Primary Completion: May 12, 2014
• Study Completion: January 9, 2019
• Last Updated: May 13, 2020
• Results First Posted: May 13, 2020

Record last verified: 2020-04

Locations

RU (9); AU (4); TH (1); US (21); GB (12); CZ (4); PR (1); PL (6); BE (3); DE (9); CA (6)