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

NCT ID: NCT01752634

Last Updated: 2020-05-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 397 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-04-14
• Study Completion Date: 2019-01-09

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.

Detailed Description

At baseline (BSL), subjects whose eligibility was confirmed were randomized to one of the following four treatment groups.

• 75 mg secukinumab
• 150 mg secukinumab
• 300 mg secukinumab
• Placebo At Week 16, all subjects were classified as responders (≥ 20% improvement from BSL in both tender and swollen joint counts) or non-responders.

Subjects who were randomized to a secukinumab treatment group at baseline were targeted to remain on the same dose for the entire trial.

Subjects who were randomized to placebo at baseline were re-randomized at Week 16 as follows:

Placebo non-responders received secukinumab 150 mg s.c. or 300 mg s.c. (1:1) every 4 weeks, starting after the efficacy assessments at Week 16.

Placebo responders continued to receive placebo at Week 16 and Week 20 and received secukinumab 150 mg s.c. or 300 mg s.c. (1:1) every 4 weeks, starting after the efficacy assessments at Week 24.

This was a double-blind, double-dummy, randomized treatment trial until week 52 analysis was completed and open label afterwards.

An amendment to the study protocol (after all patients were in the trial for 2-3 years) introduced changes whereby patients previously treated with secukinumab 75 mg s.c. could change to receive 150 mg s.c. or 300 mg s.c., and patients previously treated with secukinumab 150 mg s.c. could change to receive 300 mg s.c., as deemed appropriate by the investigators.

Conditions

Psoriatic Arthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Secukinumab (AIN457) 75 mg s.c.

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

Group Type: EXPERIMENTAL

Secukinumab (AIN457)

Intervention Type: DRUG

Secukinumab (AIN457)

Secukinumab (AIN457) 150 mg s.c.

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

Group Type: EXPERIMENTAL

Secukinumab (AIN457)

Intervention Type: DRUG

Secukinumab (AIN457)

Secukinumab (AIN457) 300 mg s.c.

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

Group Type: EXPERIMENTAL

Secukinumab (AIN457)

Intervention Type: DRUG

Secukinumab (AIN457)

Placebo s.c.

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.

Group Type: PLACEBO_COMPARATOR

Secukinumab (AIN457)

Intervention Type: DRUG

Secukinumab (AIN457)

Placebo

Intervention Type: DRUG

Placebo PFS for s.c. administration.

Interventions

Secukinumab (AIN457)

Secukinumab (AIN457)

Intervention Type: DRUG

Placebo

Placebo PFS for s.c. administration.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Peoria, Arizona, United States

Novartis Investigative Site

Aventura, Florida, United States

Novartis Investigative Site

Palm Harbor, Florida, United States

Novartis Investigative Site

Sarasota, Florida, United States

Novartis Investigative Site

Tamarac, Florida, United States

Novartis Investigative Site

Tampa, Florida, United States

Novartis Investigative Site

Zephyrhills, Florida, United States

Novartis Investigative Site

Lincoln, Nebraska, United States

Novartis Investigative Site

Omaha, Nebraska, United States

Novartis Investigative Site

Freehold, New Jersey, United States

Novartis Investigative Site

Syracuse, New York, United States

Novartis Investigative Site

Asheville, North Carolina, United States

Novartis Investigative Site

Charlotte, North Carolina, United States

Novartis Investigative Site

Oklahoma City, Oklahoma, United States

Novartis Investigative Site

Oklahoma City, Oklahoma, United States

Novartis Investigative Site

Duncansville, Pennsylvania, United States

Novartis Investigative Site

Charleston, South Carolina, United States

Novartis Investigative Site

Columbia, South Carolina, United States

Novartis Investigative Site

Greenville, South Carolina, United States

Novartis Investigative Site

League City, Texas, United States

Novartis Investigative Site

Mesquite, Texas, United States

Novartis Investigative Site

Kogarah, New South Wales, Australia

Novartis Investigative Site

Maroochydore, Queensland, Australia

Novartis Investigative Site

Hobart, Tasmania, Australia

Novartis Investigative Site

Malvern East, Victoria, Australia

Novartis Investigative Site

Genk, , Belgium

Novartis Investigative Site

Hasselt, , Belgium

Novartis Investigative Site

Leuven, , Belgium

Novartis Investigative Site

Winnipeg, Manitoba, Canada

Novartis Investigative Site

Waterloo, Ontario, Canada

Novartis Investigative Site

Pointe-Claire, Quebec, Canada

Novartis Investigative Site

Québec, Quebec, Canada

Novartis Investigative Site

Sainte-Foy, Quebec, Canada

Novartis Investigative Site

Trois-Rivières, Quebec, Canada

Novartis Investigative Site

Bruntál, Czech Republic, Czechia

Novartis Investigative Site

Pardubice, Czech Republic, Czechia

Novartis Investigative Site

Prague, , Czechia

Novartis Investigative Site

Uherské Hradiště, , Czechia

Novartis Investigative Site

Aachen, , Germany

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Erlangen, , Germany

Novartis Investigative Site

Erlangen, , Germany

Novartis Investigative Site

Germering, , Germany

Novartis Investigative Site

Hamburg, , Germany

Novartis Investigative Site

Herne, , Germany

Novartis Investigative Site

Würzburg, , Germany

Novartis Investigative Site

Zerbst, , Germany

Novartis Investigative Site

Lodz, , Poland

Novartis Investigative Site

Poznan, , Poland

Novartis Investigative Site

Poznan, , Poland

Novartis Investigative Site

Warsaw, , Poland

Novartis Investigative Site

Warsaw, , Poland

Novartis Investigative Site

Wroclaw, , Poland

Novartis Investigative Site

Ponce, , Puerto Rico

Novartis Investigative Site

Chelyabinsk, , Russia

Novartis Investigative Site

Kazan', , Russia

Novartis Investigative Site

Moscow, , Russia

Novartis Investigative Site

Petrozavodsk, , Russia

Novartis Investigative Site

Rostov-on-Don, , Russia

Novartis Investigative Site

Saint Petersburg, , Russia

Novartis Investigative Site

Sestroretsk, , Russia

Novartis Investigative Site

Yaroslavl, , Russia

Novartis Investigative Site

Yekaterinburg, , Russia

Novartis Investigative Site

Bangkok, , Thailand

Novartis Investigative Site

London, England, United Kingdom

Novartis Investigative Site

Salford, Manchester, United Kingdom

Novartis Investigative Site

Cannock, Staffordshire, United Kingdom

Novartis Investigative Site

Guildford, Surrey, United Kingdom

Novartis Investigative Site

Dudley, West Midlands, United Kingdom

Novartis Investigative Site

Leeds, West Yorkshire, United Kingdom

Novartis Investigative Site

Blackpool, , United Kingdom

Novartis Investigative Site

Cambridge, , United Kingdom

Novartis Investigative Site

Glasgow, , United Kingdom

Novartis Investigative Site

London, , United Kingdom

Novartis Investigative Site

London, , United Kingdom

Novartis Investigative Site

Southampton, , United Kingdom

Countries

United States; Australia; Belgium; Canada; Czechia; Germany; Poland; Puerto Rico; Russia; Thailand; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 38446397 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 38268157 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34795065 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31801620 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31203228 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30526678 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29880010 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29409133 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28968735 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26135703 (View on PubMed)

Other Identifiers

2012-004439-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CAIN457F2312

Identifier Type: -

Identifier Source: org_study_id