Clinical trial NCT02349295: A Study of Ixekizumab (LY2439821) in Participants With Active Psoriatic Arthritis
Official title: A Multicenter, Randomized, Double-Blind, Placebo Controlled 24-Week Study Followed by Long Term Evaluation of Efficacy and Safety of Ixekizumab (LY2439821) in Biologic Disease-Modifying Antirheumatic Drug-Experienced Patients With Active Psoriatic Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Psoriatic Arthritis
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2015-01-28
Enrollment: 363
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main purpose of this study is to evaluate how effective and safe the study drug known as ixekizumab is in participants with active psoriatic arthritis.


Eligibility criteria: Inclusion Criteria:

* Presents with established diagnosis of active psoriatic arthritis (PsA) for at least 6 months, and currently meets Classification for Psoriatic Arthritis (CASPAR) criteria
* Active PsA defined as the presence of at least 3 tender and at least 3 swollen joints
* Presence of active psoriatic skin lesion or a history of plaque psoriasis (Ps)
* Men must agree to use a reliable method of birth control or remain abstinent during the study
* Women must agree to use reliable birth control or remain abstinent during the study and for at least 12 weeks after stopping treatment
* Have been treated with 1 or more conventional disease-modifying antirheumatic drugs (cDMARDs)
* Have had prior treatment with at least 1 and not more than 2 tumor necrosis factor (TNF) inhibitors. The participant must have discontinued at least 1 TNF inhibitor due to either an inadequate response (based on a minimum of 12 weeks on therapy) or documented intolerance.

Exclusion Criteria:

* Current use of biologic agents for treatment of Ps or PsA
* Inadequate response to greater than 2 biologic DMARDs
* Current use of more than one cDMARDs
* Diagnosis of active inflammatory arthritic syndromes or spondyloarthropathies other than PsA
* Have received treatment with interleukin (IL) -17 or IL12/23 targeted monoclonal antibody (MAb) therapy
* Serious disorder or illness other than psoriatic arthritis
* Serious infection within the last 3 months
* Breastfeeding or nursing (lactating) women

Primary outcomes:
measure: Percentage of Participants Achieving American College of Rheumatology 20 Index (ACR20)
timeFrame: Week 24
Secondary outcomes:
measure: Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score
timeFrame: Baseline, Week 24
measure: Percentage of Participants Achieving ACR20
timeFrame: Week 12
measure: Percentage of Participants Achieving American College of Rheumatology 50 Index (ACR50)
timeFrame: Week 24
measure: Percentage of Participants Achieving American College of Rheumatology 70 Index (ACR70)
timeFrame: Week 24
measure: Percentage of Participants With Psoriasis Area and Severity Index (PASI) 75
timeFrame: Week 12
measure: Percentage of Patients Achieving Minimal Disease Activity (MDA)
timeFrame: Week 24
measure: Percentage of Patients Achieving Complete Resolution in Enthesitis as Assessed by the Leeds Enthesitis Index (LEI)
timeFrame: Week 24
measure: Change From Baseline in Itch Numeric Rating Scale (NRS)
timeFrame: Baseline, Week 12
measure: Change From Baseline in Tender Joint Count (TJC)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Swollen Joint Count (SJC)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Participants Assessment of Pain Visual Analog Scale (VAS)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Patients Global Assessment of Disease Activity VAS
timeFrame: Baseline, Week 24
measure: Change From Baseline in Physicians Global Assessment of Disease Activity VAS
timeFrame: Baseline, Week 24
measure: Change From Baseline in C-Reactive Protein (CRP)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Disease Activity Score-CRP (DAS28-CRP)
timeFrame: Baseline, Week 24
measure: Change From Baseline in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Score
timeFrame: Baseline, Week 24
measure: Change From Baseline in Fatigue Severity Numeric Rating Scale (NRS) Score
timeFrame: Baseline, Week 24
measure: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Scores: Physical Component Summary (PCS)
timeFrame: Baseline, Week 24
measure: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Scores: Mental Component Summary (MCS)
timeFrame: Baseline, Week 24
measure: Number of Participants With Treatment Emergent Anti-Drug Antibodies (TE-ADA)
timeFrame: Week 24
measure: Pharmacokinetics (PK):Minimum Observed Serum Concentration at Steady State (Ctrough,ss) of Ixekizumab
timeFrame: All immunogenicity samples post the first Ixekizumab dose (Week 4, 12, 24, 36, and 52) and PK samples collected per dedicated sparse sampling plan (4-5 samples per patient) across Weeks 1 through 24 and Early termination visit (ETV)
measure: Pharmacokinetics: Area Under the Concentration-Time Curve for Dosing Interval (Tau) at Steady State [AUC(Tau,Steady State)] of Ixekizumab
timeFrame: All immunogenicity samples post the first Ixekizumab dose (Week 4, 12, 24, 36, and 52) and PK samples collected per dedicated sparse sampling plan (4-5 samples per patient) across Weeks 1 through 24 and Early termination visit (ETV)
measure: Percentage of Participants Achieving ACR 20
timeFrame: Week 52 and Week 156
measure: Percentage of Participants Achieving ACR 50
timeFrame: Week 52 and Week 156
measure: Percentage of Participants Achieving ACR 70
timeFrame: Week 52 and Week 156
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Rheumatology Associates PC
state: Alabama
city: Glendale
country: United States
facility: Arizona Arthritis & Rheumatology Research
state: Arizona
city: Mesa
country: United States
facility: Arizona Arthritis & Rheumatology Research, PLLC
state: Arizona
city: Phoenix
country: United States
facility: Arizona Arthritis & Rheumatology Research
state: Arizona
city: Little Rock
country: United States
facility: Little Rock Diagnostic Clinic
state: Arkansas
city: La Jolla
country: United States
facility: University of California - San Diego
state: California
city: La Mesa
country: United States
facility: Purushotham & Akther Kotha MD Inc
state: California
city: Palo Alto
country: United States
facility: Stanford University Hospital
state: California
city: San Leandro
country: United States
facility: East Bay Rheumatology Medical Group
state: California
city: Tustin
country: United States
facility: Office: Dr Robin K Dore
state: California
city: Boca Raton
country: United States
facility: Rheumatology Associates of South Florida
state: Florida
city: Naples
country: United States
facility: Jeffrey Alper MD Research
state: Florida
city: Orange Park
country: United States
facility: Arthritis & Osteoporosis Treatment Center, PA
state: Florida
city: Zephyrhills
country: United States
facility: Florida Medical Clinic PA
state: Florida
city: Indianapolis
country: United States
facility: Diagnostic Rheumatology and Research
state: Indiana
city: Cedar Rapids
country: United States
facility: Physicians Clinic of Iowa
state: Iowa
city: Wichita
country: United States
facility: Heartland Research Associates
state: Kansas
city: Lexington
country: United States
facility: Bluegrass Community Research. Inc
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins Arthritis Center
state: Maryland
city: Cumberland
country: United States
facility: Klein and Associates MD, PA
state: Maryland
city: Hagerstown
country: United States
facility: Klein and Associates MD, PA
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Lansing
country: United States
facility: Beals Institute PC
state: Michigan
city: Tupelo
country: United States
facility: North MS Medical Clinics, Inc.
state: Mississippi
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Kalispell
country: United States
facility: Glacier View Research Institute
state: Montana
city: Lincoln
country: United States
facility: Physician Research Collaboration, LLC
state: Nebraska
city: Clifton
country: United States
facility: New Jersey Physicians
state: New Jersey
city: Toms River
country: United States
facility: Atlantic Coastal Research
state: New Jersey
city: Voorhees
country: United States
facility: Arthritis, Rheumatic & Back Disease Associates
state: New Jersey
city: Albuquerque
country: United States
facility: Albuquerque Rehabilitation & Rheumatology, PC
state: New Mexico
city: Albany
country: United States
facility: The Center for Rheumatology
state: New York
city: Brooklyn
country: United States
facility: Weill Cornell Medical College
state: New York
city: Rochester
country: United States
facility: Allergy Asthma Immunology of Rochester, AAIR Research Ctr
state: New York
city: Smithtown
country: United States
facility: Rheumatology Associates of Long Island
state: New York
city: Charlotte
country: United States
facility: Arthritis and Osteoporosis Consultants of the Carolinas
state: North Carolina
city: Charlotte
country: United States
facility: DJL Clinical Research, PLLC
state: North Carolina
city: Hickory
country: United States
facility: PMG Research of Hickory, LLC
state: North Carolina
city: Dayton
country: United States
facility: STAT Research
state: Ohio
city: Oklahoma City
country: United States
facility: Health Research Institute
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Duncansville
country: United States
facility: Altoona Center for Clinical Research
state: Pennsylvania
city: Limerick
country: United States
facility: PMA Medical Specialists, LLC
state: Pennsylvania
city: Wyomissing
country: United States
facility: Clinical Research Center of Reading, LLC
state: Pennsylvania
city: Wyomissing
country: United States
facility: Pennsylvania Regional Center for Arthritis & Osteoarthritis
state: Pennsylvania
city: Memphis
country: United States
facility: Methodist Healthcare
state: Tennessee
city: Memphis
country: United States
facility: Ramesh C. Gupta MD
state: Tennessee
city: Austin
country: United States
facility: Austin Rheumatology Research PA
state: Texas
city: Austin
country: United States
facility: Austin Regional Clinic
state: Texas
city: Dallas
country: United States
facility: Arthritis Care & Diagnostic Center P.A.
state: Texas
city: Houston
country: United States
facility: Pioneer Research Solutions
state: Texas
city: Houston
country: United States
facility: Houston Institute for Clinical Research
state: Texas
city: Houston
country: United States
facility: Accurate Clinical Research
state: Texas
city: League City
country: United States
facility: Accurate Clinical Research
state: Texas
city: Lubbock
country: United States
facility: Arthritis & Osteoporosis Associates LLP
state: Texas
city: Kennewick
country: United States
facility: Kadlec Clinic Rheumatology
state: Washington
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Spokane
country: United States
facility: Arthritis Northwest PLLC
state: Washington
city: Franklin
country: United States
facility: Rheumatology and Immunotherapy Center
state: Wisconsin
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Maroochydore
country: Australia
facility: Coast Joint Care
state: Queensland
city: Camberwell
country: Australia
facility: Emeritus Research
state: Victoria
city: Praha
country: Czechia
facility: CCBR Czech Prague, s.r.o.
city: Uherske Hradiste
country: Czechia
facility: MEDICAL PLUS, s.r.o.
city: Zlin
country: Czechia
facility: PV-MEDICAL s.r.o. Revmatologicka ambulance
city: Chambray-lès-Tours
country: France
facility: Hôpital Trousseau, CHRU de Tours
city: Montpellier Cedex 5
country: France
facility: CHU de Montpellier-Hopital Arnaud de Villeneuve
city: Nantes Cedex 1
country: France
facility: Chru De Nantes Hotel-Dieu
city: Paris CEDEX 14
country: France
facility: Hopital Cochin
city: Toulouse
country: France
facility: Hopital Purpan
city: Vandoeuvre Les Nancy
country: France
facility: CHU Brabois
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
state: Baden-Württemberg
city: Würzburg
country: Germany
facility: Universitätsklinikum Würzburg
state: Bayern
city: Frankfurt am Main
country: Germany
facility: Klinikum der Johann Wolfgang Goethe-Universität Frankfurt
state: Hessen
city: Herne
country: Germany
facility: Rheumazentrum Ruhrgebiet
state: Nordrhein-Westfalen
city: Dresden
country: Germany
facility: Krankenhaus Dresden-Friedrichstadt Städtisches Klinikum
state: Sachsen
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus
state: Sachsen
city: Leipzig
country: Germany
facility: Universität Leipzig - Universitätsklinikum
state: Sachsen
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin
city: Hamburg
country: Germany
facility: HRF Hamburger Rheuma Forschungszentrum
city: Milano
country: Italy
facility: Istituto Ortopedico Gaetano Pini
city: Pisa
country: Italy
facility: Azienda Ospedaliera - Universitaria Pisana
city: Krakow
country: Poland
facility: Malopolskie Centrum Medyczne S.C.
city: Krakow
country: Poland
facility: Medica pro Familia Sp z o.o. S.K.A
city: Poznan
country: Poland
facility: AI Centrum Medyczne
city: Warszawa
country: Poland
facility: Medica pro Familia Sp z o.o. S.K.A
city: Warszawa
country: Poland
facility: Rheuma Medicus Zakład Opieki Zdrowotnej
city: Sevilla
country: Spain
facility: Hospital Infanta Luisa
state: Andalucia
city: Sabadell
country: Spain
facility: Centro de Salud Mental Parc Tauli
state: Barcelona
city: Santander
country: Spain
facility: Hospital Universitario Marques De Valdecilla
state: Cantabria
city: Fuenlabrada
country: Spain
facility: Hospital De Fuenlabrada
state: Madrid
city: Bilbao
country: Spain
facility: Hospital De Basurto
state: Vizcaya
city: La Coruña
country: Spain
facility: Complexo Hospitalario Universitario A Coruña, CHUAC
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Málaga
city: Sevilla
country: Spain
facility: Hospital Universitario Nuestra Señora de Valme
city: Tainan City
country: Taiwan
facility: Chi-Mei Hospital, Liouying
state: Yongkang Dist
city: Kaohsiung City (r.o.c)
country: Taiwan
facility: Chang Gung Memorial Hospital - Kaohsiung
city: Taichung City
country: Taiwan
facility: Chung Shan Medical University Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taoyuan City
country: Taiwan
facility: Chang Gung Memorial Hospital - Linkou
city: Basildon
country: United Kingdom
facility: Basildon and Thurrock University Hospital
state: Essex
city: Goodmayes
country: United Kingdom
facility: King George Hospital
state: Essex
city: Harlow
country: United Kingdom
facility: Princess Alexandra Hospital
state: Essex
city: London
country: United Kingdom
facility: Whipps Cross University Hospital
state: Surrey
city: Wolverhampton
country: United Kingdom
facility: New Cross Hospital
state: West Midlands
city: Leeds
country: United Kingdom
facility: Chapel Allerton Hospital
state: West Yorkshire
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References:
citation: Eder L, Tony HP, Odhav S, Agirregoikoa EG, Korkosz M, Schwartzman S, Sprabery AT, Gellett AM, Park SY, Bertram CC, Ogdie A. Responses to Ixekizumab in Male and Female Patients with Psoriatic Arthritis: Results from Two Randomized, Phase 3 Clinical Trials. Rheumatol Ther. 2022 Jun;9(3):919-933. doi: 10.1007/s40744-022-00445-w. Epub 2022 Apr 9.
citation: Deodhar AA, Combe B, Accioly AP, Bolce R, Zhu D, Gellett AM, Sprabery AT, Burmester GR. Safety of ixekizumab in patients with psoriatic arthritis: data from four clinical trials with over 2000 patient-years of exposure. Ann Rheum Dis. 2022 Jul;81(7):944-950. doi: 10.1136/annrheumdis-2021-222027. Epub 2022 Apr 7.
citation: Combe B, Tsai TF, Huffstutter JE, Sprabery AT, Lin CY, Park SY, Kronbergs A, Hufford MM, Nash P. Ixekizumab, with or without concomitant methotrexate, improves signs and symptoms of PsA: week 52 results from Spirit-P1 and Spirit-P2 studies. Arthritis Res Ther. 2021 Jan 27;23(1):41. doi: 10.1186/s13075-020-02388-5.
citation: Orbai AM, Gratacos J, Turkiewicz A, Hall S, Dokoupilova E, Combe B, Nash P, Gallo G, Bertram CC, Gellett AM, Sprabery AT, Birt J, Macpherson L, Geneus VJ, Constantin A. Efficacy and Safety of Ixekizumab in Patients with Psoriatic Arthritis and Inadequate Response to TNF Inhibitors: 3-Year Follow-Up (SPIRIT-P2). Rheumatol Ther. 2021 Mar;8(1):199-217. doi: 10.1007/s40744-020-00261-0. Epub 2020 Dec 5.
citation: Schweikert B, Malmberg C, Nunez M, Dilla T, Sapin C, Hartz S. Cost-effectiveness analysis of ixekizumab versus secukinumab in patients with psoriatic arthritis and concomitant moderate-to-severe psoriasis in Spain. BMJ Open. 2020 Aug 13;10(8):e032552. doi: 10.1136/bmjopen-2019-032552.
citation: Combe B, Rahman P, Kameda H, Canete JD, Gallo G, Agada N, Xu W, Genovese MC. Safety results of ixekizumab with 1822.2 patient-years of exposure: an integrated analysis of 3 clinical trials in adult patients with psoriatic arthritis. Arthritis Res Ther. 2020 Jan 21;22(1):14. doi: 10.1186/s13075-020-2099-0.
citation: Tillett W, Lin CY, Zbrozek A, Sprabery AT, Birt J. A Threshold of Meaning for Work Disability Improvement in Psoriatic Arthritis Measured by the Work Productivity and Activity Impairment Questionnaire. Rheumatol Ther. 2019 Sep;6(3):379-391. doi: 10.1007/s40744-019-0155-5. Epub 2019 Jun 1.
citation: Coates LC, Orbai AM, Morita A, Benichou O, Kerr L, Adams DH, Shuler CL, Birt J, Helliwell PS. Achieving minimal disease activity in psoriatic arthritis predicts meaningful improvements in patients' health-related quality of life and productivity. BMC Rheumatol. 2018 Aug 13;2:24. doi: 10.1186/s41927-018-0030-y. eCollection 2018.
citation: Gladman DD, Orbai AM, Klitz U, Wei JC, Gallo G, Birt J, Rathmann S, Shrom D, Marzo-Ortega H. Ixekizumab and complete resolution of enthesitis and dactylitis: integrated analysis of two phase 3 randomized trials in psoriatic arthritis. Arthritis Res Ther. 2019 Jan 29;21(1):38. doi: 10.1186/s13075-019-1831-0.
citation: Genovese MC, Combe B, Kremer JM, Tsai TF, Behrens F, Adams DH, Lee C, Kerr L, Nash P. Safety and efficacy of ixekizumab in patients with PsA and previous inadequate response to TNF inhibitors: week 52 results from SPIRIT-P2. Rheumatology (Oxford). 2018 Nov 1;57(11):2001-2011. doi: 10.1093/rheumatology/key182.
citation: Nash P, Kirkham B, Okada M, Rahman P, Combe B, Burmester GR, Adams DH, Kerr L, Lee C, Shuler CL, Genovese M; SPIRIT-P2 Study Group. Ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors: results from the 24-week randomised, double-blind, placebo-controlled period of the SPIRIT-P2 phase 3 trial. Lancet. 2017 Jun 10;389(10086):2317-2327. doi: 10.1016/S0140-6736(17)31429-0. Epub 2017 May 24.