A Study of Ixekizumab (LY2439821) in Participants With Active Psoriatic Arthritis (SPIRIT-P2)

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

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.

Study Overview

• Status: Completed
• Conditions: Psoriatic Arthritis
• Intervention / Treatment: Drug: Placebo; Drug: Ixekizumab 80 mg Q2W; Drug: Ixekizumab 80 mg Q4W

• Study Type: Interventional
• Enrollment (Actual): 363
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
  • Queensland
    • Maroochydore, Queensland, Australia, 4558
      • Coast Joint Care
  • Victoria
    • Camberwell, Victoria, Australia, 3124
      • Emeritus Research
• Czechia
  • Praha, Czechia, 13000
    • CCBR Czech Prague, s.r.o.
  • Uherske Hradiste, Czechia, 686 01
    • MEDICAL PLUS, s.r.o.
  • Zlin, Czechia, 760 01
    • PV-MEDICAL s.r.o. Revmatologicka ambulance
• France
  • Chambray-lès-Tours, France, 37170
    • Hôpital Trousseau, CHRU de Tours
  • Montpellier Cedex 5, France, 34295
    • CHU de Montpellier-Hopital Arnaud de Villeneuve
  • Nantes Cedex 1, France, 44093
    • Chru De Nantes Hotel-Dieu
  • Paris CEDEX 14, France, 75679
    • Hôpital Cochin
  • Toulouse, France, 31059
    • Hopital Purpan
  • Vandoeuvre Les Nancy, France, 54511
    • CHU Brabois
• Germany
  • Berlin, Germany, 10117
    • Charité Universitätsmedizin Berlin
  • Hamburg, Germany, 20095
    • HRF Hamburger Rheuma Forschungszentrum
  • Baden-Württemberg
    • Heidelberg, Baden-Württemberg, Germany, 69120
      • Universitätsklinikum Heidelberg
  • Bayern
    • Würzburg, Bayern, Germany, 97080
      • Universitatsklinikum Wurzburg
  • Hessen
    • Frankfurt am Main, Hessen, Germany, 60590
      • Klinikum der Johann Wolfgang Goethe-Universität Frankfurt
  • Nordrhein-Westfalen
    • Herne, Nordrhein-Westfalen, Germany, 44649
      • Rheumazentrum Ruhrgebiet
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
      • Universitätsklinikum Carl Gustav Carus
    • Dresden, Sachsen, Germany, 01067
      • Krankenhaus Dresden-Friedrichstadt Städtisches Klinikum
    • Leipzig, Sachsen, Germany, 04103
      • Universität Leipzig - Universitätsklinikum
  • Schleswig-Holstein
    • Lübeck, Schleswig-Holstein, Germany, 23538
      • Universitätsklinikum Schleswig-Holstein
• Italy
  • Milano, Italy, 20122
    • Istituto Ortopedico Gaetano Pini
  • Pisa, Italy, 56126
    • Azienda Ospedaliera - Universitaria Pisana
• Poland
  • Krakow, Poland, 30-510
    • Malopolskie Centrum Medyczne s.c.
  • Krakow, Poland, 30002
    • Medica pro Familia Sp z o.o. S.K.A
  • Poznan, Poland, 61-113
    • AI Centrum Medyczne
  • Warszawa, Poland, 01-868
    • Medica pro Familia Sp z o.o. S.K.A
  • Warszawa, Poland, 02-118
    • Rheuma Medicus Zakład Opieki Zdrowotnej
• Spain
  • La Coruña, Spain, 15006
    • Complexo Hospitalario Universitario A Coruña, CHUAC
  • Malaga, Spain, 29009
    • Hospital Regional Universitario de Malaga
  • Sevilla, Spain, 46014
    • Hospital Universitario Nuestra Señora de Valme
  • Andalucia
    • Sevilla, Andalucia, Spain, 41007
      • Hospital Infanta Luisa
  • Barcelona
    • Sabadell, Barcelona, Spain, 08208
      • Centro de Salud Mental Parc Tauli
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marqués de Valdecilla
  • Madrid
    • Fuenlabrada, Madrid, Spain, 28942
      • Hospital De Fuenlabrada
  • Vizcaya
    • Bilbao, Vizcaya, Spain, 48013
      • Hospital de Basurto
• Taiwan
  • Kaohsiung City (r.o.c), Taiwan, 83301
    • Chang Gung Memorial Hospital - Kaohsiung
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
  • Taichung, Taiwan, 40705
    • Taichung Veterans General Hospital
  • Taichung City, Taiwan, 40201
    • Chung Shan Medical University Hospital
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
  • Taoyuan City, Taiwan, 33305
    • Chang Gung Memorial Hospital - Linkou
  • Yongkang Dist
    • Tainan City, Yongkang Dist, Taiwan
      • Chi-Mei Hospital, Liouying
• United Kingdom
  • Essex
    • Basildon, Essex, United Kingdom, SS16 5NL
      • Basildon and Thurrock University Hospital
    • Goodmayes, Essex, United Kingdom, IG7 4DY
      • King George Hospital
    • Harlow, Essex, United Kingdom, CM20 1QX
      • Princess Alexandra Hospital
  • Surrey
    • London, Surrey, United Kingdom, E11 1NR
      • Whipps Cross University Hospital
  • West Midlands
    • Wolverhampton, West Midlands, United Kingdom, WV10 0QP
      • New Cross Hospital
  • West Yorkshire
    • Leeds, West Yorkshire, United Kingdom, LS7 4SA
      • Chapel Allerton Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Rheumatology Associates PC
  • Arizona
    • Glendale, Arizona, United States, 85304
      • Arizona Arthritis & Rheumatology Research
    • Mesa, Arizona, United States, 85210
      • Arizona Arthritis & Rheumatology Research, PLLC
    • Phoenix, Arizona, United States, 85032
      • Arizona Arthritis & Rheumatology Research
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Little Rock Diagnostic Clinic
  • California
    • La Jolla, California, United States, 92093
      • University of California - San Diego
    • La Mesa, California, United States, 91942
      • Purushotham & Akther Kotha MD Inc
    • Palo Alto, California, United States, 94304
      • Stanford University Hospital
    • San Leandro, California, United States, 94578
      • East Bay Rheumatology Medical Group
    • Tustin, California, United States, 92780
      • Office: Dr Robin K Dore
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Rheumatology Associates of South Florida
    • Naples, Florida, United States, 34102
      • Jeffrey Alper MD Research
    • Orange Park, Florida, United States, 32073
      • Arthritis & Osteoporosis Treatment Center, PA
    • Zephyrhills, Florida, United States, 33542-7505
      • Florida Medical Clinic PA
  • Indiana
    • Indianapolis, Indiana, United States, 46227
      • Diagnostic Rheumatology and Research
  • Iowa
    • Cedar Rapids, Iowa, United States, 52403
      • Physicians Clinic of Iowa
  • Kansas
    • Wichita, Kansas, United States, 67207
      • Heartland Research Associates
  • Kentucky
    • Lexington, Kentucky, United States, 40504
      • Bluegrass Community Research. Inc
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins Arthritis Center
    • Cumberland, Maryland, United States, 21502
      • Klein and Associates MD, PA
    • Hagerstown, Maryland, United States, 21740
      • Klein and Associates MD, PA
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • Michigan
    • Lansing, Michigan, United States, 48917
      • Beals Institute PC
  • Mississippi
    • Tupelo, Mississippi, United States, 38801
      • North MS Medical Clinics, Inc.
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Montana
    • Kalispell, Montana, United States, 59901
      • Glacier View Research Institute
  • Nebraska
    • Lincoln, Nebraska, United States, 68516
      • Physician Research Collaboration, LLC
  • New Jersey
    • Clifton, New Jersey, United States, 07012
      • New Jersey Physicians
    • Toms River, New Jersey, United States, 08755
      • Atlantic Coastal Research
    • Voorhees, New Jersey, United States, 08043
      • Arthritis, Rheumatic & Back Disease Associates
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Rehabilitation & Rheumatology, PC
  • New York
    • Albany, New York, United States, 12203
      • The Center for Rheumatology
    • Brooklyn, New York, United States, 11201
      • Weill Cornell Medical College
    • Rochester, New York, United States, 14618
      • Allergy Asthma Immunology of Rochester, AAIR Research Ctr
    • Smithtown, New York, United States, 11787
      • Rheumatology Associates of Long Island
  • North Carolina
    • Charlotte, North Carolina, United States, 28210
      • DJL Clinical Research, PLLC
    • Charlotte, North Carolina, United States, 28207
      • Arthritis and Osteoporosis Consultants of the Carolinas
    • Hickory, North Carolina, United States, 28602
      • PMG Research of Hickory, LLC
  • Ohio
    • Dayton, Ohio, United States, 45417
      • Stat Research
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • Health Research Institute
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center for Clinical Research
    • Limerick, Pennsylvania, United States, 19468
      • PMA Medical Specialists, LLC
    • Wyomissing, Pennsylvania, United States, 19610
      • Clinical Research Center of Reading, LLC
    • Wyomissing, Pennsylvania, United States, 19610
      • Pennsylvania Regional Center for Arthritis & Osteoarthritis
  • Tennessee
    • Memphis, Tennessee, United States, 38104-3499
      • Methodist Healthcare
    • Memphis, Tennessee, United States, 38119
      • Ramesh C. Gupta MD
  • Texas
    • Austin, Texas, United States, 78731
      • Austin Regional Clinic
    • Austin, Texas, United States, 78705
      • Austin Rheumatology Research PA
    • Dallas, Texas, United States, 75231
      • Arthritis Care & Diagnostic Center P.A.
    • Houston, Texas, United States, 77008
      • Pioneer Research Solutions
    • Houston, Texas, United States, 77074
      • Houston Institute for Clinical Research
    • Houston, Texas, United States, 77084
      • Accurate Clinical Research
    • League City, Texas, United States, 77573
      • Accurate Clinical Research
    • Lubbock, Texas, United States, 79424
      • Arthritis & Osteoporosis Associates LLP
  • Washington
    • Kennewick, Washington, United States, 99336
      • Kadlec Clinic Rheumatology
    • Seattle, Washington, United States, 98122
      • Swedish Medical Center
    • Spokane, Washington, United States, 99204
      • Arthritis Northwest PLLC
  • Wisconsin
    • Franklin, Wisconsin, United States, 53132
      • Rheumatology and Immunotherapy Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ixekizumab 80 milligram (mg) every 2 Weeks (Q2W); Blinded Treatment Period (Week(wk) 0-24): Participants (pts) received a starting dose of 160 mg of ixekizumab (ixe) given as 2 subcutaneous (SC) injections at Wk 0 followed by 1 SC injection of 80 mg of ixe Q2W given on Wks 2,4,6,8,10,12,14,16,18,20,22, and 24.Week 16 inadequate responders (IR) from the placebo treatment group who were re-randomized (1:1) to ixe 80 mg Q2W and IR from ixekizumab 80 mg Q2W who continued on ixekizumab 80 mg Q2W. Pts receive rescue therapy while receiving ixekizumab given as 1 injection of 80 mg Q2W given on Wks 16,18,20,22,24. Extension Period (Wk24-156):Pts who were randomized to ixe 80 mg Q2W at week 0 and continued on ixe 80 mg Q2W during the Extension Period. Pts who received ixekizumab 80 mg Q2W,who were either completed the study or discontinued the study early entered the post-treatment follow-up period (12-24 weeks).	Drug: Placebo; Administered SC; Drug: Ixekizumab 80 mg Q2W; Administered SC; Other Names: LY2439821
Experimental: Ixekizumab 80 mg Q4W; Blinded Treatment Period (Week 0-24): Participants (pts) received a starting dose of 160 mg of ixekizumab (ixe) given as 2 subcutaneous (SC) injections at Wk 0 followed by 1 SC injection of 80 mg of ixe Q4W given on Wks 4, 8 and 12 alternating with placebo for ixe injections Q4W given on Wks 2,6,10,14,18, and 22.Week 16 inadequate responders (IR) from the placebo treatment group who were re-randomized (1:1) to ixe 80 mg Q4W and IR from ixekizumab 80 mg Q4W who continued on ixekizumab 80 mg Q4W. Pts receive rescue therapy while receiving ixekizumab given as 1 injection of 80 mg Q4W given on Wks 16 and 20 alternating with placebo for ixe injections Q4W given on Wks 18 and 22.Extension Period (Wk24-156):Pts who were randomized to ixe 80 mg Q4W at week 0 and continued on ixe 80 mg Q4W during the Extension Period.Pts who received ixekizumab 80 mg Q4W,who were either completed the study or discontinued the study early entered the post-treatment follow-up period (12-24 weeks).	Drug: Placebo; Administered SC; Drug: Ixekizumab 80 mg Q4W; Administered SC; Other Names: LY2439821
Placebo Comparator: Placebo; Blinded Treatment Period (Wk 0-24): Pts received placebo for Ixe as 2 SC injections followed by 1 SC injection Q2W given on Wks 2,4,6,8,10,12,14,16,18,20,22 and 24. Pts initially randomized to placebo treatment group in the double blind treatment period,flagged as IR at Wk 16,re-randomized to ixe 80 mg Q2W/Q4W for the remainder of the current period and following period. Extended Treatment Period (Wk 24-156): Pts who were randomized to placebo at Week 0 then randomized to ixekizumab 80 mg Q2W/Q4W during the Extension Period.Pts who remained on placebo at the completion of the double blind treatment period received the first dose of ixe (160 mg starting dose) at Wk 24.Pts who were IRs at Wk 16 and were re-randomized to ixe at Wk 16 received the first dose of ixe (160 mg starting dose) at Wk 16. Pts who received placebo,who were either completed the study or discontinued the study early entered the post-treatment follow-up period (12-24 weeks).	Drug: Placebo; Administered SC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving American College of Rheumatology 20 Index (ACR20)	ACR20 response is defined as a greater than or equal to (≥) 20% improvement from baseline for tender joint count (TJC) and swollen joint count (SJC) and in at least 3 of the following 5 criteria: Participant's assessment of Joint Pain visual analog scale (VAS), Participant's Global Assessment of Disease Activity VAS (PatGA), Physician's Global Assessment of the Disease Activity VAS (PGA), Participant's Assessment of Physical Function using the Health Assessment Questionnaire Disability Index (HAQ-DI), or Acute Phase Reactant as measured by high sensitivity C-reactive protein (hs-CRP).	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score	HAQ-DI is a participant reported questionnaire that measures disease-associated disability(physical function).It consists of 24 questions with 8 domains: dressing/grooming,arising,eating,walking,hygiene,reach,grip and other daily activities. The disability section scores the participant's self-perception on degree of difficulty (0=without any difficulty,1=with some difficulty,2=with much difficulty,3=unable to do)covering the 8 domains.The HAQ-DI is a composite ranging from 0-3 with lower scores indicating less functional disability.The reported use of special aids/devices and/or the need for assistance of another person to perform these activities is assessed.Least Square (LS) mean calculated using Mixed Model Repeated Measurements (MMRM) analysis with treatment,baseline score,geographic region, TNFi experience,visit, treatment-by-visit interaction(itcn), geographic region-by-visit itcn,TNFi experience-by-visit itcn and baseline score-by-visit itcn.	Baseline, Week 24
Percentage of Participants Achieving ACR20	ACR20 response is defined as a ≥20% improvement from baseline for TJC and SJC and in at least 3 of the following 5 criteria: Participant's assessment of Joint Pain VAS, Participant's Global Assessment of Disease Activity VAS, Physician's Global Assessment of the Disease Activity VAS, Participant's Assessment of Physical Function using the HAQ-DI, or hs-CRP.	Week 12
Percentage of Participants Achieving American College of Rheumatology 50 Index (ACR50)	ACR50 response is defined as a ≥50% improvement from baseline for TJC and SJC and in at least 3 of the following 5 criteria: Participant's assessment of Joint Pain VAS, Participant's Global Assessment of Disease Activity VAS, Physician's Global Assessment of the Disease Activity VAS, Participant's Assessment of Physical Function using the HAQ-DI, or hs-CRP.	Week 24
Percentage of Participants Achieving American College of Rheumatology 70 Index (ACR70)	ACR70 response is defined as a ≥70% improvement from baseline for TJC and SJC and in at least 3 of the following 5 criteria: Participant's assessment of Joint Pain VAS, Participant's Global Assessment of Disease Activity VAS, Physician's Global Assessment of the Disease Activity VAS, Participant's Assessment of Physical Function using the HAQ-DI, or hs-CRP.	Week 24
Percentage of Participants With Psoriasis Area and Severity Index (PASI) 75	The PASI is an index that combines assessments of the extent of body-surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of desquamation, erythema, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no psoriasis to 72 for the most severe disease. Participants achieving PASI 75 were defined as having an improvement of at least 75% in the PASI compared to their baseline measures.	Week 12
Percentage of Patients Achieving Minimal Disease Activity (MDA)	It uses a composite of 7 key outcome measures (includes PASI) used in PsA to encompass all of the domains of the disease to measure the overall state of a patients' disease. The LEI is used to assess tender entheseal points. Patients are classified as achieving MDA if they fulfill 5 of 7 outcome measures: 1. TJC ≤1, 2. SJC ≤1, 3. PASI total score ≤1 or BSA ≤3, 4. patient pain VAS score of ≤15, 5. patient global VAS score of ≤20, 6. HAQ-DI score ≤0.5, 7. tender entheseal points (6 entheseal points) ≤1.	Week 24
Percentage of Patients Achieving Complete Resolution in Enthesitis as Assessed by the Leeds Enthesitis Index (LEI)	The LEI was developed specifically for use in PsA. It measures enthesitis at 6 sites (lateral epicondyle, left and right; medial femoral condyle, left and right; Achilles tendon insertion, left and right). Each site was assigned a score of 0 (absent) or 1 (present); the results from each site were then added to produce a total score (range 0 to 6). So, "0" indicates good score here.	Week 24
Change From Baseline in Itch Numeric Rating Scale (NRS)	The Itch NRS is a participant-administered, 11-point horizontal scale anchored at 0 and 10, with 0 representing "no itch" and 10 representing "worst itch imaginable." Overall severity of a participants itching from psoriasis was indicated by circling the number that best described the worst level of itching in the past 24 hours. LS mean was calculated using MMRM analysis with treatment, baseline score, geographic region, TNFi experience, visit, treatment-by-visit interaction, geographic region-by-visit interaction, TNFi experience-by-visit interaction, and baseline score-by-visit interaction.	Baseline, Week 12
Change From Baseline in Tender Joint Count (TJC)	TJC is the number of tender and painful joints determined for each participant by examination of 68 joints. Joints were assessed by pressure and joint manipulation on physical examination. Participants were asked for pain sensations on these manipulations and watched for spontaneous pain reactions. Any positive response on pressure, movement, or both was translated into a single tender-versus-nontender dichotomy. LS mean was calculated using MMRM analysis with treatment, baseline score, geographic region, TNFi experience, visit, treatment-by-visit interaction, geographic region-by-visit interaction, TNFi experience-by-visit interaction, and baseline score-by-visit interaction.	Baseline, Week 24
Change From Baseline in Swollen Joint Count (SJC)	SJC is the number of swollen joints determined for each participant by examination of 66 joints. Joints were classified as either swollen or not swollen. Swelling was defined as palpable fluctuating synovitis of the joint. LS mean was calculated using MMRM analysis with treatment, baseline score, geographic region, TNFi experience, visit, treatment-by-visit interaction, geographic region-by-visit interaction, TNFi experience-by-visit interaction, and baseline score-by-visit interaction.	Baseline, Week 24
Change From Baseline in Participants Assessment of Pain Visual Analog Scale (VAS)	The pain VAS is a participant-administered single-item scale designed to measure current joint pain from Psoriatic arthritis (PsA) using a 100-millimeter(mm) horizontal VAS. Overall severity of participant's joint pain from PsA is indicated by marking a vertical tick on the horizontal 100-mm scale, where the left end from 0 mm (no pain) to right end 100 mm (worst possible joint pain). LS mean was calculated using MMRM analysis with treatment, baseline score, geographic region, TNFi experience, visit, treatment-by-visit interaction, geographic region-by-visit interaction, TNFi experience-by-visit interaction, and baseline score-by-visit interaction.	Baseline, Week 24
Change From Baseline in Patients Global Assessment of Disease Activity VAS	The patient's overall assessment of his or her PsA activity will be recorded using a 100-mm horizontal VAS, where 0 represents no disease activity and 100 represents extremely active disease. LS mean was calculated using MMRM analysis with treatment, baseline score, geographic region, TNFi experience, visit, treatment-by-visit interaction, geographic region-by-visit interaction, TNFi experience-by-visit interaction, and baseline score-by-visit interaction.	Baseline, Week 24
Change From Baseline in Physicians Global Assessment of Disease Activity VAS	The investigator will be asked to give an overall assessment of the severity of the participant's current PsA activity using a 100-mm horizontal VAS, where 0 represents no disease activity and 100 represents extremely active disease. LS mean was calculated using MMRM analysis with treatment, baseline score, geographic region, TNFi experience, visit, treatment-by-visit interaction, geographic region-by-visit interaction, TNFi experience-by-visit interaction, and baseline score-by-visit interaction.	Baseline, Week 24
Change From Baseline in C-Reactive Protein (CRP)	C-reactive protein (CRP) is a disease related biomarker and measured in milligrams per liter. LS mean was calculated using MMRM analysis with treatment, baseline score, geographic region, TNFi experience, visit, treatment-by-visit interaction, geographic region-by-visit interaction, TNFi experience-by-visit interaction, and baseline score-by-visit interaction.	Baseline, Week 24
Change From Baseline in Disease Activity Score-CRP (DAS28-CRP)	The DAS28-CRP is a measure of disease activity in 28 joints that consists of a composite numerical score with the following variables: TJC28, SJC28, hs-CRP (measured in mg/L), and Participant's Global Assessment of Disease Activity recorded by participants on a 0 to 100 millimeter (mm) VAS. For DAS28-CRP, the Tender Joint Count 28 (TJC28) and Swollen Joint Count (SJC28) are a subset of TJC and SJC, and include 14 joints on each side of the body: 2 shoulders, 2 elbows, 2 wrists, 10 metacarpophalangeal joints, the 2 interphalangeal joints of the thumb, the 8 proximal interphalangeal joints, and the 2 knees. DAS28 values range from 0 to 9.4. Higher values indicate more severe symptoms and greater functional impairment. LS mean was calculated using MMRM analysis with treatment, baseline score, geographic region, TNFi experience, visit, treatment-by-visit interaction, geographic region-by-visit interaction, TNFi experience-by-visit interaction, and baseline score-by-visit interaction.	Baseline, Week 24
Change From Baseline in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Score	The BASDAI is a self-administered measure used to answer 6 questions with a 0 to 10 centimeter (cm) VAS pertaining to the 5 major symptoms of axial activity. To give each symptom equal weighting, the mean of the 2 scores relating to morning stiffness was taken. The resulting 0 to 50 score was divided by 5 to give a final 0 to 10 BASDAI Score. BASDAI ranges from 0-10. Higher scores represent greater disease activity. LS mean was calculated using MMRM analysis with treatment, baseline score, geographic region, TNFi experience, visit, treatment-by-visit interaction, geographic region-by-visit interaction, TNFi experience-by-visit interaction, and baseline score-by-visit interaction.	Baseline, Week 24
Change From Baseline in Fatigue Severity Numeric Rating Scale (NRS) Score	The Fatigue Severity NRS is a participant-administered single-item 11-point horizontal scale anchored at 0 and 10, with 0 representing "no fatigue" and 10 representing "as bad as you can imagine." Participants rated their fatigue (feeling tired or worn out) by circling the 1 number that described their worst level of fatigue during the past 24 hours. LS mean was calculated using MMRM analysis with treatment, baseline score, geographic region, TNFi experience, visit, treatment-by-visit interaction, geographic region-by-visit interaction, TNFi experience-by-visit interaction, and baseline score-by-visit interaction.	Baseline, Week 24
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Scores: Physical Component Summary (PCS)	The SF-36 is a participant-reported outcome measure evaluating participant's health status. It comprises 36 items covering 8 domains: physical functioning, role physical, role emotional, bodily pain, vitality, social functioning, mental health, and general health. Items are answered on Likert scales of varying lengths. The 8 domains are regrouped into the PCS and MCS scores. The summary scores range from 0 to 100, with higher scores indicating better levels of function and/or better health. In this study, the SF-36 acute version was used, which has a 1 week recall period. LS mean was calculated using MMRM analysis with treatment, baseline score, geographic region, TNFi experience, visit, treatment-by-visit interaction, geographic region-by-visit interaction, TNFi experience-by-visit interaction, and baseline score-by-visit interaction.	Baseline, Week 24
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Scores: Mental Component Summary (MCS)	The SF-36 is a participant-reported outcome measure evaluating participant's health status. It comprises 36 items covering 8 domains: physical functioning, role physical, role emotional, bodily pain, vitality, social functioning, mental health, and general health. Items are answered on Likert scales of varying lengths. The 8 domains are regrouped into the PCS and MCS scores. The summary scores range from 0 to 100, with higher scores indicating better levels of function and/or better health. In this study, the SF-36 acute version was used, which has a 1 week recall period. LS mean was calculated using MMRM analysis with treatment, baseline score, geographic region, TNFi experience, visit, treatment-by-visit interaction, geographic region-by-visit interaction, TNFi experience-by-visit interaction, and baseline score-by-visit interaction.	Baseline, Week 24
Number of Participants With Treatment Emergent Anti-Drug Antibodies (TE-ADA)	Number of participants with positive treatment emergent anti-ixekizumab antibodies was summarized by treatment group.	Week 24
Pharmacokinetics (PK):Minimum Observed Serum Concentration at Steady State (Ctrough,ss) of Ixekizumab	The Ctrough is the minimum observed serum concentration at steady state of Ixekizumab. The Ctrough at Week 24 was reported.	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)
Pharmacokinetics: Area Under the Concentration-Time Curve for Dosing Interval (Tau) at Steady State [AUC(Tau,Steady State)] of Ixekizumab	The AUC(Tau,Steady State) is the area under the concentration-time curve for dosing interval (Tau) at steady state of ixekizumab (Tau is 28 days for 80 mg Q4W cohort, and is 14 days for 80mg Q2W cohort, respectively).	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)
Percentage of Participants Achieving ACR 20	ACR20 response is defined as a ≥20% improvement from baseline for TJC and SJC and in at least 3 of the following 5 criteria: Participant's assessment of Joint Pain VAS, Participant's Global Assessment of Disease Activity VAS, Physician's Global Assessment of the Disease Activity VAS, Participant's Assessment of Physical Function using the HAQ-DI, or hs-CRP.	Week 52 and Week 156
Percentage of Participants Achieving ACR 50	ACR50 response is defined as a ≥50% improvement from baseline for TJC and SJC and in at least 3 of the following 5 criteria: Participant's assessment of Joint Pain VAS, Participant's Global Assessment of Disease Activity VAS, Physician's Global Assessment of the Disease Activity VAS, Participant's Assessment of Physical Function using the HAQ-DI, or hs-CRP.	Week 52 and Week 156
Percentage of Participants Achieving ACR 70	ACR70 response is defined as a ≥70% improvement from baseline for TJC and SJC and in at least 3 of the following 5 criteria: Participant's assessment of Joint Pain VAS, Participant's Global Assessment of Disease Activity VAS, Physician's Global Assessment of the Disease Activity VAS, Participant's Assessment of Physical Function using the HAQ-DI, or hs-CRP.	Week 52 and Week 156

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 31, 2014
• Primary Completion (Actual): September 9, 2016
• Study Completion (Actual): June 26, 2019

Study Registration Dates

• First Submitted: October 10, 2014
• First Submitted That Met QC Criteria: January 23, 2015
• First Posted (Estimate): January 28, 2015

Study Record Updates

• Last Update Posted (Actual): July 1, 2020
• Last Update Submitted That Met QC Criteria: June 19, 2020
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Joint Diseases; Musculoskeletal Diseases; Skin Diseases, Papulosquamous; Spinal Diseases; Bone Diseases; Spondylarthropathies; Spondylarthritis; Spondylitis; Psoriasis; Arthritis; Arthritis, Psoriatic; Dermatologic Agents; Ixekizumab
• Other Study ID Numbers: 14310; I1F-MC-RHBE (Other Identifier: Eli Lilly and Company); 2011-002328-42 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• IPD Sharing Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and european union (EU), whichever is later. Data will be indefinitely available for requesting.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR