Clinical trial NCT02696785: A Study of Ixekizumab (LY2439821) in bDMARD-Naive Participants With Radiographic Axial Spondyloarthritis
Official title: A Multicenter, Randomized, Double-Blind, Active and Placebo-Controlled 16-Week Study Followed by Long-Term Evaluation of Efficacy and Safety of Ixekizumab (LY2439821) in bDMARD-Naive Patients With Radiographic Axial Spondyloarthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Spondyloarthritis
Keywords: Ankylosing Spondylitis
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2016-03-02
Enrollment: 341
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 the safety and efficacy of the study drug known as ixekizumab in biological disease-modifying anti-rheumatic drugs (bDMARDs)-naive participants with radiographic axial spondyloarthritis (rad-axSpA).


Eligibility criteria: Inclusion Criteria:

* Are ambulatory.
* Diagnosis of radiographic axial spondyloarthritis (rad-xSpA) with sacroiliitis defined radiographically according to the modified New York criteria.
* Participants have a history of back pain ≥3 months with age at onset \<45 years.
* In the past had an inadequate response to at least 2 non-steroidal anti-inflammatory drugs (for duration 4 weeks) or cannot tolerate NSAIDS.
* If taking NSAIDS be on a stable dose for at least 2 weeks prior to randomization.
* Have a history of prior therapy for axSpa for at least 12 weeks prior to screening.

Exclusion Criteria:

* Have total ankylosis of the spine.
* Have received any prior, or are currently receiving, treatment with biologics, tumor necrosis factor inhibitors or other immunomodulatory agents.
* Have recently received a live vaccine within 12 weeks or have had a vaccination with Bacillus Calmette-Guerin (BCG) within the past year.
* Have an ongoing or serious infection within the last 12 weeks or evidence of active tuberculosis.
* Have a compromised immune system.
* Have any other serious and/or uncontrolled diseases.
* Have either a current diagnosis or a recent history of malignant disease.
* Have had major surgery within 8 weeks of baseline, or will require surgery during the study.
* Are pregnant or breastfeeding.

Primary outcomes:
measure: Percentage of Participants Achieving an Assessment of Spondyloarthritis International Society 40 (ASAS40) Response
timeFrame: Week 16
Secondary outcomes:
measure: Percentage of Participants Achieving an ASAS20 Response
timeFrame: Week 16
measure: Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS)
timeFrame: Baseline, Week 16
measure: Percentage of Participants Achieving Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI50) Response
timeFrame: Week 16
measure: Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI)
timeFrame: Baseline, Week 16
measure: Percentage of Participants Achieving ASDAS Inactive Disease
timeFrame: Week 16
measure: Change From Baseline in Magnetic Resonance Imaging (MRI) of the Spine (Ankylosing Spondylitis Spinal Magnetic Resonance Imaging [ASSpiMRI] - Berlin Score)
timeFrame: Baseline, Week 16
measure: Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores
timeFrame: Baseline, Week 16
measure: Change From Baseline in ASAS Health Index (ASAS HI)
timeFrame: Baseline, Week 16
measure: Change From Baseline in the Measure of High Sensitivity C-Reactive Protein (CRP)
timeFrame: Baseline, Week 16
measure: Change From Baseline in Mobility on the Bath Ankylosing Spondylitis Metrology Index (BASMI)
timeFrame: Baseline, Week 16
measure: Change From Baseline in Chest Expansion
timeFrame: Baseline, Week 16
measure: Change From Baseline in Occiput to Wall Distance
timeFrame: Baseline, Week 16
measure: Change From Baseline in MRI Sacroiliac Joint(s) (SIJ) Spondyloarthritis Research Consortium of Canada (SPARCC) Score
timeFrame: Baseline, Week 16
measure: Change From Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES)
timeFrame: Baseline, Week 16
measure: Change From Baseline in SPARCC Enthesitis Score
timeFrame: Baseline, Week 16
measure: Change From Baseline in Severity of Peripheral Arthritis by Tender (TJC)
timeFrame: Baseline, Week 16
measure: Number of Participants With Anterior Uveitis or Uveitis Flares
timeFrame: Baseline through Week 16
measure: Change From Baseline in the Fatigue Numeric Rating Scale (NRS) Score
timeFrame: Baseline, Week 16
measure: Change From Baseline in the Jenkins Sleep Evaluation Questionnaire (JSEQ)
timeFrame: Baseline, Week 16
measure: Change From Baseline in the Work Productivity Activity Impairment Spondyloarthritis (WPAI-SpA) Scores
timeFrame: Baseline, Week 16
measure: Change From Baseline in ASAS-Nonsteroidal Anti-Inflammatory Drug (NSAID) Score
timeFrame: Baseline, Week 52
measure: Number of Participants With Anti Ixekizumab Antibodies
timeFrame: Week 16
measure: Pharmacokinetics: Trough Ixekizumab Concentration at Steady State (Ctrough ss)
timeFrame: Week 16
measure: Change From Baseline in Severity of Peripheral Arthritis by Swollen Joint Count (SJC)
timeFrame: Baseline, Week 16
measure: Change From Baseline in Magnetic Resonance Imaging (MRI) of the Spine (Spondyloarthritis Research Consortium of Canada [SPARCC] Score)
timeFrame: Baseline, Week 16
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Arizona Arthritis Research, PLC
state: Arizona
city: Huntington Beach
country: United States
facility: Care Access Research - Huntington Beach
state: California
city: Palm Desert
country: United States
facility: Desert Medical Advances
state: California
city: Colorado Springs
country: United States
facility: Arthritis Assoc. & Osteoporosis Ctr of Colorado Springs, LLC
state: Colorado
city: Denver
country: United States
facility: Denver Arthritis Center
state: Colorado
city: Trumbull
country: United States
facility: New England Research Associates
state: Connecticut
city: Sarasota
country: United States
facility: Sarasota Arthritis Center
state: Florida
city: Marietta
country: United States
facility: Marietta Rheumatology
state: Georgia
city: Elizabethtown
country: United States
facility: Center for Arthritis & Osteoporosis
state: Kentucky
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: Saint Louis
country: United States
facility: Arthritis Consultants
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: Raleigh
country: United States
facility: Shanahan Rheumatology & Immunotherapy
state: North Carolina
city: Columbia
country: United States
facility: Articularis Healthcare Group, INC dba Columbia Arthritis Ctr
state: South Carolina
city: North Charleston
country: United States
facility: Low Country Research Center
state: South Carolina
city: Houston
country: United States
facility: Univ of Texas Health Science Center - Houston
state: Texas
city: Spokane
country: United States
facility: Arthritis Northwest Rheumatology
state: Washington
city: Brno
country: Czechia
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Berlin
country: Germany
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Hyōgo
country: Japan
facility: "For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician
city: Gwangjin-gu
country: Korea, Republic of
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Seoul
country: Korea, Republic of
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Warszawa
country: Netherlands
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Taichung City
country: Taiwan
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Taichung
country: Taiwan
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Taipei
country: Taiwan
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
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: van der Horst-Bruinsma IE, de Vlam K, Walsh JA, Bolce R, Hunter T, Sandoval D, Zhu D, Geneus V, Soriano ER, Magrey M. Baseline Characteristics and Treatment Response to Ixekizumab Categorised by Sex in Radiographic and Non-radiographic Axial Spondylarthritis Through 52 Weeks: Data from Three Phase III Randomised Controlled Trials. Adv Ther. 2022 Jun;39(6):2806-2819. doi: 10.1007/s12325-022-02132-2. Epub 2022 Apr 16.
citation: Maksymowych WP, Bolce R, Gallo G, Seem E, Geneus VJ, Sandoval DM, Ostergaard M, Tada K, Baraliakos X, Deodhar A, Gensler LS. Ixekizumab in radiographic axial spondyloarthritis with and without elevated C-reactive protein or positive magnetic resonance imaging. Rheumatology (Oxford). 2022 Nov 2;61(11):4324-4334. doi: 10.1093/rheumatology/keac104.
citation: van der Heijde D, Ostergaard M, Reveille JD, Baraliakos X, Kronbergs A, Sandoval DM, Li X, Carlier H, Adams DH, Maksymowych WP. Spinal Radiographic Progression and Predictors of Progression in Patients With Radiographic Axial Spondyloarthritis Receiving Ixekizumab Over 2 Years. J Rheumatol. 2022 Mar;49(3):265-273. doi: 10.3899/jrheum.210471. Epub 2021 Dec 1.
citation: Deodhar AA, Mease PJ, Rahman P, Navarro-Compan V, Strand V, Hunter T, Bolce R, Leon L, Lauzon S, Marzo-Ortega H. Ixekizumab improves spinal pain, function, fatigue, stiffness, and sleep in radiographic axial Spondyloarthritis: COAST-V/W 52-week results. BMC Rheumatol. 2021 Sep 20;5(1):35. doi: 10.1186/s41927-021-00205-3.
citation: Dougados M, Wei JC, Landewe R, Sieper J, Baraliakos X, Van den Bosch F, Maksymowych WP, Ermann J, Walsh JA, Tomita T, Deodhar A, van der Heijde D, Li X, Zhao F, Bertram CC, Gallo G, Carlier H, Gensler LS; COAST-V and COAST-W Study Groups. Efficacy and safety of ixekizumab through 52 weeks in two phase 3, randomised, controlled clinical trials in patients with active radiographic axial spondyloarthritis (COAST-V and COAST-W). Ann Rheum Dis. 2020 Feb;79(2):176-185. doi: 10.1136/annrheumdis-2019-216118. Epub 2019 Nov 4.
citation: Mease P, Walsh JA, Baraliakos X, Inman R, de Vlam K, Wei JC, Hunter T, Gallo G, Sandoval D, Zhao F, Dong Y, Bolce R, Marzo-Ortega H. Translating Improvements with Ixekizumab in Clinical Trial Outcomes into Clinical Practice: ASAS40, Pain, Fatigue, and Sleep in Ankylosing Spondylitis. Rheumatol Ther. 2019 Sep;6(3):435-450. doi: 10.1007/s40744-019-0165-3. Epub 2019 Jun 28.