A Study of Ixekizumab (LY2439821) in Participants With Nonradiographic Axial Spondyloarthritis (COAST-X)

• ClinicalTrials.gov Identifier: NCT02757352
• Recruitment Status: Completed
• First Posted: May 2, 2016
• Results First Posted: March 13, 2020
• Last Update Posted: March 13, 2020
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: April 28, 2016
• First Posted Date: May 2, 2016
• Results First Submitted Date: February 28, 2020
• Results First Posted Date: March 13, 2020
• Last Update Posted Date: March 13, 2020
• Actual Study Start Date: August 2, 2016
• Actual Primary Completion Date: March 1, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 28, 2020)

• Percentage of Participants Achieving an Assessment of Spondyloarthritis International Society 40 (ASAS40) Response [ Time Frame: Week 16 ]
  ASAS40 is defined as a greater than or equal to (≥)40% improvement and an absolute improvement from baseline of ≥2 units (ranges 0 to 10) in at least 3 of the 4 domains (Patient Global, Spinal Pain, Function, and Inflammation), without any worsening in the remaining domain. 1) Patient Global: How active was your spondylitis during the last week? score ranges 0 (not active) to 10 (very active). 2) Spinal Pain: How much spinal pain due to Ankylosing spondylitis? score ranges 0 (no pain) to 10 (severe pain). 3) Bath Ankylosing Spondylitis Functional Index: Participant is asked to rate the difficulty associated with 10 individual basic functional activities. Responses were captured using numeric rating scale (NRS) (ranges 0 to 10) with a higher score of worse function. 4) Inflammation based on mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) question 5 and 6 (mean of intensity, duration of stiffness). Score ranges (0 (non) to 10 (very severe).
• Percentage of Participants Achieving an ASAS40 Response [ Time Frame: Week 52 ]
  ASAS40 is defined as a greater than or equal to (≥)40% improvement and an absolute improvement from baseline of ≥2 units (ranges 0 to 10) in at least 3 of the 4 domains (Patient Global, Spinal Pain, Function, and Inflammation), without any worsening in the remaining domain. 1) Patient Global: How active was your spondylitis during the last week? score ranges 0 (not active) to 10 (very active). 2) Spinal Pain: How much spinal pain due to Ankylosing spondylitis? score ranges 0 (no pain) to 10 (severe pain). 3) Bath Ankylosing Spondylitis Functional Index: Participant is asked to rate the difficulty associated with 10 individual basic functional activities. Responses were captured using numeric rating scale (NRS) (ranges 0 to 10) with a higher score of worse function. 4) Inflammation based on mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) question 5 and 6 (mean of intensity, duration of stiffness). Score ranges (0 (non) to 10 (very severe).

• Original Primary Outcome Measures (submitted: April 28, 2016): Proportion of Participants Achieving an Assessment of Spondyloarthritis International Society 40 (ASAS40) Response [ Time Frame: Week 16 ]

Current Secondary Outcome Measures (submitted: February 28, 2020)

• Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) [ Time Frame: Baseline, Week 16 ]
  ASDAS is a composite index to assess disease activity in axial spondyloarthritis (axSpA). ASDAS parameters used with (C-reactive protein [CRP] as acute phase reactant) are: 1) Total back pain 2) Patient global 3) Peripheral pain/swelling, duration of morning stiffness 4) CRP in mg/L: ASDAScrp is calculated with the equation: 0.121 × total back pain + 0.110×patient global + 0.073 × peripheral pain/swelling + 0.058 × duration of morning stiffness + 0.579 × Ln(CRP+1). CRP is in milligram/liter (mg/L), the range of other variables is from 0 to 10. Data from five variables combined to yield a score (0.6361 to no defined upper limit), where higher scores indicated higher disease activity. Ln represents the natural logarithm. Least squares mean (LS Mean) was derived from mixed models repeated measure analysis (MMRM) with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.
• Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) [ Time Frame: Baseline, Week 52 ]
  ASDAS is a composite index to assess disease activity in axSpA. ASDAS parameters used (with CRP as acute phase reactant) are: 1 )Total back pain 2) Patient global 3) Peripheral pain/swelling 4) Duration of morning stiffness 5) CRP in mg/L: ASDAScrp is calculated with the following equation: 0.121 × total back pain + 0.110 × patient global + 0.073 × peripheral pain/swelling + 0.058 × duration of morning stiffness + 0.579 × Ln(CRP+1). CRP is in milligram/liter (mg/L), the range of other variables is from 0 to 10. Data from five variables combined to yield a score (0.6361 to no defined upper limit), where higher scores indicated higher disease activity. Ln represents the natural logarithm. LS Mean was derived from MMRM with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.
• Number of Participants Without Clinically Meaningful Changes in Background Therapy [ Time Frame: Baseline through Week 52 ]
  Number of participants without changes in background therapy while on originally randomized treatment.
• Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) Score [ Time Frame: Baseline, Week 16 ]
  The SF-36 is a 36-item patient-administered measure designed to be a short, multipurpose assessment of health in the areas of physical functioning, role - physical, role - emotional, bodily pain, vitality, social functioning, mental health, and general health. The Physical Component Summary score ranges from 0 to 100; higher scores indicate better levels of function and/or better health. LS Mean was derived from MMRM with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.
• Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) Score [ Time Frame: Baseline, Week 52 ]
  The medical outcomes study 36-item short-form health survey (SF-36) SF-36 PCS are summarized using the t-scores. The summary scores range from 0 to 100, with higher scores indicating better levels of function and/or better health. LS Mean was derived from MMRM with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.
• Percentage of Participants Achieving ASDAS Low Disease Activity [ Time Frame: Week 16 ]
  ASDAS is a composite index to assess disease activity in axSpA. ASDAS low disease activity is defined as a score of <2.1. The parameters used for the ASDAS (with CRP as acute phase reactant) are total back pain, patient global, peripheral pain/swelling, duration of morning stiffness and CRP in mg/L. The ASDAScrp is calculated with the following equation: 0.121×total back pain+0.110×patient global+0.073×peripheral pain/swelling+0.058×duration of morning stiffness+0.579×Ln(CRP+1). CRP is in mg/liter, the range of other variables is from 0(normal) to 10(very severe); Ln represents the natural logarithm). Data from five variables combined to yield a score (0.6361 to no defined upper limit), where higher the score worse the disease activity.
• Percentage of Participants Achieving ASDAS Low Disease Activity [ Time Frame: Week 52 ]
  ASDAS is a composite index to assess disease activity in axSpA. ASDAS low disease activity is defined as a score of <2.1. The parameters used for the ASDAS (with CRP as acute phase reactant) are total back pain, patient global, peripheral pain/swelling, duration of morning stiffness and CRP in mg/L. The ASDAScrp is calculated with the following equation: 0.121×total back pain+0.110×patient global+0.073×peripheral pain/swelling+0.058×duration of morning stiffness+0.579×Ln(CRP+1). CRP is in mg/liter, the range of other variables is from 0(normal) to 10(very severe); Ln represents the natural logarithm). Data from five variables combined to yield a score (0.6361 to no defined upper limit), where higher the score worse the disease activity.
• Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) [ Time Frame: Baseline, Week 16 ]
  The BASDAI is a participant-reported assessment consisting of 6 questions that relate to 5 major symptoms relevant to axial spondyloarthritis (axSpA): 1) Fatigue, 2) Spinal pain, 3) Peripheral arthritis, 4) Enthesitis, 5) Intensity, and 6) Duration of morning stiffness. Participants need to score each item with a score from 0 to 10 (NRS). Total score is obtained from the average of symptom scores ranging 0 (no problem) to 10 (worst problem), with a higher score indicating more severe AS symptom. LS mean was derived from MMRM with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.
• Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) [ Time Frame: Baseline, Week 52 ]
  The BASDAI is a participant-reported assessment consisting of 6 questions that relate to 5 major symptoms relevant to axial spondyloarthritis (axSpA): 1) Fatigue, 2) Spinal pain, 3) Peripheral arthritis, 4) Enthesitis, 5) Intensity, and 6) Duration of morning stiffness. Participants need to score each item with a score from 0 to 10 (NRS). Total score is obtained from the average of symptom scores ranging 0 (no problem) to 10 (worst problem), with a higher score indicating more severe AS symptom. LS mean was derived from MMRM with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.
• Change From Baseline in Magnetic Resonance Imaging (MRI) of the Sacroiliac Joint (SIJ) Spondyloarthritis Research Consortium of Canada (SPARCC) Score [ Time Frame: Baseline, Week 16 ]
  Both left and right SIJ are scored for bone marrow edema. Each side has 6 slices and each slice has 6 scoring units, and each scoring unit has a score of 0 or 1. Total SIJ SPARCC scores can range from 0 to 72 with higher scores reflecting worse disease. LS Mean was derived from ANCOVA model with treatment, geographic region, screening MRI/CRP status and baseline value as fixed factors.
• Change From Baseline in SPARCC Enthesitis Score [ Time Frame: Baseline, Week 52 ]
  The SPARCC enthesitis is an index used to measure the severity of enthesitis. The SPARCC assesses 16 sites for enthesitis using a score of "0" for no activity or "1" for activity. Sites assessed include Medial epicondyle (left/right [L/R]), Lateral epicondyle (L/R), Supraspinatus insertion into greater tuberosity of humerus (L/R), Greater trochanter (L/R), Quadriceps insertion into superior border of patella (L/R), Patellar ligament insertion into inferior pole of patella or tibial tubercle (L/R), Achilles tendon insertion into calcaneum (L/R), and Plantar fascia insertion into calcaneum (L/R). The SPARCC is the sum of all site scores (range 0 to 16). Higher scores indicate more severe enthesitis. LS Mean was derived from MMRM with treatment, geographic region, screening MRI/CRP status, baseline value visit, baseline value-by-visit and treatment-by-visit interaction as fixed factors.
• Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) [ Time Frame: Baseline, Week 52 ]
  BASFI is a participant-reported assessment that establishes a participant's functional baseline and subsequent response to treatment. Participants were asked to rate the difficulty associated with 10 individual basic functional activities. Participant responded to each question using a NRS scale (range 0 to 10), with a higher score indicating worse functioning. The participant's final BASFI score is the mean of the 10 item scores with the minimum value of 0 and a possible maximum value of 10, with a higher score indicating worse function. LS Mean was derived from MMRM with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.
• Percentage of Participants Achieving ASDAS Inactive Disease [ Time Frame: Week 52 ]
  ASDAS is a composite index to assess disease activity in axSpA. ASDAS Inactive Disease is defined as a score of less than (<)1.3. The parameters used for the ASDAS (with CRP as acute phase reactant) are total back pain, patient global, peripheral pain/swelling, duration of morning stiffness and CRP in mg/L. The ASDAScrp is calculated with the following equation: 0.121×total back pain+0.110×patient global+0.073×peripheral pain/swelling+0.058×duration of morning stiffness+0.579×Ln(CRP+1). (CRP is in mg/liter, the range of other variables is from 0(normal) to 10(very severe); Ln represents the natural logarithm). Data from five variables combined to yield a score (0.6361 to no defined upper limit), where higher the score worse the disease activity.
• Change From Baseline in the Measure of High Sensitivity C-Reactive Protein (CRP) [ Time Frame: Baseline, Week 52 ]
  High-sensitivity C-reactive protein (hs-CRP) was the measure of acute phase reactant and was measured with a high sensitivity assay at the central laboratory to help assess the effect of ixekizumab on disease activity. LS Mean was derived from MMRM with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.
• Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) [ Time Frame: Baseline, Week 52 ]
  Bath Ankylosing Spondylitis Metrology Index (BASMI) is a combined index comprising the following 5 clinical measurements of spinal mobility in participants with axSpA: 1) Lateral spinal flexion 2) Tragus-to-wall distance 3) Lumbar flexion (modified Schrober) 4) Maximal intermalleolar distance, and 5) Cervical rotation. The BASMI includes these 5 measurements that were each scaled to a score of 0 to 10 depending on the result of the assessment (BASMI linear function). The average score of the 5 assessments gives the BASMI linear result. LS Mean was derived from MMRM with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.
• Change From Baseline in Chest Expansion [ Time Frame: Baseline, Week 52 ]
  While participants have their hands resting on or behind the head, the assessor has measured the chest's encircled length by centimeter at the fourth intercostal level anteriorly. The difference between maximal inspiration and expiration in centimeters was recorded. Two tries were recorded. The better measurement (larger difference) of 2 tries (in centimeters) was used for analyses. LS Mean was derived from MMRM with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.
• Change From Baseline in Occiput to Wall Distance [ Time Frame: Baseline, Week 52 ]
  The participant is to make a maximum effort to touch the head against the wall when standing with heels and back against the wall (occiput). Then the distance from occiput to wall is measured. Two tries will be recorded. The better (smaller) measurement of 2 tries (in centimeters) will be used for analyses. LS Mean was derived from MMRM with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.
• Change From Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) [ Time Frame: Baseline, Week 52 ]
  Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) is an index used to measure the severity of enthesitis. The MASES assesses 13 sites for enthesitis using a score of "0" for no activity or "1" for activity. Sites assessed included costochondral 1 (right/left [R/L]), costochondral 7 (R/L), spinal iliaca anterior superior (R/L), crista iliaca (R/L), spina iliaca posterior (R/L), processus spinosus L5, and achilles tendon proximal insertion (R/L). The MASES is the sum of all site scores (range 0 to 13); higher scores indicate more severe enthesitis. LS mean was derived from MMRM with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.
• Change From Baseline in Severity of Peripheral Arthritis by Tender (TJC) and Swollen Joint Count (SJC) Scores of 44 Joints [ Time Frame: Baseline, Week 52 ]
  The number of tender and painful joints was determined by examination of 46 joints (23 joints on each side of the participants body). The 46 joints are assessed and classified as tender or not tender. Sum of all joints checked to be tender/painful divided by number of evaluable joints which is multiplied by 46 to obtain TJC score. The scores ranges from 0 (no tender/painful joints) to 46 (all joints tender/painful). Swollen joint count SJC was determined by examination of 44 joints (22 joints on each side of the participants body). The joints are classified as swollen or not swollen. Sum of all joints checked to be swollen divided by number of evaluable joints which is multiplied by 44 to obtain SJC score. Score ranges from 0 (not swollen) to 44 (all joints swollen). LS mean was derived from MMRM with treatment, geographic region, screening MRI/CRP status and baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.
• Number of Participants With Anterior Uveitis [ Time Frame: Baseline through Week 52 ]
  Number of participants with anterior uveitis. Anterior uveitis is an inflammation of the middle layer of the eye which includes the iris (colored part of the eye) and the adjacent tissue, known as the ciliary body.
• Change From Baseline in the Fatigue Numeric Rating Scale (NRS) Score [ Time Frame: Baseline, Week 52 ]
  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 rate their fatigue (feeling tired or worn out) by circling the one number that describes their worst level of fatigue during the previous 24 hours. LS Mean was derived from MMRM with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.
• Change From Baseline in ASAS Health Index (ASAS HI) [ Time Frame: Baseline, Week 52 ]
  ASAS-HI is a disease-specific health-index instrument designed to assess the impact of interventions for SpA, including axSpA. The 17-item instrument has scores ranging from 0 (good health) to 17 (poor health). Each item consists of one question that the participant needs to respond to with either "I agree" (score of 1) or "I do not agree" (score of 0). A score of "1" is given where the item is affirmed, indicating adverse health. All item scores are summed to give a total score or index. LS Mean was derived MMRM with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.
• Change From Baseline in the Jenkins Sleep Evaluation Questionnaire (JSEQ) [ Time Frame: Baseline, Week 52 ]
  Jenkins Sleep Evaluation Questionnaire (JSEQ) is a 4 item scale designed to estimate sleep problems in clinical research. The JSEQ assesses the frequency of sleep disturbance in 4 categories: 1) trouble falling asleep, 2) waking up several times during the night, 3) having trouble staying asleep (including waking up far too early), and 4) waking up after the usual amount of sleep feeling tired and worn out. Patients report the numbers of days they experience each of these problems in the past month on a 6 point Likert Scale ranging from 0 = "no days" to 5 = "22-30 days. The total JSEQ score ranges from 0 to 20, with higher scores indicating greater sleep disturbance. LS Mean was derived from using MMRM with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.
• Change From Baseline in the Work Productivity Activity Impairment Spondyloarthritis (WPAI-SpA) Scores [ Time Frame: Baseline, Week 52 ]
  The WPAI-SpA consists of 6 questions to determine employment status, hours missed from work because of SpA, hours missed from work for other reasons, hours actually worked, the degree to which SpA affected work productivity while at work, and the degree to which SpA affected activities outside of work. The WPAI-SpA has been validated in the rad-axSpA patient population. Four scores are derived: percentage of absenteeism, percentage of presenteeism (reduced productivity while at work), an overall work impairment score that combines absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. The computed percentage range for each sub-scale was from 0-100, with higher scores indicating greater impairment and less productivity. LS Mean was derived from ANCOVA with treatment, geographic region, screening MRI/CRP status and baseline value.
• Change From Baseline in ASAS-Nonsteroidal Anti-Inflammatory Drug (NSAID) Score [ Time Frame: Baseline, Week 52 ]
  ASAS-NSAID score is used to present the NSAID intake by considering the type of NSAID, the total dose, & the number of days taking NSAID during a period of interest (PI). For NSAID equivalent scoring system, range is from 0 to 100, the higher the score, the greater the NSAID intake. ASAS-NSAID score= (equivalent NSAID score) x (days of intake during PI) x (days per week)/(PI in days).
• Number of Participants With Treatment Emergent (TE) Anti-Ixekizumab Antibodies [ Time Frame: Week 52 ]
  A treatment-emergent positive anti-drug antibody (TE-ADA+) participant will be defined as a 4-fold increase over a positive baseline antibody titer (Tier 3); or for a negative baseline titer, a participant with an increase from the baseline to a level of ≥ 1:10.
• Pharmacokinetics (PK): Trough Concentration at Steady State (Ctrough ss) [ Time Frame: Week 52 ]
  PK trough serum concentration samples were collected at steady state (Ctrough ss)

Original Secondary Outcome Measures (submitted: April 28, 2016)

• Proportion of Participants Achieving an ASAS40 Response [ Time Frame: Week 52 ]
• Change from Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) [ Time Frame: Baseline, Week 16 ]
• Change from Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) [ Time Frame: Baseline, Week 16 ]
• Change from Baseline in Magnetic Resonance Imaging (MRI) of the Sacroiliac Joint (SIJ) Spondyloarthritis Research Consortium of Canada (SPARCC) Score [ Time Frame: Baseline, Week 16 ]
• Percent of Participants without Clinically Meaningful Changes in Background Therapy [ Time Frame: Week 52 ]
• Change from Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) [ Time Frame: Baseline, Week 52 ]
• Proportion of Participants Achieving ASDAS Inactive Disease [ Time Frame: Week 16 ]
• Change from Baseline in the Measure of High Sensitivity C-Reactive Protein (CRP) [ Time Frame: Baseline, Week 52 ]
• Change from Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) [ Time Frame: Baseline, Week 52 ]
• Change from Baseline in Chest Expansion [ Time Frame: Baseline, Week 52 ]
• Change from Baseline in Occiput to Wall Distance [ Time Frame: Baseline, Week 52 ]
• Change from Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) [ Time Frame: Baseline, Week 52 ]
• Change from Baseline in SPARCC Enthesitis Score [ Time Frame: Baseline, Week 52 ]
• Change from Baseline in Severity of Peripheral Arthritis by Tender (TJC) and Swollen Joint Count (SJC) Scores of 46/44 Joints [ Time Frame: Baseline, Week 52 ]
• Proportion of Participants with Anterior Uveitis or Uveitis Flares [ Time Frame: Baseline through Week 52 ]
• Change from Baseline in the Fatigue Numeric Rating Scale (NRS) Score [ Time Frame: Baseline, Week 52 ]
• Change from Baseline in ASAS Health Index (ASAS HI) [ Time Frame: Baseline, Week 52 ]
• Change from Baseline in the Jenkins Sleep Evaluation Questionnaire (JSEQ) [ Time Frame: Baseline, Week 52 ]
• Change from Baseline in the Work Productivity Activity Impairment Spondyloarthritis (WPAI-SpA) Scores [ Time Frame: Baseline, Week 52 ]
• Change from Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores [ Time Frame: Baseline, Week 52 ]
• Change from Baseline in ASAS-Nonsteroidal Anti-Inflammatory Drug (NSAID) Score [ Time Frame: Baseline, Week 52 ]
• Number of Participants with Anti-Ixekizumab Antibodies [ Time Frame: Week 52 ]
• Pharmacokinetics (PK): Trough Concentration at Steady State (Ctrough ss) [ Time Frame: Week 52 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Ixekizumab (LY2439821) in Participants With Nonradiographic Axial Spondyloarthritis
• Official Title: A 52-Week Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Ixekizumab (LY2439821) in bDMARD Naive Patients With Nonradiographic Axial Spondyloarthritis
• Brief Summary: The main purpose of this study is to evaluate the safety and efficacy of the study drug known as ixekizumab in biologic disease modifying antirheumatic drug (bDMARD) naïve participants with nonradiographic axial spondyloarthritis (nonrad-axSpA).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Axial Spondyloarthritis

Intervention

• Drug: Ixekizumab
  Administered SC
  Other Name: LY2439821
• Drug: Placebo
  Administered SC

Study Arms

• Experimental: Q2W Ixekizumab

  Participants received a starting dose of 80 or 160 milligram (mg) of ixekizumab given subcutaneously (SC) at week 0 followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 52 during the double-blind period.

  Inadequate responders (IR) as determined by investigators could switch to ixekizumab 80 mg Q2W open label between week 16 and 44.

  Intervention: Drug: Ixekizumab
• Experimental: Q4W Ixekizumab

  Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every four weeks (Q4W) to week 52 during the double-blind period.

  Inadequate responders as determined by investigators could switch to ixekizumab 80 mg Q2W open label week 16 and 44.

  Intervention: Drug: Ixekizumab
• Placebo Comparator: Placebo

  Participants received placebo as 2 SC injections Q2W to week 52 during double-blind period.

  Inadequate responders as determined by investigators could switch to ixekizumab 80 mg Q2W open label between week 16 and 44.

  Intervention: Drug: Placebo

Publications *

• 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.
• Deodhar A, Mease P, Marzo-Ortega H, Hunter T, Sandoval D, Kronbergs A, Lauzon S, Leung A, Navarro-Compan V. Ixekizumab improves sleep and work productivity in patients with non-radiographic axial spondyloarthritis: results from the COAST-X trial at 52 weeks. BMC Rheumatol. 2021 Sep 25;5(1):50. doi: 10.1186/s41927-021-00218-y.
• Deodhar A, Mease P, Rahman P, Navarro-Compan V, Marzo-Ortega H, Hunter T, Sandoval D, Kronbergs A, Leon L, Shan M, Leung A, De Vlam K, Strand V. Ixekizumab Improves Patient-Reported Outcomes in Non-Radiographic Axial Spondyloarthritis: Results from the Coast-X Trial. Rheumatol Ther. 2021 Mar;8(1):135-150. doi: 10.1007/s40744-020-00254-z. Epub 2020 Dec 7.
• Walsh JA, Magrey MN, Baraliakos X, Inui K, Weng MY, Lubrano E, van der Heijde D, Boonen A, Gensler LS, Strand V, Braun J, Hunter T, Li X, Zhu B, Leon L, Calderon DMS, Kiltz U. Improvement of Functioning and Health With Ixekizumab in the Treatment of Active Nonradiographic Axial Spondyloarthritis in a 52-Week, Randomized, Controlled Trial. Arthritis Care Res (Hoboken). 2022 Mar;74(3):451-460. doi: 10.1002/acr.24482. Epub 2022 Jan 26.
• Deodhar A, van der Heijde D, Gensler LS, Kim TH, Maksymowych WP, Ostergaard M, Poddubnyy D, Marzo-Ortega H, Bessette L, Tomita T, Leung A, Hojnik M, Gallo G, Li X, Adams D, Carlier H, Sieper J; COAST-X Study Group. Ixekizumab for patients with non-radiographic axial spondyloarthritis (COAST-X): a randomised, placebo-controlled trial. Lancet. 2020 Jan 4;395(10217):53-64. doi: 10.1016/S0140-6736(19)32971-X. Epub 2019 Dec 5.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 28, 2020): 303
• Original Estimated Enrollment (submitted: April 28, 2016): 300
• Actual Study Completion Date: May 7, 2019
• Actual Primary Completion Date: March 1, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Are ambulatory.
• Diagnosis of nonradiographic axial spondyloarthritis (nr-axSpA) and fulfilling the 2009 Assessment of Spondyloarthritis International Society (ASAS) classification criteria.
• Have a history of back pain ≥3 months with age at onset <45 years.
• Have active nr-axSpA defined as BASDAI ≥4 and total back pain ≥4 on a numeric rating scale (NRS) at screening and baseline.
• Have objective signs of inflammation by presence of sacroiliitis on MRI and/or presence of elevated C-reactive protein (CRP).
• In the past had an inadequate response to at least 2 non-steroidal anti-inflammatory drugs (NSAIDS) for duration of 4 weeks or cannot tolerate NSAIDS.
• If taking NSAIDS be on 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 radiographic sacroiliitis fulfilling the 1984 modified New York criteria.
• Have received any prior, or are currently receiving treatment with biologics, tumor necrosis factor inhibitors or other immunomodulatory agents.
• Have 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.
• Have evidence of active anterior uveitis (an acute episode) within the last 42 days prior to baseline randomization.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Austria, Brazil, Canada, Czechia, Finland, Germany, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Puerto Rico, Romania, Russian Federation, United States
• Removed Location Countries: Czech Republic

Administrative Information

• NCT Number: NCT02757352
• Other Study ID Numbers: 16180; I1F-MC-RHBX ( Other Identifier: Eli Lilly and Company ); 2015-003938-27 ( EudraCT Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• 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.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• URL: https://vivli.org/

• Current Responsible Party: Eli Lilly and Company
• Original Responsible Party: Same as current
• Current Study Sponsor: Eli Lilly and Company
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: 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); Eli Lilly and Company

• PRS Account: Eli Lilly and Company
• Verification Date: August 1, 2019