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COAST-W: A Study of Ixekizumab (LY2439821) in TNF Inhibitor Experienced Participants With Radiographic Axial Spondyloarthritis

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT02696798
Collaborator
(none)
316
Enrollment
99
Locations
3
Arms
36.7
Actual Duration (Months)
3.2
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The main purpose of this study is to evaluate the efficacy and safety of ixekizumab in tumor necrosis factor (TNF) inhibitor-experienced participants with radiographic axial spondyloarthritis (rad-axSpA).

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
316 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Multicenter, Randomized, Double-Blind, Placebo- Controlled 16-Week Study Followed by Long-Term Evaluation of Efficacy and Safety of Ixekizumab (LY2439821) in TNFi-Experienced Patients With Radiographic Axial Spondyloarthritis
Actual Study Start Date :
Apr 12, 2016
Actual Primary Completion Date :
May 18, 2018
Actual Study Completion Date :
May 3, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Q2W Ixekizumab

Double Blind Period: Starting dose of 80 or 160 milligrams (mg) ixekizumab given subcutaneously (SC) at baseline followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 14. Extended Treatment Period: 80 mg ixekizumab given SC Q2W from week 16 to week 52.

Drug: Ixekizumab
Administered SC
Other Names:
  • LY2439821

    		•
    Experimental: Q4W Ixekizumab

    Double Blind Period: Starting dose of 80 or 160 mg ixekizumab given SC at baseline followed by 80 mg ixekizumab given SC every four weeks (Q4W) to week 14. Extended Treatment Period: 80 mg ixekizumab given SC Q4W from week 16 to week 52.

    Drug: Ixekizumab
    Administered SC
    Other Names:
  • LY2439821

    		•
    Placebo Comparator: Placebo

    Double Blind Period: Placebo given SC Q2W to week 14. Extended Treatment Period: Starting dose of 160 mg ixekizumab given SC at week 16 followed by 80 mg ixekizumab given SC Q2W or Q4W from week 16 to week 52.

    Drug: Ixekizumab
    Administered SC
    Other Names:
  • LY2439821

    • Drug: Placebo
    Administered SC

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants Achieving an Assessment of Spondyloarthritis International Society 40 (ASAS40) Response [Week 16]

      ASAS40 is defined as improvement from baseline of greater than or equal to (>=) 40 % and absolute improvement from baseline of at least 2 units (range of 0 to 10) in at least 3 of the following 4 domains without any worsening in the remaining domain. Patient Global: How active was your spondylitis on average during the last week? score ranges 0 (not active) to 10 (very active). Spinal Pain: How much Pain of your spine due to Ankylosing spondylitis? score ranges 0 (no pain) to 10 (severe pain). Bath Ankylosing Spondylitis Functional Index (BASFI): Participant asked to rate the difficulty associated with 10 individual basic functional activities. Participant response was captured using Numeric Rating Scale (NRS) (range 0 to 10) with a higher score indicating worse function. Inflammation based on Q5 & Q6 mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (mean of intensity & duration of stiffness): Score ranges from "0" (none) and "10" (very severe).

    Secondary Outcome Measures

    1. Percentage of Participants Achieving an ASAS20 Response [Week 16]

      ASAS20 response is defined as a ≥20% improvement and an absolute improvement from baseline of ≥1 units (range 0 to 10) in ≥3 of 4 domains, and no worsening of ≥20% and ≥1 unit (range 0 to 10) in the remaining domain. Patient Global: How active was your spondylitis on average during the last week? score ranges 0 (not active) to 10 (very active). Spinal Pain: How much Pain of your spine due to Ankylosing spondylitis? score ranges 0 (no pain) to 10 (severe pain). Bath Ankylosing Spondylitis Functional Index (BASFI): Participant asked to rate the difficulty associated with 10 individual basic functional activities. Participant response was captured using Numeric Rating Scale (NRS) (range 0 to 10) with a higher score indicating worse function. Inflammation based on Q5 & Q6 mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (mean of intensity & duration of stiffness): Score ranges from "0" (none) and "10" (very severe).

    2. Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) [Baseline, Week 16]

      ASDAS is a composite index to assess disease activity in AS. 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 scores indicated higher disease activity. Least Square (LS) mean was determined by mixed-model repeated measures (MMRM) with treatment, geographic region, baseline CRP status, number of prior tumor necrosis factor inhibitor (TNFi), baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.

    3. Percentage of Participants Achieving Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI50) Response [Week 16]

      The BASDAI is a participant-reported assessment consisting of 6 questions that relate to 5 major symptoms relevant to radiographic axial spondyloarthritis (rad-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. BASDAI50 represents an improvement of ≥50% of the BASDAI score from baseline.

    4. Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) [Baseline, Week 16]

      The BASDAI is a participant-reported assessment consisting of 6 questions that relate to 5 major symptoms relevant to radiographic axial spondyloarthritis (rad-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. LSmean was determined by MMRM with factors for treatment, geographic region, baseline CRP status, number of prior TNFi, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.

    5. Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) [Baseline, Week 16]

      The BASFI is a participant-reported assessment that establishes a participant's functional baseline and subsequent response to treatment. The BASFI is composed with 10 questions to assess the disease severity, including the first 8 questions regarding to functional anatomy related activities and the remaining 2 questions related to daily activities of AS participants. Participants respond to each question using an NRS scale (range 0 to 10). The BASFI score is the average of the 10 responses and has a possible minimum value of 0 and a possible maximum value of 10, with a higher score indicating worse function. LS mean was determined by MMRM with factors for treatment, geographic region, baseline CRP status, number of prior TNFi, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.

    6. Percentage of Participants Achieving ASDAS Inactive Disease [Week 16]

      ASDAS is a composite index to assess disease activity in AS. ASDAS Inactive Disease is defined as a score of <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.

    7. Percentage of Participants Achieving ASDAS <2.1 [Week 16]

      ASDAS is a composite index to assess disease activity in AS. ASDAS <2.1 defines moderate disease activity. 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.

    8. Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores [Baseline, Week 16]

      The SF-36 is a 36-item participant 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 2 overarching domains of mental well- being and physical well-being are captured by the Mental Component Summary and Physical Component Summary scores. T-scores are used for analysis. The summary scores range from 0 to 100, with higher scores indicating better levels of function and/or better health. LSmean was determined by MMRM with factors for treatment, geographic region, baseline CRP status, number of prior TNFi, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.

    9. Change From Baseline in ASAS Health Index (ASAS HI) [Baseline, Week 16]

      The ASAS Health Index (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 1 question that the patient needs to respond to with either "I agree" (score 1) or "I do not agree (score 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 determined by MMRM with treatment, geographic region, baseline CRP status, number of prior TNFi, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.

    10. Change From Baseline in Magnetic Resonance Imaging (MRI) of the Spine (Ankylosing Spondylitis Spinal Magnetic Resonance Imaging [ASSpiMRI] - Berlin Score) [Baseline, Week 16]

      The study used MRI with fat-saturating techniques such as short tau inversion recovery (STIR) to look for the presence of bone marrow edema. The Berlin modification of Ankylosing Spondylitis spine MRI score for activity (ASspiMRI) scoring technique assesses inflammation in each of the 23 disco-vertebral units (DVU) of the spine (from C2 to S1), capturing bone marrow edema. Scores for each DVU range from 0-3 (0=normal; 1=minor bone marrow edema [less than or equal to 25% of DVU; 3=severe bone marrow edema (more that 50% of DVU)]. The composite score ranges from 0 to 69, with higher scores reflecting worse disease.LS mean was determined by analysis of covariance (ANCOVA) with treatment, geographic region, baseline CRP status, number of prior TNF inhibitors used and baseline value as fixed factors.

    11. Change From Baseline in Magnetic Resonance Imaging (MRI) of the Spine (Spondyloarthritis Research Consortium of Canada [SPARCC] Score) [Baseline, Week 16]

      MRI score of spine was assessed using SPARCC method. All 23 disco-vertebral units (DVU) of the spine (from C2 to S1) were scored for bone marrow edema. A single DVU has 18 scoring units, and each has score of 0 or 1, bringing the maximum total score to 414, the sum ranges from 0 to 414 with higher scores reflecting worse disease. Scoring was performed by central readers. LS mean was determined by ANCOVA with factors for treatment, geographic region, baseline CRP status, number of prior TNF inhibitors used and baseline value.

    12. Change From Baseline in the Measure of High Sensitivity C-Reactive Protein (CRP) [Baseline, Week 16]

      High sensitivity CRP is the measure of acute phase reactant. It was measured with a high sensitivity assay at the central laboratory to help assess the effect of ixekizumab on disease activity. High sensitivity CRP is a sensitive laboratory assay for serum levels of C-Reactive Protein, which is a biomarker of inflammation. LS mean was determined by MMRM with treatment, geographic region, baseline CRP status, number of prior TNFi, visit, and treatment-by-visit interaction as fixed factors.

    13. Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) [Baseline, Week 16]

      BASMI is a combined index comprising of 5 clinical measurements of spinal mobility in patients with radiographic axial spondyloarthritis (rad-axSpA). Lateral Spinal Flexion Tragus-to-wall distance Lumbar Flexion (modified Schober) Maximal intermalleolar distance and Cervical rotation. The BASMI linear result is the average of the 5 assessments and ranges from 0 to 10. The higher the BASMI score the more severe the patient's limitation of movement due to their AS. LS mean was determined by MMRM with treatment, geographic region, baseline CRP status, number of prior TNFi, baseline value, visit, baseline value-by-visit and treatment-by-visit interaction as fixed factors.

    14. Change From Baseline in Chest Expansion [Baseline, Week 16]

      Chest expansion is the difference, in centimeter (cm), between the circumference of the chest in maximal inspiration and maximal expiration. While patients have their hands resting on or behind the head, the assessor will measure the chest encircled length by centimeter (cm) at the fourth intercostal level anteriorly. Two tries were recorded. The better measurement (larger difference) of 2 tries (in centimeters) was used for analyses. LS mean was determined by MMRM with treatment, geographic region, baseline CRP status, number of prior TNFi, baseline value, visit, baseline value-by-visit and treatment-by-visit interaction as fixed factors.

    15. Change From Baseline in Occiput to Wall Distance [Baseline, Week 16]

      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 determined by MMRM with factors for treatment, geographic region, baseline CRP status, number of prior TNFi, baseline value, visit, baseline value-by-visit and treatment-by-visit interaction as fixed factors.

    16. Change From Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) [Baseline, Week 16]

      The 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 include costochondral 1 (right/left), costochondral 7 (right/left), spinal iliaca anterior superior (right/left), crista iliaca (right/left), spina iliaca posterior (right/left), processus spinosus L5, and Achilles tendon proximal insertion (right/left). The MASES is the sum of all site scores (range 0 to 13); higher scores indicate more severe enthesitis. LS mean was determined by MMRM with treatment, geographic region, baseline CRP status, number of prior TNFi, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.

    17. Change From Baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Score [Baseline, Week 16]

      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 determined by MMRM with treatment, geographic region, baseline CRP status, number of prior TNFi, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.

    18. Change From Baseline in Severity of Peripheral Arthritis by Tender Joint Count (TJC) Scores [Baseline, Week 16]

      The number of tender and painful joints was determined by examination of 46 joints (23 joints on each side of the body). The 46 joints were assessed and classified as tender or not tender. Sum of all joints checked to be tender/painful divided by number of evaluable joints which was multiplied by 46 to obtain TJC score. The scores ranges from 0 (no tender/painful joints) to 46 (all joints tender/painful). LS mean was determined by MMRM with treatment, geographic region, baseline CRP status, number of prior TNFi, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction.

    19. Change From Baseline in Severity of Peripheral Arthritis by Swollen Joint Count (SJC) Scores [Baseline, Week 16]

      The number of swollen joints was determined by examination of 44 joints (22 joints on each side of the body). The 44 joints were assessed and classified as swollen or not swollen. Sum of all joints checked to be swollen divided by number of evaluable joints which was multiplied by 44 to obtain SJC score. The SJC score ranges from 0 (no swollen joints) to 44 (all joints swollen). LS mean was determined by MMRM with treatment, geographic region, baseline CRP status, number of prior TNFi, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction.

    20. Percentage of Participants With Anterior Uveitis [Week 16]

      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.

    21. Change From Baseline in the Fatigue Numeric Rating Scale (NRS) Score [Baseline, Week 16]

      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 1 number that describes their worst level of fatigue during the previous 24 hours. LS mean was determined by MMRM with treatment, geographic region, baseline CRP status, number of prior TNFi, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.

    22. Change From Baseline in the Jenkins Sleep Evaluation Questionnaire (JSEQ) [Baseline, Week 16]

      The 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 determined by MMRM with treatment, geographic region, baseline CRP status, number of prior TNFi, baseline value, visit, baseline value-by-visit and treatment-by-visit interaction as fixed factors.

    23. Change From Baseline in the Work Productivity Activity Impairment Spondyloarthritis (WPAI-SpA) Scores [Baseline, Week 16]

      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 determined by ANCOVA with treatment, geographic region, baseline CRP status, number of prior TNFi and baseline value as fixed factors.

    24. Change From Baseline in ASAS-Nonsteroidal Anti-Inflammatory Drug (NSAID) Score [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, higher the score greated the NSAID intake. ASAS-NSAID score= (equivalent NSAID score) x (days of intake during PI) x (days per week)/(PI in days).

    25. Percentage of Participants With Anti-Ixekizumab Antibodies [Week 16]

      A treatment emergent - antidrug antibody (TE-ADA) positive patient is defined as: a) a patient with a >= 4-fold increase over a positive baseline antibody titer; or b) for a negative baseline titer, a patient with an increase from the baseline to a level of >= 1:10. Percentage was calculated based on the number of evaluable participants and was calculated by number of participants with treatment-emergent positive anti-ixekizumab antibodies / number of evaluable participants * 100%.

    26. Pharmacokinetics (PK): Trough Ixekizumab Concentration at Steady State (Ctrough ss) [Week 16]

      Pharmacokinetics (PK): Steady-state trough serum concentration of Ixekizumab at week 16.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Are ambulatory.

    • Have an established 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.

    • Have had prior treatment with at least 1 and not more than 2 TNF inhibitors.

    • Must have had an inadequate response to 2 or more NSAIDs at the therapeutic dose range for a total duration of at least 4 weeks OR have a history of intolerance to NSAIDs.

    • 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 never taken a TNF inhibitor medication or have taken more than 2.

    • 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Arizona Arthritis Research, PLC Phoenix Arizona United States 85032
    2 Rheumatology Center of San Diego Escondido California United States 92025
    3 Care Access Research - Huntington Beach Huntington Beach California United States 92648
    4 Desert Medical Advances Palm Desert California United States 92260
    5 Arthritis Assoc. & Osteoporosis Ctr of Colorado Springs, LLC Colorado Springs Colorado United States 80920
    6 Denver Arthritis Center Denver Colorado United States 80230
    7 Clinical Research Center of CT/NY Danbury Connecticut United States 06810
    8 Arthritis Rheumatic Disease Specialties Aventura Florida United States 33180
    9 Sarasota Arthritis Center Sarasota Florida United States 34239
    10 Marietta Rheumatology Marietta Georgia United States 30060
    11 St Luke's Clinic - Intermountain Orthopaedics Boise Idaho United States 83702
    12 Institute of Arthritis Research Idaho Falls Idaho United States 83404
    13 Center for Arthritis & Osteoporosis Elizabethtown Kentucky United States 42701
    14 Klein and Associates MD, PA Cumberland Maryland United States 21502
    15 Osteoporosis And Clinical Trial Center Hagerstown Maryland United States 21740
    16 Arthritis Consultants Saint Louis Missouri United States 63141
    17 The Center for Rheumatology Albany New York United States 12203
    18 Shanahan Rheumatology & Immunotherapy Raleigh North Carolina United States 27617
    19 Oregon Health and Science University Portland Oregon United States 97239
    20 Altoona Center for Clinical Research Duncansville Pennsylvania United States 16635
    21 Articularis Healthcare Group, INC dba Columbia Arthritis Ctr Columbia South Carolina United States 29204
    22 Low Country Research Center North Charleston South Carolina United States 29406
    23 Univ of Texas Health Science Center - Houston Houston Texas United States 77030
    24 Southwest Rheumatology, P.A. Mesquite Texas United States 75150
    25 Center for Arthritis and Rheumatic Diseases, PC Chesapeake Virginia United States 23320
    26 Arthritis Northwest Rheumatology Spokane Washington United States 99204
    27 Rheumatology and Immunotherapy Center Franklin Wisconsin United States 53132
    28 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. Rosario Argentina S2000CFJ
    29 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. Rosario Argentina S2000DEJ
    30 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. San Miguel de Tucuman Argentina T4000AXL
    31 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. San Miguel de Tucuman Argentina T4000BRD
    32 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. Curitiba Brazil 80440-080
    33 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. Goiás Brazil 74043-110
    34 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. Juiz de Fora Brazil 36010-570
    35 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. Porto Alegre Brazil 90480-000
    36 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. Sao Paulo Brazil 01244-030
    37 For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician. St. John's Canada A1C 5B8
    38 For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician. Trois-Rivieres Canada G8Z 1Y2
    39 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. Victoria Canada V8V 3M9
    40 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. Helsinki Finland 00029
    41 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. Hyvinkaa Finland 05800
    42 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. Oulu Finland 90029
    43 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. Clermont France 63003
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    85 Office: Perez-De Jesus, Amarilis Caguas Puerto Rico 00725
    86 GCM Medical Group PSC San Juan Puerto Rico 00909
    87 Mindful Medical Research San Juan Puerto Rico 00918
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    Sponsors and Collaborators

    • Eli Lilly and Company

    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

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT02696798
    Other Study ID Numbers:
    • 16179
    • I1F-MC-RHBW
    • 2015-003937-84
    First Posted:
    Mar 2, 2016
    Last Update Posted:
    Jun 17, 2020
    Last Verified:
    Jun 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Keywords provided by Eli Lilly and Company
    Ankylosing Spondylitis
    Additional relevant MeSH terms:
    Spondylitis
    Spondylarthritis
    Ixekizumab

    Study Results

    Participant Flow

    Recruitment Details Blinded Treatment Dosing Period (Week 0 to Week 16), Extended Treatment Period (Week 16 to Week 52) followed by post-treatment follow-up period occurring from last treatment visit (week 52), or Early Termination Visit (ETV) up to a minimum of 12 weeks following that visit.
    Pre-assignment Detail Participants who completed study were eligible to enroll into a long-term study (I1F-MC-RHBY [NCT03129100]) for up to 2 additional years. Participants who terminate study RHBW early or who do not enroll into Study RHBY will complete the Post-Treatment Follow-Up (PTFU) Period in study RHBW.
    Arm/Group Title PBO/IXE IXE80Q4W/IXE80Q4W IXE80Q2W/IXE80Q2W
    Arm/Group Description Blinded Treatment Dosing Period: Participants received placebo (PBO) every two weeks (Q2W) by subcutaneous (SC) injection during Week 0 to 16. Extended Treatment Period: Participants who received Placebo in blinded treatment period were re-randomized to receive ixekizumab (IXE) 80 mg every four weeks (Q4W) or 80 mg Q2W at a 1:1 ratio with starting dose of 160 mg. Post-treatment Follow-up Period: Participants did not receive any intervention during Follow-up period Blinded Treatment Dosing Period: Participants received starting dose of 80 or 160 mg ixekizumab given SC at baseline followed by 80 mg ixekizumab given SC every four weeks (Q4W) up to week 16. Extended Treatment Period: Participants received 80 mg ixekizumab given SC Q4W from week 16 to week 52. Post-treatment Follow-up Period: Participants did not receive any intervention during Follow-up period Blinded Treatment Dosing Period: Participants received starting dose of 80 or 160 milligrams (mg) ixekizumab given subcutaneously (SC) at baseline followed by 80 mg ixekizumab given SC every two weeks (Q2W) up to week 16. Extended Treatment Period: Participants received 80 mg ixekizumab given SC Q2W from week 16 to week 52. Post-treatment Follow-up Period: Participants did not receive any intervention during Follow-up period
    Period Title: Blinded Treatment Dosing Period
    STARTED 104 114 98
    COMPLETED 93 99 90
    NOT COMPLETED 11 15 8
    Period Title: Blinded Treatment Dosing Period
    STARTED 93 98 90
    COMPLETED 81 89 80
    NOT COMPLETED 12 9 10
    Period Title: Blinded Treatment Dosing Period
    STARTED 5 34 22
    COMPLETED 0 8 3
    NOT COMPLETED 5 26 19

    Baseline Characteristics

    Arm/Group Title PBO/IXE IXE80Q4W/IXE80Q4W IXE80Q2W/IXE80Q2W Total
    Arm/Group Description Blinded Treatment Dosing Period: Participants received placebo every two weeks (Q2W) by subcutaneous (SC) injection during Week 0 to 16. Extended Treatment Period: Participants who received Placebo in blinded treatment period were re-randomized to receive ixekizumab 80 mg Q4W or 80 mg Q2W at a 1:1 ratio with starting dose of 160 mg. Post-treatment Follow-up Period: Participants did not receive any intervention during Follow-up period Participants did not receive any intervention during Follow-up period Blinded Treatment Dosing Period: Participants received starting dose of 80 or 160 mg ixekizumab given SC at baseline followed by 80 mg ixekizumab given SC every four weeks (Q4W) up to week 16. Extended Treatment Period: Participants received 80 mg ixekizumab given SC Q4W from week 16 to week 52. Post-treatment Follow-up Period: Participants did not receive any intervention during Follow-up period Participants did not receive any intervention during Follow-up period Blinded Treatment Dosing Period: Participants received starting dose of 80 or 160 milligrams (mg) ixekizumab given subcutaneously (SC) at baseline followed by 80 mg ixekizumab given SC every two weeks (Q2W) up to week 16. Extended Treatment Period: Participants received 80 mg ixekizumab given SC Q2W from week 16 to week 52. Post-treatment Follow-up Period: Participants did not receive any intervention during Follow-up period Participants did not receive any intervention during Follow-up period Total of all reporting groups
    Overall Participants 104 114 98 316
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    46.6
    (12.72)
    47.4
    (13.36)
    44.2
    (10.79)
    46.1
    (12.43)
    Sex: Female, Male (Count of Participants)
    Female
    17
    16.3%
    23
    20.2%
    23
    23.5%
    63
    19.9%
    Male
    87
    83.7%
    91
    79.8%
    75
    76.5%
    253
    80.1%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    33
    31.7%
    32
    28.1%
    35
    35.7%
    100
    31.6%
    Not Hispanic or Latino
    63
    60.6%
    70
    61.4%
    53
    54.1%
    186
    58.9%
    Unknown or Not Reported
    8
    7.7%
    12
    10.5%
    10
    10.2%
    30
    9.5%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    4
    3.8%
    4
    3.5%
    4
    4.1%
    12
    3.8%
    Asian
    13
    12.5%
    14
    12.3%
    13
    13.3%
    40
    12.7%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    1
    1%
    2
    1.8%
    2
    2%
    5
    1.6%
    White
    85
    81.7%
    91
    79.8%
    78
    79.6%
    254
    80.4%
    More than one race
    1
    1%
    2
    1.8%
    1
    1%
    4
    1.3%
    Unknown or Not Reported
    0
    0%
    1
    0.9%
    0
    0%
    1
    0.3%
    Region of Enrollment (Count of Participants)
    Puerto Rico
    1
    1%
    2
    1.8%
    4
    4.1%
    7
    2.2%
    Argentina
    6
    5.8%
    7
    6.1%
    5
    5.1%
    18
    5.7%
    United States
    14
    13.5%
    14
    12.3%
    12
    12.2%
    40
    12.7%
    United Kingdom
    9
    8.7%
    6
    5.3%
    5
    5.1%
    20
    6.3%
    Spain
    3
    2.9%
    7
    6.1%
    4
    4.1%
    14
    4.4%
    Canada
    1
    1%
    5
    4.4%
    0
    0%
    6
    1.9%
    South Korea
    12
    11.5%
    11
    9.6%
    11
    11.2%
    34
    10.8%
    Netherlands
    1
    1%
    2
    1.8%
    0
    0%
    3
    0.9%
    Finland
    0
    0%
    3
    2.6%
    2
    2%
    5
    1.6%
    Brazil
    10
    9.6%
    8
    7%
    10
    10.2%
    28
    8.9%
    Poland
    22
    21.2%
    24
    21.1%
    20
    20.4%
    66
    20.9%
    Italy
    0
    0%
    1
    0.9%
    1
    1%
    2
    0.6%
    Mexico
    13
    12.5%
    13
    11.4%
    13
    13.3%
    39
    12.3%
    Israel
    5
    4.8%
    5
    4.4%
    6
    6.1%
    16
    5.1%
    France
    7
    6.7%
    5
    4.4%
    5
    5.1%
    17
    5.4%
    Germany
    0
    0%
    1
    0.9%
    0
    0%
    1
    0.3%

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants Achieving an Assessment of Spondyloarthritis International Society 40 (ASAS40) Response
    Description ASAS40 is defined as improvement from baseline of greater than or equal to (>=) 40 % and absolute improvement from baseline of at least 2 units (range of 0 to 10) in at least 3 of the following 4 domains without any worsening in the remaining domain. Patient Global: How active was your spondylitis on average during the last week? score ranges 0 (not active) to 10 (very active). Spinal Pain: How much Pain of your spine due to Ankylosing spondylitis? score ranges 0 (no pain) to 10 (severe pain). Bath Ankylosing Spondylitis Functional Index (BASFI): Participant asked to rate the difficulty associated with 10 individual basic functional activities. Participant response was captured using Numeric Rating Scale (NRS) (range 0 to 10) with a higher score indicating worse function. Inflammation based on Q5 & Q6 mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (mean of intensity & duration of stiffness): Score ranges from "0" (none) and "10" (very severe).
    Time Frame Week 16

    Outcome Measure Data

    Analysis Population Description
    All randomized participants.
    Arm/Group Title Placebo 80 mg Q4W Ixekizumab 80 mg Q2W Ixekizumab
    Arm/Group Description Participants received placebo every 2 weeks (Q2W) by subcutaneous injection. Participants received starting dose of 80 or 160 mg ixekizumab by SC injection at baseline followed by 80 mg ixekizumab given SC every four weeks (Q4W). Participants received starting dose of 80 or 160 mg ixekizumab given SC injection at baseline followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 16.
    Measure Participants 104 114 98
    Number [Percentage of participants]
    12.5
    12%
    25.4
    22.3%
    30.6
    31.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q4W Ixekizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.017
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.41
    Confidence Interval (2-Sided) 95%
    1.17 to 4.95
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q2W Ixekizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.003
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.06
    Confidence Interval (2-Sided) 95%
    1.48 to 6.33
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Percentage of Participants Achieving an ASAS20 Response
    Description ASAS20 response is defined as a ≥20% improvement and an absolute improvement from baseline of ≥1 units (range 0 to 10) in ≥3 of 4 domains, and no worsening of ≥20% and ≥1 unit (range 0 to 10) in the remaining domain. Patient Global: How active was your spondylitis on average during the last week? score ranges 0 (not active) to 10 (very active). Spinal Pain: How much Pain of your spine due to Ankylosing spondylitis? score ranges 0 (no pain) to 10 (severe pain). Bath Ankylosing Spondylitis Functional Index (BASFI): Participant asked to rate the difficulty associated with 10 individual basic functional activities. Participant response was captured using Numeric Rating Scale (NRS) (range 0 to 10) with a higher score indicating worse function. Inflammation based on Q5 & Q6 mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (mean of intensity & duration of stiffness): Score ranges from "0" (none) and "10" (very severe).
    Time Frame Week 16

    Outcome Measure Data

    Analysis Population Description
    All randomized participants.
    Arm/Group Title Placebo 80 mg Q4W Ixekizumab 80 mg Q2W Ixekizumab
    Arm/Group Description Participants received placebo every 2 weeks by subcutaneous injection. Participants received starting dose of 80 or 160 mg ixekizumab by SC injection at baseline followed by 80 mg ixekizumab given SC every four weeks (Q4W). Participants received starting dose of 80 or 160 mg ixekizumab given SC injection at baseline followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 16.
    Measure Participants 104 114 98
    Number [Percentage of Participants]
    29.8
    28.7%
    48.2
    42.3%
    46.9
    47.9%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q4W Ixekizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.006
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.20
    Confidence Interval (2-Sided) 95%
    1.26 to 3.84
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q2W Ixekizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.013
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.08
    Confidence Interval (2-Sided) 95%
    1.16 to 3.73
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS)
    Description ASDAS is a composite index to assess disease activity in AS. 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 scores indicated higher disease activity. Least Square (LS) mean was determined by mixed-model repeated measures (MMRM) with treatment, geographic region, baseline CRP status, number of prior tumor necrosis factor inhibitor (TNFi), baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.
    Time Frame Baseline, Week 16

    Outcome Measure Data

    Analysis Population Description
    All randomized participants.
    Arm/Group Title Placebo 80 mg Q4W Ixekizumab 80 mg Q2W Ixekizumab
    Arm/Group Description Participants received placebo every 2 weeks by subcutaneous injection. Participants received starting dose of 80 or 160 mg ixekizumab by SC injection at baseline followed by 80 mg ixekizumab given SC every four weeks (Q4W). Participants received starting dose of 80 or 160 mg ixekizumab given SC injection at baseline followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 16.
    Measure Participants 104 114 98
    Least Squares Mean (Standard Error) [Units on a scale]
    -0.11
    (0.099)
    -1.16
    (0.094)
    -1.13
    (0.103)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q4W Ixekizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
    Estimated Value -1.05
    Confidence Interval (2-Sided) 95%
    -1.32 to -0.79
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.135
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q2W Ixekizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
    Estimated Value -1.03
    Confidence Interval (2-Sided) 95%
    -1.30 to -0.75
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.140
    Estimation Comments
    4. Secondary Outcome
    Title Percentage of Participants Achieving Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI50) Response
    Description The BASDAI is a participant-reported assessment consisting of 6 questions that relate to 5 major symptoms relevant to radiographic axial spondyloarthritis (rad-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. BASDAI50 represents an improvement of ≥50% of the BASDAI score from baseline.
    Time Frame Week 16

    Outcome Measure Data

    Analysis Population Description
    All randomized participants.
    Arm/Group Title Placebo 80 mg Q4W Ixekizumab 80 mg Q2W Ixekizumab
    Arm/Group Description Participants received placebo every 2 weeks by subcutaneous injection. Participants received starting dose of 80 or 160 mg ixekizumab by SC injection at baseline followed by 80 mg ixekizumab given SC every four weeks (Q4W). Participants received starting dose of 80 or 160 mg ixekizumab given SC injection at baseline followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 16.
    Measure Participants 104 114 98
    Number [Percentage of Participants]
    9.6
    9.2%
    21.9
    19.2%
    23.5
    24%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q4W Ixekizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.015
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.65
    Confidence Interval (2-Sided) 95%
    1.21 to 5.84
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q2W Ixekizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.010
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.90
    Confidence Interval (2-Sided) 95%
    1.29 to 6.49
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    Title Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
    Description The BASDAI is a participant-reported assessment consisting of 6 questions that relate to 5 major symptoms relevant to radiographic axial spondyloarthritis (rad-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. LSmean was determined by MMRM with factors for treatment, geographic region, baseline CRP status, number of prior TNFi, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.
    Time Frame Baseline, Week 16

    Outcome Measure Data

    Analysis Population Description
    All randomized participants.
    Arm/Group Title Placebo 80 mg Q4W Ixekizumab 80 mg Q2W Ixekizumab
    Arm/Group Description Participants received placebo every 2 weeks by subcutaneous injection. Participants received starting dose of 80 or 160 mg ixekizumab by SC injection at baseline followed by 80 mg ixekizumab given SC every four weeks (Q4W). Participants received starting dose of 80 or 160 mg ixekizumab given SC injection at baseline followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 16.
    Measure Participants 104 114 98
    Least Squares Mean (Standard Error) [Units on a scale]
    -0.92
    (0.212)
    -2.17
    (0.202)
    -2.09
    (0.221)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q4W Ixekizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
    Estimated Value -1.24
    Confidence Interval (2-Sided) 95%
    -1.81 to -0.67
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.291
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q2W Ixekizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
    Estimated Value -1.16
    Confidence Interval (2-Sided) 95%
    -1.76 to -0.57
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.301
    Estimation Comments
    6. Secondary Outcome
    Title Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI)
    Description The BASFI is a participant-reported assessment that establishes a participant's functional baseline and subsequent response to treatment. The BASFI is composed with 10 questions to assess the disease severity, including the first 8 questions regarding to functional anatomy related activities and the remaining 2 questions related to daily activities of AS participants. Participants respond to each question using an NRS scale (range 0 to 10). The BASFI score is the average of the 10 responses and has a possible minimum value of 0 and a possible maximum value of 10, with a higher score indicating worse function. LS mean was determined by MMRM with factors for treatment, geographic region, baseline CRP status, number of prior TNFi, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.
    Time Frame Baseline, Week 16

    Outcome Measure Data

    Analysis Population Description
    All randomized participants.
    Arm/Group Title Placebo 80 mg Q4W Ixekizumab 80 mg Q2W Ixekizumab
    Arm/Group Description Participants received placebo every 2 weeks by subcutaneous injection. Participants received starting dose of 80 or 160 mg ixekizumab by SC injection at baseline followed by 80 mg ixekizumab given SC every four weeks (Q4W). Participants received starting dose of 80 or 160 mg ixekizumab given SC injection at baseline followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 16.
    Measure Participants 104 114 98
    Least Squares Mean (Standard Error) [Units on a scale]
    -0.64
    (0.215)
    -1.69
    (0.205)
    -1.92
    (0.225)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q4W Ixekizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
    Estimated Value -1.05
    Confidence Interval (2-Sided) 95%
    -1.63 to -0.47
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.295
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q2W Ixekizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
    Estimated Value -1.28
    Confidence Interval (2-Sided) 95%
    -1.89 to -0.68
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.307
    Estimation Comments
    7. Secondary Outcome
    Title Percentage of Participants Achieving ASDAS Inactive Disease
    Description ASDAS is a composite index to assess disease activity in AS. ASDAS Inactive Disease is defined as a score of <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.
    Time Frame Week 16

    Outcome Measure Data

    Analysis Population Description
    All randomized participants.
    Arm/Group Title Placebo 80 mg Q4W Ixekizumab 80 mg Q2W Ixekizumab
    Arm/Group Description Participants received placebo every 2 weeks by subcutaneous injection. Participants received starting dose of 80 or 160 mg ixekizumab by SC injection at baseline followed by 80 mg ixekizumab given SC every four weeks (Q4W). Participants received starting dose of 80 or 160 mg ixekizumab given SC injection at baseline followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 16.
    Measure Participants 104 114 98
    Number [Percentage of Participants]
    1.0
    1%
    3.5
    3.1%
    5.1
    5.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q4W Ixekizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.242
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.73
    Confidence Interval (2-Sided) 95%
    0.41 to 33.98
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q2W Ixekizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.127
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 5.42
    Confidence Interval (2-Sided) 95%
    0.62 to 47.54
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    8. Secondary Outcome
    Title Percentage of Participants Achieving ASDAS <2.1
    Description ASDAS is a composite index to assess disease activity in AS. ASDAS <2.1 defines moderate disease activity. 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.
    Time Frame Week 16

    Outcome Measure Data

    Analysis Population Description
    All randomized participants.
    Arm/Group Title Placebo 80 mg Q4W Ixekizumab 80 mg Q2W Ixekizumab
    Arm/Group Description Participants received placebo every 2 weeks by subcutaneous injection. Participants received starting dose of 80 or 160 mg ixekizumab by SC injection at baseline followed by 80 mg ixekizumab given SC every four weeks (Q4W). Participants received starting dose of 80 or 160 mg ixekizumab given SC injection at baseline followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 16.
    Measure Participants 104 114 98
    Number [Percentage of Participants]
    4.8
    4.6%
    17.5
    15.4%
    16.3
    16.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q4W Ixekizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.006
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.22
    Confidence Interval (2-Sided) 95%
    1.50 to 11.86
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q2W Ixekizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.006
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.52
    Confidence Interval (2-Sided) 95%
    1.55 to 13.18
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    9. Secondary Outcome
    Title Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores
    Description The SF-36 is a 36-item participant 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 2 overarching domains of mental well- being and physical well-being are captured by the Mental Component Summary and Physical Component Summary scores. T-scores are used for analysis. The summary scores range from 0 to 100, with higher scores indicating better levels of function and/or better health. LSmean was determined by MMRM with factors for treatment, geographic region, baseline CRP status, number of prior TNFi, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.
    Time Frame Baseline, Week 16

    Outcome Measure Data

    Analysis Population Description
    All randomized participants.
    Arm/Group Title Placebo 80 mg Q4W Ixekizumab 80 mg Q2W Ixekizumab
    Arm/Group Description Participants received placebo every 2 weeks by subcutaneous injection. Participants received starting dose of 80 or 160 mg ixekizumab by SC injection at baseline followed by 80 mg ixekizumab given SC every four weeks (Q4W). Participants received starting dose of 80 or 160 mg ixekizumab given SC injection at baseline followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 16.
    Measure Participants 104 114 98
    SF-36 MCS
    2.7410
    (0.9452)
    3.5099
    (0.9074)
    3.6514
    (0.9921)
    SF-36 PCS
    1.3638
    (0.8146)
    6.5785
    (0.7763)
    6.1223
    (0.8465)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q4W Ixekizumab
    Comments MCS
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.550
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
    Estimated Value 0.7689
    Confidence Interval (2-Sided) 95%
    -1.7629 to 3.3007
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.2863
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q2W Ixekizumab
    Comments MCS
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.495
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
    Estimated Value 0.9104
    Confidence Interval (2-Sided) 95%
    -1.7151 to 3.5360
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.3338
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q4W Ixekizumab
    Comments PCS
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
    Estimated Value 5.2147
    Confidence Interval (2-Sided) 95%
    3.0204 to 7.4090
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.1149
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q2W Ixekizumab
    Comments PCS
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
    Estimated Value 4.7585
    Confidence Interval (2-Sided) 95%
    2.4940 to 7.0230
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.1505
    Estimation Comments
    10. Secondary Outcome
    Title Change From Baseline in ASAS Health Index (ASAS HI)
    Description The ASAS Health Index (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 1 question that the patient needs to respond to with either "I agree" (score 1) or "I do not agree (score 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 determined by MMRM with treatment, geographic region, baseline CRP status, number of prior TNFi, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.
    Time Frame Baseline, Week 16

    Outcome Measure Data

    Analysis Population Description
    All randomized participants.
    Arm/Group Title Placebo 80 mg Q4W Ixekizumab 80 mg Q2W Ixekizumab
    Arm/Group Description Participants received placebo every 2 weeks by subcutaneous injection. Participants received starting dose of 80 or 160 mg ixekizumab by SC injection at baseline followed by 80 mg ixekizumab given SC every four weeks (Q4W). Participants received starting dose of 80 or 160 mg ixekizumab given SC injection at baseline followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 16.
    Measure Participants 104 114 98
    Least Squares Mean (Standard Error) [Units on a scale]
    -0.89
    (0.338)
    -1.92
    (0.322)
    -1.58
    (0.352)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q4W Ixekizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.026
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
    Estimated Value -1.03
    Confidence Interval (2-Sided) 95%
    -1.94 to -0.13
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.460
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q2W Ixekizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.149
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
    Estimated Value -0.69
    Confidence Interval (2-Sided) 95%
    -1.63 to 0.25
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.477
    Estimation Comments
    11. Secondary Outcome
    Title Change From Baseline in Magnetic Resonance Imaging (MRI) of the Spine (Ankylosing Spondylitis Spinal Magnetic Resonance Imaging [ASSpiMRI] - Berlin Score)
    Description The study used MRI with fat-saturating techniques such as short tau inversion recovery (STIR) to look for the presence of bone marrow edema. The Berlin modification of Ankylosing Spondylitis spine MRI score for activity (ASspiMRI) scoring technique assesses inflammation in each of the 23 disco-vertebral units (DVU) of the spine (from C2 to S1), capturing bone marrow edema. Scores for each DVU range from 0-3 (0=normal; 1=minor bone marrow edema [less than or equal to 25% of DVU; 3=severe bone marrow edema (more that 50% of DVU)]. The composite score ranges from 0 to 69, with higher scores reflecting worse disease.LS mean was determined by analysis of covariance (ANCOVA) with treatment, geographic region, baseline CRP status, number of prior TNF inhibitors used and baseline value as fixed factors.
    Time Frame Baseline, Week 16

    Outcome Measure Data

    Analysis Population Description
    All randomized participants with baseline and week 16 ASSpiMRI score.
    Arm/Group Title Placebo 80 mg Q4W Ixekizumab 80 mg Q2W Ixekizumab
    Arm/Group Description Participants received placebo every 2 weeks by subcutaneous injection. Participants received starting dose of 80 or 160 mg ixekizumab by SC injection at baseline followed by 80 mg ixekizumab given SC every four weeks (Q4W). Participants received starting dose of 80 or 160 mg ixekizumab given SC injection at baseline followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 16.
    Measure Participants 46 49 45
    Least Squares Mean (Standard Error) [Units on a scale]
    1.03
    (0.379)
    -0.92
    (0.373)
    -1.14
    (0.414)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q4W Ixekizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
    Estimated Value -1.95
    Confidence Interval (2-Sided) 95%
    -3.0 to -0.9
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.512
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q2W Ixekizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
    Estimated Value -2.17
    Confidence Interval (2-Sided) 95%
    -3.2 to -1.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.534
    Estimation Comments
    12. Secondary Outcome
    Title Change From Baseline in Magnetic Resonance Imaging (MRI) of the Spine (Spondyloarthritis Research Consortium of Canada [SPARCC] Score)
    Description MRI score of spine was assessed using SPARCC method. All 23 disco-vertebral units (DVU) of the spine (from C2 to S1) were scored for bone marrow edema. A single DVU has 18 scoring units, and each has score of 0 or 1, bringing the maximum total score to 414, the sum ranges from 0 to 414 with higher scores reflecting worse disease. Scoring was performed by central readers. LS mean was determined by ANCOVA with factors for treatment, geographic region, baseline CRP status, number of prior TNF inhibitors used and baseline value.
    Time Frame Baseline, Week 16

    Outcome Measure Data

    Analysis Population Description
    All randomized participants with baseline and week 16 SPARCC MRI score.
    Arm/Group Title Placebo 80 mg Q4W Ixekizumab 80 mg Q2W Ixekizumab
    Arm/Group Description Participants received placebo every 2 weeks by subcutaneous injection. Participants received starting dose of 80 or 160 mg ixekizumab by SC injection at baseline followed by 80 mg ixekizumab given SC every four weeks (Q4W). Participants received starting dose of 80 or 160 mg ixekizumab given SC injection at baseline followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 16.
    Measure Participants 46 49 45
    Least Squares Mean (Standard Error) [Units on a scale]
    3.29
    (1.402)
    -2.99
    (1.384)
    -3.97
    (1.534)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q4W Ixekizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
    Estimated Value -6.29
    Confidence Interval (2-Sided) 95%
    -10.0 to -2.5
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.896
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q2W Ixekizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
    Estimated Value -7.27
    Confidence Interval (2-Sided) 95%
    -11.2 to -3.4
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.978
    Estimation Comments
    13. Secondary Outcome
    Title Change From Baseline in the Measure of High Sensitivity C-Reactive Protein (CRP)
    Description High sensitivity CRP is the measure of acute phase reactant. It was measured with a high sensitivity assay at the central laboratory to help assess the effect of ixekizumab on disease activity. High sensitivity CRP is a sensitive laboratory assay for serum levels of C-Reactive Protein, which is a biomarker of inflammation. LS mean was determined by MMRM with treatment, geographic region, baseline CRP status, number of prior TNFi, visit, and treatment-by-visit interaction as fixed factors.
    Time Frame Baseline, Week 16

    Outcome Measure Data

    Analysis Population Description
    All randomized participants.
    Arm/Group Title Placebo 80 mg Q4W Ixekizumab 80 mg Q2W Ixekizumab
    Arm/Group Description Participants received placebo every 2 weeks by subcutaneous injection. Participants received starting dose of 80 or 160 mg ixekizumab by SC injection at baseline followed by 80 mg ixekizumab given SC every four weeks (Q4W). Participants received starting dose of 80 or 160 mg ixekizumab given SC injection at baseline followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 16.
    Measure Participants 104 114 98
    Least Squares Mean (Standard Error) [milligram per liter (mg/L)]
    9.719
    (2.7383)
    -11.096
    (2.6190)
    -8.121
    (2.8829)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q4W Ixekizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
    Estimated Value -20.816
    Confidence Interval (2-Sided) 95%
    -28.187 to -13.444
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.7463
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q2W Ixekizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
    Estimated Value -17.841
    Confidence Interval (2-Sided) 95%
    -25.518 to -10.163
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.9018
    Estimation Comments
    14. Secondary Outcome
    Title Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI)
    Description BASMI is a combined index comprising of 5 clinical measurements of spinal mobility in patients with radiographic axial spondyloarthritis (rad-axSpA). Lateral Spinal Flexion Tragus-to-wall distance Lumbar Flexion (modified Schober) Maximal intermalleolar distance and Cervical rotation. The BASMI linear result is the average of the 5 assessments and ranges from 0 to 10. The higher the BASMI score the more severe the patient's limitation of movement due to their AS. LS mean was determined by MMRM with treatment, geographic region, baseline CRP status, number of prior TNFi, baseline value, visit, baseline value-by-visit and treatment-by-visit interaction as fixed factors.
    Time Frame Baseline, Week 16

    Outcome Measure Data

    Analysis Population Description
    All randomized participants.
    Arm/Group Title Placebo 80 mg Q4W Ixekizumab 80 mg Q2W Ixekizumab
    Arm/Group Description Participants received placebo every 2 weeks by subcutaneous injection. Participants received starting dose of 80 or 160 mg ixekizumab by SC injection at baseline followed by 80 mg ixekizumab given SC every four weeks (Q4W). Participants received starting dose of 80 or 160 mg ixekizumab given SC injection at baseline followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 16.
    Measure Participants 104 114 98
    Least Squares Mean (Standard Error) [Units on a scale]
    -0.046
    (0.0939)
    -0.349
    (0.0897)
    -0.217
    (0.0981)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q4W Ixekizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.018
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
    Estimated Value -0.304
    Confidence Interval (2-Sided) 95%
    -0.555 to -0.053
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.1275
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q2W Ixekizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.194
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
    Estimated Value -0.172
    Confidence Interval (2-Sided) 95%
    -0.431 to 0.088
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.1319
    Estimation Comments
    15. Secondary Outcome
    Title Change From Baseline in Chest Expansion
    Description Chest expansion is the difference, in centimeter (cm), between the circumference of the chest in maximal inspiration and maximal expiration. While patients have their hands resting on or behind the head, the assessor will measure the chest encircled length by centimeter (cm) at the fourth intercostal level anteriorly. Two tries were recorded. The better measurement (larger difference) of 2 tries (in centimeters) was used for analyses. LS mean was determined by MMRM with treatment, geographic region, baseline CRP status, number of prior TNFi, baseline value, visit, baseline value-by-visit and treatment-by-visit interaction as fixed factors.
    Time Frame Baseline, Week 16

    Outcome Measure Data

    Analysis Population Description
    All randomized participants.
    Arm/Group Title Placebo 80 mg Q4W Ixekizumab 80 mg Q2W Ixekizumab
    Arm/Group Description Participants received placebo every 2 weeks by subcutaneous injection. Participants received starting dose of 80 or 160 mg ixekizumab by SC injection at baseline followed by 80 mg ixekizumab given SC every four weeks (Q4W). Participants received starting dose of 80 or 160 mg ixekizumab given SC injection at baseline followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 16.
    Measure Participants 104 114 98
    Least Squares Mean (Standard Error) [centimeter(cm)]
    0.04
    (0.644)
    1.27
    (0.618)
    0.27
    (0.655)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q4W Ixekizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.170
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
    Estimated Value 1.23
    Confidence Interval (2-Sided) 95%
    -0.53 to 2.99
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.893
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q2W Ixekizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.800
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
    Estimated Value 0.23
    Confidence Interval (2-Sided) 95%
    -1.57 to 2.04
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.916
    Estimation Comments
    16. Secondary Outcome
    Title Change From Baseline in Occiput to Wall Distance
    Description 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 determined by MMRM with factors for treatment, geographic region, baseline CRP status, number of prior TNFi, baseline value, visit, baseline value-by-visit and treatment-by-visit interaction as fixed factors.
    Time Frame Baseline, Week 16

    Outcome Measure Data

    Analysis Population Description
    All randomized participants.
    Arm/Group Title Placebo 80 mg Q4W Ixekizumab 80 mg Q2W Ixekizumab
    Arm/Group Description Participants received placebo every 2 weeks by subcutaneous injection. Participants received starting dose of 80 or 160 mg ixekizumab by SC injection at baseline followed by 80 mg ixekizumab given SC every four weeks (Q4W). Participants received starting dose of 80 or 160 mg ixekizumab given SC injection at baseline followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 16.
    Measure Participants 104 114 98
    Least Squares Mean (Standard Error) [cm]
    0.35
    (0.384)
    0.03
    (0.365)
    -0.65
    (0.399)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q4W Ixekizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.547
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
    Estimated Value -0.31
    Confidence Interval (2-Sided) 95%
    -1.34 to 0.71
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.521
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q2W Ixekizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.064
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
    Estimated Value -1.00
    Confidence Interval (2-Sided) 95%
    -2.06 to 0.06
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.538
    Estimation Comments
    17. Secondary Outcome
    Title Change From Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES)
    Description The 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 include costochondral 1 (right/left), costochondral 7 (right/left), spinal iliaca anterior superior (right/left), crista iliaca (right/left), spina iliaca posterior (right/left), processus spinosus L5, and Achilles tendon proximal insertion (right/left). The MASES is the sum of all site scores (range 0 to 13); higher scores indicate more severe enthesitis. LS mean was determined by MMRM with treatment, geographic region, baseline CRP status, number of prior TNFi, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.
    Time Frame Baseline, Week 16

    Outcome Measure Data

    Analysis Population Description
    All randomized participants with baseline MASES score > 0.
    Arm/Group Title Placebo 80 mg Q4W Ixekizumab 80 mg Q2W Ixekizumab
    Arm/Group Description Participants received placebo every 2 weeks by subcutaneous injection. Participants received starting dose of 80 or 160 mg ixekizumab by SC injection at baseline followed by 80 mg ixekizumab given SC every four weeks (Q4W). Participants received starting dose of 80 or 160 mg ixekizumab given SC injection at baseline followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 16.
    Measure Participants 69 82 74
    Least Squares Mean (Standard Error) [Units on a scale]
    -1.9
    (0.43)
    -1.8
    (0.40)
    -2.2
    (0.42)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q4W Ixekizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.861
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
    Estimated Value 0.1
    Confidence Interval (2-Sided) 95%
    -1.0 to 1.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.58
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q2W Ixekizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.626
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
    Estimated Value -0.3
    Confidence Interval (2-Sided) 95%
    -1.4 to 0.9
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.59
    Estimation Comments
    18. Secondary Outcome
    Title Change From Baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Score
    Description 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 determined by MMRM with treatment, geographic region, baseline CRP status, number of prior TNFi, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.
    Time Frame Baseline, Week 16

    Outcome Measure Data

    Analysis Population Description
    All randomized participants with baseline SPARCC Enthesitis score > 0.
    Arm/Group Title Placebo 80 mg Q4W Ixekizumab 80 mg Q2W Ixekizumab
    Arm/Group Description Participants received placebo every 2 weeks by subcutaneous injection. Participants received starting dose of 80 or 160 mg ixekizumab by SC injection at baseline followed by 80 mg ixekizumab given SC every four weeks (Q4W). Participants received starting dose of 80 or 160 mg ixekizumab given SC injection at baseline followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 16.
    Measure Participants 60 78 64
    Least Squares Mean (Standard Error) [Units on a scale]
    -1.9
    (0.44)
    -2.3
    (0.40)
    -1.8
    (0.45)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q4W Ixekizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.504
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
    Estimated Value -0.4
    Confidence Interval (2-Sided) 95%
    -1.6 to 0.8
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.59
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q2W Ixekizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.860
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
    Estimated Value 0.1
    Confidence Interval (2-Sided) 95%
    -1.1 to 1.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.62
    Estimation Comments
    19. Secondary Outcome
    Title Change From Baseline in Severity of Peripheral Arthritis by Tender Joint Count (TJC) Scores
    Description The number of tender and painful joints was determined by examination of 46 joints (23 joints on each side of the body). The 46 joints were assessed and classified as tender or not tender. Sum of all joints checked to be tender/painful divided by number of evaluable joints which was multiplied by 46 to obtain TJC score. The scores ranges from 0 (no tender/painful joints) to 46 (all joints tender/painful). LS mean was determined by MMRM with treatment, geographic region, baseline CRP status, number of prior TNFi, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction.
    Time Frame Baseline, Week 16

    Outcome Measure Data

    Analysis Population Description
    All randomized participants with baseline TJC > 0.
    Arm/Group Title Placebo 80 mg Q4W Ixekizumab 80 mg Q2W Ixekizumab
    Arm/Group Description Participants received placebo every 2 weeks by subcutaneous injection. Participants received starting dose of 80 or 160 mg ixekizumab by SC injection at baseline followed by 80 mg ixekizumab given SC every four weeks (Q4W). Participants received starting dose of 80 or 160 mg ixekizumab given SC injection at baseline followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 16.
    Measure Participants 65 85 69
    Least Squares Mean (Standard Error) [Tender Joint Count]
    -3.9
    (0.79)
    -4.8
    (0.69)
    -5.0
    (0.79)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q4W Ixekizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.362
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
    Estimated Value -0.9
    Confidence Interval (2-Sided) 95%
    -3.0 to 1.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.03
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q2W Ixekizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.303
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
    Estimated Value -1.1
    Confidence Interval (2-Sided) 95%
    -3.3 to 1.0
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.08
    Estimation Comments
    20. Secondary Outcome
    Title Change From Baseline in Severity of Peripheral Arthritis by Swollen Joint Count (SJC) Scores
    Description The number of swollen joints was determined by examination of 44 joints (22 joints on each side of the body). The 44 joints were assessed and classified as swollen or not swollen. Sum of all joints checked to be swollen divided by number of evaluable joints which was multiplied by 44 to obtain SJC score. The SJC score ranges from 0 (no swollen joints) to 44 (all joints swollen). LS mean was determined by MMRM with treatment, geographic region, baseline CRP status, number of prior TNFi, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction.
    Time Frame Baseline, Week 16

    Outcome Measure Data

    Analysis Population Description
    All randomized participants with baseline SJC > 0.
    Arm/Group Title Placebo 80 mg Q4W Ixekizumab 80 mg Q2W Ixekizumab
    Arm/Group Description Participants received placebo every 2 weeks by subcutaneous injection. Participants received starting dose of 80 or 160 mg ixekizumab by SC injection at baseline followed by 80 mg ixekizumab given SC every four weeks (Q4W). Participants received starting dose of 80 or 160 mg ixekizumab given SC injection at baseline followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 16.
    Measure Participants 45 48 44
    Least Squares Mean (Standard Error) [Swollen Joint Count]
    -2.4
    (0.51)
    -2.6
    (0.49)
    -3.0
    (0.54)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q4W Ixekizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.813
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
    Estimated Value -0.2
    Confidence Interval (2-Sided) 95%
    -1.5 to 1.2
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.70
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q2W Ixekizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.410
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
    Estimated Value -0.6
    Confidence Interval (2-Sided) 95%
    -2.0 to 0.8
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.71
    Estimation Comments
    21. Secondary Outcome
    Title Percentage of Participants With Anterior Uveitis
    Description 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.
    Time Frame Week 16

    Outcome Measure Data

    Analysis Population Description
    All randomized participants.
    Arm/Group Title Placebo 80 mg Q4W Ixekizumab 80 mg Q2W Ixekizumab
    Arm/Group Description Participants received placebo every 2 weeks by subcutaneous injection. Participants received starting dose of 80 or 160 mg ixekizumab by SC injection at baseline followed by 80 mg ixekizumab given SC every four weeks (Q4W). Participants received starting dose of 80 or 160 mg ixekizumab given SC injection at baseline followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 16.
    Measure Participants 104 114 98
    Number [Percentage of Participants]
    0
    0%
    1.8
    1.6%
    3.1
    3.2%
    22. Secondary Outcome
    Title Change From Baseline in the Fatigue Numeric Rating Scale (NRS) Score
    Description 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 1 number that describes their worst level of fatigue during the previous 24 hours. LS mean was determined by MMRM with treatment, geographic region, baseline CRP status, number of prior TNFi, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.
    Time Frame Baseline, Week 16

    Outcome Measure Data

    Analysis Population Description
    All randomized participants.
    Arm/Group Title Placebo 80 mg Q4W Ixekizumab 80 mg Q2W Ixekizumab
    Arm/Group Description Participants received placebo every 2 weeks by subcutaneous injection. Participants received starting dose of 80 or 160 mg ixekizumab by SC injection at baseline followed by 80 mg ixekizumab given SC every four weeks (Q4W). Participants received starting dose of 80 or 160 mg ixekizumab given SC injection at baseline followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 16.
    Measure Participants 104 114 98
    Least Squares Mean (Standard Error) [Units on a scale]
    -0.7
    (0.24)
    -2.0
    (0.23)
    -1.7
    (0.25)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q4W Ixekizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
    Estimated Value -1.2
    Confidence Interval (2-Sided) 95%
    -1.9 to -0.6
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.33
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q2W Ixekizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.005
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
    Estimated Value -1.0
    Confidence Interval (2-Sided) 95%
    -1.6 to -0.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.34
    Estimation Comments
    23. Secondary Outcome
    Title Change From Baseline in the Jenkins Sleep Evaluation Questionnaire (JSEQ)
    Description The 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 determined by MMRM with treatment, geographic region, baseline CRP status, number of prior TNFi, baseline value, visit, baseline value-by-visit and treatment-by-visit interaction as fixed factors.
    Time Frame Baseline, Week 16

    Outcome Measure Data

    Analysis Population Description
    All randomized participants.
    Arm/Group Title Placebo 80 mg Q4W Ixekizumab 80 mg Q2W Ixekizumab
    Arm/Group Description Participants received placebo every 2 weeks by subcutaneous injection. Participants received starting dose of 80 or 160 mg ixekizumab by SC injection at baseline followed by 80 mg ixekizumab given SC every four weeks (Q4W). Participants received starting dose of 80 or 160 mg ixekizumab given SC injection at baseline followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 16.
    Measure Participants 104 114 98
    Least Squares Mean (Standard Error) [Units on a scale]
    -1.8
    (0.50)
    -3.0
    (0.48)
    -2.4
    (0.52)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q4W Ixekizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.088
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
    Estimated Value -1.2
    Confidence Interval (2-Sided) 95%
    -2.5 to 0.2
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.68
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q2W Ixekizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.366
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
    Estimated Value -0.6
    Confidence Interval (2-Sided) 95%
    -2.0 to 0.7
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.70
    Estimation Comments
    24. Secondary Outcome
    Title Change From Baseline in the Work Productivity Activity Impairment Spondyloarthritis (WPAI-SpA) Scores
    Description 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 determined by ANCOVA with treatment, geographic region, baseline CRP status, number of prior TNFi and baseline value as fixed factors.
    Time Frame Baseline, Week 16

    Outcome Measure Data

    Analysis Population Description
    All randomized participants with baseline and week 16 WPAI-SpA score.
    Arm/Group Title Placebo 80 mg Q4W Ixekizumab 80 mg Q2W Ixekizumab
    Arm/Group Description Participants received placebo every 2 weeks by subcutaneous injection. Participants received starting dose of 80 or 160 mg ixekizumab by SC injection at baseline followed by 80 mg ixekizumab given SC every four weeks (Q4W). Participants received starting dose of 80 or 160 mg ixekizumab given SC injection at baseline followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 16.
    Measure Participants 99 112 96
    Overall Work Impairment Score
    -9.84
    (3.733)
    -20.97
    (4.016)
    -23.50
    (4.225)
    Percentage of Activity Impairment
    -10.1
    (2.60)
    -16.5
    (2.44)
    -18.4
    (2.74)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q4W Ixekizumab
    Comments Overall Work Impairment Score
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.038
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
    Estimated Value -11.13
    Confidence Interval (2-Sided) 95%
    -21.65 to -0.60
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.323
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q2W Ixekizumab
    Comments Overall Work Impairment Score
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.012
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
    Estimated Value -13.66
    Confidence Interval (2-Sided) 95%
    -24.23 to -3.10
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.341
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q4W Ixekizumab
    Comments Percentage of Activity Impairment
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.071
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
    Estimated Value -6.3
    Confidence Interval (2-Sided) 95%
    -13.2 to 0.5
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.50
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, 80 mg Q2W Ixekizumab
    Comments Percentage of Activity Impairment
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.024
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
    Estimated Value -8.3
    Confidence Interval (2-Sided) 95%
    -15.5 to -1.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.65
    Estimation Comments
    25. Secondary Outcome
    Title Change From Baseline in ASAS-Nonsteroidal Anti-Inflammatory Drug (NSAID) Score
    Description 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, higher the score greated the NSAID intake. ASAS-NSAID score= (equivalent NSAID score) x (days of intake during PI) x (days per week)/(PI in days).
    Time Frame Baseline, Week 52

    Outcome Measure Data

    Analysis Population Description
    Participants from extended treatment period who had NSAID Intake at baseline.
    Arm/Group Title PBO/IXE IXE80Q4W/IXE80Q4W IXE80Q2W/IXE80Q2W
    Arm/Group Description Blinded Treatment Dosing Period: Participants received placebo every two weeks (Q2W) by subcutaneous (SC) injection during Week 0 to 16. Extended Treatment Period: Participants who received Placebo in blinded treatment period were re-randomized to receive ixekizumab 80 mg Q4W or 80 mg Q2W at a 1:1 ratio. Blinded Treatment Dosing Period: Participants received starting dose of 80 or 160 mg ixekizumab given SC at baseline followed by 80 mg ixekizumab given SC every four weeks (Q4W) up to week 16. Extended Treatment Period: Participants received 80 mg ixekizumab given SC Q4W from week 16 to week 52. Blinded Treatment Dosing Period: Participants received starting dose of 80 or 160 milligrams (mg) ixekizumab given subcutaneously (SC) at baseline followed by 80 mg ixekizumab given SC every two weeks (Q2W) up to week 16. Extended Treatment Period: Participants received 80 mg ixekizumab given SC Q2W from week 16 to week 52.
    Measure Participants 69 71 58
    Mean (Standard Deviation) [Units on a scale]
    -9.84
    (34.435)
    -5.52
    (19.553)
    -2.33
    (24.019)
    26. Secondary Outcome
    Title Percentage of Participants With Anti-Ixekizumab Antibodies
    Description A treatment emergent - antidrug antibody (TE-ADA) positive patient is defined as: a) a patient with a >= 4-fold increase over a positive baseline antibody titer; or b) for a negative baseline titer, a patient with an increase from the baseline to a level of >= 1:10. Percentage was calculated based on the number of evaluable participants and was calculated by number of participants with treatment-emergent positive anti-ixekizumab antibodies / number of evaluable participants * 100%.
    Time Frame Week 16

    Outcome Measure Data

    Analysis Population Description
    All randomized participants.
    Arm/Group Title Placebo 80 mg Q4W Ixekizumab 80 mg Q2W Ixekizumab
    Arm/Group Description Participants received placebo every 2 weeks by subcutaneous injection. Participants received starting dose of 80 or 160 mg ixekizumab by SC injection at baseline followed by 80 mg ixekizumab given SC every four weeks (Q4W). Participants received starting dose of 80 or 160 mg ixekizumab given SC injection at baseline followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 16.
    Measure Participants 104 113 98
    Number [Percentage of Participants]
    2.9
    2.8%
    7.1
    6.2%
    4.1
    4.2%
    27. Secondary Outcome
    Title Pharmacokinetics (PK): Trough Ixekizumab Concentration at Steady State (Ctrough ss)
    Description Pharmacokinetics (PK): Steady-state trough serum concentration of Ixekizumab at week 16.
    Time Frame Week 16

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received study drug and have evaluable PK data.
    Arm/Group Title 80 mg Q4W Ixekizumab (Starting Dose 80 mg) 80 mg Q4W Ixekizumab (Starting Dose 160 mg) 80 mg Q2W Ixekizumab (Starting Dose 80 mg) 80 mg Q2W Ixekizumab (Starting Dose 160 mg)
    Arm/Group Description Participants received 80 mg of Ixekizumab every four weeks by subcutaneous injection. Participants received 160 mg ixekizumab at baseline followed by 80 mg ixekizumab given SC every four weeks by subcutaneous injection. Participants received 80 mg ixekizumab every two weeks by subcutaneous injection. Participants received starting dose of 160 mg ixekizumab at baseline followed by 80 mg ixekizumab every two weeks by subcutaneous injection.
    Measure Participants 60 54 48 50
    Geometric Mean (Geometric Coefficient of Variation) [Microgram per milliliters (µg/mL)]
    2.10
    (106)
    2.47
    (101)
    6.27
    (158)
    8.52
    (50)

    Adverse Events

    Time Frame Up To 76 Weeks
    Adverse Event Reporting Description All randomized participants. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
    Arm/Group Title 80 mg Q2W Ixekizumab-Blinded Treatment Period 80 mg Q4W Ixekizumab-Blinded Treatment Period PBO-Blinded Treatment Period IXE80Q2W/IXE80Q2W-Extended Treatment Period IXE80Q4W/IXE80Q4W-Extended Treatment Period PBO/IXE-Extended Treatment Period IXE80Q2W-Follow-up Period IXE80Q4W-Follow-up Period PBO-Follow-up Period
    Arm/Group Description Participants received starting dose of 80 or 160 milligrams (mg) ixekizumab given subcutaneously (SC) at baseline followed by 80 mg ixekizumab given SC every two weeks (Q2W) up to week 16. Participants received starting dose of 80 or 160 mg ixekizumab given SC at baseline followed by 80 mg ixekizumab given SC every four weeks (Q4W) up to week 16. Participants received placebo every two weeks (Q2W) by subcutaneous (SC) injection during Week 0 to 16. Participants received 80 mg ixekizumab given SC Q2W from week 16 to week 52. Participants received 80 mg ixekizumab given SC Q4W from week 16 to week 52. Participants received 80 mg ixekizumab given SC Q4W from week 16 to week 52. Participants did not receive any intervention during post-treatment follow-up period. Participants did not receive any intervention during post-treatment follow-up period. Participants did not receive any intervention during post-treatment follow-up period.
    All Cause Mortality
    80 mg Q2W Ixekizumab-Blinded Treatment Period 80 mg Q4W Ixekizumab-Blinded Treatment Period PBO-Blinded Treatment Period IXE80Q2W/IXE80Q2W-Extended Treatment Period IXE80Q4W/IXE80Q4W-Extended Treatment Period PBO/IXE-Extended Treatment Period IXE80Q2W-Follow-up Period IXE80Q4W-Follow-up Period PBO-Follow-up Period
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/98 (1%) 0/114 (0%) 0/104 (0%) 0/90 (0%) 0/98 (0%) 0/93 (0%) 0/22 (0%) 0/34 (0%) 0/5 (0%)
    Serious Adverse Events
    80 mg Q2W Ixekizumab-Blinded Treatment Period 80 mg Q4W Ixekizumab-Blinded Treatment Period PBO-Blinded Treatment Period IXE80Q2W/IXE80Q2W-Extended Treatment Period IXE80Q4W/IXE80Q4W-Extended Treatment Period PBO/IXE-Extended Treatment Period IXE80Q2W-Follow-up Period IXE80Q4W-Follow-up Period PBO-Follow-up Period
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/98 (3.1%) 4/114 (3.5%) 5/104 (4.8%) 1/90 (1.1%) 2/98 (2%) 6/93 (6.5%) 1/22 (4.5%) 2/34 (5.9%) 0/5 (0%)
    Cardiac disorders
    Acute myocardial infarction 0/98 (0%) 0 0/114 (0%) 0 0/104 (0%) 0 0/90 (0%) 0 0/98 (0%) 0 1/93 (1.1%) 1 0/22 (0%) 0 0/34 (0%) 0 0/5 (0%) 0
    Atrial tachycardia 1/98 (1%) 1 0/114 (0%) 0 0/104 (0%) 0 0/90 (0%) 0 0/98 (0%) 0 0/93 (0%) 0 0/22 (0%) 0 0/34 (0%) 0 0/5 (0%) 0
    Bradycardia 0/98 (0%) 0 0/114 (0%) 0 0/104 (0%) 0 0/90 (0%) 0 1/98 (1%) 1 1/93 (1.1%) 1 0/22 (0%) 0 0/34 (0%) 0 0/5 (0%) 0
    Gastrointestinal disorders
    Colitis ulcerative 0/98 (0%) 0 0/114 (0%) 0 1/104 (1%) 1 0/90 (0%) 0 0/98 (0%) 0 0/93 (0%) 0 0/22 (0%) 0 0/34 (0%) 0 0/5 (0%) 0
    Crohn's disease 0/98 (0%) 0 1/114 (0.9%) 1 0/104 (0%) 0 0/90 (0%) 0 0/98 (0%) 0 0/93 (0%) 0 0/22 (0%) 0 0/34 (0%) 0 0/5 (0%) 0
    Inguinal hernia 0/98 (0%) 0 0/114 (0%) 0 1/104 (1%) 1 0/90 (0%) 0 0/98 (0%) 0 1/93 (1.1%) 1 0/22 (0%) 0 0/34 (0%) 0 0/5 (0%) 0
    Infections and infestations
    Gastroenteritis 0/98 (0%) 0 0/114 (0%) 0 0/104 (0%) 0 1/90 (1.1%) 2 0/98 (0%) 0 0/93 (0%) 0 0/22 (0%) 0 0/34 (0%) 0 0/5 (0%) 0
    Peritonitis 0/98 (0%) 0 1/114 (0.9%) 1 0/104 (0%) 0 0/90 (0%) 0 0/98 (0%) 0 0/93 (0%) 0 0/22 (0%) 0 0/34 (0%) 0 0/5 (0%) 0
    Pharyngitis 0/98 (0%) 0 1/114 (0.9%) 1 0/104 (0%) 0 0/90 (0%) 0 0/98 (0%) 0 0/93 (0%) 0 0/22 (0%) 0 0/34 (0%) 0 0/5 (0%) 0
    Pneumonia 0/98 (0%) 0 0/114 (0%) 0 0/104 (0%) 0 0/90 (0%) 0 0/98 (0%) 0 1/93 (1.1%) 1 0/22 (0%) 0 0/34 (0%) 0 0/5 (0%) 0
    Sinusitis 0/98 (0%) 0 0/114 (0%) 0 0/104 (0%) 0 0/90 (0%) 0 0/98 (0%) 0 1/93 (1.1%) 1 0/22 (0%) 0 0/34 (0%) 0 0/5 (0%) 0
    Injury, poisoning and procedural complications
    Femur fracture 0/98 (0%) 0 0/114 (0%) 0 1/104 (1%) 1 0/90 (0%) 0 0/98 (0%) 0 0/93 (0%) 0 0/22 (0%) 0 0/34 (0%) 0 0/5 (0%) 0
    Investigations
    Blood creatine phosphokinase increased 1/98 (1%) 1 0/114 (0%) 0 0/104 (0%) 0 0/90 (0%) 0 0/98 (0%) 0 0/93 (0%) 0 0/22 (0%) 0 0/34 (0%) 0 0/5 (0%) 0
    Metabolism and nutrition disorders
    Hyperkalaemia 0/98 (0%) 0 0/114 (0%) 0 0/104 (0%) 0 0/90 (0%) 0 1/98 (1%) 1 0/93 (0%) 0 0/22 (0%) 0 0/34 (0%) 0 0/5 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthritis 0/98 (0%) 0 0/114 (0%) 0 1/104 (1%) 2 0/90 (0%) 0 0/98 (0%) 0 0/93 (0%) 0 0/22 (0%) 0 0/34 (0%) 0 0/5 (0%) 0
    Fracture pain 0/98 (0%) 0 1/114 (0.9%) 1 0/104 (0%) 0 0/90 (0%) 0 0/98 (0%) 0 0/93 (0%) 0 0/22 (0%) 0 0/34 (0%) 0 0/5 (0%) 0
    Osteoarthritis 0/98 (0%) 0 0/114 (0%) 0 0/104 (0%) 0 0/90 (0%) 0 0/98 (0%) 0 1/93 (1.1%) 1 0/22 (0%) 0 0/34 (0%) 0 0/5 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute promyelocytic leukaemia 0/98 (0%) 0 0/114 (0%) 0 0/104 (0%) 0 0/90 (0%) 0 0/98 (0%) 0 0/93 (0%) 0 0/22 (0%) 0 1/34 (2.9%) 1 0/5 (0%) 0
    Lung adenocarcinoma 0/98 (0%) 0 0/114 (0%) 0 0/104 (0%) 0 0/90 (0%) 0 0/98 (0%) 0 0/93 (0%) 0 1/22 (4.5%) 1 0/34 (0%) 0 0/5 (0%) 0
    Nervous system disorders
    Drop attacks 0/98 (0%) 0 0/114 (0%) 0 0/104 (0%) 0 0/90 (0%) 0 0/98 (0%) 0 1/93 (1.1%) 1 0/22 (0%) 0 0/34 (0%) 0 0/5 (0%) 0
    Loss of consciousness 0/98 (0%) 0 0/114 (0%) 0 0/104 (0%) 0 0/90 (0%) 0 0/98 (0%) 0 0/93 (0%) 0 0/22 (0%) 0 1/34 (2.9%) 1 0/5 (0%) 0
    Meralgia paraesthetica 0/98 (0%) 0 0/114 (0%) 0 0/104 (0%) 0 0/90 (0%) 0 0/98 (0%) 0 1/93 (1.1%) 1 0/22 (0%) 0 0/34 (0%) 0 0/5 (0%) 0
    Syncope 0/98 (0%) 0 0/114 (0%) 0 0/104 (0%) 0 0/90 (0%) 0 0/98 (0%) 0 0/93 (0%) 0 0/22 (0%) 0 1/34 (2.9%) 1 0/5 (0%) 0
    Psychiatric disorders
    Completed suicide 1/98 (1%) 1 0/114 (0%) 0 0/104 (0%) 0 0/90 (0%) 0 0/98 (0%) 0 0/93 (0%) 0 0/22 (0%) 0 0/34 (0%) 0 0/5 (0%) 0
    Depression 1/98 (1%) 1 0/114 (0%) 0 0/104 (0%) 0 0/90 (0%) 0 0/98 (0%) 0 0/93 (0%) 0 0/22 (0%) 0 0/34 (0%) 0 0/5 (0%) 0
    Renal and urinary disorders
    Acute kidney injury 0/98 (0%) 0 0/114 (0%) 0 0/104 (0%) 0 0/90 (0%) 0 1/98 (1%) 1 0/93 (0%) 0 0/22 (0%) 0 0/34 (0%) 0 0/5 (0%) 0
    Urinary retention 0/98 (0%) 0 0/114 (0%) 0 0/104 (0%) 0 0/90 (0%) 0 1/98 (1%) 1 0/93 (0%) 0 0/22 (0%) 0 0/34 (0%) 0 0/5 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 0/98 (0%) 0 0/114 (0%) 0 0/104 (0%) 0 0/90 (0%) 0 0/98 (0%) 0 1/93 (1.1%) 1 0/22 (0%) 0 0/34 (0%) 0 0/5 (0%) 0
    Pulmonary embolism 0/98 (0%) 0 0/114 (0%) 0 0/104 (0%) 0 0/90 (0%) 0 0/98 (0%) 0 0/93 (0%) 0 0/22 (0%) 0 1/34 (2.9%) 1 0/5 (0%) 0
    Vascular disorders
    Vasculitis 0/98 (0%) 0 0/114 (0%) 0 1/104 (1%) 1 0/90 (0%) 0 0/98 (0%) 0 0/93 (0%) 0 0/22 (0%) 0 0/34 (0%) 0 0/5 (0%) 0
    Other (Not Including Serious) Adverse Events
    80 mg Q2W Ixekizumab-Blinded Treatment Period 80 mg Q4W Ixekizumab-Blinded Treatment Period PBO-Blinded Treatment Period IXE80Q2W/IXE80Q2W-Extended Treatment Period IXE80Q4W/IXE80Q4W-Extended Treatment Period PBO/IXE-Extended Treatment Period IXE80Q2W-Follow-up Period IXE80Q4W-Follow-up Period PBO-Follow-up Period
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 25/98 (25.5%) 25/114 (21.9%) 12/104 (11.5%) 26/90 (28.9%) 19/98 (19.4%) 19/93 (20.4%) 1/22 (4.5%) 3/34 (8.8%) 1/5 (20%)
    Gastrointestinal disorders
    Diarrhoea 4/98 (4.1%) 4 6/114 (5.3%) 6 0/104 (0%) 0 2/90 (2.2%) 2 1/98 (1%) 1 3/93 (3.2%) 3 0/22 (0%) 0 0/34 (0%) 0 0/5 (0%) 0
    General disorders
    Injection site reaction 8/98 (8.2%) 21 3/114 (2.6%) 5 1/104 (1%) 1 5/90 (5.6%) 14 2/98 (2%) 2 3/93 (3.2%) 9 0/22 (0%) 0 0/34 (0%) 0 0/5 (0%) 0
    Infections and infestations
    Nasopharyngitis 4/98 (4.1%) 4 5/114 (4.4%) 5 2/104 (1.9%) 2 4/90 (4.4%) 4 3/98 (3.1%) 3 3/93 (3.2%) 3 0/22 (0%) 0 2/34 (5.9%) 2 0/5 (0%) 0
    Upper respiratory tract infection 4/98 (4.1%) 4 9/114 (7.9%) 12 3/104 (2.9%) 3 8/90 (8.9%) 10 4/98 (4.1%) 4 5/93 (5.4%) 5 0/22 (0%) 0 0/34 (0%) 0 0/5 (0%) 0
    Urinary tract infection 2/98 (2%) 2 0/114 (0%) 0 0/104 (0%) 0 5/90 (5.6%) 5 2/98 (2%) 2 2/93 (2.2%) 2 0/22 (0%) 0 0/34 (0%) 0 0/5 (0%) 0
    Vulvovaginal candidiasis 0/23 (0%) 0 0/23 (0%) 0 0/17 (0%) 0 0/22 (0%) 0 0/17 (0%) 0 1/16 (6.3%) 1 0/4 (0%) 0 0/9 (0%) 0 0/1 (0%) 0
    Investigations
    Blood triglycerides increased 0/98 (0%) 0 0/114 (0%) 0 1/104 (1%) 1 1/90 (1.1%) 1 0/98 (0%) 0 1/93 (1.1%) 1 0/22 (0%) 0 0/34 (0%) 0 1/5 (20%) 1
    Musculoskeletal and connective tissue disorders
    Arthralgia 3/98 (3.1%) 3 7/114 (6.1%) 8 4/104 (3.8%) 4 2/90 (2.2%) 2 4/98 (4.1%) 4 4/93 (4.3%) 5 1/22 (4.5%) 2 1/34 (2.9%) 1 0/5 (0%) 0
    Back pain 3/98 (3.1%) 3 1/114 (0.9%) 1 2/104 (1.9%) 2 5/90 (5.6%) 5 6/98 (6.1%) 8 0/93 (0%) 0 0/22 (0%) 0 0/34 (0%) 0 0/5 (0%) 0
    Reproductive system and breast disorders
    Vulvovaginal burning sensation 0/23 (0%) 0 0/23 (0%) 0 0/17 (0%) 0 0/22 (0%) 0 1/17 (5.9%) 1 0/16 (0%) 0 0/4 (0%) 0 0/9 (0%) 0 0/1 (0%) 0
    Vulvovaginal dryness 0/23 (0%) 0 0/23 (0%) 0 0/17 (0%) 0 0/22 (0%) 0 1/17 (5.9%) 1 0/16 (0%) 0 0/4 (0%) 0 0/9 (0%) 0 0/1 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Chief Medical Officer
    Organization Eli Lilly and Company
    Phone 800-545-5979
    Email ClinicalTrials.gov@lilly.com
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT02696798
    Other Study ID Numbers:
    • 16179
    • I1F-MC-RHBW
    • 2015-003937-84
    First Posted:
    Mar 2, 2016
    Last Update Posted:
    Jun 17, 2020
    Last Verified:
    Jun 1, 2020