A Study of Ixekizumab (LY2439821) in Chinese Participants With Radiographic Axial Spondyloarthritis

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04285229
• Collaborator: (none)
• Enrollment: 147
• Locations: 19
• Arms: 2
• Actual Duration (Months): 23.2
• Patients Per Site: 7.7
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The main purpose of this study is to evaluate the efficacy and safety of ixekizumab in Chinese participants with radiographic axial spondyloarthritis (r-axSpA).

Condition or Disease	Intervention/Treatment	Phase
Spondyloarthritis	Drug: Ixekizumab; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 147 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-Blind and Placebo-Controlled 16-Week Study Followed by Long Term Evaluation of Efficacy and Safety of Ixekizumab (LY2439821) in Chinese Patients With Radiographic Axial Spondyloarthritis
• Actual Study Start Date: Apr 10, 2020
• Actual Primary Completion Date: Mar 31, 2021
• Actual Study Completion Date: Mar 17, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ixekizumab Participants received starting dose of 160 milligrams (mg) Ixekizumab at week 0 followed by 80 mg Ixekizumab once every four weeks (Q4W) by subcutaneous injection.	Drug: Ixekizumab; Administered SC; Other Names: LY2439821
Placebo Comparator: Placebo Participants received placebo every four weeks (Q4W) by subcutaneous (SC)injection.	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 in Biological Disease-modifying Antirheumatic Drug (bDMARD)-naïve Participants [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 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).

2. 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).

3. 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, baseline C-reactive protein (CRP) status, Tumor necrosis factor (TNF) inhibitors experience, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.

4. Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Response [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. LS mean was determined by MMRM with treatment, baseline CRP status, TNF inhibitors experience, 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 treatment, baseline CRP status, TNF inhibitors experience, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.

6. 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, baseline CRP status, TNF inhibitors experience, and baseline value.

7. Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) Score [Baseline, Week 16]

   SF-36 consists of 36 questions measuring 8 health domains: physical functioning, bodily pain, role limitations due to physical problems, role limitations due to emotional problems, general health perceptions, mental health, social function, and vitality. The patient's responses are solicited using Likert scales that vary in length, with 3-6 response options per item. The SF-36 can be scored into the 8 health domains named above and two overall summary scores: physical component summary (PCS) and mental component summary (MCS) scores. The domain and summary scores range from 0 to 100; higher scores indicate better levels of function and/or better health. LS mean was determined by MMRM with factors for treatment, baseline CRP status, TNF inhibitors experience, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.

8. Change From Baseline in 36-Item SF-36 Mental Component Summary (MCS) Score [Baseline, Week 16]

   SF-36 consists of 36 questions measuring 8 health domains: physical functioning, bodily pain, role limitations due to physical problems, role limitations due to emotional problems, general health perceptions, mental health, social function, and vitality. The patient's responses are solicited using Likert scales that vary in length, with 3-6 response options per item. The SF-36 can be scored into the 8 health domains named above and two overall summary scores: physical component summary (PCS) and mental component summary (MCS) scores. The domain and summary scores range from 0 to 100; higher scores indicate better levels of function and/or better health. LS mean was determined by MMRM with factors for treatment, baseline CRP status, TNF inhibitors experience, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.

9. 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, baseline CRP status, TNF inhibitors experience, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.

10. Change From Baseline in Mobility on the 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, baseline CRP status, TNF inhibitors experience, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.

11. 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, baseline CRP status, TNF inhibitors experience, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.

12. Change From Baseline in MRI Sacroiliac Joint(s) (SIJ) Spondyloarthritis Research Consortium of Canada (SPARCC) 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 ANCOVA with factors for treatment, baseline CRP status, TNF inhibitors experience, and baseline value.

13. Number of Participants With Anterior Uveitis [Baseline through 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.

14. 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 greater the NSAID intake. ASAS-NSAID score= (equivalent NSAID score) x (days of intake during PI) x (days per week)/(PI in days).

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

    A treatment emergent - antidrug antibody (TE-ADA) positive participant is defined as: a) a participant with a >= 4-fold increase over a positive baseline antibody titer; or b) for a negative baseline titer, a participant 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%.

16. 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:

• Have an established diagnosis of radiographic axial spondyloarthritis (r-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.

• Biologic naïve or have had prior treatment with 1 tumor necrosis factor (TNF) inhibitor.

• 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 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.

• 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	Afflilated Hospital of Bengbu Medical College	Bengbu	Anhui	China	233004
2	Anhui Provincial Hospital	Hefei	Anhui	China	230001
3	Sun Yat-sen Memorial Hospital, Sun Yat-sen University	Guangzhou	Guangdong	China	510120
4	Shenzhen People's Hospital	Shenzhen	Guangdong	China	518020
5	1st Hospital affiliated to Medical College of Shantou Univer	Shantou	Guangzhou	China	515041
6	Wuhan Union Hospital	Wuhan	Hubei	China	430022
7	Wu Han Tongji Hospital	Wuhan	Hubei	China	430030
8	ZhuZhou Central Hospital	ZhuZhou	Hunan	China	412007
9	The First Affiliated Hospital of Baotou Medical College	Baotou	Inner Mongolia	China	014000
10	Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School	Nanjing	Jiangsu	China	210000
11	Jiangsu Province Hospital	Nanjing	Jiangsu	China	210029
12	Pingxiang People's Hospital	Pingxiang	Jiangxi	China	337000
13	HuaShan Hospital Affiliated To Fudan University	Shanghai	Shanghai	China	20040
14	West China Hospital Sichuan University	Chengdu	Sichuan	China	610041
15	People's Hospital of Xinjiang Uygur Autonomous Region	Urumqi	Xinjiang	China	830001
16	First Affiliated Hospital of Kunming Medical University	Kunming	Yunnan	China	650032
17	The Second Affiliated Hospital of Zhejiang University School of Medicine	Hangzhou	Zhejiang	China	310009
18	Peking University First Hospital	Beijing		China	100034
19	Beijing Hospital	Beijing		China	100730

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)

• Study Protocol - Jun 20, 2019
• Statistical Analysis Plan - Apr 28, 2021

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT04285229
• Other Study ID Numbers: 16721; I1F-MC-RHCH
• First Posted: Feb 26, 2020
• Last Update Posted: Jun 28, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Eli Lilly and Company: Ankylosing spondylitis
• Additional relevant MeSH terms: Spondylitis; Spondylarthritis; Ixekizumab

Study Results

Participant Flow

Recruitment Details	Double-Blind Treatment Period (Week 0 to Week 16), Extended Treatment Period (Week 16 to Week 52) and follow-up period (Early Termination Visit (ETV) +12 Weeks). The reported data is for primary outcome, data beyond Week 16 is in analysis stage and will be submitted with final results.

Arm/Group Title	Placebo	Ixekizumab 80mg Q4W
Arm/Group Description	Participants received placebo every four weeks (Q4W) by subcutaneous (SC) injection.	Participants received starting dose of 160 milligrams (mg) Ixekizumab at week 0 followed by 80mg Ixekizumab once every four weeks (Q4W) by subcutaneous injection.
Period Title: Overall Study
STARTED	73	74
Received at Least One Dose of Study Drug	73	74
COMPLETED	70	72
NOT COMPLETED	3	2

Baseline Characteristics

Arm/Group Title	Placebo	Ixekizumab 80mg Q4W	Total
Arm/Group Description	Participants received placebo every four weeks (Q4W) by subcutaneous (SC) injection.	Participants received starting dose of 160 milligrams (mg) Ixekizumab at week 0 followed by 80 mg Ixekizumab once every four weeks (Q4W) by subcutaneous injection.	Total of all reporting groups
Overall Participants	73	74	147
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	34.4 (8.98)	33.5 (8.89)	33.9 (8.92)
Sex: Female, Male (Count of Participants)
Female	8 11%	10 13.5%	18 12.2%
Male	65 89%	64 86.5%	129 87.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	73 100%	74 100%	147 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	73 100%	74 100%	147 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
China	73 100%	74 100%	147 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Achieving an Assessment of Spondyloarthritis International Society 40 (ASAS40) Response in Biological Disease-modifying Antirheumatic Drug (bDMARD)-naïve Participants
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 from bDMARD-naïve who had data for ASAS40.

Arm/Group Title	Placebo	Ixekizumab 80mg Q4W
Arm/Group Description	Participants received placebo every four weeks (Q4W) by subcutaneous (SC) injection.	Participants received starting dose of 160 milligrams (mg) Ixekizumab at week 0 followed by 80mg Ixekizumab once every four weeks (Q4W) by subcutaneous injection.
Measure Participants	64	66
Number [Percentage of Participants]	7.8 10.7%	40.9 55.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80mg Q4W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	7.64
	Confidence Interval	(2-Sided) 95%; 2.68 to 21.76
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants Achieving an 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	Ixekizumab 80mg Q4W
Arm/Group Description	Participants received placebo every four weeks (Q4W) by subcutaneous (SC) injection.	Participants received starting dose of 160 milligrams (mg) Ixekizumab at week 0 followed by 80mg Ixekizumab once every four weeks (Q4W) by subcutaneous injection.
Measure Participants	73	74
Number [Percentage of Participants]	8.2 11.2%	37.8 51.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80mg Q4W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	6.40
	Confidence Interval	(2-Sided) 95%; 2.42 to 16.90
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. 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	Ixekizumab 80mg Q4W
Arm/Group Description	Participants received placebo every four weeks (Q4W) by subcutaneous (SC)injection.	Participants received starting dose of 160 milligrams (mg) Ixekizumab at week 0 followed by 80mg Ixekizumab once every four weeks (Q4W) by subcutaneous injection.
Measure Participants	73	74
Number [Percentage of Participants]	35.6 48.8%	59.5 80.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80mg Q4W
	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	2.58
	Confidence Interval	(2-Sided) 95%; 1.31 to 5.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. 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, baseline C-reactive protein (CRP) status, Tumor necrosis factor (TNF) inhibitors experience, 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 who had baseline and post-baseline data for ASDAS.

Arm/Group Title	Placebo	Ixekizumab 80mg Q4W
Arm/Group Description	Participants received placebo every four weeks (Q4W) by subcutaneous (SC)injection.	Participants received starting dose of 160 milligrams (mg) Ixekizumab at week 0 followed by 80mg Ixekizumab once every four weeks (Q4W) by subcutaneous injection.
Measure Participants	73	74
Least Squares Mean (Standard Error) [Units on a scale]	-0.19 (0.103)	-1.33 (0.100)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80mg Q4W
	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
	Estimated Value	-1.14
	Confidence Interval	(2-Sided) 95%; -1.38 to -0.90
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.120
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 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. LS mean was determined by MMRM with treatment, baseline CRP status, TNF inhibitors experience, 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 who had baseline and post-baseline data for BASDAI.

Arm/Group Title	Placebo	Ixekizumab 80mg Q4W
Arm/Group Description	Participants received placebo every four weeks (Q4W) by subcutaneous (SC)injection.	Participants received starting dose of 160 milligrams (mg) Ixekizumab at week 0 followed by 80mg Ixekizumab once every four weeks (Q4W) by subcutaneous injection.
Measure Participants	73	74
Least Squares Mean (Standard Error) [Units on a scale]	-0.90 (0.231)	-2.39 (0.226)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80mg Q4W
	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
	Estimated Value	-1.49
	Confidence Interval	(2-Sided) 95%; -2.04 to -0.94
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.280
	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 treatment, baseline CRP status, TNF inhibitors experience, 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 who had baseline and post-baseline data for BASFI.

Arm/Group Title	Placebo	Ixekizumab 80mg Q4W
Arm/Group Description	Participants received placebo every four weeks (Q4W) by subcutaneous (SC)injection during.	Participants received starting dose of 160 milligrams (mg) Ixekizumab at week 0 followed by 80mg Ixekizumab once every four weeks (Q4W) by subcutaneous injection.
Measure Participants	73	74
Least Squares Mean (Standard Error) [Units on a scale]	-0.49 (0.237)	-1.36 (0.230)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80mg Q4W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.87
	Confidence Interval	(2-Sided) 95%; -1.43 to -0.32
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.280
	Estimation Comments

7. 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, baseline CRP status, TNF inhibitors experience, and baseline value.
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

All randomized participants who had baseline and post-baseline data for MRI of the Spine.

Arm/Group Title	Placebo	Ixekizumab 80mg Q4W
Arm/Group Description	Participants received placebo every four weeks (Q4W) by subcutaneous (SC)injection.	Participants received starting dose of 160 milligrams (mg) Ixekizumab at week 0 followed by 80mg Ixekizumab once every four weeks (Q4W) by subcutaneous injection.
Measure Participants	70	72
Least Squares Mean (Standard Error) [Units on a scale]	-0.93 (1.550)	-8.65 (1.507)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80mg Q4W
	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
	Estimated Value	-7.72
	Confidence Interval	(2-Sided) 95%; -10.85 to -4.60
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.580
	Estimation Comments

8. Secondary Outcome

Title	Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) Score
Description	SF-36 consists of 36 questions measuring 8 health domains: physical functioning, bodily pain, role limitations due to physical problems, role limitations due to emotional problems, general health perceptions, mental health, social function, and vitality. The patient's responses are solicited using Likert scales that vary in length, with 3-6 response options per item. The SF-36 can be scored into the 8 health domains named above and two overall summary scores: physical component summary (PCS) and mental component summary (MCS) scores. The domain and summary scores range from 0 to 100; higher scores indicate better levels of function and/or better health. LS mean was determined by MMRM with factors for treatment, baseline CRP status, TNF inhibitors experience, 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 who had baseline and post-baseline data for SF-36 PCS score.

Arm/Group Title	Placebo	Ixekizumab 80mg Q4W
Arm/Group Description	Participants received placebo every four weeks (Q4W) by subcutaneous (SC)injection.	Participants received starting dose of 160 milligrams (mg) Ixekizumab at week 0 followed by 80mg Ixekizumab once every four weeks (Q4W) by subcutaneous injection.
Measure Participants	72	74
Least Squares Mean (Standard Error) [Units on a scale]	1.23 (0.740)	3.85 (0.716)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80mg Q4W
	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
	Estimated Value	2.62
	Confidence Interval	(2-Sided) 95%; 1.07 to 4.17
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.785
	Estimation Comments

9. Secondary Outcome

Title	Change From Baseline in 36-Item SF-36 Mental Component Summary (MCS) Score
Description	SF-36 consists of 36 questions measuring 8 health domains: physical functioning, bodily pain, role limitations due to physical problems, role limitations due to emotional problems, general health perceptions, mental health, social function, and vitality. The patient's responses are solicited using Likert scales that vary in length, with 3-6 response options per item. The SF-36 can be scored into the 8 health domains named above and two overall summary scores: physical component summary (PCS) and mental component summary (MCS) scores. The domain and summary scores range from 0 to 100; higher scores indicate better levels of function and/or better health. LS mean was determined by MMRM with factors for treatment, baseline CRP status, TNF inhibitors experience, 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 who had baseline and post-baseline data for SF-36 MCS score.

Arm/Group Title	Placebo	Ixekizumab 80mg Q4W
Arm/Group Description	Participants received placebo every four weeks (Q4W) by subcutaneous (SC)injection.	Participants received starting dose of 160 milligrams (mg) Ixekizumab at week 0 followed by 80mg Ixekizumab once every four weeks (Q4W) by subcutaneous injection.
Measure Participants	72	74
Least Squares Mean (Standard Error) [Units on a scale]	-0.06 (1.027)	0.45 (1.003)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80mg Q4W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.660
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.51
	Confidence Interval	(2-Sided) 95%; -1.77 to 2.79
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.152
	Estimation Comments

10. 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, baseline CRP status, TNF inhibitors experience, 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 who had baseline and post-baseline data for CRP.

Arm/Group Title	Placebo	Ixekizumab 80mg Q4W
Arm/Group Description	Participants received placebo every four weeks (Q4W) by subcutaneous (SC)injection.	Participants received starting dose of 160 milligrams (mg) Ixekizumab at week 0 followed by 80mg Ixekizumab once every four weeks (Q4W) by subcutaneous injection.
Measure Participants	73	74
Least Squares Mean (Standard Error) [milligram per liter (mg/L)]	2.65 (1.349)	-10.10 (1.312)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80mg Q4W
	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
	Estimated Value	-12.75
	Confidence Interval	(2-Sided) 95%; -15.91 to -9.59
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.594
	Estimation Comments

11. Secondary Outcome

Title	Change From Baseline in Mobility on the 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, baseline CRP status, TNF inhibitors experience, 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 who had baseline and post-baseline data for BASMI.

Arm/Group Title	Placebo	Ixekizumab 80mg Q4W
Arm/Group Description	Participants received placebo every four weeks (Q4W) by subcutaneous (SC)injection.	Participants received starting dose of 160 milligrams (mg) Ixekizumab at week 0 followed by 80mg Ixekizumab once every four weeks (Q4W) by subcutaneous injection.
Measure Participants	70	72
Least Squares Mean (Standard Error) [Units on a scale]	0.06 (0.093)	-0.30 (0.090)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80mg Q4W
	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
	Estimated Value	-0.36
	Confidence Interval	(2-Sided) 95%; -0.57 to -0.15
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.106
	Estimation Comments

12. 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, baseline CRP status, TNF inhibitors experience, 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 who had baseline and post-baseline data for MASES.

Arm/Group Title	Placebo	Ixekizumab 80mg Q4W
Arm/Group Description	Participants received placebo every four weeks (Q4W) by subcutaneous (SC)injection during.	Participants received starting dose of 160 milligrams (mg) Ixekizumab at week 0 followed by 80mg Ixekizumab once every four weeks (Q4W) by subcutaneous injection.
Measure Participants	41	33
Least Squares Mean (Standard Error) [Units on a scale]	-1.06 (0.349)	-1.77 (0.361)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80mg Q4W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.086
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.72
	Confidence Interval	(2-Sided) 95%; -1.54 to 0.10
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.413
	Estimation Comments

13. Secondary Outcome

Title	Change From Baseline in MRI Sacroiliac Joint(s) (SIJ) Spondyloarthritis Research Consortium of Canada (SPARCC) 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 ANCOVA with factors for treatment, baseline CRP status, TNF inhibitors experience, and baseline value.
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

All randomized participants who had baseline and post-baseline data for MRI Sacroiliac Joint.

Arm/Group Title	Placebo	Ixekizumab 80mg Q4W
Arm/Group Description	Participants received placebo every four weeks (Q4W) by subcutaneous (SC)injection during.	Participants received starting dose of 160 milligrams (mg) Ixekizumab at week 0 followed by 80mg Ixekizumab once every four weeks (Q4W) by subcutaneous injection.
Measure Participants	70	72
Least Squares Mean (Standard Error) [units on a scale]	-1.31 (1.021)	-6.98 (0.986)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80mg Q4W
	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
	Estimated Value	-5.67
	Confidence Interval	(2-Sided) 95%; -7.71 to -3.62
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.034
	Estimation Comments

14. Secondary Outcome

Title	Number 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	Baseline through Week 16

Outcome Measure Data

Analysis Population Description

All randomized participants who had data for Anterior Uveitis.

Arm/Group Title	Placebo	Ixekizumab 80mg Q4W
Arm/Group Description	Participants received placebo every four weeks (Q4W) by subcutaneous (SC)injection.	Participants received starting dose of 160 milligrams (mg) Ixekizumab at week 0 followed by 80mg Ixekizumab once every four weeks (Q4W) by subcutaneous injection.
Measure Participants	73	74
Count of Participants [Participants]	0 0%	0 0%

15. 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 greater 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

[Not Specified]

Arm/Group Title

Arm/Group Description

16. Secondary Outcome

Title	Percentage of Participants With Anti-Ixekizumab Antibodies
Description	A treatment emergent - antidrug antibody (TE-ADA) positive participant is defined as: a) a participant with a >= 4-fold increase over a positive baseline antibody titer; or b) for a negative baseline titer, a participant 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 who had data for Anti-Ixekizumab Antibodies.

Arm/Group Title	Placebo	Ixekizumab 80mg Q4W
Arm/Group Description	Participants received placebo every four weeks (Q4W) by subcutaneous (SC)injection.	Participants received starting dose of 160 milligrams (mg) Ixekizumab at week 0 followed by 80mg Ixekizumab once every four weeks (Q4W) by subcutaneous injection.
Measure Participants	73	74
Number [Percentage of participants]	4.1 5.6%	13.5 18.2%

17. 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 at least one dose and had evaluable PK data.

Arm/Group Title	Ixekizumab 80mg Q4W
Arm/Group Description	Participants received starting dose of 160 milligrams (mg) Ixekizumab at week 0 followed by 80mg Ixekizumab once every four weeks (Q4W) by subcutaneous injection.
Measure Participants	74
Geometric Mean (Geometric Coefficient of Variation) [microgram per milliliters (µg/mL)]	3.89 (52)

Adverse Events

Time Frame	Baseline, up to Week 16
Adverse Event Reporting Description	All randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Arm/Group Title	Placebo		Ixekizumab 80mg Q4W
Arm/Group Description	Participants received placebo every two weeks (Q2W) by subcutaneous (SC)injection.		Participants received starting dose of 160 milligrams (mg) Ixekizumab at week 0 followed by 80mg Ixekizumab once every four weeks (Q4W) by subcutaneous injection.
All Cause Mortality
	Placebo		Ixekizumab 80mg Q4W
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/73 (0%)		0/74 (0%)
Serious Adverse Events
	Placebo		Ixekizumab 80mg Q4W
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/73 (1.4%)		2/74 (2.7%)
Gastrointestinal disorders
Upper gastrointestinal haemorrhage	0/73 (0%)	0	1/74 (1.4%)	1
Infections and infestations
Kidney infection	0/73 (0%)	0	1/74 (1.4%)	1
Male genital tract tuberculosis	0/65 (0%)	0	0/64 (0%)	0
Pyelonephritis acute	0/73 (0%)	0	1/74 (1.4%)	1
Vascular disorders
Shock	1/73 (1.4%)	1	0/74 (0%)	0
Varicose vein	0/73 (0%)	0	0/74 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		Ixekizumab 80mg Q4W
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/73 (21.9%)		28/74 (37.8%)
Blood and lymphatic system disorders
Leukopenia	0/73 (0%)	0	6/74 (8.1%)	7
General disorders
Injection site reaction	2/73 (2.7%)	2	5/74 (6.8%)	7
Hepatobiliary disorders
Hepatic function abnormal	2/73 (2.7%)	2	4/74 (5.4%)	4
Infections and infestations
Upper respiratory tract infection	11/73 (15.1%)	13	9/74 (12.2%)	12
Investigations
Alanine aminotransferase increased	2/73 (2.7%)	2	5/74 (6.8%)	7
Metabolism and nutrition disorders
Hyperuricaemia	2/73 (2.7%)	3	6/74 (8.1%)	7

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 more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.