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Clinical Trial Results:
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

Summary
EudraCT number	2015-003937-84
Trial protocol	GB FI NL DE ES PL FR IT
Global end of trial date	03 May 2019

Results information
Results version number	v1(current)
This version publication date	26 Jan 2020
First version publication date	26 Jan 2020
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

I1F-MC-RHBW

ISRCTN number

US NCT number

NCT02696798

WHO universal trial number (UTN)

Other trial identifiers

Trial Number: 16179

Sponsor organisation name

Eli Lilly and Company

Sponsor organisation address

Lilly Corporate Center, Indianapolis, IN, United States, 46285

Public contact

Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐CTLilly,

Scientific contact

Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐285‐4559,

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

03 May 2019

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

03 May 2019

Was the trial ended prematurely?

Main objective of the trial

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).

Protection of trial subjects

This study was conducted in accordance with International Conference on Harmonization (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the country or countries in which a study is conducted.

Background therapy

Evidence for comparator

Actual start date of recruitment

12 Apr 2016

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Puerto Rico: 7

Country: Number of subjects enrolled

Argentina: 18

Country: Number of subjects enrolled

United States: 40

Country: Number of subjects enrolled

United Kingdom: 20

Country: Number of subjects enrolled

Spain: 14

Country: Number of subjects enrolled

Canada: 6

Country: Number of subjects enrolled

Korea, Republic of: 34

Country: Number of subjects enrolled

Netherlands: 3

Country: Number of subjects enrolled

Finland: 5

Country: Number of subjects enrolled

Brazil: 28

Country: Number of subjects enrolled

Poland: 66

Country: Number of subjects enrolled

Italy: 2

Country: Number of subjects enrolled

Mexico: 39

Country: Number of subjects enrolled

Israel: 16

Country: Number of subjects enrolled

France: 17

Country: Number of subjects enrolled

Germany: 1

Worldwide total number of subjects

316

EEA total number of subjects

128

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

292

From 65 to 84 years

85 years and over

Subject disposition

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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.

Screening details

Participants who completed study were eligible to enroll into a long-term study (I1F-MC-RHBY [2016-002634-69]) 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.

Period 1 title

Blinded Treatment Dosing Period

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Placebo (PBO)

Arm description

Participants received placebo every two weeks (Q2W) by subcutaneous (SC) injection during Week 0 to 16.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received placebo every two weeks (Q2W) by subcutaneous (SC) injection.

IXE80Q4W

Arm description

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.

Arm type

Experimental

Investigational medicinal product name

IXE80Q4W

Investigational medicinal product code

Other name

LY2439821; Ixekizumab

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

80 or 160 milligrams (mg) of ixekizumab given subcutaneously (SC).

IXE80Q2W

Arm 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.

Arm type

Experimental

Investigational medicinal product name

IXE80Q2W

Investigational medicinal product code

Other name

LY2439821; Ixekizumab

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

80 or 160 milligrams (mg) of ixekizumab given subcutaneously (SC).

Number of subjects in period 1	Placebo (PBO)	IXE80Q4W	IXE80Q2W
Started	104	114	98
Completed	93	99	90
Not completed	11	15	8
Adverse event, serious fatal	-	-	1
Consent withdrawn by subject	7	3	4
Physician decision	-	1	-
Adverse event, non-fatal	2	9	2
Lost to follow-up	-	1	-
Lack of efficacy	2	1	1

Period 2 title

Extended Treatment Period

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

PBO/IXE

Arm description

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.

Arm type

Experimental

Investigational medicinal product name

IXE

Investigational medicinal product code

Other name

LY2439821; Ixekizumab

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

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.

IXE80Q4W/IXE80Q4W

Arm description

Participants received 80 mg ixekizumab given SC Q4W from week 16 to week 52.

Arm type

Experimental

Investigational medicinal product name

IXE80Q4W/IXE80Q4W

Investigational medicinal product code

Other name

LY2439821; Ixekizumab

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received 80 mg ixekizumab given SC Q2W from week 16 to week 52.

IXE80Q2W/IXE80Q2W

Arm description

Participants received 80 mg ixekizumab given SC Q2W from week 16 to week 52.

Arm type

Experimental

Investigational medicinal product name

IXE80Q2W/IXE80Q2W

Investigational medicinal product code

Other name

LY2439821; Ixekizumab

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received 80 mg ixekizumab given SC Q2W from week 16 to week 52.

Number of subjects in period 2 ^[1]	PBO/IXE	IXE80Q4W/IXE80Q4W	IXE80Q2W/IXE80Q2W
Started	93	98	90
Completed	81	89	80
Not completed	12	9	10
Consent withdrawn by subject	3	2	3
Physician decision	-	1	-
Adverse event, non-fatal	1	4	5
Lost to follow-up	1	-	-
Lack of efficacy	7	2	2

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: 1 participant completed blinded treatment period and entered post-treatment followup period directly.

Period 3 title

Post-treatment Follow-up Period

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Placebo

Arm description

Participants did not receive any intervention during Follow-up period

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

IXE80Q4W

Arm description

Participants did not receive any intervention during Follow-up period

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

IXE80Q2W

Arm description

Participants did not receive any intervention during Follow-up period

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Number of subjects in period 3 ^[2]	Placebo	IXE80Q4W	IXE80Q2W
Started	5	34	22
Completed	0	8	3
Not completed	5	26	19
Consent withdrawn by subject	2	8	12
Physician decision	-	2	-
Adverse event, non-fatal	2	12	6
No progressive improvement	-	1	-
Lost to follow-up	-	1	1
Lack of efficacy	1	2	-

Notes
[2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Participants who terminate RHBW early or who didn't enroll into RHBY entered Follow-Up Period.

Baseline characteristics

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Reporting group title

Placebo (PBO)

Reporting group description

Participants received placebo every two weeks (Q2W) by subcutaneous (SC) injection during Week 0 to 16.

Reporting group title

IXE80Q4W

Reporting group description

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.

Reporting group title

IXE80Q2W

Reporting 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.

Reporting group values	Placebo (PBO)	IXE80Q4W	IXE80Q2W	Total
Number of subjects	104	114	98	316
Age categorical
Units: Subjects
In utero				0
Preterm newborn infants (gestational age < 37 wks)				0
Newborns (0-27 days)				0
Infants and toddlers (28 days-23 months)				0
Children (2-11 years)				0
Adolescents (12-17 years)				0
Adults (18-64 years)				0
From 65-84 years				0
85 years and over				0
Age continuous
Units: years
arithmetic mean (standard deviation)	46.6 ( 12.72 )	47.4 ( 13.36 )	44.2 ( 10.79 )	-
Gender categorical
Units: Subjects
Female	17	23	23	63
Male	87	91	75	253
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	33	32	35	100
Not Hispanic or Latino	63	70	53	186
Unknown or Not Reported	8	12	10	30
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	4	4	4	12
Asian	13	14	13	40
Native Hawaiian or Other Pacific Islander	0	0	0	0
Black or African American	1	2	2	5
White	85	91	78	254
More than one race	1	2	1	4
Unknown or Not Reported	0	1	0	1
Region of Enrollment
Units: Subjects
Puerto Rico	1	2	4	7
Argentina	6	7	5	18
United States	14	14	12	40
United Kingdom	9	6	5	20
Spain	3	7	4	14
Canada	1	5	0	6
South Korea	12	11	11	34
Netherlands	1	2	0	3
Finland	0	3	2	5
Brazil	10	8	10	28
Poland	22	24	20	66
Italy	0	1	1	2
Mexico	13	13	13	39
Israel	5	5	6	16
France	7	5	5	17
Germany	0	1	0	1

End points

Top of page

Reporting group title

Placebo (PBO)

Reporting group description

Participants received placebo every two weeks (Q2W) by subcutaneous (SC) injection during Week 0 to 16.

Reporting group title

IXE80Q4W

Reporting group description

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.

Reporting group title

IXE80Q2W

Reporting 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.

Reporting group title

PBO/IXE

Reporting group description

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.

Reporting group title

IXE80Q4W/IXE80Q4W

Reporting group description

Participants received 80 mg ixekizumab given SC Q4W from week 16 to week 52.

Reporting group title

IXE80Q2W/IXE80Q2W

Reporting group description

Participants received 80 mg ixekizumab given SC Q2W from week 16 to week 52.

Reporting group title

Placebo

Reporting group description

Participants did not receive any intervention during Follow-up period

Reporting group title

IXE80Q4W

Reporting group description

Participants did not receive any intervention during Follow-up period

Reporting group title

IXE80Q2W

Reporting group description

Participants did not receive any intervention during Follow-up period

Subject analysis set title

Placebo

Subject analysis set type

Per protocol

Subject analysis set description

Participants received placebo every 2 weeks (Q2W) by subcutaneous injection.

Subject analysis set title

80 mg Q4W Ixekizumab

Subject analysis set type

Per protocol

Subject analysis set description

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).

Subject analysis set title

80 mg Q2W Ixekizumab

Subject analysis set type

Per protocol

Subject analysis set description

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.

Subject analysis set title

80 mg Q4W Ixekizumab (Starting Dose 80 mg)

Subject analysis set type

Per protocol

Subject analysis set description

Participants received 80 mg of Ixekizumab every four weeks by subcutaneous injection.

Subject analysis set title

80 mg Q4W Ixekizumab (Starting Dose 160 mg)

Subject analysis set type

Per protocol

Subject analysis set description

Participants received 160 mg ixekizumab at baseline followed by 80 mg ixekizumab given SC every four weeks by subcutaneous injection.

Subject analysis set title

80 mg Q2W Ixekizumab (Starting Dose 80 mg)

Subject analysis set type

Per protocol

Subject analysis set description

Participants received 80 mg ixekizumab every two weeks by subcutaneous injection.

Subject analysis set title

80 mg Q2W Ixekizumab (Starting Dose 160 mg)

Subject analysis set type

Per protocol

Subject analysis set description

Participants received starting dose of 160 mg ixekizumab at baseline followed by 80 mg ixekizumab every two weeks by subcutaneous injection.

Primary: Percentage of Participants Achieving an Assessment of Spondyloarthritis International Society 40 (ASAS40) Response

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End point title

Percentage of Participants Achieving an Assessment of Spondyloarthritis International Society 40 (ASAS40) Response

End point description

ASAS40 is defined as improvement from baseline of >= 40 % and absolute improvement from baseline of at least 2 units in at least 3 of the following 4 domains without any worsening in the remaining domain. 1) Patient Global: How active was your Ankylosing spondylitis (AS) (on average during the last week? score ranges 0 (not active) to 10 (very active). 2) Spinal Pain: How much Pain of your spine due to AS? ranges 0 (no pain) to 10 (severe pain). 3) Bath Ankylosing Spondylitis Functional Index : 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. 4) Inflammation based on Q5 & Q6 mean of Bath Ankylosing Spondylitis Disease Activity Index (mean of intensity & duration of stiffness): Score ranges from "0" (none) and "10" (very severe). Analysis Population Description (APD): All randomized participants.

End point type

Primary

End point timeframe

Week 16

End point values	Placebo	80 mg Q4W Ixekizumab	80 mg Q2W Ixekizumab
Number of subjects analysed	104	114	98
Units: Percentage of participants
number (not applicable)	12.5	25.4	30.6

ASAS40 Response

Comparison groups

Placebo v 80 mg Q4W Ixekizumab

Number of subjects included in analysis

218

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.017

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.41

Confidence interval

level

95%

sides

2-sided

lower limit

1.17

upper limit

4.95

ASAS40 Response

Comparison groups

Placebo v 80 mg Q2W Ixekizumab

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.06

Confidence interval

level

95%

sides

2-sided

lower limit

1.48

upper limit

6.33

Secondary: Percentage of Participants Achieving an ASAS20 Response

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End point title

Percentage of Participants Achieving an ASAS20 Response

End point 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. 1) Patient Global: How active was your spondylitis on average during the last week? score ranges 0 (not active) to 10 (very active). 2) Spinal Pain: How much Pain of your spine due to Ankylosing spondylitis? score ranges 0 (no pain) to 10 (severe pain). 3) 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. 4) 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). APD: All randomized participants.

End point type

Secondary

End point timeframe

Week 16

End point values	Placebo	80 mg Q4W Ixekizumab	80 mg Q2W Ixekizumab
Number of subjects analysed	104	114	98
Units: Percentage of Participants
number (not applicable)	29.8	48.2	46.9

ASAS20 Response

Comparison groups

Placebo v 80 mg Q4W Ixekizumab

Number of subjects included in analysis

218

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.006

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.2

Confidence interval

level

95%

sides

2-sided

lower limit

1.26

upper limit

3.84

ASAS20 Response

Comparison groups

Placebo v 80 mg Q2W Ixekizumab

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.013

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.08

Confidence interval

level

95%

sides

2-sided

lower limit

1.16

upper limit

3.73

Secondary: Change from Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS)

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End point title

Change from Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS)

End point 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 1) Total back pain, 2) Patient global, 3) Peripheral pain/swelling, 4) Duration of morning stiffness and 5) CRP in mg/L. The ASDAScrp is calculated with the equation: 0.121×total back pain+0.110×patient global+0.073×peripheral pain/swelling+0.058×duration of morning stiffness+0.579×Ln(CRP+1). (CRP is in mg/liter, the range of other variables is from (0 to 10); Ln represents the natural logarithm). Data from five variables combined to yield a score (0.6361 to no defined upper limit), where higher scores 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-byvisit,and treatment-by-visit interaction as fixed factors. APD: All randomized participants.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Placebo	80 mg Q4W Ixekizumab	80 mg Q2W Ixekizumab
Number of subjects analysed	104	114	98
Units: Units on a scale
least squares mean (standard error)	-0.11 ( 0.099 )	-1.16 ( 0.094 )	-1.13 ( 0.103 )

ASDAS

Comparison groups

Placebo v 80 mg Q4W Ixekizumab

Number of subjects included in analysis

218

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean Difference (Final Values)

Point estimate

-1.05

Confidence interval

level

95%

sides

2-sided

lower limit

-1.32

upper limit

-0.79

Variability estimate

Standard error of the mean

Dispersion value

0.135

ASDAS

Comparison groups

Placebo v 80 mg Q2W Ixekizumab

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean Difference (Final Values)

Point estimate

-1.03

Confidence interval

level

95%

sides

2-sided

lower limit

-1.3

upper limit

-0.75

Variability estimate

Standard error of the mean

Dispersion value

0.14

Secondary: Percentage of Participants Achieving Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI50) Response

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End point title

Percentage of Participants Achieving Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI50) Response

End point 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. APD: All randomized participants.

End point type

Secondary

End point timeframe

Week 16

End point values	Placebo	80 mg Q4W Ixekizumab	80 mg Q2W Ixekizumab
Number of subjects analysed	104	114	98
Units: Percentage of Participants
number (not applicable)	9.6	21.9	23.5

BASDAI50

Comparison groups

Placebo v 80 mg Q4W Ixekizumab

Number of subjects included in analysis

218

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.015

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.65

Confidence interval

level

95%

sides

2-sided

lower limit

1.21

upper limit

5.84

BASDAI50

Comparison groups

Placebo v 80 mg Q2W Ixekizumab

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.01

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.9

Confidence interval

level

95%

sides

2-sided

lower limit

1.29

upper limit

6.49

Secondary: Change from baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)

Top of page

End point title

Change from baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)

End point 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. APD: All randomized participants.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Placebo	80 mg Q4W Ixekizumab	80 mg Q2W Ixekizumab
Number of subjects analysed	104	114	98
Units: Units on a scale
least squares mean (standard error)	-0.92 ( 0.212 )	-2.17 ( 0.202 )	-2.09 ( 0.221 )

BASDAI

Comparison groups

Placebo v 80 mg Q4W Ixekizumab

Number of subjects included in analysis

218

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean Difference (Final Values)

Point estimate

-1.24

Confidence interval

level

95%

sides

2-sided

lower limit

-1.81

upper limit

-0.67

Variability estimate

Standard error of the mean

Dispersion value

0.291

BASDAI

Comparison groups

Placebo v 80 mg Q2W Ixekizumab

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean Difference (Final Values)

Point estimate

-1.16

Confidence interval

level

95%

sides

2-sided

lower limit

-1.76

upper limit

-0.57

Variability estimate

Standard error of the mean

Dispersion value

0.301

Secondary: Change from Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI)

Top of page

End point title

Change from Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI)

End point 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. APD: All randomized participants.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Placebo	80 mg Q4W Ixekizumab	80 mg Q2W Ixekizumab
Number of subjects analysed	104	114	98
Units: Units on a scale
least squares mean (standard error)	-0.64 ( 0.215 )	-1.69 ( 0.205 )	-1.92 ( 0.225 )

BASFI

Comparison groups

Placebo v 80 mg Q4W Ixekizumab

Number of subjects included in analysis

218

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean Difference (Final Values)

Point estimate

-1.05

Confidence interval

level

95%

sides

2-sided

lower limit

-1.63

upper limit

-0.47

Variability estimate

Standard error of the mean

Dispersion value

0.295

BASFI

Comparison groups

Placebo v 80 mg Q2W Ixekizumab

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean Difference (Final Values)

Point estimate

-1.28

Confidence interval

level

95%

sides

2-sided

lower limit

-1.89

upper limit

-0.68

Variability estimate

Standard error of the mean

Dispersion value

0.307

Secondary: Percentage of Participants Achieving ASDAS Inactive Disease

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End point title

Percentage of Participants Achieving ASDAS Inactive Disease

End point description

The ASDAS is a self-administered questionnaire/objective laboratory evaluation. The questionnaire assesses disease activity (patient global), back pain, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and duration of morning stiffness on a numeric rating scale (from 0 to 10, with 0 being none and 10 representing a duration of ≥2 hours). The laboratory parameter is a measurement of high-sensitivity C-reactive protein (mg/L) (hs-CRP). Data from five variables (disease activity, back pain, duration of morning stiffness, peripheral pain/swelling, and hs-CRP) are combined to yield a score (0.6361 to no defined upper limit), where higher the score worse the disease activity. ASDAS Inactive Disease is defined as a score of <1.3. APD: All randomized participants.

End point type

Secondary

End point timeframe

Week 16

End point values	Placebo	80 mg Q4W Ixekizumab	80 mg Q2W Ixekizumab
Number of subjects analysed	104	114	98
Units: Percentage of Participants
number (not applicable)	1.0	3.5	5.1

ASDAS Inactive Disease

Comparison groups

Placebo v 80 mg Q4W Ixekizumab

Number of subjects included in analysis

218

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.242

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.73

Confidence interval

level

95%

sides

2-sided

lower limit

0.41

upper limit

33.98

ASDAS Inactive Disease

Comparison groups

Placebo v 80 mg Q2W Ixekizumab

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.127

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

5.42

Confidence interval

level

95%

sides

2-sided

lower limit

0.62

upper limit

47.54

Secondary: Percentage of Participants Achieving ASDAS <2.1

Top of page

End point title

Percentage of Participants Achieving ASDAS <2.1

End point description

The ASDAS is a self-administered questionnaire/objective laboratory evaluation. The questionnaire assesses disease activity (patient global), back pain, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and duration of morning stiffness on a numeric rating scale (from 0 to 10, with 0 being none and 10 representing a duration of ≥2 hours). The laboratory parameter is a measurement of high-sensitivity C-reactive protein (mg/L) (hs-CRP). Data from five variables (disease activity, back pain, duration of morning stiffness, peripheral pain/swelling, and hs-CRP) are combined to yield a score (0.6361 to no defined upper limit), where higher the score worse the disease activity. ASDAS <2.1 defines moderate disease activity. APD: All randomized participants.

End point type

Secondary

End point timeframe

Week 16

End point values	Placebo	80 mg Q4W Ixekizumab	80 mg Q2W Ixekizumab
Number of subjects analysed	104	114	98
Units: Percentage of Participants
number (not applicable)	4.8	17.5	16.3

ASDAS <2.1

Comparison groups

Placebo v 80 mg Q4W Ixekizumab

Number of subjects included in analysis

218

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.006

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.22

Confidence interval

level

95%

sides

2-sided

lower limit

1.5

upper limit

11.86

ASDAS <2.1

Comparison groups

Placebo v 80 mg Q2W Ixekizumab

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.006

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.52

Confidence interval

level

95%

sides

2-sided

lower limit

1.55

upper limit

13.18

Secondary: Change from Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores

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End point title

Change from Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores

End point 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. APD: All randomized participants.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Placebo	80 mg Q4W Ixekizumab	80 mg Q2W Ixekizumab
Number of subjects analysed	104	114	98
Units: Units on a scale
least squares mean (standard error)
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 )

SF-36 MCS

Comparison groups

Placebo v 80 mg Q4W Ixekizumab

Number of subjects included in analysis

218

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.55

Method

Mixed models analysis

Parameter type

LS Mean Difference (Final Values)

Point estimate

0.7689

Confidence interval

level

95%

sides

2-sided

lower limit

-1.7629

upper limit

3.3007

Variability estimate

Standard error of the mean

Dispersion value

1.2863

SF-36 MCS

Comparison groups

Placebo v 80 mg Q2W Ixekizumab

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.495

Method

Mixed models analysis

Parameter type

LS Mean Difference (Final Values)

Point estimate

0.9104

Confidence interval

level

95%

sides

2-sided

lower limit

-1.7151

upper limit

3.536

Variability estimate

Standard error of the mean

Dispersion value

1.3338

SF-36 PCS

Comparison groups

Placebo v 80 mg Q4W Ixekizumab

Number of subjects included in analysis

218

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean Difference (Final Values)

Point estimate

5.2147

Confidence interval

level

95%

sides

2-sided

lower limit

3.0204

upper limit

7.409

Variability estimate

Standard error of the mean

Dispersion value

1.1149

SF-36 PCS

Comparison groups

Placebo v 80 mg Q2W Ixekizumab

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean Difference (Final Values)

Point estimate

4.7585

Confidence interval

level

95%

sides

2-sided

lower limit

2.494

upper limit

7.023

Variability estimate

Standard error of the mean

Dispersion value

1.1505

Secondary: Change from Baseline in ASAS Health Index (ASAS HI)

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End point title

Change from Baseline in ASAS Health Index (ASAS HI)

End point 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. APD: All randomized participants.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Placebo	80 mg Q4W Ixekizumab	80 mg Q2W Ixekizumab
Number of subjects analysed	104	114	98
Units: Units on a scale
least squares mean (standard error)	-0.89 ( 0.338 )	-1.92 ( 0.322 )	-1.58 ( 0.352 )

ASAS HI

Comparison groups

Placebo v 80 mg Q4W Ixekizumab

Number of subjects included in analysis

218

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.026

Method

Mixed models analysis

Parameter type

LS Mean Difference (Final Values)

Point estimate

-1.03

Confidence interval

level

95%

sides

2-sided

lower limit

-1.94

upper limit

-0.13

Variability estimate

Standard error of the mean

Dispersion value

0.46

ASAS HI

Comparison groups

Placebo v 80 mg Q2W Ixekizumab

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.149

Method

Mixed models analysis

Parameter type

LS Mean Difference (Final Values)

Point estimate

-0.69

Confidence interval

level

95%

sides

2-sided

lower limit

-1.63

upper limit

0.25

Variability estimate

Standard error of the mean

Dispersion value

0.477

Secondary: Change from Baseline in Magnetic Resonance Imaging (MRI) of the Spine (Ankylosing Spondylitis Spinal Magnetic Resonance Imaging [ASSpiMRI] – Berlin Score)

Top of page

End point title

Change from Baseline in Magnetic Resonance Imaging (MRI) of the Spine (Ankylosing Spondylitis Spinal Magnetic Resonance Imaging [ASSpiMRI] – Berlin Score)

End point 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. APD: All randomized participants with baseline and week 16 ASSpiMRI score.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Placebo	80 mg Q4W Ixekizumab	80 mg Q2W Ixekizumab
Number of subjects analysed	46	49	45
Units: Units on a scale
least squares mean (standard error)	1.03 ( 0.379 )	-0.92 ( 0.373 )	-1.14 ( 0.414 )

ASSpiMRI score

Comparison groups

Placebo v 80 mg Q4W Ixekizumab

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

LS Mean Difference (Final Values)

Point estimate

-1.95

Confidence interval

level

95%

sides

2-sided

lower limit

-3

upper limit

-0.9

Variability estimate

Standard error of the mean

Dispersion value

0.512

ASSpiMRI score

Comparison groups

Placebo v 80 mg Q2W Ixekizumab

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

LS Mean Difference (Final Values)

Point estimate

-2.17

Confidence interval

level

95%

sides

2-sided

lower limit

-3.2

upper limit

-1.1

Variability estimate

Standard error of the mean

Dispersion value

0.534

Secondary: Change from Baseline in Magnetic Resonance Imaging (MRI) of the Spine (Spondyloarthritis Research Consortium of Canada [SPARCC] score)

Top of page

End point title

Change from Baseline in Magnetic Resonance Imaging (MRI) of the Spine (Spondyloarthritis Research Consortium of Canada [SPARCC] score)

End point 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. APD: All randomized participants with baseline and week 16 SPARCC MRI score.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Placebo	80 mg Q4W Ixekizumab	80 mg Q2W Ixekizumab
Number of subjects analysed	46	49	45
Units: Units on a scale
least squares mean (standard error)	3.29 ( 1.402 )	-2.99 ( 1.384 )	-3.97 ( 1.534 )

SPARCC score

Comparison groups

Placebo v 80 mg Q4W Ixekizumab

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001

Method

ANCOVA

Parameter type

LS Mean Difference (Final Values)

Point estimate

-6.29

Confidence interval

level

95%

sides

2-sided

lower limit

-10

upper limit

-2.5

Variability estimate

Standard error of the mean

Dispersion value

1.896

SPARCC score

Comparison groups

Placebo v 80 mg Q2W Ixekizumab

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

LS Mean Difference (Final Values)

Point estimate

-7.27

Confidence interval

level

95%

sides

2-sided

lower limit

-11.2

upper limit

-3.4

Variability estimate

Standard error of the mean

Dispersion value

1.978

Secondary: Change from Baseline in the Measure of High Sensitivity C-Reactive Protein (CRP)

Top of page

End point title

Change from Baseline in the Measure of High Sensitivity C-Reactive Protein (CRP)

End point 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. APD: All randomized participants.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Placebo	80 mg Q4W Ixekizumab	80 mg Q2W Ixekizumab
Number of subjects analysed	104	114	98
Units: milligram per liter (mg/L)
least squares mean (standard error)	9.719 ( 2.7383 )	-11.096 ( 2.6190 )	-8.121 ( 2.8829 )

High Sensitivity C-Reactive Protein

Comparison groups

Placebo v 80 mg Q4W Ixekizumab

Number of subjects included in analysis

218

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean Difference (Final Values)

Point estimate

-20.816

Confidence interval

level

95%

sides

2-sided

lower limit

-28.187

upper limit

-13.444

Variability estimate

Standard error of the mean

Dispersion value

3.7463

High Sensitivity C-Reactive Protein

Comparison groups

Placebo v 80 mg Q2W Ixekizumab

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean Difference (Final Values)

Point estimate

-17.841

Confidence interval

level

95%

sides

2-sided

lower limit

-25.518

upper limit

-10.163

Variability estimate

Standard error of the mean

Dispersion value

3.9018

Secondary: Change from Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI)

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End point title

Change from Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI)

End point description

BASMI is a combined index comprising of 5 clinical measurements of spinal mobility in patients with radaxSpA. 1) Lateral Spinal Flexion 2) Tragus-to-wall distance 3) Lumbar Flexion (modified Schober) 4) Maximal intermalleolar distance and 5) 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. APD: All randomized participants.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Placebo	80 mg Q4W Ixekizumab	80 mg Q2W Ixekizumab
Number of subjects analysed	104	114	98
Units: Units on a scale
least squares mean (standard error)	-0.046 ( 0.0939 )	-0.349 ( 0.0897 )	-0.217 ( 0.0981 )

BASMI

Comparison groups

Placebo v 80 mg Q4W Ixekizumab

Number of subjects included in analysis

218

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.018

Method

Mixed models analysis

Parameter type

LS Mean Difference (Final Values)

Point estimate

-0.304

Confidence interval

level

95%

sides

2-sided

lower limit

-0.555

upper limit

-0.053

Variability estimate

Standard error of the mean

Dispersion value

0.1275

BASMI

Comparison groups

Placebo v 80 mg Q2W Ixekizumab

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.194

Method

Mixed models analysis

Parameter type

LS Mean Difference (Final Values)

Point estimate

-0.172

Confidence interval

level

95%

sides

2-sided

lower limit

-0.431

upper limit

0.088

Variability estimate

Standard error of the mean

Dispersion value

0.1319

Secondary: Change from Baseline in Chest Expansion

Top of page

End point title

Change from Baseline in Chest Expansion

End point 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. APD: All randomized participants.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Placebo	80 mg Q4W Ixekizumab	80 mg Q2W Ixekizumab
Number of subjects analysed	104	114	98
Units: centimeter(cm)
least squares mean (standard error)	0.04 ( 0.644 )	1.27 ( 0.618 )	0.27 ( 0.655 )

Chest Expansion

Comparison groups

Placebo v 80 mg Q4W Ixekizumab

Number of subjects included in analysis

218

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.17

Method

Mixed models analysis

Parameter type

LS Mean Difference (Final Values)

Point estimate

1.23

Confidence interval

level

95%

sides

2-sided

lower limit

-0.53

upper limit

2.99

Variability estimate

Standard error of the mean

Dispersion value

0.893

Chest Expansion

Comparison groups

Placebo v 80 mg Q2W Ixekizumab

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8

Method

Mixed models analysis

Parameter type

LS Mean Difference (Final Values)

Point estimate

0.23

Confidence interval

level

95%

sides

2-sided

lower limit

-1.57

upper limit

2.04

Variability estimate

Standard error of the mean

Dispersion value

0.916

Secondary: Change from Baseline in Occiput to Wall Distance

Top of page

End point title

Change from Baseline in Occiput to Wall Distance

End point 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. APD: All randomized participants.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Placebo	80 mg Q4W Ixekizumab	80 mg Q2W Ixekizumab
Number of subjects analysed	104	114	98
Units: cm
least squares mean (standard error)	0.35 ( 0.384 )	0.03 ( 0.365 )	-0.65 ( 0.399 )

Occiput to Wall Distance

Comparison groups

Placebo v 80 mg Q4W Ixekizumab

Number of subjects included in analysis

218

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.547

Method

Mixed models analysis

Parameter type

LS Mean Difference (Final Values)

Point estimate

-0.31

Confidence interval

level

95%

sides

2-sided

lower limit

-1.34

upper limit

0.71

Variability estimate

Standard error of the mean

Dispersion value

0.521

Occiput to Wall Distance

Comparison groups

Placebo v 80 mg Q2W Ixekizumab

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.064

Method

Mixed models analysis

Parameter type

LS Mean Difference (Final Values)

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.06

upper limit

0.06

Variability estimate

Standard error of the mean

Dispersion value

0.538

Secondary: Change from Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES)

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End point title

Change from Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES)

End point 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. APD: All randomized participants with baseline MASES score>0.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Placebo	80 mg Q4W Ixekizumab	80 mg Q2W Ixekizumab
Number of subjects analysed	69	82	74
Units: Units on a scale
least squares mean (standard error)	-1.9 ( 0.43 )	-1.8 ( 0.40 )	-2.2 ( 0.42 )

MASES

Comparison groups

Placebo v 80 mg Q4W Ixekizumab

Number of subjects included in analysis

151

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.861

Method

Mixed models analysis

Parameter type

LS Mean Difference (Final Values)

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

1.3

Variability estimate

Standard error of the mean

Dispersion value

0.58

MASES

Comparison groups

Placebo v 80 mg Q2W Ixekizumab

Number of subjects included in analysis

143

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.626

Method

Mixed models analysis

Parameter type

LS Mean Difference (Final Values)

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

0.9

Variability estimate

Standard error of the mean

Dispersion value

0.59

Secondary: Change from Baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Score

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End point title

Change from Baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Score

End point 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. APD: All randomized participants with baseline SPARCC Enthesitis score>0.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Placebo	80 mg Q4W Ixekizumab	80 mg Q2W Ixekizumab
Number of subjects analysed	60	78	64
Units: Units on a scale
least squares mean (standard error)	-1.9 ( 0.44 )	-2.3 ( 0.40 )	-1.8 ( 0.45 )

SPARCC- Enthesitis Score

Comparison groups

Placebo v 80 mg Q4W Ixekizumab

Number of subjects included in analysis

138

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.504

Method

Mixed models analysis

Parameter type

LS Mean Difference (Final Values)

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.6

upper limit

0.8

Variability estimate

Standard error of the mean

Dispersion value

0.59

SPARCC- Enthesitis Score

Comparison groups

Placebo v 80 mg Q2W Ixekizumab

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.86

Method

Mixed models analysis

Parameter type

LS Mean Difference (Final Values)

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

1.3

Variability estimate

Standard error of the mean

Dispersion value

0.62

Secondary: Change from Baseline in Severity of Peripheral Arthritis by Tender Joint Count (TJC) Scores

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End point title

Change from Baseline in Severity of Peripheral Arthritis by Tender Joint Count (TJC) Scores

End point 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. APD: All randomized participants with baseline TJC>0.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Placebo	80 mg Q4W Ixekizumab	80 mg Q2W Ixekizumab
Number of subjects analysed	65	85	69
Units: Tender Joint Count
least squares mean (standard error)	-3.9 ( 0.79 )	-4.8 ( 0.69 )	-5.0 ( 0.79 )

TJC Scores

Comparison groups

Placebo v 80 mg Q4W Ixekizumab

Number of subjects included in analysis

150

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.362

Method

Mixed models analysis

Parameter type

LS Mean Difference (Final Values)

Point estimate

-0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-3

upper limit

1.1

Variability estimate

Standard error of the mean

Dispersion value

1.03

TJC Scores

Comparison groups

Placebo v 80 mg Q2W Ixekizumab

Number of subjects included in analysis

134

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.303

Method

Mixed models analysis

Parameter type

LS Mean Difference (Final Values)

Point estimate

-1.1

Confidence interval

level

95%

sides

2-sided

lower limit

-3.3

upper limit

Variability estimate

Standard error of the mean

Dispersion value

1.08

Secondary: Change from Baseline in Severity of Peripheral Arthritis by Swollen Joint Count (SJC) Scores

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End point title

Change from Baseline in Severity of Peripheral Arthritis by Swollen Joint Count (SJC) Scores

End point 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. APD: All randomized participants with baseline SJC>0.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Placebo	80 mg Q4W Ixekizumab	80 mg Q2W Ixekizumab
Number of subjects analysed	45	48	44
Units: Swollen Joint Count
least squares mean (standard error)	-2.4 ( 0.51 )	-2.6 ( 0.49 )	-3.0 ( 0.54 )

SJC Scores

Comparison groups

Placebo v 80 mg Q4W Ixekizumab

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.813

Method

Mixed models analysis

Parameter type

LS Mean Difference (Final Values)

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1.5

upper limit

1.2

Variability estimate

Standard error of the mean

Dispersion value

0.7

SJC Scores

Comparison groups

Placebo v 80 mg Q2W Ixekizumab

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.41

Method

Mixed models analysis

Parameter type

LS Mean Difference (Final Values)

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

0.8

Variability estimate

Standard error of the mean

Dispersion value

0.71

Secondary: Percentage of Participants with Anterior Uveitis

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End point title

Percentage of Participants with Anterior Uveitis

End point 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. APD: All randomized participants.

End point type

Secondary

End point timeframe

Week 16

End point values	Placebo	80 mg Q4W Ixekizumab	80 mg Q2W Ixekizumab
Number of subjects analysed	104	114	98
Units: Percentage of Participants
number (not applicable)	0	1.8	3.1

Anterior Uveitis

Comparison groups

Placebo v 80 mg Q4W Ixekizumab

Number of subjects included in analysis

218

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.499

Method

Fisher exact

Parameter type

Incidence Rate

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

4.2

Anterior Uveitis

Comparison groups

Placebo v 80 mg Q2W Ixekizumab

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.112

Method

Fisher exact

Parameter type

Incidence Rate

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

6.5

Secondary: Change from Baseline in the Fatigue Numeric Rating Scale (NRS) Score

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End point title

Change from Baseline in the Fatigue Numeric Rating Scale (NRS) Score

End point 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. APD: All randomized participants.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Placebo	80 mg Q4W Ixekizumab	80 mg Q2W Ixekizumab
Number of subjects analysed	104	114	98
Units: Units on a scale
least squares mean (standard error)	-0.7 ( 0.24 )	-2.0 ( 0.23 )	-1.7 ( 0.25 )

Fatigue NRS Score

Comparison groups

Placebo v 80 mg Q4W Ixekizumab

Number of subjects included in analysis

218

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean Difference (Final Values)

Point estimate

-1.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

-0.6

Variability estimate

Standard error of the mean

Dispersion value

0.33

Fatigue NRS Score

Comparison groups

80 mg Q2W Ixekizumab v Placebo

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.005

Method

Mixed models analysis

Parameter type

LS Mean Difference (Final Values)

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-1.6

upper limit

-0.3

Variability estimate

Standard error of the mean

Dispersion value

0.34

Secondary: Change from Baseline in the Jenkins Sleep Evaluation Questionnaire (JSEQ)

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End point title

Change from Baseline in the Jenkins Sleep Evaluation Questionnaire (JSEQ)

End point 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. APD: All randomized participants.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Placebo	80 mg Q4W Ixekizumab	80 mg Q2W Ixekizumab
Number of subjects analysed	104	114	98
Units: Units on a scale
least squares mean (standard error)	-1.8 ( 0.50 )	-3.0 ( 0.48 )	-2.4 ( 0.52 )

JSEQ

Comparison groups

Placebo v 80 mg Q4W Ixekizumab

Number of subjects included in analysis

218

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.088

Method

Mixed models analysis

Parameter type

LS Mean Difference (Final Values)

Point estimate

-1.2

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

0.2

Variability estimate

Standard error of the mean

Dispersion value

0.68

JSEQ

Comparison groups

Placebo v 80 mg Q2W Ixekizumab

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.366

Method

Mixed models analysis

Parameter type

LS Mean Difference (Final Values)

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

0.7

Variability estimate

Standard error of the mean

Dispersion value

0.7

Secondary: Change from Baseline in the Work Productivity Activity Impairment Spondyloarthritis (WPAI-SpA) Scores

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End point title

Change from Baseline in the Work Productivity Activity Impairment Spondyloarthritis (WPAI-SpA) Scores

End point 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. APD: All randomized participants with baseline and week 16 WPAI-SpA score.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Placebo	80 mg Q4W Ixekizumab	80 mg Q2W Ixekizumab
Number of subjects analysed	99 ^[1]	112 ^[2]	96 ^[3]
Units: Units on a scale
least squares mean (standard error)
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 )

Notes
[1] - N=54 for Overall Work Impairment Score
[2] - N= 44 for Overall Work Impairment Score
[3] - N= 43 for Overall Work Impairment Score

Overall Work Impairment Score

Statistical analysis description

Subjects in this analysis: 98

Comparison groups

Placebo v 80 mg Q4W Ixekizumab

Number of subjects included in analysis

211

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.038

Method

ANCOVA

Parameter type

LS Mean Difference (Final Values)

Point estimate

-11.13

Confidence interval

level

95%

sides

2-sided

lower limit

-21.65

upper limit

-0.6

Variability estimate

Standard error of the mean

Dispersion value

5.323

Overall Work Impairment Score

Statistical analysis description

Subjects in this analysis: 97

Comparison groups

Placebo v 80 mg Q2W Ixekizumab

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.012

Method

ANCOVA

Parameter type

LS Mean Difference (Final Values)

Point estimate

-13.66

Confidence interval

level

95%

sides

2-sided

lower limit

-24.23

upper limit

-3.1

Variability estimate

Standard error of the mean

Dispersion value

5.341

Percentage of Activity Impairment

Comparison groups

Placebo v 80 mg Q4W Ixekizumab

Number of subjects included in analysis

211

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.071

Method

ANCOVA

Parameter type

LS Mean Difference (Final Values)

Point estimate

-6.3

Confidence interval

level

95%

sides

2-sided

lower limit

-13.2

upper limit

0.5

Variability estimate

Standard error of the mean

Dispersion value

3.5

Percentage of Activity Impairment

Comparison groups

Placebo v 80 mg Q2W Ixekizumab

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.024

Method

ANCOVA

Parameter type

LS Mean Difference (Final Values)

Point estimate

-8.3

Confidence interval

level

95%

sides

2-sided

lower limit

-15.5

upper limit

-1.1

Variability estimate

Standard error of the mean

Dispersion value

3.65

Secondary: Change from Baseline in ASAS-Nonsteroidal Anti-Inflammatory Drug (NSAID) Score

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End point title

Change from Baseline in ASAS-Nonsteroidal Anti-Inflammatory Drug (NSAID) Score

End point 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). APD: Participants from extended treatment period who had NSAID Intake at baseline.

End point type

Secondary

End point timeframe

Baseline, Week 52

End point values	PBO/IXE	IXE80Q4W/IXE80Q4W	IXE80Q2W/IXE80Q2W
Number of subjects analysed	69	71	58
Units: Units on a scale
arithmetic mean (standard deviation)	-9.84 ( 34.435 )	-5.52 ( 19.553 )	-2.33 ( 24.019 )

No statistical analyses for this end point

Secondary: Percentage of Participants with Anti-Ixekizumab Antibodies

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End point title

Percentage of Participants with Anti-Ixekizumab Antibodies

End point description

A 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 of participants with treatment-emergent positive anti-ixekizumab antibodies was summarized by treatment group. 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%. APD: All randomized participants.

End point type

Secondary

End point timeframe

Week 16

End point values	Placebo	80 mg Q4W Ixekizumab	80 mg Q2W Ixekizumab
Number of subjects analysed	104	113	98
Units: Percentage of Participants
number (not applicable)	2.9	7.1	4.1

No statistical analyses for this end point

Secondary: Pharmacokinetics (PK): Trough Ixekizumab Concentration at Steady State (Ctrough ss)

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End point title

Pharmacokinetics (PK): Trough Ixekizumab Concentration at Steady State (Ctrough ss)

End point description

Pharmacokinetics (PK): Steady-state trough serum concentration of Ixekizumab at week 16. APD: All randomized participants who received study drug and have evaluable PK data.

End point type

Secondary

End point timeframe

Predose, Week 1, 2, 4, 8, 12 and Week 16

End point values	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)
Number of subjects analysed	60	54	48	50
Units: Microgram/milliliters (µg/mL)
geometric mean (geometric coefficient of variation)
Week 16	2.10 ( 106 )	2.47 ( 101 )	6.27 ( 158 )	8.52 ( 50 )

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Blinded Treatment, Extended Treatment and Follow-Up Periods

Adverse event reporting additional description

I1F-MC-RHBW

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

22.0

Reporting group title

IXE80Q2W-blinded treatment period

Reporting group description

Reporting group title

IXE80Q4W-blinded treatment period

Reporting group description

Reporting group title

PBO-blinded treatment period

Reporting group description

Reporting group title

IXE80Q2W/IXE80Q2W-extended treatment period

Reporting group description

Reporting group title

IXE80Q4W/IXE80Q4W-extended treatment period

Reporting group description

Reporting group title

IXE80Q2W-follow-up period

Reporting group description

Reporting group title

PBO/IXE-extended treatment period

Reporting group description

Reporting group title

IXE80Q4W-follow-up period

Reporting group description

Reporting group title

PBO-follow-up period

Reporting group description

Serious adverse events	IXE80Q2W-blinded treatment period	IXE80Q4W-blinded treatment period	PBO-blinded treatment period	IXE80Q2W/IXE80Q2W-extended treatment period	IXE80Q4W/IXE80Q4W-extended treatment period	IXE80Q2W-follow-up period	PBO/IXE-extended treatment period	IXE80Q4W-follow-up period	PBO-follow-up period
Total subjects affected by serious adverse events
subjects affected / exposed	3 / 98 (3.06%)	4 / 114 (3.51%)	5 / 104 (4.81%)	1 / 90 (1.11%)	2 / 98 (2.04%)	1 / 22 (4.55%)	6 / 93 (6.45%)	2 / 34 (5.88%)	0 / 5 (0.00%)
number of deaths (all causes)	1	0	0	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
acute promyelocytic leukaemia
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 98 (0.00%)	0 / 114 (0.00%)	0 / 104 (0.00%)	0 / 90 (0.00%)	0 / 98 (0.00%)	0 / 22 (0.00%)	0 / 93 (0.00%)	1 / 34 (2.94%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
lung adenocarcinoma
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 98 (0.00%)	0 / 114 (0.00%)	0 / 104 (0.00%)	0 / 90 (0.00%)	0 / 98 (0.00%)	1 / 22 (4.55%)	0 / 93 (0.00%)	0 / 34 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
vasculitis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 98 (0.00%)	0 / 114 (0.00%)	1 / 104 (0.96%)	0 / 90 (0.00%)	0 / 98 (0.00%)	0 / 22 (0.00%)	0 / 93 (0.00%)	0 / 34 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
dyspnoea
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 98 (0.00%)	0 / 114 (0.00%)	0 / 104 (0.00%)	0 / 90 (0.00%)	0 / 98 (0.00%)	0 / 22 (0.00%)	1 / 93 (1.08%)	0 / 34 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
pulmonary embolism
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 98 (0.00%)	0 / 114 (0.00%)	0 / 104 (0.00%)	0 / 90 (0.00%)	0 / 98 (0.00%)	0 / 22 (0.00%)	0 / 93 (0.00%)	1 / 34 (2.94%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
completed suicide
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 98 (1.02%)	0 / 114 (0.00%)	0 / 104 (0.00%)	0 / 90 (0.00%)	0 / 98 (0.00%)	0 / 22 (0.00%)	0 / 93 (0.00%)	0 / 34 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
depression
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 98 (1.02%)	0 / 114 (0.00%)	0 / 104 (0.00%)	0 / 90 (0.00%)	0 / 98 (0.00%)	0 / 22 (0.00%)	0 / 93 (0.00%)	0 / 34 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
blood creatine phosphokinase increased
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 98 (1.02%)	0 / 114 (0.00%)	0 / 104 (0.00%)	0 / 90 (0.00%)	0 / 98 (0.00%)	0 / 22 (0.00%)	0 / 93 (0.00%)	0 / 34 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
femur fracture
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 98 (0.00%)	0 / 114 (0.00%)	1 / 104 (0.96%)	0 / 90 (0.00%)	0 / 98 (0.00%)	0 / 22 (0.00%)	0 / 93 (0.00%)	0 / 34 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
acute myocardial infarction
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 98 (0.00%)	0 / 114 (0.00%)	0 / 104 (0.00%)	0 / 90 (0.00%)	0 / 98 (0.00%)	0 / 22 (0.00%)	1 / 93 (1.08%)	0 / 34 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
atrial tachycardia
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 98 (1.02%)	0 / 114 (0.00%)	0 / 104 (0.00%)	0 / 90 (0.00%)	0 / 98 (0.00%)	0 / 22 (0.00%)	0 / 93 (0.00%)	0 / 34 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
bradycardia
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 98 (0.00%)	0 / 114 (0.00%)	0 / 104 (0.00%)	0 / 90 (0.00%)	1 / 98 (1.02%)	0 / 22 (0.00%)	1 / 93 (1.08%)	0 / 34 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
drop attacks
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 98 (0.00%)	0 / 114 (0.00%)	0 / 104 (0.00%)	0 / 90 (0.00%)	0 / 98 (0.00%)	0 / 22 (0.00%)	1 / 93 (1.08%)	0 / 34 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
loss of consciousness
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 98 (0.00%)	0 / 114 (0.00%)	0 / 104 (0.00%)	0 / 90 (0.00%)	0 / 98 (0.00%)	0 / 22 (0.00%)	0 / 93 (0.00%)	1 / 34 (2.94%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
meralgia paraesthetica
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 98 (0.00%)	0 / 114 (0.00%)	0 / 104 (0.00%)	0 / 90 (0.00%)	0 / 98 (0.00%)	0 / 22 (0.00%)	1 / 93 (1.08%)	0 / 34 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
syncope
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 98 (0.00%)	0 / 114 (0.00%)	0 / 104 (0.00%)	0 / 90 (0.00%)	0 / 98 (0.00%)	0 / 22 (0.00%)	0 / 93 (0.00%)	1 / 34 (2.94%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
colitis ulcerative
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 98 (0.00%)	0 / 114 (0.00%)	1 / 104 (0.96%)	0 / 90 (0.00%)	0 / 98 (0.00%)	0 / 22 (0.00%)	0 / 93 (0.00%)	0 / 34 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
crohn's disease
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 98 (0.00%)	1 / 114 (0.88%)	0 / 104 (0.00%)	0 / 90 (0.00%)	0 / 98 (0.00%)	0 / 22 (0.00%)	0 / 93 (0.00%)	0 / 34 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
inguinal hernia
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 98 (0.00%)	0 / 114 (0.00%)	1 / 104 (0.96%)	0 / 90 (0.00%)	0 / 98 (0.00%)	0 / 22 (0.00%)	1 / 93 (1.08%)	0 / 34 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
acute kidney injury
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 98 (0.00%)	0 / 114 (0.00%)	0 / 104 (0.00%)	0 / 90 (0.00%)	1 / 98 (1.02%)	0 / 22 (0.00%)	0 / 93 (0.00%)	0 / 34 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
urinary retention
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 98 (0.00%)	0 / 114 (0.00%)	0 / 104 (0.00%)	0 / 90 (0.00%)	1 / 98 (1.02%)	0 / 22 (0.00%)	0 / 93 (0.00%)	0 / 34 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
arthritis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 98 (0.00%)	0 / 114 (0.00%)	1 / 104 (0.96%)	0 / 90 (0.00%)	0 / 98 (0.00%)	0 / 22 (0.00%)	0 / 93 (0.00%)	0 / 34 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
fracture pain
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 98 (0.00%)	1 / 114 (0.88%)	0 / 104 (0.00%)	0 / 90 (0.00%)	0 / 98 (0.00%)	0 / 22 (0.00%)	0 / 93 (0.00%)	0 / 34 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
osteoarthritis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 98 (0.00%)	0 / 114 (0.00%)	0 / 104 (0.00%)	0 / 90 (0.00%)	0 / 98 (0.00%)	0 / 22 (0.00%)	1 / 93 (1.08%)	0 / 34 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
gastroenteritis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 98 (0.00%)	0 / 114 (0.00%)	0 / 104 (0.00%)	1 / 90 (1.11%)	0 / 98 (0.00%)	0 / 22 (0.00%)	0 / 93 (0.00%)	0 / 34 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
peritonitis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 98 (0.00%)	1 / 114 (0.88%)	0 / 104 (0.00%)	0 / 90 (0.00%)	0 / 98 (0.00%)	0 / 22 (0.00%)	0 / 93 (0.00%)	0 / 34 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
pharyngitis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 98 (0.00%)	1 / 114 (0.88%)	0 / 104 (0.00%)	0 / 90 (0.00%)	0 / 98 (0.00%)	0 / 22 (0.00%)	0 / 93 (0.00%)	0 / 34 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
pneumonia
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 98 (0.00%)	0 / 114 (0.00%)	0 / 104 (0.00%)	0 / 90 (0.00%)	0 / 98 (0.00%)	0 / 22 (0.00%)	1 / 93 (1.08%)	0 / 34 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
sinusitis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 98 (0.00%)	0 / 114 (0.00%)	0 / 104 (0.00%)	0 / 90 (0.00%)	0 / 98 (0.00%)	0 / 22 (0.00%)	1 / 93 (1.08%)	0 / 34 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
hyperkalaemia
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 98 (0.00%)	0 / 114 (0.00%)	0 / 104 (0.00%)	0 / 90 (0.00%)	1 / 98 (1.02%)	0 / 22 (0.00%)	0 / 93 (0.00%)	0 / 34 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	IXE80Q2W-blinded treatment period	IXE80Q4W-blinded treatment period	PBO-blinded treatment period	IXE80Q2W/IXE80Q2W-extended treatment period	IXE80Q4W/IXE80Q4W-extended treatment period	IXE80Q2W-follow-up period	PBO/IXE-extended treatment period	IXE80Q4W-follow-up period	PBO-follow-up period
Total subjects affected by non serious adverse events
subjects affected / exposed	25 / 98 (25.51%)	25 / 114 (21.93%)	12 / 104 (11.54%)	26 / 90 (28.89%)	19 / 98 (19.39%)	1 / 22 (4.55%)	19 / 93 (20.43%)	3 / 34 (8.82%)	1 / 5 (20.00%)
Investigations
blood triglycerides increased
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 98 (0.00%)	0 / 114 (0.00%)	1 / 104 (0.96%)	1 / 90 (1.11%)	0 / 98 (0.00%)	0 / 22 (0.00%)	1 / 93 (1.08%)	0 / 34 (0.00%)	1 / 5 (20.00%)
occurrences all number	0	0	1	1	0	0	1	0	1
General disorders and administration site conditions
injection site reaction
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	8 / 98 (8.16%)	3 / 114 (2.63%)	1 / 104 (0.96%)	5 / 90 (5.56%)	2 / 98 (2.04%)	0 / 22 (0.00%)	3 / 93 (3.23%)	0 / 34 (0.00%)	0 / 5 (0.00%)
occurrences all number	21	5	1	14	2	0	9	0	0
Gastrointestinal disorders
diarrhoea
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	4 / 98 (4.08%)	6 / 114 (5.26%)	0 / 104 (0.00%)	2 / 90 (2.22%)	1 / 98 (1.02%)	0 / 22 (0.00%)	3 / 93 (3.23%)	0 / 34 (0.00%)	0 / 5 (0.00%)
occurrences all number	4	6	0	2	1	0	3	0	0
Reproductive system and breast disorders
vulvovaginal burning sensation
alternative dictionary used: MedDRA 22.0
subjects affected / exposed ^[1]	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 17 (0.00%)	0 / 22 (0.00%)	1 / 17 (5.88%)	0 / 4 (0.00%)	0 / 16 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
vulvovaginal dryness
alternative dictionary used: MedDRA 22.0
subjects affected / exposed ^[2]	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 17 (0.00%)	0 / 22 (0.00%)	1 / 17 (5.88%)	0 / 4 (0.00%)	0 / 16 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Musculoskeletal and connective tissue disorders
arthralgia
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	3 / 98 (3.06%)	7 / 114 (6.14%)	4 / 104 (3.85%)	2 / 90 (2.22%)	4 / 98 (4.08%)	1 / 22 (4.55%)	4 / 93 (4.30%)	1 / 34 (2.94%)	0 / 5 (0.00%)
occurrences all number	3	8	4	2	4	2	5	1	0
back pain
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	3 / 98 (3.06%)	1 / 114 (0.88%)	2 / 104 (1.92%)	5 / 90 (5.56%)	6 / 98 (6.12%)	0 / 22 (0.00%)	0 / 93 (0.00%)	0 / 34 (0.00%)	0 / 5 (0.00%)
occurrences all number	3	1	2	5	8	0	0	0	0
Infections and infestations
nasopharyngitis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	4 / 98 (4.08%)	5 / 114 (4.39%)	2 / 104 (1.92%)	4 / 90 (4.44%)	3 / 98 (3.06%)	0 / 22 (0.00%)	3 / 93 (3.23%)	2 / 34 (5.88%)	0 / 5 (0.00%)
occurrences all number	4	5	2	4	3	0	3	2	0
upper respiratory tract infection
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	4 / 98 (4.08%)	9 / 114 (7.89%)	3 / 104 (2.88%)	8 / 90 (8.89%)	4 / 98 (4.08%)	0 / 22 (0.00%)	5 / 93 (5.38%)	0 / 34 (0.00%)	0 / 5 (0.00%)
occurrences all number	4	12	3	10	4	0	5	0	0
urinary tract infection
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	2 / 98 (2.04%)	0 / 114 (0.00%)	0 / 104 (0.00%)	5 / 90 (5.56%)	2 / 98 (2.04%)	0 / 22 (0.00%)	2 / 93 (2.15%)	0 / 34 (0.00%)	0 / 5 (0.00%)
occurrences all number	2	0	0	5	2	0	2	0	0
vulvovaginal candidiasis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed ^[3]	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 17 (0.00%)	0 / 22 (0.00%)	0 / 17 (0.00%)	0 / 4 (0.00%)	1 / 16 (6.25%)	0 / 9 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: This event is gender specific, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
[2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: This event is gender specific, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
[3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: This event is gender specific, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.

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Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: 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

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Participants Achieving an Assessment of Spondyloarthritis International Society 40 (ASAS40) Response

Primary: Percentage of Participants Achieving an Assessment of Spondyloarthritis International Society 40 (ASAS40) Response

Secondary: Percentage of Participants Achieving an ASAS20 Response

Secondary: Percentage of Participants Achieving an ASAS20 Response

Secondary: Change from Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS)

Secondary: Change from Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS)

Secondary: Percentage of Participants Achieving Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI50) Response

Secondary: Percentage of Participants Achieving Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI50) Response

Secondary: Change from baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)

Secondary: Change from baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)

Secondary: Change from Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI)

Secondary: Change from Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI)

Secondary: Percentage of Participants Achieving ASDAS Inactive Disease

Secondary: Percentage of Participants Achieving ASDAS Inactive Disease

Secondary: Percentage of Participants Achieving ASDAS <2.1

Secondary: Percentage of Participants Achieving ASDAS <2.1

Secondary: Change from Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores

Secondary: Change from Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores

Secondary: Change from Baseline in ASAS Health Index (ASAS HI)

Secondary: Change from Baseline in ASAS Health Index (ASAS HI)

Secondary: Change from Baseline in Magnetic Resonance Imaging (MRI) of the Spine (Ankylosing Spondylitis Spinal Magnetic Resonance Imaging [ASSpiMRI] – Berlin Score)

Secondary: Change from Baseline in Magnetic Resonance Imaging (MRI) of the Spine (Ankylosing Spondylitis Spinal Magnetic Resonance Imaging [ASSpiMRI] – Berlin Score)

Secondary: Change from Baseline in Magnetic Resonance Imaging (MRI) of the Spine (Spondyloarthritis Research Consortium of Canada [SPARCC] score)

Secondary: Change from Baseline in Magnetic Resonance Imaging (MRI) of the Spine (Spondyloarthritis Research Consortium of Canada [SPARCC] score)

Secondary: Change from Baseline in the Measure of High Sensitivity C-Reactive Protein (CRP)

Secondary: Change from Baseline in the Measure of High Sensitivity C-Reactive Protein (CRP)

Secondary: Change from Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI)

Secondary: Change from Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI)

Secondary: Change from Baseline in Chest Expansion

Secondary: Change from Baseline in Chest Expansion

Secondary: Change from Baseline in Occiput to Wall Distance

Secondary: Change from Baseline in Occiput to Wall Distance

Secondary: Change from Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES)

Secondary: Change from Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES)

Secondary: Change from Baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Score

Secondary: Change from Baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Score

Secondary: Change from Baseline in Severity of Peripheral Arthritis by Tender Joint Count (TJC) Scores

Secondary: Change from Baseline in Severity of Peripheral Arthritis by Tender Joint Count (TJC) Scores

Secondary: Change from Baseline in Severity of Peripheral Arthritis by Swollen Joint Count (SJC) Scores

Secondary: Change from Baseline in Severity of Peripheral Arthritis by Swollen Joint Count (SJC) Scores

Secondary: Percentage of Participants with Anterior Uveitis

Secondary: Percentage of Participants with Anterior Uveitis

Secondary: Change from Baseline in the Fatigue Numeric Rating Scale (NRS) Score

Secondary: Change from Baseline in the Fatigue Numeric Rating Scale (NRS) Score

Secondary: Change from Baseline in the Jenkins Sleep Evaluation Questionnaire (JSEQ)

Secondary: Change from Baseline in the Jenkins Sleep Evaluation Questionnaire (JSEQ)

Secondary: Change from Baseline in the Work Productivity Activity Impairment Spondyloarthritis (WPAI-SpA) Scores

Secondary: Change from Baseline in the Work Productivity Activity Impairment Spondyloarthritis (WPAI-SpA) Scores

Secondary: Change from Baseline in ASAS-Nonsteroidal Anti-Inflammatory Drug (NSAID) Score

Secondary: Change from Baseline in ASAS-Nonsteroidal Anti-Inflammatory Drug (NSAID) Score

Secondary: Percentage of Participants with Anti-Ixekizumab Antibodies

Secondary: Percentage of Participants with Anti-Ixekizumab Antibodies

Secondary: Pharmacokinetics (PK): Trough Ixekizumab Concentration at Steady State (Ctrough ss)

Secondary: Pharmacokinetics (PK): Trough Ixekizumab Concentration at Steady State (Ctrough ss)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
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