Download PDF

Clinical Trial Results:
A Multicenter, Randomized, Double-Blind, Active and Placebo-Controlled 16 Week Study Followed by Long Term Evaluation of Efficacy and Safety of Ixekizumab (LY2439821) in bDMARD-Naive Patients with Radiographic Axial Spondyloarthritis.

Summary
EudraCT number	2015-003932-11
Trial protocol	DE HU PL NL CZ
Global end of trial date	17 Oct 2018

Results information
Results version number	v2(current)
This version publication date	29 Dec 2019
First version publication date	10 Oct 2019
Other versions	v1
Version creation reason	Correction of full data set Correction of full data set

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

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

I1F-MC-RHBV

ISRCTN number

US NCT number

NCT02696785

WHO universal trial number (UTN)

Other trial identifiers

Trial Number: 16178

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

17 Oct 2018

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

17 Oct 2018

Was the trial ended prematurely?

Main objective of the trial

The main purpose of this study is to evaluate the safety and efficacy of the study drug known as ixekizumab in biological disease-modifying anti-rheumatic drugs (bDMARDs)-naive participants with radiographic axial spondyloarthritis (rad-axSpA).

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

02 May 2016

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Korea, Republic of: 47

Country: Number of subjects enrolled

Netherlands: 4

Country: Number of subjects enrolled

United States: 15

Country: Number of subjects enrolled

Japan: 7

Country: Number of subjects enrolled

Taiwan: 51

Country: Number of subjects enrolled

Germany: 3

Country: Number of subjects enrolled

Canada: 9

Country: Number of subjects enrolled

Hungary: 10

Country: Number of subjects enrolled

Mexico: 30

Country: Number of subjects enrolled

Poland: 62

Country: Number of subjects enrolled

Russian Federation: 48

Country: Number of subjects enrolled

Czech Republic: 54

Worldwide total number of subjects

340

EEA total number of subjects

133

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)

326

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Blinded treatment period (Week 0 to Week 16), followed by extended treatment period (Week 16 to Week 52), followed by post treatment period for a maximum of 24 weeks. Washout period occurred for only Adalimumab group for 6 weeks (Week 14 to Week 20).

Screening details

Participants who completed study were eligible to enroll into a long-term study (Study I1F-MC-RHBY [RHBY]) for up to 2 additional years. Participants that do not enroll into study RHBY will complete the Post-Treatment Follow-Up Period.

Period 1 title

Blinded Treatment 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 by subcutaneous injection.

Arm type

Experimental

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 by subcutaneous injection.

Adalimumab

Arm description

Blinded Treatment Period:Participants received 40mg Adalimumab every two weeks by SC injection.

Arm type

Active comparator

Investigational medicinal product name

Adalimumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received 40mg Adalimumab by subcutaneous injection every two weeks.

IXE80Q2W

Arm description

Participants received starting dose of either 80 milligrams (mg) or 160mg Ixekizumab at week 0 followed by 80mg Ixekizumab every two weeks by subcutaneous injection.

Arm type

Experimental

Investigational medicinal product name

Ixekizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received starting dose of either 80 milligrams (mg) or 160mg Ixekizumab at week 0 followed by 80mg Ixekizumab every two weeks by subcutaneous injection.

IXE80Q4W

Arm description

Participants received starting dose of either 80 milligrams (mg) or 160mg Ixekizumab at week 0 followed by 80mg Ixekizumab every four weeks by subcutaneous injection.

Arm type

Experimental

Investigational medicinal product name

Ixekizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received starting dose of either 80 milligrams (mg) or 160mg Ixekizumab at week 0 followed by 80mg Ixekizumab every four weeks by subcutaneous injection.

Number of subjects in period 1	Placebo (PBO)	Adalimumab	IXE80Q2W	IXE80Q4W
Started	86	90	83	81
Received at least one dose of study drug	86	90	83	81
Completed	86	88	79	78
Not completed	0	2	4	3
Consent withdrawn by subject	-	1	1	2
Adverse event, non-fatal	-	1	3	-
Lack of efficacy	-	-	-	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 received starting dose of 160mg Ixekizumab at week 16 followed by 80mg Ixekizumab either every two weeks (Q2W) or every four weeks (Q4W) by subcutaneous (SC) injection.

Arm type

Experimental

Investigational medicinal product name

Ixekizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received starting dose of 160mg Ixekizumab at week 16 followed by 80mg Ixekizumab either every two weeks (Q2W) or every four weeks (Q4W) by subcutaneous (SC) injection during extended treatment period.

Adalimumab/PBO/IXE

Arm description

Participants who received Adalimumab in blinded treatment period received 80mg Ixekizumab either Q2W or Q4W by SC injection during extension treatment period. Washout Period: Participants received placebo for 6 weeks.

Arm type

Experimental

Investigational medicinal product name

Ixekizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received 80mg Ixekizumab either Q2W or Q4W by SC injection.

IXE80Q2W/IXE80Q2W

Arm description

Participants received starting dose of either 80 milligrams (mg) or 160mg Ixekizumab at week 0 followed by 80mg Ixekizumab every two weeks by subcutaneous injection.

Arm type

Experimental

Investigational medicinal product name

Ixekizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received starting dose of either 80 milligrams (mg) or 160mg Ixekizumab at week 0 followed by 80mg Ixekizumab every two weeks by subcutaneous injection.

IXE80Q4W/IXE80Q4W

Arm description

Participants received starting dose of either 80 milligrams (mg) or 160mg Ixekizumab at week 0 followed by 80mg Ixekizumab every four weeks by subcutaneous injection.

Arm type

Experimental

Investigational medicinal product name

Ixekizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received starting dose of either 80 milligrams (mg) or 160mg Ixekizumab at week 0 followed by 80mg Ixekizumab every two weeks by subcutaneous injection.

Number of subjects in period 2 ^[1]	PBO/IXE	Adalimumab/PBO/IXE	IXE80Q2W/IXE80Q2W	IXE80Q4W/IXE80Q4W
Started	86	86	79	78
Completed	83	80	74	72
Not completed	3	6	5	6
Consent withdrawn by subject	1	2	3	5
Adverse event, non-fatal	2	3	2	1
Lack of efficacy	-	1	-	-

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: Adalimumab group has two participants in the washout period discontinuing the study. 1 participant with Lack if efficacy, 1 participant with consent with drawn by subject.

Period 3 title

Follow-up Period

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Placebo (PBO)

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

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

Number of subjects in period 3 ^[2]	Placebo (PBO)	IXE80Q2W	IXE80Q4W
Started	1	24	16
Completed	0	11	8
Not completed	1	13	8
Consent withdrawn by subject	1	5	4
Adverse event, non-fatal	-	8	2
Lost to follow-up	-	-	1
Lack of efficacy	-	-	1

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 completed study were eligible to enroll RHBY directly without entering Follow-Up period.

Baseline characteristics

Top of page

Reporting group title

Placebo (PBO)

Reporting group description

Participants received placebo every two weeks by subcutaneous injection.

Reporting group title

Adalimumab

Reporting group description

Blinded Treatment Period:Participants received 40mg Adalimumab every two weeks by SC injection.

Reporting group title

IXE80Q2W

Reporting group description

Participants received starting dose of either 80 milligrams (mg) or 160mg Ixekizumab at week 0 followed by 80mg Ixekizumab every two weeks by subcutaneous injection.

Reporting group title

IXE80Q4W

Reporting group description

Participants received starting dose of either 80 milligrams (mg) or 160mg Ixekizumab at week 0 followed by 80mg Ixekizumab every four weeks by subcutaneous injection.

Reporting group values	Placebo (PBO)	Adalimumab	IXE80Q2W	IXE80Q4W	Total
Number of subjects	86	90	83	81	340
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)	42.7 ± 12.01	41.8 ± 11.44	41.3 ± 11.17	41.0 ± 12.13	-
Gender categorical
Units: Subjects
Female	15	17	19	13	64
Male	71	73	64	68	276
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	11	7	8	8	34
Not Hispanic or Latino	67	74	68	66	275
Unknown or Not Reported	8	9	7	7	31
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	4	2	4	4	14
Asian	28	29	25	25	107
Native Hawaiian or Other Pacific Islander	0	0	0	0	0
Black or African American	0	0	0	0	0
White	52	57	52	52	213
More than one race	2	2	2	0	6
Unknown or Not Reported	0	0	0	0	0
Region of Enrollment
Units: Subjects
South Korea	10	14	12	11	47
Netherlands	0	2	2	0	4
United States	5	3	4	3	15
Japan	3	3	0	1	7
Taiwan	13	12	13	13	51
Germany	0	2	1	0	3
Canada	2	3	2	2	9
Hungary	3	2	2	3	10
Mexico	8	7	8	7	30
Poland	16	15	15	16	62
Russia	12	13	11	12	48
Czech Republic	14	14	13	13	54

End points

Top of page

Reporting group title

Placebo (PBO)

Reporting group description

Participants received placebo every two weeks by subcutaneous injection.

Reporting group title

Adalimumab

Reporting group description

Blinded Treatment Period:Participants received 40mg Adalimumab every two weeks by SC injection.

Reporting group title

IXE80Q2W

Reporting group description

Participants received starting dose of either 80 milligrams (mg) or 160mg Ixekizumab at week 0 followed by 80mg Ixekizumab every two weeks by subcutaneous injection.

Reporting group title

IXE80Q4W

Reporting group description

Participants received starting dose of either 80 milligrams (mg) or 160mg Ixekizumab at week 0 followed by 80mg Ixekizumab every four weeks by subcutaneous injection.

Reporting group title

PBO/IXE

Reporting group description

Participants received starting dose of 160mg Ixekizumab at week 16 followed by 80mg Ixekizumab either every two weeks (Q2W) or every four weeks (Q4W) by subcutaneous (SC) injection.

Reporting group title

Adalimumab/PBO/IXE

Reporting group description

Reporting group title

IXE80Q2W/IXE80Q2W

Reporting group description

Participants received starting dose of either 80 milligrams (mg) or 160mg Ixekizumab at week 0 followed by 80mg Ixekizumab every two weeks by subcutaneous injection.

Reporting group title

IXE80Q4W/IXE80Q4W

Reporting group description

Participants received starting dose of either 80 milligrams (mg) or 160mg Ixekizumab at week 0 followed by 80mg Ixekizumab every four weeks by subcutaneous injection.

Reporting group title

Placebo (PBO)

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.

Reporting group title

IXE80Q4W

Reporting group description

Participants did not receive any intervention during Follow-up period.

Subject analysis set title

PBO/IXE

Subject analysis set type

Per protocol

Subject analysis set description

Participants received placebo every two weeks during blinded treatment period and starting dose of 160mg Ixekizumab at week 16 followed by 80mg Ixekizumab either Q2W or Q4W extended treatment period by subcutaneous injection.

Subject analysis set title

Adalimumab/IXE

Subject analysis set type

Per protocol

Subject analysis set description

Participants received 40mg Adalimumab every two weeks during blinded treatment period and 80mg Ixekizumab either Q2W or Q4W during extended treatment period by subcutaneous injection.

Subject analysis set title

IXE80Q4W/IXE80Q4W

Subject analysis set type

Per protocol

Subject analysis set description

Participants received starting dose of either 80 milligrams (mg) or 160mg Ixekizumab at week 0 followed by 80mg Ixekizumab every four weeks during blinded treatment and extension period by subcutaneous injection.

Subject analysis set title

IXE80Q2W/IXE80Q2W

Subject analysis set type

Per protocol

Subject analysis set description

Participants received starting dose of either 80 milligrams (mg) or 160mg Ixekizumab at week 0 followed by 80mg Ixekizumab every two weeks during blinded treatment and extension period by subcutaneous injection.

Subject analysis set title

IXE160/80Q4W

Subject analysis set type

Per protocol

Subject analysis set description

Participants received starting dose of 160mg Ixekizumab at week 0 followed by 80mg Ixekizumab every four weeks by subcutaneous injection.

Subject analysis set title

IXE160/80Q2W

Subject analysis set type

Per protocol

Subject analysis set description

Participants received starting dose of 160mg Ixekizumab at week 0 followed by 80mg Ixekizumab every two weeks by subcutaneous injection.

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

Top of page

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 greater than or equal to (>=) 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 domains. 1.Patient Global: How active was your spondylitis on average during the last week? score range 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: Participant is asked to rate the difficulty associated with 10 individual basic functional activities. Participants response is captured using NRS scale (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

Primary

End point timeframe

Week 16

End point values	Placebo (PBO)	Adalimumab	IXE80Q2W	IXE80Q4W
Number of subjects analysed	86 ^[1]	90	83	81
Units: percentage of participants
number (not applicable)	18.4	35.6	51.8	48.1

Notes
[1] - Total participants 87, one participant who did not receive study drug is included in the analysis.

Statistical Analysis 1

Comparison groups

Placebo (PBO) v Adalimumab

Number of subjects included in analysis

176

Analysis specification

Pre-specified

Analysis type

superiority ^[2]

P-value

= 0.005

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.73

Confidence interval

level

95%

sides

2-sided

lower limit

1.35

upper limit

5.52

Notes
[2] - Total participants 177. one participant who did not receive study drug is included in the analysis.

Statistical Analysis 2

Comparison groups

Placebo (PBO) v IXE80Q4W

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority ^[3]

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.45

Confidence interval

level

95%

sides

2-sided

lower limit

2.2

upper limit

9.03

Notes
[3] - Total participants 168. one participant who did not receive study drug is included in the analysis.

Statistical Analysis 3

Comparison groups

Placebo (PBO) v IXE80Q2W

Number of subjects included in analysis

169

Analysis specification

Pre-specified

Analysis type

superiority ^[4]

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

5.09

Confidence interval

level

95%

sides

2-sided

lower limit

2.52

upper limit

10.28

Notes
[4] - Total participants 170. one participant who did not receive study drug is included in the analysis.

Secondary: Percentage of Participants Achieving an ASAS20 Response

Top of page

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 in ≥3 of 4 following 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 range 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: Participant is asked to rate the difficulty associated with 10 individual basic functional activities. Participants response is captured using NRS scale (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). Analysis Population Description (APD): All Randomized Participants.

End point type

Secondary

End point timeframe

Week 16

End point values	Placebo (PBO)	Adalimumab	IXE80Q2W	IXE80Q4W
Number of subjects analysed	86	90	83	81
Units: percentage of participants
number (not applicable)	40.2	58.9	68.7	64.2

Statistical Analysis 1

Comparison groups

Adalimumab v Placebo (PBO)

Number of subjects included in analysis

176

Analysis specification

Pre-specified

Analysis type

superiority ^[5]

P-value

= 0.007

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.3

Confidence interval

level

95%

sides

2-sided

lower limit

1.25

upper limit

4.23

Notes
[5] - Total participants 177. one participant who did not receive study drug is included in the analysis.

Statistical Analysis 2

Comparison groups

Placebo (PBO) v IXE80Q4W

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority ^[6]

P-value

= 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.78

Confidence interval

level

95%

sides

2-sided

lower limit

1.48

upper limit

5.24

Notes
[6] - Total participants 168. one participant who did not receive study drug is included in the analysis.

Statistical Analysis 3

Comparison groups

Placebo (PBO) v IXE80Q2W

Number of subjects included in analysis

169

Analysis specification

Pre-specified

Analysis type

superiority ^[7]

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.39

Confidence interval

level

95%

sides

2-sided

lower limit

1.79

upper limit

6.41

Notes
[7] - Total participants 170. one participant who did not receive study drug is included in the analysis.

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

Top of page

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 the following: 1.Total back pain 2.Patient global 3.Peripheral pain/swelling 4.Duration of morning stiffness 5.CRP in mg/L The ASDAScrp is calculated with the following equation: 0.121 × total back pain + 0.110 × patient global + 0.073 × peripheral pain/swelling + 0.058 × duration of morning stiffness + 0.579 × Ln(CRP+1). CRP is in mg/liter, the range of other variables is from 0 to 10.Data from five variables combined to yield a score (0.6361 to no defined upper limit), where higher scores indicated higher disease activity. Ln represents the natural logarithm. Least Square (LS) Mean was calculated using mixed model repeated measures (MMRM) model with treatment, geographic region, baseline CRP status, 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 (PBO)	Adalimumab	IXE80Q2W	IXE80Q4W
Number of subjects analysed	86 ^[8]	90	83	81
Units: score on a scale
least squares mean (standard error)	-0.46 ± 0.099	-1.30 ± 0.096	-1.37 ± 0.101	-1.43 ± 0.102

Notes
[8] - Total participants 87, one participant who did not receive study drug is included in the analysis.

Statistical Analysis 1

Comparison groups

Placebo (PBO) v Adalimumab

Number of subjects included in analysis

176

Analysis specification

Pre-specified

Analysis type

superiority ^[9]

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-0.84

Confidence interval

level

95%

sides

2-sided

lower limit

-1.11

upper limit

-0.57

Variability estimate

Standard error of the mean

Dispersion value

0.137

Notes
[9] - Total participants 177. one participant who did not receive study drug is included in the analysis.

Statistical Analysis 2

Comparison groups

Placebo (PBO) v IXE80Q4W

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority ^[10]

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-0.97

Confidence interval

level

95%

sides

2-sided

lower limit

-1.25

upper limit

-0.7

Variability estimate

Standard error of the mean

Dispersion value

0.141

Notes
[10] - Total participants 168. one participant who did not receive study drug is included in the analysis.

Statistical Analysis 3

Comparison groups

Placebo (PBO) v IXE80Q2W

Number of subjects included in analysis

169

Analysis specification

Pre-specified

Analysis type

superiority ^[11]

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-0.91

Confidence interval

level

95%

sides

2-sided

lower limit

-1.18

upper limit

-0.63

Variability estimate

Standard error of the mean

Dispersion value

0.14

Notes
[11] - Total participants 170. one participant who did not receive study drug is included in the analysis.

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

Top of page

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 measuring discomfort, pain, and fatigue. 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). 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 (PBO)	Adalimumab	IXE80Q2W	IXE80Q4W
Number of subjects analysed	86 ^[12]	90	83	81
Units: percentage of participants
number (not applicable)	17.2	32.2	43.4	42.0

Notes
[12] - Total participants 87, one participant who did not receive study drug is included in the analysis.

Statistical Analysis 1

Comparison groups

Placebo (PBO) v Adalimumab

Number of subjects included in analysis

176

Analysis specification

Pre-specified

Analysis type

superiority ^[13]

P-value

= 0.012

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.53

Confidence interval

level

95%

sides

2-sided

lower limit

1.23

upper limit

5.21

Notes
[13] - Total participants 177. one participant who did not receive study drug is included in the analysis.

Statistical Analysis 2

Comparison groups

Placebo (PBO) v IXE80Q4W

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority ^[14]

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.74

Confidence interval

level

95%

sides

2-sided

lower limit

1.82

upper limit

7.7

Notes
[14] - Total participants 168. one participant who did not receive study drug is included in the analysis.

Statistical Analysis 3

Comparison groups

Placebo (PBO) v IXE80Q2W

Number of subjects included in analysis

169

Analysis specification

Pre-specified

Analysis type

superiority ^[15]

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.9

Confidence interval

level

95%

sides

2-sided

lower limit

1.91

upper limit

7.98

Notes
[15] - Total participants 170. one participant who did not receive study drug is included in the analysis.

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 participants functional baseline and subsequent response to treatment. To complete the BASFI, a participant is asked to rate the difficulty associated with 10 individual basic functional activities. Participants respond to each question using an NRS scale (range 0 to 10) with a higher score indicating worse function. The participants final BASFI score is the mean of the 10 item scores has a possible minimum value of 0 and a possible maximum value of 10, with a higher score indicating worse function. LSMean was calculated using MMRM model with treatment, geographic region, baseline CRP status, 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 (PBO)	Adalimumab	IXE80Q2W	IXE80Q4W
Number of subjects analysed	86 ^[16]	90	83	81
Units: score on a scale
least squares mean (standard error)	-1.16 ± 0.215	-2.14 ± 0.209	-2.43 ± 0.219	-2.39 ± 0.222

Notes
[16] - Total participants 87, one participant who did not receive study drug is included in the analysis.

Statistical Analysis 1

Comparison groups

Placebo (PBO) v Adalimumab

Number of subjects included in analysis

176

Analysis specification

Pre-specified

Analysis type

superiority ^[17]

P-value

= 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-0.97

Confidence interval

level

95%

sides

2-sided

lower limit

-1.56

upper limit

-0.39

Variability estimate

Standard error of the mean

Dispersion value

0.299

Notes
[17] - Total participants 177. one participant who did not receive study drug is included in the analysis.

Statistical Analysis 2

Comparison groups

IXE80Q4W v Placebo (PBO)

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority ^[18]

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-1.22

Confidence interval

level

95%

sides

2-sided

lower limit

-1.83

upper limit

-0.62

Variability estimate

Standard error of the mean

Dispersion value

0.307

Notes
[18] - Total participants 168. one participant who did not receive study drug is included in the analysis.

Statistical Analysis 3

Comparison groups

Placebo (PBO) v IXE80Q2W

Number of subjects included in analysis

169

Analysis specification

Pre-specified

Analysis type

superiority ^[19]

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-1.27

Confidence interval

level

95%

sides

2-sided

lower limit

-1.86

upper limit

-0.67

Variability estimate

Standard error of the mean

Dispersion value

0.304

Notes
[19] - Total participants 170. one participant who did not receive study drug is included in the analysis.

Secondary: Percentage of Participants Achieving ASDAS Inactive Disease

Top of page

End point title

Percentage of Participants Achieving ASDAS Inactive Disease

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 the following: 1.Total back pain 2.Patient global 3.Peripheral pain/swelling 4.Duration of morning stiffness 5.CRP in mg/L The ASDAScrp is calculated with the following equation: 0.121 × total back pain + 0.110 × patient global + 0.073 × peripheral pain/swelling + 0.058 × duration of morning stiffness + 0.579 × Ln(CRP+1). CRP is in mg/liter, the range of other variables is from 0 to 10.Data from five variables combined to yield a score (0.6361 to no defined upper limit), where higher scores indicated higher disease activity. Ln represents the natural logarithm. 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 (PBO)	Adalimumab	IXE80Q2W	IXE80Q4W
Number of subjects analysed	86 ^[20]	90	83	81
Units: percentage of Participants
number (not applicable)	2.3	15.6	10.8	16.0

Notes
[20] - Total participants 87, one participant who did not receive study drug is included in the analysis.

Statistical Analysis 1

Comparison groups

Adalimumab v Placebo (PBO)

Number of subjects included in analysis

176

Analysis specification

Pre-specified

Analysis type

superiority ^[21]

P-value

= 0.009

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

7.62

Confidence interval

level

95%

sides

2-sided

lower limit

1.67

upper limit

34.68

Notes
[21] - Total participants 177. one participant who did not receive study drug is included in the analysis.

Statistical Analysis 2

Comparison groups

Placebo (PBO) v IXE80Q4W

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority ^[22]

P-value

= 0.007

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

8.03

Confidence interval

level

95%

sides

2-sided

lower limit

1.75

upper limit

36.83

Notes
[22] - Total participants 168. one participant who did not receive study drug is included in the analysis.

Statistical Analysis 3

Comparison groups

Placebo (PBO) v IXE80Q2W

Number of subjects included in analysis

169

Analysis specification

Pre-specified

Analysis type

superiority ^[23]

P-value

= 0.041

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

5.13

Confidence interval

level

95%

sides

2-sided

lower limit

1.07

upper limit

24.49

Notes
[23] - Total participants 170. one participant who did not receive study drug is included in the analysis.

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 Berlin modification of Ankylosing Spondylitis spine MRI score for activity (ASspiMRI) scoring technique assesses inflammation in each of 23 disco-vertebral units (DVU). All 23 disco-vertebral units (DVU) of the spine (from C2 to S1) are scored for 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. LSMean was calculated using ANCOVA model with treatment, geographic region, baseline CRP status and baseline value as fixed factors. APD: All Randomized Participants with baseline and week 16 Berlin score.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Placebo (PBO)	Adalimumab	IXE80Q2W	IXE80Q4W
Number of subjects analysed	81	82	76	78
Units: score on a scale
least squares mean (standard error)	-0.15 ± 0.323	-2.92 ± 0.314	-2.54 ± 0.330	-2.77 ± 0.328

Statistical Analysis 1

Comparison groups

Placebo (PBO) v Adalimumab

Number of subjects included in analysis

163

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

LSMean Difference

Point estimate

-2.78

Confidence interval

level

95%

sides

2-sided

lower limit

-3.7

upper limit

-1.9

Variability estimate

Standard error of the mean

Dispersion value

0.447

Statistical Analysis 2

Comparison groups

Placebo (PBO) v IXE80Q4W

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

LSMean Difference

Point estimate

-2.62

Confidence interval

level

95%

sides

2-sided

lower limit

-3.5

upper limit

-1.7

Variability estimate

Standard error of the mean

Dispersion value

0.45

Statistical Analysis 3

Comparison groups

Placebo (PBO) v IXE80Q2W

Number of subjects included in analysis

157

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

LSMean Difference

Point estimate

-2.39

Confidence interval

level

95%

sides

2-sided

lower limit

-3.3

upper limit

-1.5

Variability estimate

Standard error of the mean

Dispersion value

0.452

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

Top of page

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 calculated using MMRM model with treatment, geographic region, baseline CRP status, 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 (PBO)	Adalimumab	IXE80Q2W	IXE80Q4W
Number of subjects analysed	86 ^[24]	90	83	81
Units: score on a scale
least squares mean (standard error)
PCS	3.6432 ± 0.7530	6.9005 ± 0.7310	7.9686 ± 0.7665	7.6952 ± 0.7768
MCS	2.1229 ± 0.8431	2.5550 ± 0.8225	2.5696 ± 0.8650	2.7502 ± 0.8763

Notes
[24] - Total participants 87, one participant who did not receive study drug is included in the analysis.

Statistical Analysis 1

Statistical analysis description

PCS

Comparison groups

Placebo (PBO) v Adalimumab

Number of subjects included in analysis

176

Analysis specification

Pre-specified

Analysis type

superiority ^[25]

P-value

= 0.002

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

3.2574

Confidence interval

level

95%

sides

2-sided

lower limit

1.2041

upper limit

5.3106

Variability estimate

Standard error of the mean

Dispersion value

1.0437

Notes
[25] - Total participants 177. one participant who did not receive study drug is included in the analysis.

Statistical Analysis 2

Statistical analysis description

PCS

Comparison groups

Placebo (PBO) v IXE80Q4W

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority ^[26]

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

4.052

Confidence interval

level

95%

sides

2-sided

lower limit

1.9432

upper limit

6.1608

Variability estimate

Standard error of the mean

Dispersion value

1.072

Notes
[26] - Total participants 168. one participant who did not receive study drug is included in the analysis.

Statistical Analysis 3

Statistical analysis description

PCS

Comparison groups

Placebo (PBO) v IXE80Q2W

Number of subjects included in analysis

169

Analysis specification

Pre-specified

Analysis type

superiority ^[27]

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

4.3254

Confidence interval

level

95%

sides

2-sided

lower limit

2.2321

upper limit

6.4186

Variability estimate

Standard error of the mean

Dispersion value

1.0641

Notes
[27] - Total participants 170. one participant who did not receive study drug is included in the analysis.

Statistical Analysis 4

Statistical analysis description

MCS

Comparison groups

Placebo (PBO) v Adalimumab

Number of subjects included in analysis

176

Analysis specification

Pre-specified

Analysis type

superiority ^[28]

P-value

= 0.713

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

0.4321

Confidence interval

level

95%

sides

2-sided

lower limit

-1.8732

upper limit

2.7373

Variability estimate

Standard error of the mean

Dispersion value

1.1718

Notes
[28] - Total participants 177. one participant who did not receive study drug is included in the analysis.

Statistical Analysis 5

Statistical analysis description

MCS

Comparison groups

Placebo (PBO) v IXE80Q4W

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority ^[29]

P-value

= 0.602

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

0.6273

Confidence interval

level

95%

sides

2-sided

lower limit

-1.7387

upper limit

2.9934

Variability estimate

Standard error of the mean

Dispersion value

1.2028

Notes
[29] - Total participants 167. one participant who did not receive study drug is included in the analysis.

Statistical Analysis 6

Statistical analysis description

MCS

Comparison groups

Placebo (PBO) v IXE80Q2W

Number of subjects included in analysis

169

Analysis specification

Pre-specified

Analysis type

superiority ^[30]

P-value

= 0.709

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

0.4467

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9097

upper limit

2.803

Variability estimate

Standard error of the mean

Dispersion value

1.1978

Notes
[30] - Total participants 169. one participant who did not receive study drug is included in the analysis.

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

Top of page

End point title

Change from Baseline in ASAS Health Index (ASAS HI)

End point description

ASAS HI is a disease-specific health-index instrument designed to assess the impact of interventions for SpA, including axSpA. The 17-item instrument has scores ranging from 0 (good health) to 17 (poor health). Each item consists of one question that the participant needs to respond to with either "I agree" (score of 1) or "I do not agree" (score of 0). A score of "1" is given where the item is affirmed, indicating adverse health. All item scores are summed to give a total score or index. LSMean was calculated using MMRM model with treatment, geographic region, baseline CRP status, 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 (PBO)	Adalimumab	IXE80Q2W	IXE80Q4W
Number of subjects analysed	86 ^[31]	90	83	81
Units: score on a scale
least squares mean (standard error)	-1.25 ± 0.300	-2.30 ± 0.292	-2.74 ± 0.306	-2.36 ± 0.311

Notes
[31] - Total participants 87, one participant who did not receive study drug is included in the analysis.

Statistical Analysis 1

Comparison groups

Placebo (PBO) v Adalimumab

Number of subjects included in analysis

176

Analysis specification

Pre-specified

Analysis type

superiority ^[32]

P-value

= 0.012

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-1.05

Confidence interval

level

95%

sides

2-sided

lower limit

-1.87

upper limit

-0.23

Variability estimate

Standard error of the mean

Dispersion value

0.416

Notes
[32] - Total participants 177. one participant who did not receive study drug is included in the analysis.

Statistical Analysis 2

Comparison groups

Placebo (PBO) v IXE80Q4W

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority ^[33]

P-value

= 0.01

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-1.11

Confidence interval

level

95%

sides

2-sided

lower limit

-1.95

upper limit

-0.27

Variability estimate

Standard error of the mean

Dispersion value

0.428

Notes
[33] - Total participants 168. one participant who did not receive study drug is included in the analysis.

Statistical Analysis 3

Comparison groups

IXE80Q2W v Placebo (PBO)

Number of subjects included in analysis

169

Analysis specification

Pre-specified

Analysis type

superiority ^[34]

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-1.49

Confidence interval

level

95%

sides

2-sided

lower limit

-2.32

upper limit

-0.66

Variability estimate

Standard error of the mean

Dispersion value

0.423

Notes
[34] - Total participants 170. one participant who did not receive study drug is included in the analysis.

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 will be measured with a high sensitivity assay at the central laboratory to help assess the effect of Ixekizumab on disease activity. LSMean was calculated using MMRM model with treatment, geographic region, baseline CRP status, 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 (PBO)	Adalimumab	IXE80Q2W	IXE80Q4W
Number of subjects analysed	86 ^[35]	90	83	81
Units: Milliragm per Litre (mg/mL)
least squares mean (standard error)	1.426 ± 1.9244	-7.202 ± 1.8688	-6.565 ± 1.9582	-5.209 ± 1.9803

Notes
[35] - Total participants 87, one participant who did not receive study drug is included in the analysis.

Statistical Analysis 1

Comparison groups

Placebo (PBO) v Adalimumab

Number of subjects included in analysis

176

Analysis specification

Pre-specified

Analysis type

superiority ^[36]

P-value

= 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-8.628

Confidence interval

level

95%

sides

2-sided

lower limit

-13.885

upper limit

-3.371

Variability estimate

Standard error of the mean

Dispersion value

2.6724

Notes
[36] - Total participants 177. one participant who did not receive study drug is included in the analysis.

Statistical Analysis 2

Comparison groups

Placebo (PBO) v IXE80Q4W

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority ^[37]

P-value

= 0.016

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-6.635

Confidence interval

level

95%

sides

2-sided

lower limit

-12.033

upper limit

-1.238

Variability estimate

Standard error of the mean

Dispersion value

2.7438

Notes
[37] - Total participants 168. one participant who did not receive study drug is included in the analysis.

Statistical Analysis 3

Comparison groups

Placebo (PBO) v IXE80Q2W

Number of subjects included in analysis

169

Analysis specification

Pre-specified

Analysis type

superiority ^[38]

P-value

= 0.004

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-7.991

Confidence interval

level

95%

sides

2-sided

lower limit

-13.351

upper limit

-2.631

Variability estimate

Standard error of the mean

Dispersion value

2.7248

Notes
[38] - Total participants 169. one participant who did not receive study drug is included in the analysis.

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

Top of page

End point title

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

End point description

The BASMI is a combined index comprising the following 5 clinical measurements of spinal mobility in participants with rad-axSpA. 1) Lateral spinal flexion 2)Tragus-to-wall distance 3) Lumbar flexion (modified Schrober) 4) Maximal intermalleolar distance 5)Cervical rotation. The BASMI includes these 5 measurements that are each scaled to a score of 0 to 10 depending on the result of the assessment (BASMI linear function). The average score of the 5 assessments gives the BASMI linear result. The higher the BASMI score the more severe the participants limitation of movement due to their AS. LSMean was calculated using MMRM model with treatment, geographic region, baseline CRP status, 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 (PBO)	Adalimumab	IXE80Q2W	IXE80Q4W
Number of subjects analysed	86 ^[39]	90	83	81
Units: score on a scale
least squares mean (standard error)	-0.080 ± 0.0826	-0.447 ± 0.0800	-0.408 ± 0.0840	-0.447 ± 0.0858

Notes
[39] - Total participants 87, one participant who did not receive study drug is included in the analysis.

Statistical Analysis 1

Comparison groups

Placebo (PBO) v Adalimumab

Number of subjects included in analysis

176

Analysis specification

Pre-specified

Analysis type

superiority ^[40]

P-value

= 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-0.367

Confidence interval

level

95%

sides

2-sided

lower limit

-0.592

upper limit

-0.142

Variability estimate

Standard error of the mean

Dispersion value

0.1143

Notes
[40] - Total participants 177. one participant who did not receive study drug is included in the analysis.

Statistical Analysis 2

Comparison groups

Placebo (PBO) v IXE80Q4W

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority ^[41]

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-0.422

Confidence interval

level

95%

sides

2-sided

lower limit

-0.655

upper limit

-0.189

Variability estimate

Standard error of the mean

Dispersion value

0.1184

Notes
[41] - Total participants 168. one participant who did not receive study drug is included in the analysis.

Statistical Analysis 3

Comparison groups

Placebo (PBO) v IXE80Q2W

Number of subjects included in analysis

169

Analysis specification

Pre-specified

Analysis type

superiority ^[42]

P-value

= 0.005

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-0.329

Confidence interval

level

95%

sides

2-sided

lower limit

-0.558

upper limit

-0.099

Variability estimate

Standard error of the mean

Dispersion value

0.1167

Notes
[42] - Total participants 170. one participant who did not receive study drug is included in the analysis.

Secondary: Change from Baseline in Chest Expansion

Top of page

End point title

Change from Baseline in Chest Expansion

End point description

While participants have their hands resting on or behind the head, the assessor has measured the chest’s encircled length by centimeter at the fourth intercostal level anteriorly. The difference between maximal inspiration and expiration in centimeters was recorded. Two tries were recorded. The better measurement (larger difference) of 2 tries (in centimeters) was used for analyses. LSMean was calculated using MMRM model with treatment, geographic region, baseline CRP status, 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 (PBO)	Adalimumab	IXE80Q2W	IXE80Q4W
Number of subjects analysed	86 ^[43]	90	83	81
Units: Centimeters (cm)
least squares mean (standard error)	0.06 ± 0.152	0.70 ± 0.148	0.67 ± 0.155	0.49 ± 0.158

Notes
[43] - Total participants 87, one participant who did not receive study drug is included in the analysis.

Statistical Analysis 1

Comparison groups

Placebo (PBO) v Adalimumab

Number of subjects included in analysis

176

Analysis specification

Pre-specified

Analysis type

superiority ^[44]

P-value

= 0.003

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

0.63

Confidence interval

level

95%

sides

2-sided

lower limit

0.22

upper limit

1.05

Variability estimate

Standard error of the mean

Dispersion value

0.211

Notes
[44] - Total participants 177. one participant who did not receive study drug is included in the analysis.

Statistical Analysis 2

Comparison groups

Placebo (PBO) v IXE80Q4W

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority ^[45]

P-value

= 0.051

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

0.43

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

0.86

Variability estimate

Standard error of the mean

Dispersion value

0.219

Notes
[45] - Total participants 168. one participant who did not receive study drug is included in the analysis.

Statistical Analysis 3

Comparison groups

Placebo (PBO) v IXE80Q2W

Number of subjects included in analysis

169

Analysis specification

Pre-specified

Analysis type

superiority ^[46]

P-value

= 0.005

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

0.6

Confidence interval

level

95%

sides

2-sided

lower limit

0.18

upper limit

1.03

Variability estimate

Standard error of the mean

Dispersion value

0.215

Notes
[46] - Total participants 170. one participant who did not receive study drug is included in the analysis.

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. LSMean was calculated using MMRM model with treatment, geographic region, baseline CRP status, 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 (PBO)	Adalimumab	IXE80Q2W	IXE80Q4W
Number of subjects analysed	86 ^[47]	90	83	81
Units: cm
least squares mean (standard error)	-0.06 ± 0.232	-0.72 ± 0.225	-0.73 ± 0.236	-0.69 ± 0.240

Notes
[47] - Total participants 87, one participant who did not receive study drug is included in the analysis.

Statistical Analysis 1

Comparison groups

Placebo (PBO) v Adalimumab

Number of subjects included in analysis

176

Analysis specification

Pre-specified

Analysis type

superiority ^[48]

P-value

= 0.039

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-0.67

Confidence interval

level

95%

sides

2-sided

lower limit

-1.3

upper limit

-0.03

Variability estimate

Standard error of the mean

Dispersion value

0.321

Notes
[48] - Total participants 177. one participant who did not receive study drug is included in the analysis.

Statistical Analysis 2

Comparison groups

Placebo (PBO) v IXE80Q4W

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority ^[49]

P-value

= 0.057

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-0.63

Confidence interval

level

95%

sides

2-sided

lower limit

-1.28

upper limit

0.02

Variability estimate

Standard error of the mean

Dispersion value

0.33

Notes
[49] - Total participants 168. one participant who did not receive study drug is included in the analysis.

Statistical Analysis 3

Comparison groups

Placebo (PBO) v IXE80Q2W

Number of subjects included in analysis

169

Analysis specification

Pre-specified

Analysis type

superiority ^[50]

P-value

= 0.042

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-0.67

Confidence interval

level

95%

sides

2-sided

lower limit

-1.31

upper limit

-0.03

Variability estimate

Standard error of the mean

Dispersion value

0.327

Notes
[50] - Total participants 170. one participant who did not receive study drug is included in the analysis.

Secondary: Change from Baseline in MRI sacroiliac joint(s) (SIJ) Spondyloarthritis Research Consortium of Canada (SPARCC) Score

Top of page

End point title

Change from Baseline in MRI sacroiliac joint(s) (SIJ) Spondyloarthritis Research Consortium of Canada (SPARCC) Score

End point description

Both left and right SIJ are scored for bone marrow edema.Each side has 6 slices and each slice has 6 scoring units, and each scoring unit has a score of 0 or 1. Total SIJ SPARCC scores can range from 0 to 72 with higher scores reflecting worse disease. LSMean was calculated using ANCOVA model with treatment, geographic region, baseline CRP status and baseline value as fixed factors. APD: All randomized participants with baseline and week 16 SPARCC score.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Placebo (PBO)	Adalimumab	IXE80Q2W	IXE80Q4W
Number of subjects analysed	81	82	77	78
Units: score on a scale
least squares mean (standard error)	0.92 ± 0.582	-4.21 ± 0.568	-4.25 ± 0.591	-3.97 ± 0.590

Statistical Analysis 1

Comparison groups

Placebo (PBO) v Adalimumab

Number of subjects included in analysis

163

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

LSMean Difference

Point estimate

-5.13

Confidence interval

level

95%

sides

2-sided

lower limit

-6.7

upper limit

-3.5

Variability estimate

Standard error of the mean

Dispersion value

0.806

Statistical Analysis 2

Comparison groups

Placebo (PBO) v IXE80Q4W

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

LSMean Difference

Point estimate

-4.89

Confidence interval

level

95%

sides

2-sided

lower limit

-6.5

upper limit

-3.3

Variability estimate

Standard error of the mean

Dispersion value

0.812

Statistical Analysis 3

Comparison groups

Placebo (PBO) v IXE80Q2W

Number of subjects included in analysis

158

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

LSMean Difference

Point estimate

-5.17

Confidence interval

level

95%

sides

2-sided

lower limit

-6.8

upper limit

-3.6

Variability estimate

Standard error of the mean

Dispersion value

0.816

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

Top of page

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. LSMean was calculated using MMRM model with treatment, geographic region, baseline CRP status, 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 (PBO)	Adalimumab	IXE80Q2W	IXE80Q4W
Number of subjects analysed	56	51	50	49
Units: score on a scale
least squares mean (standard error)	-2.1 ± 0.34	-2.6 ± 0.34	-2.4 ± 0.35	-2.3 ± 0.36

Statistical Analysis 1

Comparison groups

Placebo (PBO) v Adalimumab

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.317

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

0.5

Variability estimate

Standard error of the mean

Dispersion value

0.48

Statistical Analysis 2

Comparison groups

Placebo (PBO) v IXE80Q4W

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.683

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

0.8

Variability estimate

Standard error of the mean

Dispersion value

0.48

Statistical Analysis 3

Comparison groups

Placebo (PBO) v IXE80Q2W

Number of subjects included in analysis

106

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1.3

upper limit

0.6

Variability estimate

Standard error of the mean

Dispersion value

0.48

Secondary: Change from Baseline in SPARCC Enthesitis Score

Top of page

End point title

Change from Baseline in 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. LSMean was calculated using MMRM model with treatment, geographic region, baseline CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors. APD: All Randomized Participants with baseline SPARCC score > 0.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Placebo (PBO)	Adalimumab	IXE80Q2W	IXE80Q4W
Number of subjects analysed	41	40	35	40
Units: score on a scale
least squares mean (standard error)	-2.1 ± 0.40	-2.9 ± 0.40	-2.6 ± 0.43	-2.7 ± 0.40

Statistical Analysis 1

Comparison groups

Placebo (PBO) v Adalimumab

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.154

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

0.3

Variability estimate

Standard error of the mean

Dispersion value

0.56

Statistical Analysis 2

Comparison groups

IXE80Q4W v Placebo (PBO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.255

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-1.8

upper limit

0.5

Variability estimate

Standard error of the mean

Dispersion value

0.56

Statistical Analysis 3

Comparison groups

Placebo (PBO) v IXE80Q2W

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.398

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.6

upper limit

0.7

Variability estimate

Standard error of the mean

Dispersion value

0.58

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

Top of page

End point title

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

End point description

The number of tender and painful joints was determined by examination of 46 joints (23 joints on each side of the participants body. The 46 joints are assessed and classified as tender or not tender. sum of all joints checked to be tender/painful divided by number of evaluable joints which is multiplied by 46 to obtain TJC score. The scores ranges from 0 (no tender/painful joints) to 46 (all joints tender/painful). LSMean was calculated using MMRM model with treatment, geographic region, baseline CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors. APD: All Randomized Participants with baseline TJC > 0.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Placebo (PBO)	Adalimumab	IXE80Q2W	IXE80Q4W
Number of subjects analysed	51	49	45	44
Units: score on a scale
least squares mean (standard error)	-2.0 ± 0.53	-2.2 ± 0.55	-3.3 ± 0.58	-2.5 ± 0.58

Statistical Analysis 1

Comparison groups

Placebo (PBO) v Adalimumab

Number of subjects included in analysis

100

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.783

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1.7

upper limit

1.3

Variability estimate

Standard error of the mean

Dispersion value

0.76

Statistical Analysis 2

Comparison groups

Placebo (PBO) v IXE80Q4W

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.55

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

1.1

Variability estimate

Standard error of the mean

Dispersion value

0.78

Statistical Analysis 3

Comparison groups

Placebo (PBO) v IXE80Q2W

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.091

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-1.3

Confidence interval

level

95%

sides

2-sided

lower limit

-2.8

upper limit

0.2

Variability estimate

Standard error of the mean

Dispersion value

0.77

Secondary: Number of Participants with Anterior Uveitis or Uveitis Flares

Top of page

End point title

Number of Participants with Anterior Uveitis or Uveitis Flares

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

Baseline through Week 16

End point values	Placebo (PBO)	Adalimumab	IXE80Q2W	IXE80Q4W
Number of subjects analysed	86 ^[51]	90	83	81
Units: Count of Participants
number (not applicable)	0	0	0	1

Notes
[51] - Total participants 87, one participant who did not receive study drug is included in the analysis.

No statistical analyses for this end point

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

Top of page

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 one number that describes their worst level of fatigue during the previous 24 hours. LSMean was calculated using MMRM model with treatment, geographic region, baseline CRP status, 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 (PBO)	Adalimumab	IXE80Q2W	IXE80Q4W
Number of subjects analysed	86 ^[52]	90	83	81
Units: score on a scale
least squares mean (standard error)	-1.4 ± 0.23	-2.2 ± 0.23	-2.1 ± 0.24	-2.5 ± 0.24

Notes
[52] - Total participants 87, one participant who did not receive study drug is included in the analysis.

Statistical Analysis 1

Comparison groups

Placebo (PBO) v Adalimumab

Number of subjects included in analysis

176

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.027

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.3

upper limit

-0.1

Variability estimate

Standard error of the mean

Dispersion value

0.32

Statistical Analysis 2

Comparison groups

Placebo (PBO) v IXE80Q4W

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-1.7

upper limit

-0.4

Variability estimate

Standard error of the mean

Dispersion value

0.33

Statistical Analysis 3

Comparison groups

IXE80Q2W v Placebo (PBO)

Number of subjects included in analysis

169

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.035

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.3

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.33

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

Top of page

End point title

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

End point description

The 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. Participants report the number 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. LSMean was calculated using MMRM model with treatment, geographic region, baseline CRP status, 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 (PBO)	Adalimumab	IXE80Q2W	IXE80Q4W
Number of subjects analysed	86 ^[53]	90	83	81
Units: score on a scale
least squares mean (standard error)	-1.5 ± 0.41	-2.7 ± 0.40	-3.0 ± 0.42	-2.5 ± 0.43

Notes
[53] - Total participants 87, one participant who did not receive study drug is included in the analysis.

Statistical Analysis 1

Comparison groups

Placebo (PBO) v Adalimumab

Number of subjects included in analysis

176

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.041

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-1.2

Confidence interval

level

95%

sides

2-sided

lower limit

-2.3

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.57

Statistical Analysis 2

Comparison groups

Placebo (PBO) v IXE80Q4W

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.125

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-2.1

upper limit

0.3

Variability estimate

Standard error of the mean

Dispersion value

0.59

Statistical Analysis 3

Comparison groups

Placebo (PBO) v IXE80Q2W

Number of subjects included in analysis

169

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.013

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-1.4

Confidence interval

level

95%

sides

2-sided

lower limit

-2.6

upper limit

-0.3

Variability estimate

Standard error of the mean

Dispersion value

0.58

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

Top of page

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. Greater scores indicate greater impairment and less productivity. LSMean was calculated using ANCOVA model with treatment, geographic region, baseline CRP status and baseline value as fixed factors. APD: All Randomized Participants with baseline and week 16 WPAI score.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Placebo (PBO)	Adalimumab	IXE80Q2W	IXE80Q4W
Number of subjects analysed	86	88	83	80
Units: score on a scale
least squares mean (standard error)
Overall Work Impairment Score	-17.82 ± 3.254	-21.44 ± 2.921	-24.06 ± 3.299	-21.36 ± 3.061
Percentage of Activity Impairment	-14.1 ± 2.28	-21.1 ± 2.22	-23.4 ± 2.30	-23.0 ± 2.35

Statistical Analysis 1

Statistical analysis description

Overall Work Impairment Score Subjects in analysis: 110

Comparison groups

Placebo (PBO) v Adalimumab

Number of subjects included in analysis

174

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.408

Method

ANCOVA

Parameter type

LSMean Difference

Point estimate

-3.62

Confidence interval

level

95%

sides

2-sided

lower limit

-12.21

upper limit

4.98

Variability estimate

Standard error of the mean

Dispersion value

4.36

Statistical Analysis 2

Statistical analysis description

Overall Work Impairment Score. Subjects in Analysis: 105

Comparison groups

Placebo (PBO) v IXE80Q4W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.422

Method

ANCOVA

Parameter type

LSMean Difference

Point estimate

-3.53

Confidence interval

level

95%

sides

2-sided

lower limit

-12.2

upper limit

5.13

Variability estimate

Standard error of the mean

Dispersion value

4.393

Statistical Analysis 3

Statistical analysis description

Overall Work Impairment Score Subjects in this Analysis: 97

Comparison groups

Placebo (PBO) v IXE80Q2W

Number of subjects included in analysis

169

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.175

Method

ANCOVA

Parameter type

LSMean Difference

Point estimate

-6.24

Confidence interval

level

95%

sides

2-sided

lower limit

-15.27

upper limit

2.8

Variability estimate

Standard error of the mean

Dispersion value

4.582

Statistical Analysis 4

Statistical analysis description

Percentage of Activity Impairment

Comparison groups

Placebo (PBO) v Adalimumab

Number of subjects included in analysis

174

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

LSMean Difference

Point estimate

-7

Confidence interval

level

95%

sides

2-sided

lower limit

-13.2

upper limit

-0.7

Variability estimate

Standard error of the mean

Dispersion value

3.16

Statistical Analysis 5

Statistical analysis description

Percentage of Activity Impairment

Comparison groups

Placebo (PBO) v IXE80Q4W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

LSMean Difference

Point estimate

-8.9

Confidence interval

level

95%

sides

2-sided

lower limit

-15.2

upper limit

-2.5

Variability estimate

Standard error of the mean

Dispersion value

3.22

Statistical Analysis 6

Statistical analysis description

Percentage of Activity Impairment

Comparison groups

Placebo (PBO) v IXE80Q2W

Number of subjects included in analysis

169

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

LSMean Difference

Point estimate

-9.3

Confidence interval

level

95%

sides

2-sided

lower limit

-15.5

upper limit

-3

Variability estimate

Standard error of the mean

Dispersion value

3.19

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

Top of page

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).. ASAS-NSAID score=(equivalent NSAID score)x(days of intake during PI)x(days per week)/(PI in days). Higher scores indicate greater NSAIDs intake. 0= no intake, 100 = equivalent NSAID intake. Participants in Extended Treatment Period Population Who had NSAID Intake at Baseline.

End point type

Secondary

End point timeframe

Baseline, Week 52

End point values	PBO/IXE	Adalimumab/IXE	IXE80Q4W/IXE80Q4W	IXE80Q2W/IXE80Q2W
Number of subjects analysed	78	80	71	76
Units: score on a scale
arithmetic mean (standard deviation)	-10.28 ± 27.472	-5.91 ± 20.861	-7.62 ± 25.430	-9.91 ± 27.940

No statistical analyses for this end point

Secondary: Number of Participants with Anti Ixekizumab Antibodies

Top of page

End point title

Number of Participants with Anti Ixekizumab Antibodies

End point description

A treatment emergent - antidrug antibody (TE-ADA) positive patient is defined as: a) a patient with a >= 4-fold increase over a positive baseline antibody titer; or b) for a negative baseline titer, a patient with an increase from the baseline to a level of >= 1:10. APD: All randomized participants.

End point type

Secondary

End point timeframe

Week 16

End point values	Placebo (PBO)	Adalimumab	IXE80Q2W	IXE80Q4W
Number of subjects analysed	86	90	83	81
Units: participants
number (not applicable)	2	5	2	2

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

APD: All randomized participants who received at least one dose of Ixekizumab.

End point type

Secondary

End point timeframe

Week 16

End point values	IXE160/80Q4W	IXE160/80Q2W
Number of subjects analysed	39	38
Units: microgram per millilitre (μg/mL)
geometric mean (geometric coefficient of variation)	3.88 ± 55	11.3 ± 43

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

The number of swollen joints was determined by examination of 44 joints (22 joints on each side of the participants body. The 44 joints are assessed and classified as swollen or not swollen. "sum of all joints checked to be swollen" divided by "number of evaluable joints" and then multiplied by 44 to obtain SJC score. The SJC score ranges from 0 (no swollen joints) to 44 (all joints swollen). LSMean was calculated using MMRM model with treatment, geographic region, baseline CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors. APD: All Randomized Participants with baseline SJC > 0.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Placebo (PBO)	Adalimumab	IXE80Q2W	IXE80Q4W
Number of subjects analysed	22	23	20	24
Units: score on a scale
least squares mean (standard error)	-1.7 ± 0.55	-2.7 ± 0.53	-2.7 ± 0.57	-3.6 ± 0.53

Statistical Analysis 1

Comparison groups

Placebo (PBO) v Adalimumab

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.166

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-1.1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.6

upper limit

0.4

Variability estimate

Standard error of the mean

Dispersion value

0.76

Statistical Analysis 2

Comparison groups

Placebo (PBO) v IXE80Q4W

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.11

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-1.9

Confidence interval

level

95%

sides

2-sided

lower limit

-3.4

upper limit

-0.4

Variability estimate

Standard error of the mean

Dispersion value

0.73

Statistical Analysis 3

Comparison groups

Placebo (PBO) v IXE80Q2W

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.182

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.6

upper limit

0.5

Variability estimate

Standard error of the mean

Dispersion value

0.77

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 (DVUs) of the spine (from C2 to S1) are scored for bone marrow edema. A single DVU has a scoring range of 0 to 18, bringing the maximum total score to 414, with higher scores reflecting worse disease. Scoring was performed by central readers. LSMean was calculated using ANCOVA model with treatment, geographic region, baseline CRP status and baseline value as fixed factors. APD: All Randomized participants with baseline and week 16 SPARCC MRI score for spine.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Placebo (PBO)	Adalimumab	IXE80Q2W	IXE80Q4W
Number of subjects analysed	81	82	76	78
Units: score on a scale
least squares mean (standard error)	-1.51 ± 1.147	-11.57 ± 1.113	-9.58 ± 1.168	-11.02 ± 1.160

Statistical Analysis 1

Comparison groups

Placebo (PBO) v Adalimumab

Number of subjects included in analysis

163

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

LSMean Difference

Point estimate

-10.07

Confidence interval

level

95%

sides

2-sided

lower limit

-13.2

upper limit

-6.9

Variability estimate

Standard error of the mean

Dispersion value

1.588

Statistical Analysis 2

Comparison groups

Placebo (PBO) v IXE80Q4W

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

LSMean Difference

Point estimate

-9.51

Confidence interval

level

95%

sides

2-sided

lower limit

-12.6

upper limit

-6.4

Variability estimate

Standard error of the mean

Dispersion value

1.591

Statistical Analysis 3

Comparison groups

Placebo (PBO) v IXE80Q2W

Number of subjects included in analysis

157

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

LSMean Difference

Point estimate

-8.08

Confidence interval

level

95%

sides

2-sided

lower limit

-11.2

upper limit

-4.9

Variability estimate

Standard error of the mean

Dispersion value

1.603

Adverse events

Top of page

Timeframe for reporting adverse events

Up to 76 Weeks

Adverse event reporting additional description

All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

21.1

Reporting group title

IXE80Q4W-blinded treatment period

Reporting group description

Reporting group title

IXE80Q2W-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

ADA-blinded treatment period

Reporting group description

Reporting group title

IXE80Q4W/IXE80Q4W-extended treatment period

Reporting group description

Reporting group title

PBO/IXE-extended treatment period

Reporting group description

Reporting group title

ADA/PBO-washout treatment period

Reporting group description

Reporting group title

ADA/PBO/IXE-extended treatment period

Reporting group description

Reporting group title

IXE80Q2W-follow-up period

Reporting group description

Reporting group title

IXE80Q4W-follow-up period

Reporting group description

Reporting group title

PBO-follow-up period

Reporting group description

IXE80Q4W-blinded treatment period

IXE80Q2W-blinded treatment period

PBO-blinded treatment period

IXE80Q2W/IXE80Q2W-extended treatment period

ADA-blinded treatment period

IXE80Q4W/IXE80Q4W-extended treatment period

PBO/IXE-extended treatment period

ADA/PBO-washout treatment period

ADA/PBO/IXE-extended treatment period

IXE80Q2W-follow-up period

IXE80Q4W-follow-up period

PBO-follow-up period

Total subjects affected by serious adverse events

subjects affected / exposed

1 / 81 (1.23%)

1 / 83 (1.20%)

0 / 86 (0.00%)

3 / 79 (3.80%)

3 / 90 (3.33%)

4 / 78 (5.13%)

4 / 86 (4.65%)

0 / 88 (0.00%)

7 / 86 (8.14%)

0 / 24 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

number of deaths (all causes)

number of deaths resulting from adverse events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

bladder cancer

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 81 (0.00%)

0 / 83 (0.00%)

0 / 86 (0.00%)

0 / 79 (0.00%)

0 / 90 (0.00%)

0 / 78 (0.00%)

0 / 86 (0.00%)

0 / 88 (0.00%)

1 / 86 (1.16%)

0 / 24 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

parathyroid tumour benign

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 81 (0.00%)

0 / 83 (0.00%)

0 / 86 (0.00%)

0 / 79 (0.00%)

0 / 90 (0.00%)

0 / 78 (0.00%)

0 / 86 (0.00%)

0 / 88 (0.00%)

1 / 86 (1.16%)

0 / 24 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

skin papilloma

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 81 (0.00%)

0 / 83 (0.00%)

0 / 86 (0.00%)

1 / 79 (1.27%)

0 / 90 (0.00%)

0 / 78 (0.00%)

0 / 86 (0.00%)

0 / 88 (0.00%)

0 / 86 (0.00%)

0 / 24 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Investigations

blood creatine phosphokinase increased

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 81 (0.00%)

0 / 83 (0.00%)

0 / 86 (0.00%)

0 / 79 (0.00%)

0 / 90 (0.00%)

1 / 78 (1.28%)

0 / 86 (0.00%)

0 / 88 (0.00%)

0 / 86 (0.00%)

0 / 24 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

ankle fracture

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 81 (0.00%)

0 / 83 (0.00%)

0 / 86 (0.00%)

0 / 79 (0.00%)

1 / 90 (1.11%)

0 / 78 (0.00%)

0 / 86 (0.00%)

0 / 88 (0.00%)

0 / 86 (0.00%)

0 / 24 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

avulsion fracture

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 81 (0.00%)

0 / 83 (0.00%)

0 / 86 (0.00%)

1 / 79 (1.27%)

0 / 90 (0.00%)

0 / 78 (0.00%)

0 / 86 (0.00%)

0 / 88 (0.00%)

0 / 86 (0.00%)

0 / 24 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

cervical vertebral fracture

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 81 (0.00%)

0 / 83 (0.00%)

0 / 86 (0.00%)

0 / 79 (0.00%)

0 / 90 (0.00%)

0 / 78 (0.00%)

1 / 86 (1.16%)

0 / 88 (0.00%)

0 / 86 (0.00%)

0 / 24 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

post procedural haematoma

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 81 (0.00%)

0 / 83 (0.00%)

0 / 86 (0.00%)

0 / 79 (0.00%)

0 / 90 (0.00%)

0 / 78 (0.00%)

0 / 86 (0.00%)

0 / 88 (0.00%)

1 / 86 (1.16%)

0 / 24 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

radius fracture

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 81 (0.00%)

0 / 83 (0.00%)

0 / 86 (0.00%)

0 / 79 (0.00%)

0 / 90 (0.00%)

1 / 78 (1.28%)

0 / 86 (0.00%)

0 / 88 (0.00%)

0 / 86 (0.00%)

0 / 24 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

road traffic accident

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 81 (0.00%)

0 / 83 (0.00%)

0 / 86 (0.00%)

0 / 79 (0.00%)

0 / 90 (0.00%)

1 / 78 (1.28%)

0 / 86 (0.00%)

0 / 88 (0.00%)

0 / 86 (0.00%)

0 / 24 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac disorders

atrioventricular block complete

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 81 (0.00%)

0 / 83 (0.00%)

0 / 86 (0.00%)

0 / 79 (0.00%)

0 / 90 (0.00%)

0 / 78 (0.00%)

1 / 86 (1.16%)

0 / 88 (0.00%)

0 / 86 (0.00%)

0 / 24 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nervous system disorders

cerebral haemorrhage

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 81 (0.00%)

0 / 83 (0.00%)

0 / 86 (0.00%)

0 / 79 (0.00%)

0 / 90 (0.00%)

0 / 78 (0.00%)

0 / 86 (0.00%)

0 / 88 (0.00%)

1 / 86 (1.16%)

0 / 24 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

subarachnoid haemorrhage

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 81 (0.00%)

0 / 83 (0.00%)

0 / 86 (0.00%)

0 / 79 (0.00%)

0 / 90 (0.00%)

0 / 78 (0.00%)

0 / 86 (0.00%)

0 / 88 (0.00%)

1 / 86 (1.16%)

0 / 24 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood and lymphatic system disorders

lymphadenitis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 81 (0.00%)

0 / 83 (0.00%)

0 / 86 (0.00%)

0 / 79 (0.00%)

0 / 90 (0.00%)

0 / 78 (0.00%)

1 / 86 (1.16%)

0 / 88 (0.00%)

0 / 86 (0.00%)

0 / 24 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Reproductive system and breast disorders

adnexal torsion

alternative dictionary used: MedDRA 21.1

subjects affected / exposed ^[1]

0 / 13 (0.00%)

0 / 19 (0.00%)

0 / 15 (0.00%)

0 / 18 (0.00%)

1 / 17 (5.88%)

0 / 13 (0.00%)

0 / 15 (0.00%)

0 / 17 (0.00%)

0 / 16 (0.00%)

0 / 9 (0.00%)

0 / 3 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

crohn's disease

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 81 (0.00%)

1 / 83 (1.20%)

0 / 86 (0.00%)

0 / 79 (0.00%)

0 / 90 (0.00%)

0 / 78 (0.00%)

0 / 86 (0.00%)

0 / 88 (0.00%)

1 / 86 (1.16%)

0 / 24 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

dyspepsia

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 81 (0.00%)

1 / 83 (1.20%)

0 / 86 (0.00%)

0 / 79 (0.00%)

0 / 90 (0.00%)

0 / 78 (0.00%)

0 / 86 (0.00%)

0 / 88 (0.00%)

0 / 86 (0.00%)

0 / 24 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Skin and subcutaneous tissue disorders

erythema multiforme

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 81 (0.00%)

1 / 83 (1.20%)

0 / 86 (0.00%)

0 / 79 (0.00%)

0 / 90 (0.00%)

0 / 78 (0.00%)

0 / 86 (0.00%)

0 / 88 (0.00%)

0 / 86 (0.00%)

0 / 24 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal and urinary disorders

nephrolithiasis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 81 (0.00%)

0 / 83 (0.00%)

0 / 86 (0.00%)

0 / 79 (0.00%)

0 / 90 (0.00%)

0 / 78 (0.00%)

0 / 86 (0.00%)

0 / 88 (0.00%)

1 / 86 (1.16%)

0 / 24 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

arthritis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 81 (0.00%)

0 / 83 (0.00%)

0 / 86 (0.00%)

0 / 79 (0.00%)

0 / 90 (0.00%)

1 / 78 (1.28%)

0 / 86 (0.00%)

0 / 88 (0.00%)

0 / 86 (0.00%)

0 / 24 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

osteoarthritis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 81 (0.00%)

0 / 83 (0.00%)

0 / 86 (0.00%)

0 / 79 (0.00%)

0 / 90 (0.00%)

0 / 78 (0.00%)

1 / 86 (1.16%)

0 / 88 (0.00%)

0 / 86 (0.00%)

0 / 24 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

plica syndrome

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 81 (0.00%)

0 / 83 (0.00%)

0 / 86 (0.00%)

1 / 79 (1.27%)

0 / 90 (0.00%)

0 / 78 (0.00%)

0 / 86 (0.00%)

0 / 88 (0.00%)

0 / 86 (0.00%)

0 / 24 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infections and infestations

appendicitis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 81 (0.00%)

0 / 83 (0.00%)

0 / 86 (0.00%)

0 / 79 (0.00%)

1 / 90 (1.11%)

0 / 78 (0.00%)

0 / 86 (0.00%)

0 / 88 (0.00%)

0 / 86 (0.00%)

0 / 24 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

cellulitis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 81 (0.00%)

0 / 83 (0.00%)

0 / 86 (0.00%)

0 / 79 (0.00%)

0 / 90 (0.00%)

0 / 78 (0.00%)

1 / 86 (1.16%)

0 / 88 (0.00%)

0 / 86 (0.00%)

0 / 24 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

gastroenteritis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 81 (0.00%)

1 / 83 (1.20%)

0 / 86 (0.00%)

0 / 79 (0.00%)

0 / 90 (0.00%)

0 / 78 (0.00%)

0 / 86 (0.00%)

0 / 88 (0.00%)

0 / 86 (0.00%)

0 / 24 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pneumonia haemophilus

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 81 (0.00%)

0 / 83 (0.00%)

0 / 86 (0.00%)

0 / 79 (0.00%)

0 / 90 (0.00%)

0 / 78 (0.00%)

0 / 86 (0.00%)

0 / 88 (0.00%)

1 / 86 (1.16%)

0 / 24 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

tonsillitis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 81 (0.00%)

0 / 83 (0.00%)

0 / 86 (0.00%)

1 / 79 (1.27%)

0 / 90 (0.00%)

0 / 78 (0.00%)

0 / 86 (0.00%)

0 / 88 (0.00%)

0 / 86 (0.00%)

0 / 24 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

urinary tract infection

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

1 / 81 (1.23%)

0 / 83 (0.00%)

0 / 86 (0.00%)

0 / 79 (0.00%)

0 / 90 (0.00%)

0 / 78 (0.00%)

0 / 86 (0.00%)

0 / 88 (0.00%)

0 / 86 (0.00%)

0 / 24 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

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

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

IXE80Q4W-blinded treatment period

IXE80Q2W-blinded treatment period

PBO-blinded treatment period

IXE80Q2W/IXE80Q2W-extended treatment period

ADA-blinded treatment period

IXE80Q4W/IXE80Q4W-extended treatment period

PBO/IXE-extended treatment period

ADA/PBO-washout treatment period

ADA/PBO/IXE-extended treatment period

IXE80Q2W-follow-up period

IXE80Q4W-follow-up period

PBO-follow-up period

Total subjects affected by non serious adverse events

subjects affected / exposed

11 / 81 (13.58%)

18 / 83 (21.69%)

12 / 86 (13.95%)

21 / 79 (26.58%)

16 / 90 (17.78%)

14 / 78 (17.95%)

26 / 86 (30.23%)

8 / 88 (9.09%)

20 / 86 (23.26%)

2 / 24 (8.33%)

2 / 16 (12.50%)

1 / 1 (100.00%)

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

uterine leiomyoma

alternative dictionary used: MedDRA 21.1

subjects affected / exposed ^[2]

0 / 13 (0.00%)

0 / 19 (0.00%)

0 / 15 (0.00%)

0 / 18 (0.00%)

1 / 17 (5.88%)

0 / 13 (0.00%)

0 / 15 (0.00%)

0 / 17 (0.00%)

0 / 16 (0.00%)

0 / 9 (0.00%)

0 / 3 (0.00%)

0 / 1 (0.00%)

occurrences all number

General disorders and administration site conditions

injection site reaction

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 81 (0.00%)

7 / 83 (8.43%)

2 / 86 (2.33%)

6 / 79 (7.59%)

3 / 90 (3.33%)

3 / 78 (3.85%)

8 / 86 (9.30%)

0 / 88 (0.00%)

8 / 86 (9.30%)

0 / 24 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences all number

Eye disorders

ocular discomfort

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 81 (0.00%)

0 / 83 (0.00%)

0 / 86 (0.00%)

0 / 79 (0.00%)

0 / 90 (0.00%)

0 / 78 (0.00%)

0 / 86 (0.00%)

0 / 88 (0.00%)

0 / 86 (0.00%)

0 / 24 (0.00%)

0 / 16 (0.00%)

1 / 1 (100.00%)

occurrences all number

Reproductive system and breast disorders

adnexal torsion

alternative dictionary used: MedDRA 21.1

subjects affected / exposed ^[3]

0 / 13 (0.00%)

0 / 19 (0.00%)

0 / 15 (0.00%)

0 / 18 (0.00%)

1 / 17 (5.88%)

0 / 13 (0.00%)

0 / 15 (0.00%)

0 / 17 (0.00%)

0 / 16 (0.00%)

0 / 9 (0.00%)

0 / 3 (0.00%)

0 / 1 (0.00%)

occurrences all number

menopausal symptoms

alternative dictionary used: MedDRA 21.1

subjects affected / exposed ^[4]

0 / 13 (0.00%)

0 / 19 (0.00%)

0 / 15 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 13 (0.00%)

0 / 15 (0.00%)

0 / 17 (0.00%)

0 / 16 (0.00%)

0 / 9 (0.00%)

0 / 3 (0.00%)

1 / 1 (100.00%)

occurrences all number

menstruation irregular

alternative dictionary used: MedDRA 21.1

subjects affected / exposed ^[5]

0 / 13 (0.00%)

0 / 19 (0.00%)

1 / 15 (6.67%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 13 (0.00%)

0 / 15 (0.00%)

0 / 17 (0.00%)

0 / 16 (0.00%)

0 / 9 (0.00%)

0 / 3 (0.00%)

0 / 1 (0.00%)

occurrences all number

Gastrointestinal disorders

diarrhoea

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 81 (0.00%)

2 / 83 (2.41%)

2 / 86 (2.33%)

4 / 79 (5.06%)

4 / 90 (4.44%)

2 / 78 (2.56%)

0 / 86 (0.00%)

0 / 88 (0.00%)

1 / 86 (1.16%)

1 / 24 (4.17%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences all number

Musculoskeletal and connective tissue disorders

back pain

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 81 (0.00%)

1 / 83 (1.20%)

1 / 86 (1.16%)

1 / 79 (1.27%)

1 / 90 (1.11%)

3 / 78 (3.85%)

0 / 86 (0.00%)

0 / 88 (0.00%)

1 / 86 (1.16%)

0 / 24 (0.00%)

2 / 16 (12.50%)

0 / 1 (0.00%)

occurrences all number

Infections and infestations

nasopharyngitis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

6 / 81 (7.41%)

5 / 83 (6.02%)

6 / 86 (6.98%)

7 / 79 (8.86%)

6 / 90 (6.67%)

8 / 78 (10.26%)

17 / 86 (19.77%)

6 / 88 (6.82%)

7 / 86 (8.14%)

0 / 24 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences all number

upper respiratory tract infection

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

7 / 81 (8.64%)

4 / 83 (4.82%)

4 / 86 (4.65%)

8 / 79 (10.13%)

2 / 90 (2.22%)

4 / 78 (5.13%)

4 / 86 (4.65%)

2 / 88 (2.27%)

4 / 86 (4.65%)

1 / 24 (4.17%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences all number

vaginal infection

alternative dictionary used: MedDRA 21.1

subjects affected / exposed ^[6]

0 / 13 (0.00%)

0 / 19 (0.00%)

0 / 15 (0.00%)

0 / 18 (0.00%)

1 / 17 (5.88%)

0 / 13 (0.00%)

0 / 15 (0.00%)

0 / 17 (0.00%)

0 / 16 (0.00%)

0 / 9 (0.00%)

0 / 3 (0.00%)

0 / 1 (0.00%)

occurrences all number

Notes
[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: Gender specific adverse event, 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: Gender specific adverse event, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
[4] - 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: Gender specific adverse event, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
[5] - 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: Gender specific adverse event, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
[6] - 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: Gender specific adverse event, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

23 Dec 2016

To remove specific limitation of enrolling equal numbers of participants with elevated/non-elevated CRP such that all patients who meet protocol eligibility criteria can be enrolled independent of having elevated or nonelevated CRP.

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

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: A Multicenter, Randomized, Double-Blind, Active and Placebo-Controlled 16 Week Study Followed by Long Term Evaluation of Efficacy and Safety of Ixekizumab (LY2439821) in bDMARD-Naive Patients with Radiographic Axial Spondyloarthritis.

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 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: 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 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 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 Mobility on the Bath Ankylosing Spondylitis Metrology Index (BASMI)

Secondary: Change from Baseline in Mobility on the 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 MRI sacroiliac joint(s) (SIJ) Spondyloarthritis Research Consortium of Canada (SPARCC) Score

Secondary: Change from Baseline in MRI sacroiliac joint(s) (SIJ) Spondyloarthritis Research Consortium of Canada (SPARCC) Score

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 SPARCC Enthesitis Score

Secondary: Change from Baseline in SPARCC Enthesitis Score

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

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

Secondary: Number of Participants with Anterior Uveitis or Uveitis Flares

Secondary: Number of Participants with Anterior Uveitis or Uveitis Flares

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: Number of Participants with Anti Ixekizumab Antibodies

Secondary: Number of Participants with Anti Ixekizumab Antibodies

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

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

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

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

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)

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, Active and Placebo-Controlled 16 Week Study Followed by Long Term Evaluation of Efficacy and Safety of Ixekizumab (LY2439821) in bDMARD-Naive Patients with Radiographic Axial Spondyloarthritis.