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Clinical Trial Results:
A 52 Week Multicenter, Randomized, Double-Blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of Ixekizumab (LY2439821) in bDMARD Naive Patients with Nonradiographic Axial Spondyloarthritis

Summary
EudraCT number	2015-003938-27
Trial protocol	DE RO FI CZ AT PL NL
Global end of trial date	07 May 2019

Results information
Results version number	v1(current)
This version publication date	15 Mar 2020
First version publication date	15 Mar 2020
Other versions

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

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Trial information

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Sponsor protocol code

I1F-MC-RHBX

ISRCTN number

US NCT number

NCT02757352

WHO universal trial number (UTN)

Other trial identifiers

Trial Number: 16180

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

07 May 2019

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

07 May 2019

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 biologic disease modifying antirheumatic drug (bDMARD) naïve participants with nonradiographic axial spondyloarthritis (nonrad-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 Aug 2016

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Czech Republic: 44

Country: Number of subjects enrolled

Argentina: 23

Country: Number of subjects enrolled

Romania: 9

Country: Number of subjects enrolled

United States: 28

Country: Number of subjects enrolled

Japan: 16

Country: Number of subjects enrolled

Russian Federation: 27

Country: Number of subjects enrolled

Canada: 6

Country: Number of subjects enrolled

Austria: 3

Country: Number of subjects enrolled

Korea, Republic of: 22

Country: Number of subjects enrolled

Netherlands: 1

Country: Number of subjects enrolled

Finland: 10

Country: Number of subjects enrolled

Brazil: 3

Country: Number of subjects enrolled

Poland: 57

Country: Number of subjects enrolled

Mexico: 42

Country: Number of subjects enrolled

Germany: 11

Worldwide total number of subjects

302

EEA total number of subjects

135

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)

296

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

This study has 3 periods: Period 1 - Screening; Period 2 - A Double-Blind Treatment Period (Weeks 0 Up to 52); (Inadequate Responders [IR] Week 16-52) followed by a Follow-Up Period (Up to 24 Weeks after last visit).

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

Double-Blind Period (Week 0-16)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Investigator, Subject

Are arms mutually exclusive

Yes

Placebo

Arm description

Participants received placebo (PBO) as 2 subcutaneous (SC) injections every two weeks (Q2W) to week 52.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Administered SC

Ixekizumab 80 mg Q4W (IXEQ4W)

Arm description

Participants received a starting dose of 80 or 160 milligram (mg) of ixekizumab given subcutaneously (SC) at week 0 followed by 80 mg ixekizumab given SC every four weeks (Q4W) to week 52.

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 a starting dose of 80 or 160 milligram (mg) of ixekizumab given subcutaneously (SC) at week 0 followed by 80 mg ixekizumab given SC every four weeks (Q4W) to week 52.

Ixekizumab 80 mg Q2W (IXEQ2W)

Arm description

Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 52.

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 a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC (Q2W) to week 52.

Number of subjects in period 1	Placebo	Ixekizumab 80 mg Q4W (IXEQ4W)	Ixekizumab 80 mg Q2W (IXEQ2W)
Started	104	96	102
Received at least one dose of study drug	104	96	102
Completed	97	95	98
Not completed	7	1	4
Consent withdrawn by subject	5	1	2
Adverse event, non-fatal	2	-	1
Lost to follow-up	-	-	1

Period 2 title

Double-Blind Period (Week 16-52)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Placebo

Arm description

Participants received placebo as 2 subcutaneous (SC) injections every two weeks (Q2W) to week 52.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Administered SC

Ixekizumab 80 mg Q4W (IXEQ4W)

Arm description

Participants received a starting dose of 80 or 160 milligram (mg) of ixekizumab given subcutaneously (SC) at week 0 followed by 80 mg ixekizumab given SC every four weeks (Q4W) to week 52.

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 a starting dose of 80 or 160 milligram (mg) of ixekizumab given subcutaneously (SC) at week 0 followed by 80 mg ixekizumab given SC every four weeks (Q4W) to week 52.

Ixekizumab 80 mg Q2W (IXEQ2W)

Arm description

Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 52.

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 a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC (Q2W) to week 52.

Number of subjects in period 2	Placebo	Ixekizumab 80 mg Q4W (IXEQ4W)	Ixekizumab 80 mg Q2W (IXEQ2W)
Started	97	95	98
Completed	34	52	52
Not completed	63	43	46
Consent withdrawn by subject	1	1	4
Adverse event, non-fatal	-	1	-
Classified as Inadequate Responders (IR)	62	40	42
Lack of efficacy	-	1	-

Period 3 title

IR Open Label Period (Week 16- Week 52)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

PBO Inadequate Responders (IR)/Ixekizumab 80 mg Q2W (IXE80Q2W)

Arm description

Participants who received placebo in double blind period and were inadequate responders as determined by investigators switched to ixekizumab 80 mg Q2W open label between week 16 to 44.

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 who received placebo in double blind period and were inadequate responders as determined by investigators switched to ixekizumab 80 mg Q2W open label between week 16 to 44.

Ixekizumab 80 mg Q4W IR (IXE80Q4WIR)/IXE80Q2W

Arm description

Participants who received ixekizumab 80 mg Q4W in double blind period and were inadequate responders as determined by investigators switched to ixekizumab 80 mg Q2W open label between week 16 to 44.

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 who received ixekizumab 80 mg Q4W in double blind period and were inadequate responders as determined by investigators switched to ixekizumab 80 mg Q2W open label between week 16 to 44.

IXE80Q2WIR/IXE80Q2W

Arm description

Participants who received ixekizumab 80 mg Q2W in double blind period and were inadequate responders as determined by investigators continued on the same regimen of ixekizumab 80 mg Q2W open label between week 16 to 44.

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

Number of subjects in period 3	PBO Inadequate Responders (IR)/Ixekizumab 80 mg Q2W (IXE80Q2W)	Ixekizumab 80 mg Q4W IR (IXE80Q4WIR)/IXE80Q2W	IXE80Q2WIR/IXE80Q2W
Started	62	40	42
Initiated Other Biologic Rescue	2 ^[1]	0 ^[2]	3 ^[3]
Completed	55	37	35
Not completed	7	3	7
Consent withdrawn by subject	2	1	1
Physician decision	-	-	1
Adverse event, non-fatal	3	-	1
Pregnancy	-	1	-
Lack of efficacy	2	1	4

Notes
[1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Inadequate responders who initiated other biologic rescue were also counted in the not completed row.
[2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Inadequate responders who initiated other biologic rescue were also counted in the not completed row.
[3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Inadequate responders who initiated other biologic rescue were also counted in the not completed row.

Period 4 title

Follow-Up Period

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Placebo

Arm description

Participants discontinued the study early and entered the post-treatment follow-up period. Participants received placebo immediately prior to entering the post-treatment follow-up period.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Ixekizumab 80 mg Q4W

Arm description

Participants discontinued the study early and entered the post-treatment follow-up period. Participants received ixekizumab 80 mg Q4W immediately prior to entering the post-treatment follow-up period.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Ixekizumab 80 mg Q2W

Arm description

Participants discontinued the study early and entered the post-treatment follow-up period. Participants received ixekizumab 80 mg Q2W immediately prior to entering the post-treatment follow-up period

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Other Biologic Treatment

Arm description

Participants who discontinued study treatment and were on other biologic therapy prior to entering Follow-up period.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Number of subjects in period 4	Placebo	Ixekizumab 80 mg Q4W	Ixekizumab 80 mg Q2W	Other Biologic Treatment
Started	3	5	28	5
Completed	2	4	18	2
Not completed	1	1	10	3
Consent withdrawn by subject	-	1	6	2
Adverse event, non-fatal	1	-	2	-
Lost to follow-up	-	-	1	-
Withdrawal due to loss of efficacy	-	-	-	1
Lack of efficacy	-	-	1	-

Baseline characteristics

Top of page

Reporting group title

Placebo

Reporting group description

Participants received placebo (PBO) as 2 subcutaneous (SC) injections every two weeks (Q2W) to week 52.

Reporting group title

Ixekizumab 80 mg Q4W (IXEQ4W)

Reporting group description

Participants received a starting dose of 80 or 160 milligram (mg) of ixekizumab given subcutaneously (SC) at week 0 followed by 80 mg ixekizumab given SC every four weeks (Q4W) to week 52.

Reporting group title

Ixekizumab 80 mg Q2W (IXEQ2W)

Reporting group description

Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 52.

Reporting group values	Placebo	Ixekizumab 80 mg Q4W (IXEQ4W)	Ixekizumab 80 mg Q2W (IXEQ2W)	Total
Number of subjects	104	96	102	302
Age categorical
Units: Subjects
Age continuous
Age
Units: years
arithmetic mean (standard deviation)	39.9 ( 12.36 )	40.9 ( 14.47 )	40.0 ( 12.01 )	-
Gender categorical
Gender
Units: Subjects
Female	61	46	53	160
Male	43	50	49	142
Ethnicity (NIH/OMB)
Ethnicity
Units: Subjects
Hispanic or Latino	25	24	31	80
Not Hispanic or Latino	67	57	63	187
Unknown or Not Reported	12	15	8	35
Race (NIH/OMB)
Race
Units: Subjects
American Indian or Alaska Native	8	2	3	13
Asian	17	13	11	41
Native Hawaiian or Other Pacific Islander	0	0	0	0
Black or African American	0	0	0	0
White	75	80	83	238
More than one race	3	1	5	9
Unknown or Not Reported	1	0	0	1
Region of Enrollment
Region of Enrollment
Units: Subjects
Argentina	8	6	9	23
Romania	4	1	4	9
United States	10	9	9	28
Czechia	15	16	13	44
Japan	6	5	5	16
Russia	12	7	8	27
Canada	1	3	2	6
Austria	0	1	2	3
South Korea	9	7	6	22
Netherlands	0	0	1	1
Finland	4	3	3	10
Brazil	0	1	2	3
Poland	19	18	20	57
Mexico	14	13	15	42
Germany	2	6	3	11

End points

Top of page

Reporting group title

Placebo

Reporting group description

Participants received placebo (PBO) as 2 subcutaneous (SC) injections every two weeks (Q2W) to week 52.

Reporting group title

Ixekizumab 80 mg Q4W (IXEQ4W)

Reporting group description

Participants received a starting dose of 80 or 160 milligram (mg) of ixekizumab given subcutaneously (SC) at week 0 followed by 80 mg ixekizumab given SC every four weeks (Q4W) to week 52.

Reporting group title

Ixekizumab 80 mg Q2W (IXEQ2W)

Reporting group description

Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 52.

Reporting group title

Placebo

Reporting group description

Participants received placebo as 2 subcutaneous (SC) injections every two weeks (Q2W) to week 52.

Reporting group title

Ixekizumab 80 mg Q4W (IXEQ4W)

Reporting group description

Participants received a starting dose of 80 or 160 milligram (mg) of ixekizumab given subcutaneously (SC) at week 0 followed by 80 mg ixekizumab given SC every four weeks (Q4W) to week 52.

Reporting group title

Ixekizumab 80 mg Q2W (IXEQ2W)

Reporting group description

Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 52.

Reporting group title

PBO Inadequate Responders (IR)/Ixekizumab 80 mg Q2W (IXE80Q2W)

Reporting group description

Participants who received placebo in double blind period and were inadequate responders as determined by investigators switched to ixekizumab 80 mg Q2W open label between week 16 to 44.

Reporting group title

Ixekizumab 80 mg Q4W IR (IXE80Q4WIR)/IXE80Q2W

Reporting group description

Participants who received ixekizumab 80 mg Q4W in double blind period and were inadequate responders as determined by investigators switched to ixekizumab 80 mg Q2W open label between week 16 to 44.

Reporting group title

IXE80Q2WIR/IXE80Q2W

Reporting group description

Reporting group title

Placebo

Reporting group description

Participants discontinued the study early and entered the post-treatment follow-up period. Participants received placebo immediately prior to entering the post-treatment follow-up period.

Reporting group title

Ixekizumab 80 mg Q4W

Reporting group description

Reporting group title

Ixekizumab 80 mg Q2W

Reporting group description

Participants discontinued the study early and entered the post-treatment follow-up period. Participants received ixekizumab 80 mg Q2W immediately prior to entering the post-treatment follow-up period

Reporting group title

Other Biologic Treatment

Reporting group description

Participants who discontinued study treatment and were on other biologic therapy prior to entering Follow-up period.

Subject analysis set title

IXE80Q2W-Q2W

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants received a starting dose of 80 ixekizumab as an SC injection at baseline followed by 80 mg of ixe every two weeks (Q2W) week 2 to week 52.

Subject analysis set title

IXE80Q4W-Q4W

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants received a starting dose of 80 ixekizumab as an SC injection followed by 80 mg of ixekizumab Q4W week 4 to week 52.

Subject analysis set title

PBO-IXE80Q2W

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants who received placebo in double blind period and were inadequate responders switched to ixekizumab 80 mg Q2W open-label between week 16 - 44.

Subject analysis set title

IXE80Q4W-Q2W

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants who received ixekizumab 80 mg Q4W in double blind period and were inadequate responders switched to ixekizumab 80 mg Q2W open label between week 16 - 44.

Subject analysis set title

IXEQ2W (80S)/IXEQ2W

Subject analysis set type

Sub-group analysis

Subject analysis set description

Ixekizumab was administered subcutaneously every 2 weeks with an 80 mg starting dose at week 0. 80 mg subcutaneously (80S)

Subject analysis set title

IXEQ2W (80S)/IXEQ2W Open Label

Subject analysis set type

Sub-group analysis

Subject analysis set description

Ixekizumab was administered every 2 weeks with an 80 mg starting dose at Week 0, then ixekizumab 80 mg Q2W open label between Week 16 and Week 52.

Subject analysis set title

IXEQ2W (160S)/IXEQ2W

Subject analysis set type

Sub-group analysis

Subject analysis set description

Ixekizumab was administered subcutaneously every 2 weeks with 160 mg starting dose at week 0. 160 mg subcutaneously (160S)

Subject analysis set title

IXEQ2W (160s)/IXEQ2W Open Label

Subject analysis set type

Sub-group analysis

Subject analysis set description

Ixekizumab was administered subcutaneously every 2 weeks with 160 mg starting dose at week 0 then ixekizumab 80 mg Q2W open label between Week 16 and Week 52.

Subject analysis set title

IXEQ4W (80S) IXEQ4W

Subject analysis set type

Sub-group analysis

Subject analysis set description

Ixekizumab was administered subcutaneously every 4 weeks with an 80 mg starting dose at week 0.

Subject analysis set title

IXEQ4W (80S)/IXEQ2W Open Label

Subject analysis set type

Sub-group analysis

Subject analysis set description

Ixekizumab was administered subcutaneously every 4 weeks with an 80 mg starting dose at week 0 then ixekizumab 80 mg Q2W open label between Week 16 and Week 52.

Subject analysis set title

IXEQ4W (160S)/IXEQ4W

Subject analysis set type

Sub-group analysis

Subject analysis set description

Ixekizumab was administered subcutaneously every 4 weeks with 160 mg starting dose at week 0.

Subject analysis set title

IXEQ4W (160S) IXEQ2W Open Label

Subject analysis set type

Sub-group analysis

Subject analysis set description

Ixekizumab was administered subcutaneously every 4 weeks with 160 mg starting dose at week 0 then ixekizumab 80 mg Q2W open label between Week 16 and Week 52.

Subject analysis set title

PBO/IXEQ2W Open Label

Subject analysis set type

Sub-group analysis

Subject analysis set description

Placebo was administered at week 0 then ixekizumab 80 mg Q2W open label between Week 16 and Week 52.

Subject analysis set title

IXEQ2W(80S)

Subject analysis set type

Sub-group analysis

Subject analysis set description

PK analysis at Week 16

Subject analysis set title

IXEQ2W(160S)

Subject analysis set type

Sub-group analysis

Subject analysis set description

PK analysis at Week 16

Subject analysis set title

IXEQ4W(80S)

Subject analysis set type

Sub-group analysis

Subject analysis set description

PK analysis at Week 16

Subject analysis set title

IXEQ4W(160S)

Subject analysis set type

Sub-group analysis

Subject analysis set description

PK analysis at Week 16

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

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End point title

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

End point description

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

End point type

Primary

End point timeframe

Week 16

End point values	Placebo	Ixekizumab 80 mg Q4W (IXEQ4W)	Ixekizumab 80 mg Q2W (IXEQ2W)
Number of subjects analysed	104 ^[1]	96 ^[2]	102 ^[3]
Units: percentage of participants
number (not applicable)	19.0	35.4	40.2

Notes
[1] - Total participants 105. One participant who did not receive study drug is included in the analysis.
[2] - All randomized participants.
[3] - All randomized participants.

Statistical Analysis ASAS40

Comparison groups

Placebo v Ixekizumab 80 mg Q4W (IXEQ4W)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority ^[4]

P-value

= 0.009

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.36

Confidence interval

level

95%

sides

2-sided

lower limit

1.23

upper limit

4.51

Notes
[4] - Total participants 201. One participant who did not receive study drug was included in the analysis.

Statistical Analysis ASAS40

Comparison groups

Placebo v Ixekizumab 80 mg Q2W (IXEQ2W)

Number of subjects included in analysis

206

Analysis specification

Pre-specified

Analysis type

superiority ^[5]

P-value

= 0.002

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

5.25

Notes
[5] - Total participants 207. One participant who did not receive study drug was included in the analysis.

Primary: Percentage of Participants Achieving an ASAS40 Response

Top of page

End point title

Percentage of Participants Achieving an ASAS40 Response

End point description

End point type

Primary

End point timeframe

Week 52

End point values	Placebo	Ixekizumab 80 mg Q4W (IXEQ4W)	Ixekizumab 80 mg Q2W (IXEQ2W)
Number of subjects analysed	104 ^[6]	96 ^[7]	102 ^[8]
Units: percentage of participants
number (not applicable)	13.3	30.2	31.4

Notes
[6] - Total participants 105. One participant who did not receive study drug is included in the analysis.
[7] - All randomized participants.
[8] - All randomized participants.

Percentage of Participants Achieving ASAS40

Comparison groups

Placebo v Ixekizumab 80 mg Q4W (IXEQ4W)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority ^[9]

P-value

= 0.004

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.82

Confidence interval

level

95%

sides

2-sided

lower limit

1.38

upper limit

5.77

Notes
[9] - Total participants 201. One participant who did not receive study drug was included in the analysis.

Percentage of Participants Achieving ASAS40

Comparison groups

Placebo v Ixekizumab 80 mg Q2W (IXEQ2W)

Number of subjects included in analysis

206

Analysis specification

Pre-specified

Analysis type

superiority ^[10]

P-value

= 0.004

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.85

Confidence interval

level

95%

sides

2-sided

lower limit

1.4

upper limit

5.77

Notes
[10] - Total participants 207. One participant who received at least one dose of study drug was included in the analysis.

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

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End point title

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

End point description

ASDAS is a composite index to assess disease activity in axial spondyloarthritis (axSpA). ASDAS parameters used with (C-reactive protein [CRP] as acute phase reactant) are: 1) Total back pain 2) Patient global 3) Peripheral pain/swelling, duration of morning stiffness 4) CRP in mg/L: ASDAScrp is calculated with the equation: 0.121 × total back pain + 0.110×patient global + 0.073 × peripheral pain/swelling + 0.058 × duration of morning stiffness + 0.579 × Ln(CRP+1). CRP is in milligram/liter (mg/L), the range of other variables is from 0 to 10. Data from five variables combined to yield a score (0.6361 to no defined upper limit), where higher scores indicated higher disease activity. Ln represents the natural logarithm. Least squares mean (LS Mean) was derived from mixed models repeated measure analysis (MMRM) with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Placebo	Ixekizumab 80 mg Q4W (IXEQ4W)	Ixekizumab 80 mg Q2W (IXEQ2W)
Number of subjects analysed	104 ^[11]	96 ^[12]	102 ^[13]
Units: score on a scale
least squares mean (standard error)	-0.58 ( 0.095 )	-1.12 ( 0.097 )	-1.26 ( 0.095 )

Notes
[11] - All randomized participants with evaluable data.
[12] - All randomized participants with evaluable data.
[13] - All randomized participants with evaluable data.

Statistical analysis ASDAS

Comparison groups

Placebo v Ixekizumab 80 mg Q4W (IXEQ4W)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-0.54

Confidence interval

level

95%

sides

2-sided

lower limit

-0.81

upper limit

-0.28

Variability estimate

Standard error of the mean

Dispersion value

0.136

Statistical analysis ASDAS

Comparison groups

Placebo v Ixekizumab 80 mg Q2W (IXEQ2W)

Number of subjects included in analysis

206

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-0.68

Confidence interval

level

95%

sides

2-sided

lower limit

-0.94

upper limit

-0.41

Variability estimate

Standard error of the mean

Dispersion value

0.134

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 axSpA. ASDAS parameters used (with CRP as acute phase reactant) are: 1 )Total back pain 2) Patient global 3) Peripheral pain/swelling 4) Duration of morning stiffness 5) CRP in mg/L: ASDAScrp is calculated with the following equation: 0.121 × total back pain + 0.110 × patient global + 0.073 × peripheral pain/swelling + 0.058 × duration of morning stiffness + 0.579 × Ln(CRP+1). CRP is in milligram/liter (mg/L), the range of other variables is from 0 to 10. Data from five variables combined to yield a score (0.6361 to no defined upper limit), where higher scores indicated higher disease activity. Ln represents the natural logarithm. LS Mean was derived from MMRM with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.

End point type

Secondary

End point timeframe

Baseline, Week 52

End point values	Placebo	Ixekizumab 80 mg Q4W (IXEQ4W)	Ixekizumab 80 mg Q2W (IXEQ2W)
Number of subjects analysed	104 ^[14]	96 ^[15]	102 ^[16]
Units: score on a scale
least squares mean (standard error)	-0.78 ( 0.136 )	-1.39 ( 0.116 )	-1.47 ( 0.116 )

Notes
[14] - All randomized participants with evaluable data.
[15] - All randomized participants with evaluable data.
[16] - All randomized participants with evaluable data.

Statistical Analysis ASDAS

Comparison groups

Placebo v Ixekizumab 80 mg Q4W (IXEQ4W)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-0.61

Confidence interval

level

95%

sides

2-sided

lower limit

-0.96

upper limit

-0.26

Variability estimate

Standard error of the mean

Dispersion value

0.179

Statistical Analysis ASDAS

Comparison groups

Placebo v Ixekizumab 80 mg Q2W (IXEQ2W)

Number of subjects included in analysis

206

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-0.69

Confidence interval

level

95%

sides

2-sided

lower limit

-1.05

upper limit

-0.34

Variability estimate

Standard error of the mean

Dispersion value

0.178

Secondary: Number of Participants without Clinically Meaningful Changes in Background Therapy

Top of page

End point title

Number of Participants without Clinically Meaningful Changes in Background Therapy

End point description

Number of participants without changes in background therapy while on originally randomized treatment.

End point type

Secondary

End point timeframe

Baseline, Week 52

End point values	Placebo	Ixekizumab 80 mg Q4W (IXEQ4W)	Ixekizumab 80 mg Q2W (IXEQ2W)
Number of subjects analysed	104 ^[17]	96 ^[18]	102 ^[19]
Units: participants
number (not applicable)	98	90	100

Notes
[17] - Total participants 105. One participant who did not receive study drug is included in the analysis.
[18] - All randomized participants.
[19] - All randomized participants.

No statistical analyses for this end point

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

Top of page

End point title

Change from Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) Score

End point description

The SF-36 is a 36-item patient-administered measure designed to be a short, multipurpose assessment of health in the areas of physical functioning, role – physical, role – emotional, bodily pain, vitality, social functioning, mental health, and general health. The Physical Component Summary score ranges from 0 to 100; higher scores indicate better levels of function and/or better health. LS Mean was derived from MMRM with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Placebo	Ixekizumab 80 mg Q4W (IXEQ4W)	Ixekizumab 80 mg Q2W (IXEQ2W)
Number of subjects analysed	104 ^[20]	96 ^[21]	102 ^[22]
Units: score on a scale
least squares mean (standard error)	5.2103 ( 0.7999 )	8.0612 ( 0.8129 )	7.9600 ( 0.8023 )

Notes
[20] - All randomized participants with evaluable data.
[21] - All randomized participants with evaluable data.
[22] - All randomized participants with evaluable data.

Change from Baseline in 36-Item Short Form Health

Comparison groups

Placebo v Ixekizumab 80 mg Q4W (IXEQ4W)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.013

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

2.8509

Confidence interval

level

95%

sides

2-sided

lower limit

0.6092

upper limit

5.0926

Variability estimate

Standard error of the mean

Dispersion value

1.139

Change from Baseline in 36-Item Short Form Health

Comparison groups

Placebo v Ixekizumab 80 mg Q2W (IXEQ2W)

Number of subjects included in analysis

206

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.015

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

2.7497

Confidence interval

level

95%

sides

2-sided

lower limit

0.5299

upper limit

4.9694

Variability estimate

Standard error of the mean

Dispersion value

1.1278

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

Top of page

End point title

Change from Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) Score

End point description

The medical outcomes study 36-item short-form health survey (SF-36) SF-36 PCS are summarized using the t-scores. The summary scores range from 0 to 100, with higher scores indicating better levels of function and/or better health. LS Mean was derived from MMRM with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.

End point type

Secondary

End point timeframe

Baseline, Week 52

End point values	Placebo	Ixekizumab 80 mg Q4W (IXEQ4W)	Ixekizumab 80 mg Q2W (IXEQ2W)
Number of subjects analysed	104 ^[23]	96 ^[24]	102 ^[25]
Units: score on a scale
least squares mean (standard error)	4.7210 ( 1.2459 )	8.9211 ( 1.0783 )	9.3291 ( 1.0810 )

Notes
[23] - All randomized participants with evaluable data.
[24] - All randomized participants with evaluable data.
[25] - All randomized participants with evaluable data.

Change from Baseline in 36-Item Short Form Health

Comparison groups

Placebo v Ixekizumab 80 mg Q4W (IXEQ4W)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.012

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

4.2001

Confidence interval

level

95%

sides

2-sided

lower limit

0.9525

upper limit

7.4477

Variability estimate

Standard error of the mean

Dispersion value

1.6467

Change from Baseline in 36-Item Short Form Health

Comparison groups

Placebo v Ixekizumab 80 mg Q2W (IXEQ2W)

Number of subjects included in analysis

206

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.006

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

4.6081

Confidence interval

level

95%

sides

2-sided

lower limit

1.3629

upper limit

7.8533

Variability estimate

Standard error of the mean

Dispersion value

1.6455

Secondary: Percentage of Participants Achieving ASDAS Low Disease Activity

Top of page

End point title

Percentage of Participants Achieving ASDAS Low Disease Activity

End point description

ASDAS is a composite index to assess disease activity in axSpA. ASDAS low disease activity is defined as a score of <2.1. The parameters used for the ASDAS (with CRP as acute phase reactant) are total back pain, patient global, peripheral pain/swelling, duration of morning stiffness and CRP in mg/L. The ASDAScrp is calculated with the following equation: 0.121×total back pain+0.110×patient global+0.073×peripheral pain/swelling+0.058×duration of morning stiffness+0.579×Ln(CRP+1). CRP is in mg/liter, the range of other variables is from 0(normal) to 10(very severe); Ln represents the natural logarithm). Data from five variables combined to yield a score (0.6361 to no defined upper limit), where higher the score worse the disease activity.

End point type

Secondary

End point timeframe

Week 16

End point values	Placebo	Ixekizumab 80 mg Q4W (IXEQ4W)	Ixekizumab 80 mg Q2W (IXEQ2W)
Number of subjects analysed	104 ^[26]	94 ^[27]	102 ^[28]
Units: percentage of participants
number (not applicable)	12.4	27.7	32.4

Notes
[26] - Total participants 105. One participant who did not receive study drug is included in the analysis.
[27] - All randomized participants with baseline ASDAS <2.1.
[28] - All randomized participants with baseline ASDAS <2.1.

Statistical Analysis ASDAS Low Disease

Comparison groups

Placebo v Ixekizumab 80 mg Q4W (IXEQ4W)

Number of subjects included in analysis

198

Analysis specification

Pre-specified

Analysis type

superiority ^[29]

P-value

= 0.008

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.73

Confidence interval

level

95%

sides

2-sided

lower limit

1.3

upper limit

5.76

Notes
[29] - Total participants 199. One participant who did not receive study drug is included in the analysis.

Statistical Analysis ASDAS Low Disease

Comparison groups

Placebo v Ixekizumab 80 mg Q2W (IXEQ2W)

Number of subjects included in analysis

206

Analysis specification

Pre-specified

Analysis type

superiority ^[30]

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.43

Confidence interval

level

95%

sides

2-sided

lower limit

1.66

upper limit

7.08

Notes
[30] - Total participants 207. One participant who did not receive study drug is included in the analysis.

Secondary: Percentage of Participants Achieving ASDAS Low Disease Activity

Top of page

End point title

Percentage of Participants Achieving ASDAS Low Disease Activity

End point description

End point type

Secondary

End point timeframe

Week 52

End point values	Placebo	Ixekizumab 80 mg Q4W (IXEQ4W)	Ixekizumab 80 mg Q2W (IXEQ2W)
Number of subjects analysed	104 ^[31]	94 ^[32]	102 ^[33]
Units: percentage of participants
number (not applicable)	8.6	29.8	27.5

Notes
[31] - Total participants 105. One participant who did not receive study drug is included in the analysis.
[32] - All randomized participants with baseline ASDAS <2.1.
[33] - All randomized participants with baseline ASDAS <2.1.

Statistical analysis ASDAS Low Disease

Comparison groups

Placebo v Ixekizumab 80 mg Q4W (IXEQ4W)

Number of subjects included in analysis

198

Analysis specification

Pre-specified

Analysis type

superiority ^[34]

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.58

Confidence interval

level

95%

sides

2-sided

lower limit

2.02

upper limit

10.41

Notes
[34] - Total participants 199. One participant who did not receive study drug is included in the analysis.

Statistical analysis ASDAS Low Disease

Comparison groups

Placebo v Ixekizumab 80 mg Q2W (IXEQ2W)

Number of subjects included in analysis

206

Analysis specification

Pre-specified

Analysis type

superiority ^[35]

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.99

Confidence interval

level

95%

sides

2-sided

lower limit

1.76

upper limit

9.05

Notes
[35] - Total participants 207. One participant who did not receive study drug is included in the analysis.

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

Top of page

End point title

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

End point description

The BASDAI is a participant-reported assessment consisting of 6 questions that relate to 5 major symptoms relevant to axial spondyloarthritis (axSpA): 1) Fatigue, 2) Spinal pain, 3) Peripheral arthritis, 4) Enthesitis, 5) Intensity, and 6) Duration of morning stiffness. Participants need to score each item with a score from 0 to 10 (NRS). Total score is obtained from the average of symptom scores ranging 0 (no problem) to 10 (worst problem), with a higher score indicating more severe AS symptom. LS mean was derived from MMRM with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Placebo	Ixekizumab 80 mg Q4W (IXEQ4W)	Ixekizumab 80 mg Q2W (IXEQ2W)
Number of subjects analysed	104 ^[36]	96 ^[37]	102 ^[38]
Units: score on a scale
least squares mean (standard error)	-1.51 ( 0.216 )	-2.18 ( 0.220 )	-2.52 ( 0.217 )

Notes
[36] - All randomized participants with evaluable data.
[37] - All randomized participants with evaluable data.
[38] - All randomized participants with evaluable data.

Change from Baseline in BASDAI

Comparison groups

Placebo v Ixekizumab 80 mg Q4W (IXEQ4W)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.031

Method

Mixed models analysis

Parameter type

LS Means Square Difference

Point estimate

-0.67

Confidence interval

level

95%

sides

2-sided

lower limit

-1.28

upper limit

-0.06

Variability estimate

Standard error of the mean

Dispersion value

0.308

Change from Baseline in BASDAI

Comparison groups

Placebo v Ixekizumab 80 mg Q2W (IXEQ2W)

Number of subjects included in analysis

206

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-1.01

Confidence interval

level

95%

sides

2-sided

lower limit

-1.61

upper limit

-0.41

Variability estimate

Standard error of the mean

Dispersion value

0.305

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

Top of page

End point title

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

End point description

End point type

Secondary

End point timeframe

Baseline, Week 52

End point values	Placebo	Ixekizumab 80 mg Q4W (IXEQ4W)	Ixekizumab 80 mg Q2W (IXEQ2W)
Number of subjects analysed	104 ^[39]	96 ^[40]	102 ^[41]
Units: score on a scale
least squares mean (standard error)	-1.76 ( 0.305 )	-2.89 ( 0.266 )	-3.04 ( 0.266 )

Notes
[39] - All randomized participants with evaluable data.
[40] - All randomized participants with evaluable data.
[41] - All randomized participants with evaluable data.

Change from Baseline in BASDAI

Comparison groups

Placebo v Ixekizumab 80 mg Q4W (IXEQ4W)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.006

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-1.13

Confidence interval

level

95%

sides

2-sided

lower limit

-1.92

upper limit

-0.33

Variability estimate

Standard error of the mean

Dispersion value

0.404

Change from Baseline in BASDAI

Comparison groups

Placebo v Ixekizumab 80 mg Q2W (IXEQ2W)

Number of subjects included in analysis

206

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-1.29

Confidence interval

level

95%

sides

2-sided

lower limit

-2.08

upper limit

-0.49

Variability estimate

Standard error of the mean

Dispersion value

0.404

Secondary: Change from Baseline in Magnetic Resonance Imaging (MRI) of the Sacroiliac Joint (SIJ) Spondyloarthritis Research Consortium of Canada (SPARCC) Score

Top of page

End point title

Change from Baseline in Magnetic Resonance Imaging (MRI) of the Sacroiliac Joint (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. LS Mean was derived from ANCOVA model with treatment, geographic region, screening MRI/CRP status and baseline value as fixed factors.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Placebo	Ixekizumab 80 mg Q4W (IXEQ4W)	Ixekizumab 80 mg Q2W (IXEQ2W)
Number of subjects analysed	90 ^[42]	85 ^[43]	92 ^[44]
Units: score on a scale
least squares mean (standard error)	-0.31 ( 0.539 )	-3.38 ( 0.549 )	-4.52 ( 0.530 )

Notes
[42] - All randomized participants with baseline and Week 16 SPARCC score.
[43] - All randomized participants with baseline and Week 16 SPARCC score.
[44] - All randomized participants with baseline and Week 16 SPARCC score.

Statistical analysis MRI SPARCC

Comparison groups

Placebo v Ixekizumab 80 mg Q4W (IXEQ4W)

Number of subjects included in analysis

175

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-3.07

Confidence interval

level

95%

sides

2-sided

lower limit

-4.58

upper limit

-1.57

Variability estimate

Standard error of the mean

Dispersion value

0.764

Statistical analysis MRI SPARCC

Comparison groups

Placebo v Ixekizumab 80 mg Q2W (IXEQ2W)

Number of subjects included in analysis

182

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-4.2

Confidence interval

level

95%

sides

2-sided

lower limit

-5.68

upper limit

-2.72

Variability estimate

Standard error of the mean

Dispersion value

0.751

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. LS Mean was derived from MMRM with treatment, geographic region, screening MRI/CRP status, baseline value visit, baseline value-by-visit and treatment-by-visit interaction as fixed factors.

End point type

Secondary

End point timeframe

Baseline, Week 52

End point values	Placebo	Ixekizumab 80 mg Q4W (IXEQ4W)	Ixekizumab 80 mg Q2W (IXEQ2W)
Number of subjects analysed	86 ^[45]	65 ^[46]	74 ^[47]
Units: score on a scale
least squares mean (standard error)	-2.87 ( 0.447 )	-2.99 ( 0.427 )	-3.14 ( 0.407 )

Notes
[45] - All randomized participants with a baseline SPARCC score >0.
[46] - All randomized participants with a baseline SPARCC score >0.
[47] - All randomized participants with a baseline SPARCC score >0.

Change from Baseline in SPARCC Enthesitis Score

Comparison groups

Placebo v Ixekizumab 80 mg Q4W (IXEQ4W)

Number of subjects included in analysis

151

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.849

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-0.12

Confidence interval

level

95%

sides

2-sided

lower limit

-1.35

upper limit

1.11

Variability estimate

Standard error of the mean

Dispersion value

0.621

Change from Baseline in SPARCC Enthesitis Score

Comparison groups

Placebo v Ixekizumab 80 mg Q2W (IXEQ2W)

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.648

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-0.28

Confidence interval

level

95%

sides

2-sided

lower limit

-1.48

upper limit

0.93

Variability estimate

Standard error of the mean

Dispersion value

0.608

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

BASFI is a participant-reported assessment that establishes a participant’s functional baseline and subsequent response to treatment. Participants were asked to rate the difficulty associated with 10 individual basic functional activities. Participant responded to each question using a NRS scale (range 0 to 10), with a higher score indicating worse functioning. The participant’s final BASFI score is the mean of the 10 item scores with the minimum value of 0 and a possible maximum value of 10, with a higher score indicating worse function. LS Mean was derived from MMRM with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.

End point type

Secondary

End point timeframe

Baseline, Week 52

End point values	Placebo	Ixekizumab 80 mg Q4W (IXEQ4W)	Ixekizumab 80 mg Q2W (IXEQ2W)
Number of subjects analysed	104 ^[48]	96 ^[49]	102 ^[50]
Units: score on a scale
least squares mean (standard error)	-1.57 ( 0.333 )	-2.63 ( 0.292 )	-2.75 ( 0.291 )

Notes
[48] - All randomized participants with evaluable data.
[49] - All randomized participants with evaluable data.
[50] - All randomized participants with evaluable data.

Change from Baseline in BASFI

Comparison groups

Placebo v Ixekizumab 80 mg Q4W (IXEQ4W)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.018

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-1.06

Confidence interval

level

95%

sides

2-sided

lower limit

-1.93

upper limit

-0.18

Variability estimate

Standard error of the mean

Dispersion value

0.443

Change from Baseline in BASFI

Comparison groups

Placebo v Ixekizumab 80 mg Q2W (IXEQ2W)

Number of subjects included in analysis

206

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.008

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-1.18

Confidence interval

level

95%

sides

2-sided

lower limit

-2.05

upper limit

-0.31

Variability estimate

Standard error of the mean

Dispersion value

0.442

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 axSpA. ASDAS Inactive Disease is defined as a score of less than (<)1.3. The parameters used for the ASDAS (with CRP as acute phase reactant) are total back pain, patient global, peripheral pain/swelling, duration of morning stiffness and CRP in mg/L. The ASDAScrp is calculated with the following equation: 0.121×total back pain+0.110×patient global+0.073×peripheral pain/swelling+0.058×duration of morning stiffness+0.579×Ln(CRP+1). (CRP is in mg/liter, the range of other variables is from 0(normal) to 10(very severe); Ln represents the natural logarithm). Data from five variables combined to yield a score (0.6361 to no defined upper limit), where higher the score worse the disease activity.

End point type

Secondary

End point timeframe

Week 52

End point values	Placebo	Ixekizumab 80 mg Q4W (IXEQ4W)	Ixekizumab 80 mg Q2W (IXEQ2W)
Number of subjects analysed	104 ^[51]	96 ^[52]	102 ^[53]
Units: percentage of participants
number (not applicable)	2.9	13.5	10.8

Notes
[51] - Total participants 105. One participant who did not receive study drug is included in the analysis.
[52] - All randomized participants.
[53] - All randomized participants.

Statistical analysis Achieving ASDAS Inactive

Comparison groups

Placebo v Ixekizumab 80 mg Q4W (IXEQ4W)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority ^[54]

P-value

= 0.0011

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

5.33

Confidence interval

level

96%

sides

2-sided

lower limit

1.47

upper limit

19.4

Notes
[54] - Total participants 201. One participant who did not receive study drug is included in the analysis.

Statistical analysis Achieving ASDAS Inactive

Comparison groups

Placebo v Ixekizumab 80 mg Q2W (IXEQ2W)

Number of subjects included in analysis

206

Analysis specification

Pre-specified

Analysis type

superiority ^[55]

P-value

= 0.031

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.22

Confidence interval

level

95%

sides

2-sided

lower limit

1.14

upper limit

15.66

Notes
[55] - Total participants 207. 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 C-reactive protein (hs-CRP) was the measure of acute phase reactant and was measured with a high sensitivity assay at the central laboratory to help assess the effect of ixekizumab on disease activity. LS Mean was derived from MMRM with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.

End point type

Secondary

End point timeframe

Baseline, Week 52

End point values	Placebo	Ixekizumab 80 mg Q4W (IXEQ4W)	Ixekizumab 80 mg Q2W (IXEQ2W)
Number of subjects analysed	104 ^[56]	96 ^[57]	102 ^[58]
Units: milligram/liter (mg/L)
least squares mean (standard error)	-4.804 ( 2.0370 )	-8.611 ( 2.0028 )	-7.547 ( 1.9654 )

Notes
[56] - All randomized participants with evaluable data.
[57] - All randomized participants with evaluable data.
[58] - All randomized participants with evaluable data.

Change from Baseline in the CRP

Comparison groups

Placebo v Ixekizumab 80 mg Q4W (IXEQ4W)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.183

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-3.807

Confidence interval

level

95%

sides

2-sided

lower limit

-9.418

upper limit

1.804

Variability estimate

Standard error of the mean

Dispersion value

2.8507

Change from Baseline in the CRP

Comparison groups

Ixekizumab 80 mg Q2W (IXEQ2W) v Placebo

Number of subjects included in analysis

206

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.331

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-2.743

Confidence interval

level

95%

sides

2-sided

lower limit

-8.294

upper limit

2.807

Variability estimate

Standard error of the mean

Dispersion value

2.8202

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

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End point title

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

End point description

Bath Ankylosing Spondylitis Metrology Index (BASMI) is a combined index comprising the following 5 clinical measurements of spinal mobility in participants with axSpA: 1) Lateral spinal flexion 2) Tragus-to-wall distance 3) Lumbar flexion (modified Schrober) 4) Maximal intermalleolar distance, and 5) Cervical rotation. The BASMI includes these 5 measurements that were each scaled to a score of 0 to 10 depending on the result of the assessment (BASMI linear function). The average score of the 5 assessments gives the BASMI linear result. LS Mean was derived from MMRM with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.

End point type

Secondary

End point timeframe

Baseline, Week 52

End point values	Placebo	Ixekizumab 80 mg Q4W (IXEQ4W)	Ixekizumab 80 mg Q2W (IXEQ2W)
Number of subjects analysed	104 ^[59]	96 ^[60]	102 ^[61]
Units: score on a scale
least squares mean (standard error)	-0.17 ( 0.112 )	-0.56 ( 0.097 )	-0.48 ( 0.097 )

Notes
[59] - All randomized participants with evaluable data.
[60] - All randomized participants with evaluable data.
[61] - All randomized participants with evaluable data.

Change from Baseline in BASMI Statistical Analysis

Comparison groups

Ixekizumab 80 mg Q4W (IXEQ4W) v Placebo

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.008

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.69

upper limit

-0.1

Variability estimate

Standard error of the mean

Dispersion value

0.148

Change from Baseline in BASMI Statistical Analysis

Comparison groups

Placebo v Ixekizumab 80 mg Q2W (IXEQ2W)

Number of subjects included in analysis

206

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.038

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-0.31

Confidence interval

level

95%

sides

2-sided

lower limit

-0.6

upper limit

-0.02

Variability estimate

Standard error of the mean

Dispersion value

0.148

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. LS Mean was derived from MMRM with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.

End point type

Secondary

End point timeframe

Baseline, Week 52

End point values	Placebo	Ixekizumab 80 mg Q4W (IXEQ4W)	Ixekizumab 80 mg Q2W (IXEQ2W)
Number of subjects analysed	104 ^[62]	96 ^[63]	102 ^[64]
Units: centimeter (cm)
least squares mean (standard error)	0.57 ( 0.253 )	0.62 ( 0.206 )	0.91 ( 0.209 )

Notes
[62] - All randomized participants with evaluable data.
[63] - All randomized participants with evaluable data.
[64] - All randomized participants with evaluable data.

Change from Baseline in Chest Expansion

Comparison groups

Ixekizumab 80 mg Q4W (IXEQ4W) v Placebo

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.871

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.59

upper limit

0.7

Variability estimate

Standard error of the mean

Dispersion value

0.325

Change from Baseline in Chest Expansion

Comparison groups

Placebo v Ixekizumab 80 mg Q2W (IXEQ2W)

Number of subjects included in analysis

206

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.295

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

0.34

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3

upper limit

0.99

Variability estimate

Standard error of the mean

Dispersion value

0.327

Secondary: Change from Baseline in Occiput to Wall Distance

Top of page

End point title

Change from Baseline in Occiput to Wall Distance

End point description

The participant is to make a maximum effort to touch the head against the wall when standing with heels and back against the wall (occiput). Then the distance from occiput to wall is measured. Two tries will be recorded. The better (smaller) measurement of 2 tries (in centimeters) will be used for analyses. LS Mean was derived from MMRM with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.

End point type

Secondary

End point timeframe

Baseline, Week 52

End point values	Placebo	Ixekizumab 80 mg Q4W (IXEQ4W)	Ixekizumab 80 mg Q2W (IXEQ2W)
Number of subjects analysed	104 ^[65]	96 ^[66]	102 ^[67]
Units: cm
least squares mean (standard error)	0.04 ( 0.312 )	-0.42 ( 0.257 )	-0.73 ( 0.259 )

Notes
[65] - All randomized participants with evaluable data.
[66] - All randomized participants with evaluable data.
[67] - All randomized participants with evaluable data.

Change from Baseline in Occiput to Wall Distance

Comparison groups

Placebo v Ixekizumab 80 mg Q4W (IXEQ4W)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.257

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-0.46

Confidence interval

level

95%

sides

2-sided

lower limit

-1.26

upper limit

0.34

Variability estimate

Standard error of the mean

Dispersion value

0.406

Change from Baseline in Occiput to Wall Distance

Comparison groups

Placebo v Ixekizumab 80 mg Q2W (IXEQ2W)

Number of subjects included in analysis

206

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.057

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-0.77

Confidence interval

level

95%

sides

2-sided

lower limit

-1.56

upper limit

0.02

Variability estimate

Standard error of the mean

Dispersion value

0.402

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

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End point title

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

End point description

Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) is an index used to measure the severity of enthesitis. The MASES assesses 13 sites for enthesitis using a score of “0” for no activity or “1” for activity. Sites assessed included costochondral 1 (right/left [R/L]), costochondral 7 (R/L), spinal iliaca anterior superior (R/L), crista iliaca (R/L), spina iliaca posterior (R/L), processus spinosus L5, and achilles tendon proximal insertion (R/L). The MASES is the sum of all site scores (range 0 to 13); higher scores indicate more severe enthesitis. LS mean was derived from MMRM with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.

End point type

Secondary

End point timeframe

Baseline, Week 52

End point values	Placebo	Ixekizumab 80 mg Q4W (IXEQ4W)	Ixekizumab 80 mg Q2W (IXEQ2W)
Number of subjects analysed	104 ^[68]	96 ^[69]	102 ^[70]
Units: score on a scale
least squares mean (standard error)	-2.34 ( 0.361 )	-3.21 ( 0.342 )	-3.19 ( 0.336 )

Notes
[68] - All randomized participants with evaluable data.
[69] - All randomized participants with evaluable data.
[70] - All randomized participants with evaluable data.

Change from Baseline in MASES

Comparison groups

Placebo v Ixekizumab 80 mg Q4W (IXEQ4W)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.082

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-0.87

Confidence interval

level

95%

sides

2-sided

lower limit

-1.85

upper limit

0.11

Variability estimate

Standard error of the mean

Dispersion value

0.496

Change from Baseline in MASES

Comparison groups

Placebo v Ixekizumab 80 mg Q2W (IXEQ2W)

Number of subjects included in analysis

206

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.088

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-0.85

Confidence interval

level

95%

sides

2-sided

lower limit

-1.82

upper limit

0.13

Variability estimate

Standard error of the mean

Dispersion value

0.493

Secondary: Change from Baseline in Severity of Peripheral Arthritis by Tender (TJC) and Swollen Joint Count (SJC) Scores of 44 Joints

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End point title

Change from Baseline in Severity of Peripheral Arthritis by Tender (TJC) and Swollen Joint Count (SJC) Scores of 44 Joints

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). Swollen joint count SJC was determined by examination of 44 joints (22 joints on each side of the participants body). The joints are classified as swollen or not swollen. Sum of all joints checked to be swollen divided by number of evaluable joints which is multiplied by 44 to obtain SJC score. Score ranges from 0 (not swollen) to 44 (all joints swollen). LS mean was derived from MMRM with treatment, geographic region, screening MRI/CRP status and baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.

End point type

Secondary

End point timeframe

Baseline, Week 52

End point values	Placebo	Ixekizumab 80 mg Q4W (IXEQ4W)	Ixekizumab 80 mg Q2W (IXEQ2W)
Number of subjects analysed	104 ^[71]	96 ^[72]	102 ^[73]
Units: joint counts
least squares mean (standard error)
TJC	-0.59 ( 1.039 )	-2.38 ( 0.993 )	-4.12 ( 0.916 )
SJC	-3.66 ( 0.261 )	-4.63 ( 0.237 )	-4.41 ( 0.228 )

Notes
[71] - TJC number of participants (n) is 83 and a baseline with TJC>0. SJC n is 50 and baseline with SJC>0
[72] - TJC number of participants is 70 and baseline with TJC>0. SJC n is 51 and baseline with SJC>0.
[73] - TJC number of participants is 86 and baseline with TJC>0. SJC n is 57 and baseline with SJC>0.

Statistical analysis TJC

Statistical analysis description

TJC

Comparison groups

Placebo v Ixekizumab 80 mg Q4W (IXEQ4W)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.219

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-1.79

Confidence interval

level

95%

sides

2-sided

lower limit

-4.66

upper limit

1.09

Variability estimate

Standard error of the mean

Dispersion value

1.442

Statistical analysis TJC

Statistical analysis description

TJC

Comparison groups

Placebo v Ixekizumab 80 mg Q2W (IXEQ2W)

Number of subjects included in analysis

206

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.013

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-3.53

Confidence interval

level

95%

sides

2-sided

lower limit

-6.3

upper limit

-0.76

Variability estimate

Standard error of the mean

Dispersion value

1.388

Statistical analysis SJC

Statistical analysis description

SJC

Comparison groups

Placebo v Ixekizumab 80 mg Q4W (IXEQ4W)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.009

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-0.97

Confidence interval

level

95%

sides

2-sided

lower limit

-1.68

upper limit

-0.26

Variability estimate

Standard error of the mean

Dispersion value

0.355

Statistical analysis SJC

Statistical analysis description

SJC

Comparison groups

Placebo v Ixekizumab 80 mg Q2W (IXEQ2W)

Number of subjects included in analysis

206

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.034

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-0.76

Confidence interval

level

95%

sides

2-sided

lower limit

-1.46

upper limit

-0.06

Variability estimate

Standard error of the mean

Dispersion value

0.348

Secondary: Number of Participants with Anterior Uveitis

Top of page

End point title

Number of Participants with Anterior Uveitis

End point description

Number of participants with anterior uveitis. Anterior uveitis is an inflammation of the middle layer of the eye which includes the iris (colored part of the eye) and the adjacent tissue, known as the ciliary body.

End point type

Secondary

End point timeframe

Baseline through Week 52

End point values	Placebo	Ixekizumab 80 mg Q4W (IXEQ4W)	Ixekizumab 80 mg Q2W (IXEQ2W)
Number of subjects analysed	104 ^[74]	96 ^[75]	102 ^[76]
Units: number of participants
number (not applicable)	2	1	2

Notes
[74] - Total participants 105. One participant who did not receive study drug is included in the analysis.
[75] - All randomized participants.
[76] - All randomized participants.

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. LS Mean was derived from MMRM with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.

End point type

Secondary

End point timeframe

Baseline, Week 52

End point values	Placebo	Ixekizumab 80 mg Q4W (IXEQ4W)	Ixekizumab 80 mg Q2W (IXEQ2W)
Number of subjects analysed	104 ^[77]	96 ^[78]	102 ^[79]
Units: score on a scale
least squares mean (standard error)	-2.1 ( 0.38 )	-2.6 ( 0.32 )	-2.7 ( 0.32 )

Notes
[77] - All randomized participants with evaluable data.
[78] - All randomized participants with evaluable data.
[79] - All randomized participants with evaluable data.

Change from Baseline in the Fatigue NRS

Comparison groups

Placebo v Ixekizumab 80 mg Q4W (IXEQ4W)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.325

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.5

upper limit

0.5

Variability estimate

Standard error of the mean

Dispersion value

0.5

Change from Baseline in the Fatigue NRS

Comparison groups

Placebo v Ixekizumab 80 mg Q2W (IXEQ2W)

Number of subjects included in analysis

206

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.206

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-1.6

upper limit

0.4

Variability estimate

Standard error of the mean

Dispersion value

0.5

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. LS Mean was derived MMRM with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.

End point type

Secondary

End point timeframe

Baseline, Week 52

End point values	Placebo	Ixekizumab 80 mg Q4W (IXEQ4W)	Ixekizumab 80 mg Q2W (IXEQ2W)
Number of subjects analysed	104 ^[80]	96 ^[81]	102 ^[82]
Units: score on a scale
least squares mean (standard error)	-2.57 ( 0.455 )	-3.16 ( 0.395 )	-3.54 ( 0.396 )

Notes
[80] - All randomized participants with evaluable data.
[81] - All randomized participants with evaluable data.
[82] - All randomized participants with evaluable data.

Change from Baseline in ASAS Health Index

Comparison groups

Placebo v Ixekizumab 80 mg Q4W (IXEQ4W)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.33

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-0.59

Confidence interval

level

95%

sides

2-sided

lower limit

-1.77

upper limit

0.6

Variability estimate

Standard error of the mean

Dispersion value

0.601

Change from Baseline in ASAS Health Index

Comparison groups

Placebo v Ixekizumab 80 mg Q2W (IXEQ2W)

Number of subjects included in analysis

206

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.11

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-0.97

Confidence interval

level

95%

sides

2-sided

lower limit

-2.15

upper limit

0.22

Variability estimate

Standard error of the mean

Dispersion value

0.602

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

Jenkins Sleep Evaluation Questionnaire (JSEQ) is a 4 item scale designed to estimate sleep problems in clinical research. The JSEQ assesses the frequency of sleep disturbance in 4 categories: 1) trouble falling asleep, 2) waking up several times during the night, 3) having trouble staying asleep (including waking up far too early), and 4) waking up after the usual amount of sleep feeling tired and worn out. Patients report the numbers of days they experience each of these problems in the past month on a 6 point Likert Scale ranging from 0 = “no days” to 5 = “22-30 days. The total JSEQ score ranges from 0 to 20, with higher scores indicating greater sleep disturbance. LS Mean was derived from using MMRM with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.

End point type

Secondary

End point timeframe

Baseline, Week 52

End point values	Placebo	Ixekizumab 80 mg Q4W (IXEQ4W)	Ixekizumab 80 mg Q2W (IXEQ2W)
Number of subjects analysed	104 ^[83]	96 ^[84]	102 ^[85]
Units: units on a scale
least squares mean (standard error)	-2.9 ( 0.63 )	-3.6 ( 0.52 )	-3.6 ( 0.53 )

Notes
[83] - All randomized participants with evaluable data.
[84] - All randomized participants with evaluable data.
[85] - All randomized participants with evaluable data.

Change from Baseline in the JSEQ

Comparison groups

Placebo v Ixekizumab 80 mg Q4W (IXEQ4W)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.348

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-2.4

upper limit

0.8

Variability estimate

Standard error of the mean

Dispersion value

0.81

Change from Baseline in the JSEQ

Comparison groups

Placebo v Ixekizumab 80 mg Q2W (IXEQ2W)

Number of subjects included in analysis

206

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.386

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.3

upper limit

0.9

Variability estimate

Standard error of the mean

Dispersion value

0.82

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, with higher scores indicating greater impairment and less productivity. LS Mean was derived from ANCOVA with treatment, geographic region, screening MRI/CRP status and baseline value.

End point type

Secondary

End point timeframe

Baseline, Week 52

End point values	Placebo	Ixekizumab 80 mg Q4W (IXEQ4W)	Ixekizumab 80 mg Q2W (IXEQ2W)
Number of subjects analysed	104 ^[86]	96 ^[87]	102 ^[88]
Units: score on a scale
least squares mean (standard error)
Overall Impairment Score	-13.20 ( 3.386 )	-26.96 ( 3.439 )	-19.49 ( 3.221 )
Percentage of absenteeism	-3.11 ( 2.215 )	-9.01 ( 2.257 )	-7.26 ( 2.151 )
Percentage of presenteeism	-12.40 ( 3.200 )	-26.01 ( 3.245 )	-18.61 ( 3.047 )
Percentage of impairment in activities	-14.42 ( 2.584 )	-25.05 ( 2.617 )	-24.41 ( 2.567 )

Notes
[86] - All randomized participants with evaluable data.
[87] - All randomized participants with evaluable data.
[88] - All randomized participants with evaluable data.

Statistical analysis WPAI Overall Impairment Score

Statistical analysis description

Overall Impairment Score

Comparison groups

Placebo v Ixekizumab 80 mg Q4W (IXEQ4W)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.005

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-13.76

Confidence interval

level

95%

sides

2-sided

lower limit

-23.32

upper limit

-4.2

Variability estimate

Standard error of the mean

Dispersion value

4.835

Statistical analysis WPAI Overall Impairment Score

Statistical analysis description

Overall Impairment Score

Comparison groups

Placebo v Ixekizumab 80 mg Q2W (IXEQ2W)

Number of subjects included in analysis

206

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.183

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-6.29

Confidence interval

level

95%

sides

2-sided

lower limit

-15.58

upper limit

Variability estimate

Standard error of the mean

Dispersion value

4.697

Statistical analysis WPAI Percentage Absenteeism

Statistical analysis description

Percentage of absenteeism

Comparison groups

Placebo v Ixekizumab 80 mg Q4W (IXEQ4W)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.06

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-5.9

Confidence interval

level

95%

sides

2-sided

lower limit

-12.05

upper limit

0.26

Variability estimate

Standard error of the mean

Dispersion value

3.114

Statistical analysis WPAI Percentage Absenteeism

Statistical analysis description

Percentage of absenteeism

Comparison groups

Placebo v Ixekizumab 80 mg Q2W (IXEQ2W)

Number of subjects included in analysis

206

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.182

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-4.15

Confidence interval

level

95%

sides

2-sided

lower limit

-10.27

upper limit

1.97

Variability estimate

Standard error of the mean

Dispersion value

3.098

Statistical analysis WPAI Percentage Presentisms

Statistical analysis description

Percentage of presentisms

Comparison groups

Placebo v Ixekizumab 80 mg Q4W (IXEQ4W)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-13.61

Confidence interval

level

95%

sides

2-sided

lower limit

-22.62

upper limit

-4.6

Variability estimate

Standard error of the mean

Dispersion value

4.558

Statistical analysis WPAI Percentage Presentisms

Comparison groups

Placebo v Ixekizumab 80 mg Q2W (IXEQ2W)

Number of subjects included in analysis

206

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.164

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-6.21

Confidence interval

level

95%

sides

2-sided

lower limit

-15

upper limit

2.58

Variability estimate

Standard error of the mean

Dispersion value

4.446

Statistical analysis WPAI Percentage of Impairment

Statistical analysis description

Percentage of Impairment in Activities Performed Outside of Work

Comparison groups

Placebo v Ixekizumab 80 mg Q4W (IXEQ4W)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.004

Method

LS Mean Difference

Parameter type

LS Mean Difference

Point estimate

-10.63

Confidence interval

level

95%

sides

2-sided

lower limit

-17.85

upper limit

-3.41

Variability estimate

Standard error of the mean

Dispersion value

3.669

Statistical analysis WPAI Percentage of Impairment

Comparison groups

Placebo v Ixekizumab 80 mg Q2W (IXEQ2W)

Number of subjects included in analysis

206

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.006

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-9.99

Confidence interval

level

95%

sides

2-sided

lower limit

-17.12

upper limit

-2.86

Variability estimate

Standard error of the mean

Dispersion value

3.621

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

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End point title

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

End point description

ASAS-NSAID score is used to present the NSAID intake by considering the type of NSAID, the total dose, & the number of days taking NSAID during a period of interest (PI). For NSAID equivalent scoring system, range is from 0 to 100, the higher the score, the greater the NSAID intake. ASAS-NSAID score= (equivalent NSAID score) x (days of intake during PI) x (days per week)/(PI in days).

End point type

Secondary

End point timeframe

Baseline, Week 52

End point values	Placebo	Ixekizumab 80 mg Q4W (IXEQ4W)	Ixekizumab 80 mg Q2W (IXEQ2W)
Number of subjects analysed	96 ^[89]	81 ^[90]	95 ^[91]
Units: score on a scale
arithmetic mean (standard deviation)	-8.89 ( 29.986 )	-7.91 ( 34.257 )	-5.33 ( 20.935 )

Notes
[89] - All randomized participants who had NSAID (including COX-2 Inhibitor) intake at Baseline.
[90] - All randomized participants who had NSAID (including COX-2 Inhibitor) intake at Baseline.
[91] - All randomized participants who had NSAID (including COX-2 Inhibitor) intake at Baseline.

No statistical analyses for this end point

Secondary: Number of Participants with Treatment Emergent (TE) Anti-Ixekizumab Antibodies

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End point title

Number of Participants with Treatment Emergent (TE) Anti-Ixekizumab Antibodies

End point description

A treatment-emergent positive anti-drug antibody (TE-ADA+) participant will be defined as a 4-fold increase over a positive baseline antibody titer (Tier 3); or for a negative baseline titer, a participant with an increase from the baseline to a level of ≥ 1:10. All randomized participant who received at least one dose of ixekizumab during the study and had an evaluable baseline sample and at least 1 evaluable post baseline sample.

End point type

Secondary

End point timeframe

Week 52

End point values	IXE80Q2W-Q2W	IXE80Q4W-Q4W	PBO-IXE80Q2W	IXE80Q4W-Q2W
Number of subjects analysed	102 ^[92]	56 ^[93]	62 ^[94]	40 ^[95]
Units: participants
number (not applicable)	14	5	8	2

Notes
[92] - All randomized participant who received drug and had evaluable post baseline data.
[93] - All randomized participant who received drug and had evaluable post baseline data.
[94] - All randomized participant who received drug and had evaluable post baseline data.
[95] - All randomized participant who received drug and had evaluable post baseline data.

No statistical analyses for this end point

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

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End point title

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

End point description

PK trough serum concentration samples were collected at steady state (Ctrough ss). Geometric Coefficient Variation (CV) is a percent.

End point type

Secondary

End point timeframe

Week 52

End point values	IXEQ2W (80S)/IXEQ2W	IXEQ2W (80S)/IXEQ2W Open Label	IXEQ2W (160S)/IXEQ2W	IXEQ2W (160s)/IXEQ2W Open Label	IXEQ4W (80S) IXEQ4W	IXEQ4W (80S)/IXEQ2W Open Label	IXEQ4W (160S)/IXEQ4W	IXEQ4W (160S) IXEQ2W Open Label	PBO/IXEQ2W Open Label
Number of subjects analysed	32 ^[96]	18 ^[97]	28 ^[98]	24 ^[99]	28 ^[100]	19 ^[101]	28 ^[102]	21 ^[103]	55 ^[104]
Units: microgram/milliliter (μg/mL)
geometric mean (geometric coefficient of variation)	7.88 ( 73 )	9.56 ( 60 )	10.3 ( 61 )	10.4 ( 72 )	2.88 ( 49 )	6.45 ( 124 )	3.54 ( 79 )	11.5 ( 53 )	9.25 ( 66 )

Notes
[96] - All randomized participants who had evaluable PK data. Geometric CV is a percent.
[97] - All randomized participants who had evaluable PK data. Geometric CV is a percent.
[98] - All randomized participants who had evaluable PK data. Geometric CV is a percent.
[99] - All randomized participants who had evaluable PK data. Geometric CV is a percent.
[100] - All randomized participants who had evaluable PK data. Geometric CV is a percent.
[101] - All randomized participants who had evaluable PK data. Geometric CV is a percent.
[102] - All randomized participants who had evaluable PK data. Geometric CV is a percent.
[103] - All randomized participants who had evaluable PK data. Geometric CV is a percent.
[104] - All randomized participants who had evaluable PK data. Geometric CV is a percent.

No statistical analyses for this end point

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

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End point title

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

End point description

End point type

Secondary

End point timeframe

Week 16

End point values	IXEQ2W(80S)	IXEQ2W(160S)	IXEQ4W(80S)	IXEQ4W(160S)
Number of subjects analysed	50 ^[105]	52 ^[106]	47 ^[107]	49 ^[108]
Units: µg/mL
geometric mean (geometric coefficient of variation)	8.76 ( 84 )	10.6 ( 57 )	3.20 ( 52 )	3.46 ( 119 )

Notes
[105] - All randomized participants who had evaluable PK data. Geometric CV is percent.
[106] - All randomized participants who had evaluable PK data. Geometric CV is a percent.
[107] - All randomized participants who had evaluable PK data. Geometric CV is a percent.
[108] - All randomized participants who had evaluable PK data. Geometric CV is a percent.

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Up to 64 Weeks

Adverse event reporting additional description

All randomized participants who received at least one dose of study drug during the study. 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

22.0

Reporting group title

Ixekizumab 80 mg Q2W

Reporting group description

Reporting group title

Ixekizumab 80 mg Q4W

Reporting group description

Reporting group title

Placebo

Reporting group description

Reporting group title

IXE80Q2W IR/IXE80Q2W - Open Label

Reporting group description

Reporting group title

IXE80Q4W IR/IXE80Q2W - Open Label

Reporting group description

Reporting group title

PBO IR/IXEQ2W - Open Label

Reporting group description

Reporting group title

Other Biologic - Open Label

Reporting group description

Reporting group title

Placebo

Reporting group description

Reporting group title

Ixekizumab 80 mg Q4W

Reporting group description

Reporting group title

Ixekizumab 80 mg Q2W

Reporting group description

Reporting group title

Other Biologic Treatment

Reporting group description

Serious adverse events	Ixekizumab 80 mg Q2W	Ixekizumab 80 mg Q4W	Placebo	IXE80Q2W IR/IXE80Q2W - Open Label	IXE80Q4W IR/IXE80Q2W - Open Label	PBO IR/IXEQ2W - Open Label	Other Biologic - Open Label	Placebo	Ixekizumab 80 mg Q4W	Ixekizumab 80 mg Q2W	Other Biologic Treatment
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 102 (0.98%)	2 / 96 (2.08%)	1 / 104 (0.96%)	1 / 42 (2.38%)	0 / 40 (0.00%)	2 / 62 (3.23%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 28 (3.57%)	0 / 5 (0.00%)
number of deaths (all causes)	0	0	0	0	0	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0	0	0	0	0	0
Nervous system disorders
focal dyscognitive seizures
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 102 (0.00%)	0 / 96 (0.00%)	0 / 104 (0.00%)	0 / 42 (0.00%)	0 / 40 (0.00%)	0 / 62 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 28 (3.57%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
anaphylactoid reaction
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 102 (0.00%)	0 / 96 (0.00%)	1 / 104 (0.96%)	0 / 42 (0.00%)	0 / 40 (0.00%)	0 / 62 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 28 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
abdominal pain
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 102 (0.00%)	1 / 96 (1.04%)	0 / 104 (0.00%)	0 / 42 (0.00%)	0 / 40 (0.00%)	0 / 62 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 28 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
major depression
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 102 (0.98%)	0 / 96 (0.00%)	0 / 104 (0.00%)	0 / 42 (0.00%)	0 / 40 (0.00%)	0 / 62 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 28 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
somatic symptom disorder
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 102 (0.00%)	0 / 96 (0.00%)	0 / 104 (0.00%)	1 / 42 (2.38%)	0 / 40 (0.00%)	0 / 62 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 28 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
axial spondyloarthritis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 102 (0.00%)	0 / 96 (0.00%)	0 / 104 (0.00%)	0 / 42 (0.00%)	0 / 40 (0.00%)	0 / 62 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 28 (3.57%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
intervertebral disc protrusion
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 102 (0.00%)	0 / 96 (0.00%)	0 / 104 (0.00%)	0 / 42 (0.00%)	0 / 40 (0.00%)	1 / 62 (1.61%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 28 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
osteoarthritis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 102 (0.00%)	0 / 96 (0.00%)	0 / 104 (0.00%)	0 / 42 (0.00%)	0 / 40 (0.00%)	1 / 62 (1.61%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 28 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
erysipelas
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 102 (0.00%)	1 / 96 (1.04%)	0 / 104 (0.00%)	0 / 42 (0.00%)	0 / 40 (0.00%)	0 / 62 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 28 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
sinusitis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 102 (0.00%)	0 / 96 (0.00%)	0 / 104 (0.00%)	0 / 42 (0.00%)	0 / 40 (0.00%)	1 / 62 (1.61%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 28 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Ixekizumab 80 mg Q2W	Ixekizumab 80 mg Q4W	Placebo	IXE80Q2W IR/IXE80Q2W - Open Label	IXE80Q4W IR/IXE80Q2W - Open Label	PBO IR/IXEQ2W - Open Label	Other Biologic - Open Label	Placebo	Ixekizumab 80 mg Q4W	Ixekizumab 80 mg Q2W	Other Biologic Treatment
Total subjects affected by non serious adverse events
subjects affected / exposed	47 / 102 (46.08%)	43 / 96 (44.79%)	31 / 104 (29.81%)	13 / 42 (30.95%)	15 / 40 (37.50%)	26 / 62 (41.94%)	3 / 5 (60.00%)	1 / 3 (33.33%)	1 / 5 (20.00%)	1 / 28 (3.57%)	0 / 5 (0.00%)
Vascular disorders
hypertension
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	4 / 102 (3.92%)	6 / 96 (6.25%)	3 / 104 (2.88%)	1 / 42 (2.38%)	1 / 40 (2.50%)	0 / 62 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 28 (0.00%)	0 / 5 (0.00%)
occurrences all number	4	7	3	1	1	0	0	0	0	0	0
Nervous system disorders
headache
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	5 / 102 (4.90%)	7 / 96 (7.29%)	4 / 104 (3.85%)	1 / 42 (2.38%)	1 / 40 (2.50%)	1 / 62 (1.61%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 28 (0.00%)	0 / 5 (0.00%)
occurrences all number	5	7	4	1	1	1	0	0	0	0	0
General disorders and administration site conditions
influenza like illness
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 102 (0.00%)	0 / 96 (0.00%)	2 / 104 (1.92%)	0 / 42 (0.00%)	0 / 40 (0.00%)	0 / 62 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 28 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	4	0	0	0	0	1	0	0	0
injection site erythema
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	4 / 102 (3.92%)	3 / 96 (3.13%)	1 / 104 (0.96%)	2 / 42 (4.76%)	0 / 40 (0.00%)	5 / 62 (8.06%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 28 (0.00%)	0 / 5 (0.00%)
occurrences all number	11	7	3	5	0	6	0	0	0	0	0
injection site reaction
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	17 / 102 (16.67%)	11 / 96 (11.46%)	4 / 104 (3.85%)	3 / 42 (7.14%)	3 / 40 (7.50%)	11 / 62 (17.74%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 28 (0.00%)	0 / 5 (0.00%)
occurrences all number	56	24	7	11	28	63	0	0	0	0	0
Eye disorders
iritis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 102 (0.00%)	0 / 96 (0.00%)	0 / 104 (0.00%)	0 / 42 (0.00%)	0 / 40 (0.00%)	0 / 62 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 28 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Gastrointestinal disorders
abdominal pain upper
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 102 (0.98%)	1 / 96 (1.04%)	1 / 104 (0.96%)	0 / 42 (0.00%)	3 / 40 (7.50%)	0 / 62 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 28 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	1	1	0	3	0	0	0	0	0	0
nausea
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 102 (0.98%)	1 / 96 (1.04%)	1 / 104 (0.96%)	4 / 42 (9.52%)	2 / 40 (5.00%)	0 / 62 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 28 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	1	1	4	2	0	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
oropharyngeal pain
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	5 / 102 (4.90%)	1 / 96 (1.04%)	0 / 104 (0.00%)	1 / 42 (2.38%)	0 / 40 (0.00%)	0 / 62 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 28 (0.00%)	0 / 5 (0.00%)
occurrences all number	7	1	0	1	0	0	1	0	0	0	0
Musculoskeletal and connective tissue disorders
back pain
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	2 / 102 (1.96%)	3 / 96 (3.13%)	2 / 104 (1.92%)	0 / 42 (0.00%)	0 / 40 (0.00%)	0 / 62 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 28 (0.00%)	0 / 5 (0.00%)
occurrences all number	2	3	2	0	0	0	1	0	0	0	0
Infections and infestations
bacterial vaginosis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed ^[1]	0 / 53 (0.00%)	1 / 46 (2.17%)	0 / 61 (0.00%)	0 / 28 (0.00%)	1 / 15 (6.67%)	2 / 41 (4.88%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 19 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	1	2	0	0	0	0	0
bronchitis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	2 / 102 (1.96%)	7 / 96 (7.29%)	3 / 104 (2.88%)	1 / 42 (2.38%)	1 / 40 (2.50%)	5 / 62 (8.06%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 28 (0.00%)	0 / 5 (0.00%)
occurrences all number	2	7	4	1	1	5	0	0	0	0	0
nasopharyngitis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	16 / 102 (15.69%)	18 / 96 (18.75%)	8 / 104 (7.69%)	2 / 42 (4.76%)	7 / 40 (17.50%)	6 / 62 (9.68%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 28 (0.00%)	0 / 5 (0.00%)
occurrences all number	27	26	11	3	10	8	1	0	0	0	0
pharyngitis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	2 / 102 (1.96%)	4 / 96 (4.17%)	4 / 104 (3.85%)	2 / 42 (4.76%)	3 / 40 (7.50%)	3 / 62 (4.84%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 28 (0.00%)	0 / 5 (0.00%)
occurrences all number	2	5	4	2	3	3	0	1	0	0	0
sinusitis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	2 / 102 (1.96%)	2 / 96 (2.08%)	1 / 104 (0.96%)	3 / 42 (7.14%)	1 / 40 (2.50%)	1 / 62 (1.61%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 28 (0.00%)	0 / 5 (0.00%)
occurrences all number	2	2	1	3	1	1	0	0	0	0	0
upper respiratory tract infection
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	6 / 102 (5.88%)	4 / 96 (4.17%)	4 / 104 (3.85%)	2 / 42 (4.76%)	3 / 40 (7.50%)	4 / 62 (6.45%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 28 (3.57%)	0 / 5 (0.00%)
occurrences all number	7	4	4	2	4	5	1	0	0	1	0
vulvovaginal mycotic infection
alternative dictionary used: MedDRA 22.0
subjects affected / exposed ^[2]	0 / 53 (0.00%)	1 / 46 (2.17%)	0 / 61 (0.00%)	0 / 28 (0.00%)	1 / 15 (6.67%)	0 / 41 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 19 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	1	0	0	0	0	0	0

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

More information

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Were there any global substantial amendments to the protocol? Yes

05 Oct 2018

There are now two primary objectives to accommodate regional regulatory requirements. One secondary objective was added as a primary objective. Power estimations were added for this objective. Clarified that screening MRI/CRP status was used and not baseline.

Were there any global interruptions to the trial? No

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

None reported

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Clinical trials

Clinical Trial Results: A 52 Week Multicenter, Randomized, Double-Blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of Ixekizumab (LY2439821) in bDMARD Naive Patients with Nonradiographic Axial Spondyloarthritis

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

Primary: Percentage of Participants Achieving an ASAS40 Response

Primary: Percentage of Participants Achieving an ASAS40 Response

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

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

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

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

Secondary: Number of Participants without Clinically Meaningful Changes in Background Therapy

Secondary: Number of Participants without Clinically Meaningful Changes in Background Therapy

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

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

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

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

Secondary: Percentage of Participants Achieving ASDAS Low Disease Activity

Secondary: Percentage of Participants Achieving ASDAS Low Disease Activity

Secondary: Percentage of Participants Achieving ASDAS Low Disease Activity

Secondary: Percentage of Participants Achieving ASDAS Low Disease Activity

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

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

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

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

Secondary: Change from Baseline in Magnetic Resonance Imaging (MRI) of the Sacroiliac Joint (SIJ) Spondyloarthritis Research Consortium of Canada (SPARCC) Score

Secondary: Change from Baseline in Magnetic Resonance Imaging (MRI) of the Sacroiliac Joint (SIJ) Spondyloarthritis Research Consortium of Canada (SPARCC) Score

Secondary: Change from Baseline in SPARCC Enthesitis Score

Secondary: Change from Baseline in SPARCC Enthesitis Score

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 the Measure of High Sensitivity C-Reactive Protein (CRP)

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

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

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

Secondary: Change from Baseline in Chest Expansion

Secondary: Change from Baseline in Chest Expansion

Secondary: Change from Baseline in Occiput to Wall Distance

Secondary: Change from Baseline in Occiput to Wall Distance

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

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

Secondary: Change from Baseline in Severity of Peripheral Arthritis by Tender (TJC) and Swollen Joint Count (SJC) Scores of 44 Joints

Secondary: Change from Baseline in Severity of Peripheral Arthritis by Tender (TJC) and Swollen Joint Count (SJC) Scores of 44 Joints

Secondary: Number of Participants with Anterior Uveitis

Secondary: Number of Participants with Anterior Uveitis

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

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

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

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

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 Treatment Emergent (TE) Anti-Ixekizumab Antibodies

Secondary: Number of Participants with Treatment Emergent (TE) Anti-Ixekizumab Antibodies

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

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

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

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

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A 52 Week Multicenter, Randomized, Double-Blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of Ixekizumab (LY2439821) in bDMARD Naive Patients with Nonradiographic Axial Spondyloarthritis