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Clinical Trial Results:
A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Ustekinumab in the Treatment of Anti-TNFα Naïve Subjects With Active Radiographic Axial Spondyloarthritis

Summary
EudraCT number	2014-003679-48
Trial protocol	CZ PL
Global end of trial date	06 Sep 2017

Results information
Results version number	v1(current)
This version publication date	22 Sep 2018
First version publication date	22 Sep 2018
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

CNTO1275AKS3001

ISRCTN number

US NCT number

NCT02437162

WHO universal trial number (UTN)

Sponsor organisation name

Janssen-Cilag International N.V

Sponsor organisation address

Archimedesweg 29, Leiden, Netherlands, 2333 CM

Public contact

Clinical Registry group, Janssen-Cilag International N.V, ClinicalTrialsEU@its.jnj.com

Scientific contact

Clinical Registry group, Janssen-Cilag International N.V, ClinicalTrialsEU@its.jnj.com

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

06 Sep 2017

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

06 Sep 2017

Was the trial ended prematurely?

Yes

Main objective of the trial

The main objective of the study was to assess the efficacy of ustekinumab in adult subjects with active radiographic axial spondyloarthritis (AxSpA) who were naive to anti-tumor necrosis factor alpha (TNFα) agents, as measured by the reduction in signs and symptoms of radiographic AxSpA.

Protection of trial subjects

Safety was evaluated based on adverse events (AEs), clinical laboratory tests, vital sign measurements, physical examinations, electrocardiograms (screening only), concomitant medication review, injection-site reactions, allergic reactions, infections, and tuberculosis (TB) evaluations.

Background therapy

Evidence for comparator

Actual start date of recruitment

26 Oct 2015

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Czech Republic: 33

Country: Number of subjects enrolled

Korea, Republic of: 29

Country: Number of subjects enrolled

Poland: 50

Country: Number of subjects enrolled

Russian Federation: 101

Country: Number of subjects enrolled

Taiwan: 67

Country: Number of subjects enrolled

Ukraine: 61

Country: Number of subjects enrolled

United States: 5

Worldwide total number of subjects

346

EEA total number of subjects

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)

341

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

A total of 347 subjects were randomized and 346 subjects were treated (116 subjects to placebo, 116 subjects to ustekinumab 45 mg, and 114 subjects to 90 mg).

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor

Are arms mutually exclusive

Yes

Placebo

Arm description

Subjects received placebo subcutaneous (SC) injection at Weeks 0, 4, and 16. At Week 16, subjects who met EE criteria (less than [<] 10 percent [%] improvement from baseline in both total back pain and morning stiffness measures at both Week 12 and Week 16) were administered open-label golimumab 50 milligram (mg) SC administrations at Week 16 and every 4 weeks (q4w) thereafter through Week 52. At Week 24 all subjects (with the exception of subjects who qualified for early escape [EE]) were re-randomized to receive either ustekinumab 45 or 90 milligram (mg) SC injection at Weeks 24 and 28 followed by every 12 weeks (q12w) dosing through Week 100.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects received placebo subcutaneous (SC) injection.

Investigational medicinal product name

Golimumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects who met early escape (EE) criteria were administered open-label golimumab 50 mg SC administrations at Week 16 and every 4 weeks (q4w) thereafter through Week 52.

Investigational medicinal product name

Ustekinumab 45 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects (with the exception of subjects who qualified for EE) were re-randomized to receive ustekinumab 45 mg SC injection at Weeks 24 and 28 followed by q12w dosing.

Investigational medicinal product name

Ustekinumab 90 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects (with the exception of subjects who qualified for EE) were re-randomized to receive ustekinumab 90 mg SC injection at Weeks 24 and 28 followed by every 12 weeks (q12w) dosing.

Ustekinumab 45mg

Arm description

Subjects received ustekinumab 45 mg SC injection at Weeks 0 and 4, followed by every 12 week dosing, with the last administration of study agent at Week 100. At Week 16, subjects who met EE criteria were administered open-label golimumab 50 mg SC administrations at Week 16 and q4w thereafter through Week 52. At Week 24, subjects received placebo SC injection to maintain the blind.

Arm type

Experimental

Investigational medicinal product name

Ustekinumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects received ustekinumab 45 mg SC injection at Weeks 0 and 4, followed by every 12 week dosing.

Investigational medicinal product name

Golimumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects who met EE criteria were administered with golimumab 50 mg SC administrations at Week 16 and q4w thereafter through Week 52.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects received placebo SC injection to maintain the blind at Week 24.

Ustekinumab 90mg

Arm description

Subjects received ustekinumab 90 mg SC injection at Weeks 0 and 4, followed by q12w dosing, with the last administration of study agent at Week 100. At Week 16, subjects who meet EE criteria were administered open-label golimumab 50 mg SC administrations at Week 16 and q4w thereafter through Week 52. At Week 24, subjects received placebo SC injection to maintain the blind.

Arm type

Experimental

Investigational medicinal product name

Ustekinumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects received ustekinumab 90 mg SC injection at Weeks 0 and 4, followed by q12w dosing.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects received placebo SC injection to maintain the blind at Week 24.

Investigational medicinal product name

Golimumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects who met EE criteria were administered with golimumab 50 mg SC administrations at Week 16 and q4w thereafter through Week 52.

Number of subjects in period 1	Placebo	Ustekinumab 45mg	Ustekinumab 90mg
Started	116	116	114
Early escape at Week 16	26	21	14
Cross over at week 24	87	0 ^[1]	0 ^[2]
Completed	9	8	6
Not completed	107	108	108
Study discontinued by Sponsor	93	98	97
Consent withdrawn by subject	13	7	9
Adverse event, non-fatal	-	1	-
Death	-	1	-
Unspecified	-	-	1
Lost to follow-up	1	-	1
Protocol deviation	-	1	-

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: Subjects who did not met EE criteria at Week 16 were crossed over to Ustekinumab 45 or 90 mg at Week 24.
[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: Subjects who did not met EE criteria at Week 16 were crossed over to Ustekinumab 45 or 90 mg at Week 24.

Baseline characteristics

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Reporting group title

Placebo

Reporting group description

Reporting group title

Ustekinumab 45mg

Reporting group description

Reporting group title

Ustekinumab 90mg

Reporting group description

Reporting group values	Placebo	Ustekinumab 45mg	Ustekinumab 90mg	Total
Number of subjects	116	116	114	346
Title for AgeCategorical
Units: subjects
<65	115	115	111	341
>=65	1	1	3	5
Title for AgeContinuous
Units: years
arithmetic mean (standard deviation)	38.3 ± 11.35	39.2 ± 10.5	39.5 ± 11.32	-
Title for Gender
Units: subjects
Female	15	23	14	52
Male	101	93	100	294

End points

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Reporting group title

Placebo

Reporting group description

Reporting group title

Ustekinumab 45mg

Reporting group description

Reporting group title

Ustekinumab 90mg

Reporting group description

Primary: Percentage of Subjects Who Achieved an Assessment of Spondyloarthritis international Society (ASAS) 40 Response at Week 24

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End point title

Percentage of Subjects Who Achieved an Assessment of Spondyloarthritis international Society (ASAS) 40 Response at Week 24

End point description

ASAS 40 is defined as improvement from baseline of >= 40 percent (%) and with an absolute improvement from baseline of at least 2 on a 0 to 10 cm scale in at least 3 of the following 4 domains: Patient's global assessment (0 to 10 cm; 0=very well, 10=very poor), Total back pain (0 to 10 cm; 0=no pain, 10=most severe pain), BASFI (self-assessment represented as mean (0 to 10 cm; 0=easy to 10=impossible) of 10 questions, 8 of which relate to participant's functional anatomy and 2 of which relate to a participant's ability to cope with life), Inflammation (0 to 10 cm; 0=none,10=very severe); and absence of deterioration (no worsening at all from baseline in the remaining domain) from baseline in the potential remaining domain.FAS included all subjects who were randomized and received at least one administration of study agent. Subjects analyzed based on randomized treatment group they assigned to regardless of treatment received.

End point type

Primary

End point timeframe

Week 24

End point values	Placebo	Ustekinumab 45mg	Ustekinumab 90mg
Number of subjects analysed	116	116	114
Units: Percentage of subjects
number (not applicable)	28.4	31.0	28.1

Statistical Analysis 1

Comparison groups

Placebo v Ustekinumab 45mg

Number of subjects included in analysis

232

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.669

Method

Cochran-Mantel-Haenszel

Parameter type

Percentage difference

Point estimate

2.586

Confidence interval

level

95%

sides

2-sided

lower limit

-9.138

upper limit

14.31

Statistical Analysis 2

Comparison groups

Placebo v Ustekinumab 90mg

Number of subjects included in analysis

230

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.913

Method

Cochran-Mantel-Haenszel

Parameter type

Percentage difference

Point estimate

-0.646

Confidence interval

level

95%

sides

2-sided

lower limit

-12.18

upper limit

10.887

Secondary: Percentage of Subjects Who Achieved an ASAS 20 Response at Week 24

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End point title

Percentage of Subjects Who Achieved an ASAS 20 Response at Week 24

End point description

ASAS 20 is an improvement from baseline of >= 20% and with an absolute improvement from baseline of at least 1 on a 0 to 10 scale in at least 3 of the following 4 domains: Patient global;Total back pain; BASFI (0 to 10 cm; 0=easy to 10=impossible) of 10 questions, 8 of which relate to participant's functional anatomy and 2 relate to participant's ability to cope with everyday life); Inflammation(0 to 10cm;0=none,10=very severe) and absence of deterioration from baseline (>=20% and worsening of at least 1 on a 0 to 10 scale) in the potential remaining domain. ASAS20 response based on imputed data using treatment failure(consider non-responders at and after treatment failure),early escape rules(consider non-responder at Week 20 and 24),non-responder[NRI] (missing responses at post baseline visit imputed as non-responder). FAS population was included. Subjects analyzed based on randomized treatment group they were assigned to regardless of treatment received.

End point type

Secondary

End point timeframe

Week 24

End point values	Placebo	Ustekinumab 45mg	Ustekinumab 90mg
Number of subjects analysed	116	116	114
Units: Percentage of subjects
number (not applicable)	44.8	55.2	50.0

No statistical analyses for this end point

Secondary: Percentage of Subjects who Achieved at Least a 50 Percent (%) Improvement From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 24

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End point title

Percentage of Subjects who Achieved at Least a 50 Percent (%) Improvement From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 24

End point description

BASDAI used to measure AS disease severity,consists of 6 questions:fatigue,spinal pain,arthralgia,enthesitis (inflammation of tendons and ligaments),morning stiffness(2questions:duration and severity). Each question to answer 10 cm visual analog scale(VAS),0(none),10(very severe) and for the last question related to morning stiffness duration: 0(0 hours), 10(2 or more hours).Final BASDAI score (ranging 0-10) is average of overall total score. Higher BASDAI score indicates more severe AS symptom. Missing data is imputed using treatment failure(consider non-responders at and after treatment failure),early escape rules(consider non-responder at Week 20 and 24),non-responder[NRI](missing responses at post baseline visit imputed as non-responder). FAS included all subjects who were randomized and received at least one administration of study agent. Subjects analyzed based on randomized treatment group they were assigned to regardless of treatment received.

End point type

Secondary

End point timeframe

Week 24

End point values	Placebo	Ustekinumab 45mg	Ustekinumab 90mg
Number of subjects analysed	116	116	114
Units: Percentage of subejcts
number (not applicable)	27.6	25.0	25.4

No statistical analyses for this end point

Secondary: Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) Total Score at Week 24

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End point title

Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) Total Score at Week 24

End point description

BASFI composed 10 questions (each question answered with VAS (0-10 cm) to assess disease severity,including first 8 questions regarding to functional anatomy related activities and remaining 2 questions related to daily activities of AS subjects. Each question is 10cm VAS with value 0(easy), 10(impossible). Final BASFI score mean of 10 scores. BASFI score is average of 10 responses, has minimum value of 0, maximum value 10. Higher BASFI score indicates more severe functional limitations of subject due to AS. Early escape rule was applied (measurement value at Wk20 and Wk 24 was set as missing). FAS included all subjects who were randomized and received at least one administration of study agent. Subjects analyzed based on randomized treatment group were assigned regardless of treatment received. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this endpoint.

End point type

Secondary

End point timeframe

Baseline and Week 24

End point values	Placebo	Ustekinumab 45mg	Ustekinumab 90mg
Number of subjects analysed	88	95	99
Units: Units on a scale
arithmetic mean (standard deviation)	-1.85 ± 2.133	-2.11 ± 2.266	-2.07 ± 2.502

No statistical analyses for this end point

Secondary: Percentage of Subjects who Achieved Ankylosing Spondylitis Disease Activity Score-C Reactive Protein (ASDAS-CRP) Inactive Disease (<1.3) at Week 24

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End point title

Percentage of Subjects who Achieved Ankylosing Spondylitis Disease Activity Score-C Reactive Protein (ASDAS-CRP) Inactive Disease (<1.3) at Week 24

End point description

ASDAS includes CRP milligram per liter(mg/L); four additional self-reported items (rated on 0-10cm VAS or 0-10 NRS) included total back pain (TBP),duration of morning stiffness (DMS), peripheral pain(PP)/swelling and patient global assessment(PGA). ASDAS calculated as:ASDAS(CRP)=(0.121*TBP)+(0.110*PG)+(0.073*PP/swelling)+(0.058*DMS)+(0.579*Ln(CRP+1), disease activity, TBP, PP/swelling on NRS (0 [normal] to 10 [very severe]), DMS on NRS (0 to10, 0 none, 10 representing duration =>2 hours). Inactive disease(ID) defined as ASDAS score <1.3. ASDAS (CRP) ID is based on imputed data using treatment failure(consider non-responders at and after treatment failure),early escape rules(consider non-responder at Week 20 and 24), NRI(missing responses at post baseline visit imputed as non-responder). FAS included subjects who were randomized and received at least one administration of study agent. Subjects analyzed based on randomized treatment group they assigned regardless treatment received.

End point type

Secondary

End point timeframe

Week 24

End point values	Placebo	Ustekinumab 45mg	Ustekinumab 90mg
Number of subjects analysed	116	116	114
Units: Percentage of subjects
number (not applicable)	3.4	1.7	2.6

No statistical analyses for this end point

Secondary: Change From Baseline in hsCRP Through Week 24

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End point title

Change From Baseline in hsCRP Through Week 24

End point description

Change from baseline in hsCRP levels were reported. hsCRP is a sensitive laboratory assay for serum levels of C-Reactive Protein, which is a biomarker of inflammation. Early escape rule was applied (measurement value at Week 20 and Week 24 was set as missing). FAS included all subjects who were randomized and received at least one administration of study agent. Subjects analyzed based on randomized treatment group they were assigned to regardless of treatment received. Here 'n' signifies number of subjects who were analyzed at each specified timepoint, for each arm, respectively.

End point type

Secondary

End point timeframe

Baseline, Week 4, 8, 12, 16, 20 and 24

End point values	Placebo	Ustekinumab 45mg	Ustekinumab 90mg
Number of subjects analysed	116	116	114
Units: Milligrams per decilitre (mg/dL)
arithmetic mean (standard deviation)
Week 4 (n=115,116,113)	-0.10 ± 1.459	-0.54 ± 1.488	-0.74 ± 1.839
Week 8 (n=116,115,114)	-0.16 ± 1.478	-0.59 ± 1.236	-0.66 ± 2.213
Week 12 (n=115,115,112)	-0.18 ± 1.571	-0.80 ± 1.853	-0.84 ± 2.262
Week 16 (n=115,116,114)	-0.11 ± 1.456	-0.39 ± 3.166	-0.86 ± 2.261
Week 20 (n=88,93,99)	-0.34 ± 1.450	-0.73 ± 1.792	-0.79 ± 2.240
Week 24 (n=87,95,98)	-0.41 ± 1.737	-0.72 ± 1.617	-0.92 ± 2.274

No statistical analyses for this end point

Secondary: Change From Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) at Week 16 and 24

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End point title

Change From Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) at Week 16 and 24

End point description

Assessment of enthesitis was performed in the following 7 domains: 1) 1st costochondral joint left and right, 2) 7th costochondral joint left and right, 3) posterior superior iliac spine left and right, 4) anterior superior iliac spine left and right, 5) iliac crest left and right, 6) 5th lumbar spinous process and 7) proximal insertion of Achilles tendon left and right. Entheses were scored as either 0 (nontender) or 1 (tender) yielding total MASES ranging from 0 (no tenderness) to 13 (worst possible score; severe tenderness). Early escape rule was applied (measurement value at Wk 20 and Wk 24 was set as missing). Population included subset of FAS with enthesitis at baseline. Subjects analyzed based on randomized treatment group they were assigned to regardless of treatment received. Here 'n' signifies number of subjects who were analyzed at each specified timepoint, for each arm, respectively.

End point type

Secondary

End point timeframe

Baseline, Week 16 and 24

End point values	Placebo	Ustekinumab 45mg	Ustekinumab 90mg
Number of subjects analysed	87	92	83
Units: Units on a scale
arithmetic mean (standard deviation)
Week 16 (n=62,59,58)	-1.53 ± 3.347	-1.47 ± 3.564	-1.17 ± 3.101
Week 24 (n=35,38,44)	-1.66 ± 3.481	-1.84 ± 3.301	-1.73 ± 3.060

No statistical analyses for this end point

Secondary: Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Week 16 and 24

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End point title

Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Week 16 and 24

End point description

The Bath Ankylosing Spondylitis Metrology Index linear function is a combined index of 5 clinical measurements (performed by the Joint Assessor) which reflect axial mobility in the AS patient. The measurements to assess mobility are: 1)Tragus-to-wall; 2)Modified Schober (lumbar flexion); 3)Cervical rotation angle; 4)Lateral spinal flexion; 5)Intermalleolar distance. The BASMI linear result is the average of the 5 assessments and ranges from 0 to 10. The higher the BASMI score the more severe the patient’s limitation of movement due to their AS. Early escape rule was applied (measurement value was set as missing).FAS included all subjects who were randomized and received at least one administration of study agent. Subjects analyzed based on randomized treatment group they were assigned to regardless of treatment received. 'n' signifies number of subjects who were analyzed at each specified timepoint, for each arm, respectively.

End point type

Secondary

End point timeframe

Baseline, Week 16 and 24

End point values	Placebo	Ustekinumab 45mg	Ustekinumab 90mg
Number of subjects analysed	116	116	114
Units: Units on a scale
arithmetic mean (standard deviation)
Week 16 (n=114,114,111)	-0.26 ± 1.015	-0.26 ± 1.044	-0.17 ± 0.840
Week 24 (n=87,92,97)	-0.36 ± 0.943	-0.37 ± 0.946	-0.27 ± 0.877

No statistical analyses for this end point

Secondary: Change from Baseline in Ankylosing Spondylitis Quality of Life questionnaire (ASQoL) Score at Week 16 and 24

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End point title

Change from Baseline in Ankylosing Spondylitis Quality of Life questionnaire (ASQoL) Score at Week 16 and 24

End point description

The ASQoL is a self-administered health-related quality of life (HRQOL) instrument. It consists of 18 items requesting a Yes or No response to questions related to the impact of the disease/condition (including pain) on sleep, mood, motivation, ability to cope, activities of daily living, independence, relationships, and social life. A score of 1 is given to a response of “yes” on each item and all item scores are summed to a total score with a range of 0 to 18. Higher scores indicate worse HRQOL. Early Escape rule was applied (measurement value was set as missing). FAS included all subjects who were randomized and received at least one administration of study agent. Subjects analyzed based on randomized treatment group they were assigned to regardless of treatment received. Here 'n' signifies number of subjects who were analyzed at each specified timepoint, for each arm, respectively.

End point type

Secondary

End point timeframe

Baseline, Week 16 and 24

End point values	Placebo	Ustekinumab 45mg	Ustekinumab 90mg
Number of subjects analysed	116	116	114
Units: Units on a scale
arithmetic mean (standard deviation)
Week 16 (n=114,116,113)	-2.61 ± 4.385	-3.03 ± 4.416	-2.93 ± 3.954
Week 24 (n=87,94,98)	-4.21 ± 4.441	-4.48 ± 4.808	-4.31 ± 4.537

No statistical analyses for this end point

Secondary: Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Week 16 and 24

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End point title

Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Week 16 and 24

End point description

FACIT-Fatigue score calculated according to 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Subjects scored each item on 5-point scale:0 (Not at all) to 4(Very much). larger participant's response to questions (exception of 2 negatively stated), greater participant's fatigue. All questions, except for 2 negatively stated ones, code was reversed, new score was calculated(4 minus participant's response). Sum of all responses resulted in FACIT-Fatigue score for total possible score of 0 (worst score) to 52 (best score). Early escape rule was applied (measurement value was set as missing).FAS included all subjects who were randomized and received at least one administration of study agent. Subjects analyzed based on randomized treatment group they were assigned to regardless of treatment received. 'n' signifies number of subjects who were analyzed at each specified timepoint, for each arm, respectively.

End point type

Secondary

End point timeframe

Baseline, Week 16 and 24

End point values	Placebo	Ustekinumab 45mg	Ustekinumab 90mg
Number of subjects analysed	116	116	114
Units: Units on a scale
arithmetic mean (standard deviation)
Week 16 (n=114,116,113)	5.71 ± 9.499	5.44 ± 9.528	5.96 ± 9.325
Week 24 (n=87,94,98)	8.78 ± 10.472	7.67 ± 10.348	8.59 ± 10.597

No statistical analyses for this end point

Secondary: Change From Baseline in Norm-Based SF-36 Physical Component Summary (PCS) and SF-36 Mental Component Summary (MCS) at Week 16 and 24

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End point title

Change From Baseline in Norm-Based SF-36 Physical Component Summary (PCS) and SF-36 Mental Component Summary (MCS) at Week 16 and 24

End point description

Medical Outcome Study health measure SF-36 questionnaire is well-validated and widely used quality-of-life instrument. It is self-administered survey consists of 8 multi-item scales: The 4 subscales of SF-36 comprises the PCS(physical functioning, role-physical, bodily pain, and general health), 4 subscales of SF-36, MCS score(vitality, social functioning, role-emotional,mental health). PCS and MCS scored from 0 to 100 with higher scores means better health (worst value is 0 and best value is 100), which are scored using norm-based system. Early escape rule was applied (measurement value at W20 and 24 was set as missing). FAS included all subjects who were randomized and received at least one administration of study agent. Subjects analyzed based on randomized treatment group they were assigned to regardless of treatment received. Here 'n' signifies number of subjects who were analyzed at each specified timepoint, for each arm.

End point type

Secondary

End point timeframe

Baseline, Week 16 and 24

End point values	Placebo	Ustekinumab 45mg	Ustekinumab 90mg
Number of subjects analysed	116	116	114
Units: Units on a scale
arithmetic mean (standard deviation)
SF-36 PCS; change at Wk16 (n=114,116,114)	4.09 ± 7.618	3.66 ± 6.172	5.17 ± 6.494
SF-36 PCS; change at Wk 24 (n=87,94,98)	7.69 ± 8.001	6.34 ± 6.198	7.20 ± 7.343
SF-36 MCS; change at Wk16 (n=114,116,114)	4.56 ± 9.113	3.69 ± 9.690	4.06 ± 9.034
SF-36 MCS; change at Wk 24 (n=87,94,98)	5.05 ± 9.758	4.82 ± 10.841	5.46 ± 8.911

No statistical analyses for this end point

Secondary: Change From Baseline in BASDAI Inflammation Score Through Week 24

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End point title

Change From Baseline in BASDAI Inflammation Score Through Week 24

End point description

The BASDAI is used to measure the ankylosing spondylitis (AS) disease severity. It consists of 6 questions: fatigue, spinal pain, arthralgia (joint pain) or swelling, enthesitis (inflammation of tendons and ligaments), and morning stiffness. Each question is an easy to answer 10 centimeter (cm) visual analog scale (VAS), with 0 being none, and 10 being very severe and the last question: 0=0 hours, 10=2 or more hours. Change from baseline in inflammation was assessed by calculating the average of the Last 2 Questions of the BASDAI Concerning Morning Stiffness. Early escape rule was applied (measurement value was set as missing). FAS included subjects who were randomized and received at least one administration of study agent and analyzed based on randomized treatment group assigned regardless treatment received. 'n' signifies number of participants analyzed for this endpoint at specific timepoints.

End point type

Secondary

End point timeframe

Baseline, Week 4, 8, 12, 16, 20 and 24

End point values	Placebo	Ustekinumab 45mg	Ustekinumab 90mg
Number of subjects analysed	116	116	114
Units: Units on a scale
arithmetic mean (standard deviation)
Week 4 (n=116,116,114)	-0.86 ± 1.650	-1.09 ± 1.748	-1.25 ± 1.871
Week 8 (n=116,115,114)	-1.45 ± 1.970	-1.80 ± 2.192	-1.88 ± 2.160
Week 12 (n=116,115,112)	-1.63 ± 2.110	-1.89 ± 2.143	-1.88 ± 2.110
Week 16 (n=115,116,114)	-1.82 ± 2.221	-1.98 ± 2.394	-1.97 ± 2.299
Week 20 (n=86,92,98)	-2.48 ± 2.200	-2.61 ± 2.089	-2.51 ± 2.429
Week 24 (n=88,95,99)	-2.64 ± 2.194	-2.81 ± 2.257	-2.74 ± 2.592

No statistical analyses for this end point

Secondary: Change From Baseline in Composite and Domain Scores of Medical Outcomes Study Sleep Scale (MOS-SS) at Week 16 and 24

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End point title

Change From Baseline in Composite and Domain Scores of Medical Outcomes Study Sleep Scale (MOS-SS) at Week 16 and 24

End point description

Sleep problems (SP) assessed using the 12-item MOS-SS, a generic instrument designed to assess 6 dimensions of sleep: Sleep disturbance(SD), Somnolence, Sleep adequacy (SA), Snoring, Awaken short of breath (ASB) or headache, Quantity of sleep(QS)/optimal sleep(OS) during past 4W. 6 dimensions used to generate composite Sleep Problems Index (SPI). Increase in score from baseline represents improvement. SD, snoring, somnolence, ASB, SP index have score ranges 0(no SP) to 100 (greater SP), negative change indicates improvement. SA scored 0 (least SA) to 100 (better SA), positive change indicates improvement. QS is scored 0 (less QS) to 24 (greater QS), positive change indicates improvement. EE rule was applied (measurement value was set as missing). FAS included subjects randomized, received at least one administration of study agent and analyzed as per treatment group assigned regardless treatment received. 'n': number of subjects analyzed for this endpoint at specific timepoint.

End point type

Secondary

End point timeframe

Baseline, Week 16 and 24

End point values	Placebo	Ustekinumab 45mg	Ustekinumab 90mg
Number of subjects analysed	116	116	114
Units: Units on a scale
arithmetic mean (standard deviation)
W16: sleep disturbance (n=114,116,113)	3.15 ± 7.103	4.13 ± 7.815	2.79 ± 6.233
W24: sleep disturbance (n=88,94,98)	4.57 ± 7.335	5.85 ± 8.991	4.79 ± 7.232
W16: somnolence (n=114,116,113)	3.79 ± 7.996	2.06 ± 7.901	2.73 ± 8.525
W24: somnolence (n=88,94,98)	4.99 ± 8.019	3.16 ± 8.612	4.52 ± 9.131
W16: sleep adequacy (n=114,116,113)	1.78 ± 7.713	1.42 ± 9.301	1.50 ± 7.851
W24: sleep adequacy (n=88,94,98)	3.03 ± 7.245	1.75 ± 9.148	3.41 ± 7.689
W16: snoring (n=114,116,113)	0.47 ± 7.026	1.24 ± 5.753	1.14 ± 6.520
W24: snoring (n=88,94,98)	0.86 ± 7.506	1.21 ± 6.715	2.64 ± 7.569
W16:awaken short of breath/headache(n=114,116,113)	3.93 ± 12.209	3.66 ± 11.355	5.53 ± 12.602
W24:awaken short of breath/headache (n=88,94,98)	3.48 ± 11.179	2.76 ± 11.385	3.97 ± 12.426
W16: sleep problems index(n=114,116,113)	3.72 ± 7.341	3.76 ± 8.160	3.19 ± 6.695
W24:sleep problems index(n=88,94,98)	5.10 ± 7.338	4.96 ± 8.794	5.16 ± 7.795

No statistical analyses for this end point

Secondary: Change From Baseline in Composite and Domain Scores of Medical Outcomes Study Sleep Scale (MOS-SS)-Quantity of Sleep/Optimal Sleep at Week 16 and 24

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End point title

Change From Baseline in Composite and Domain Scores of Medical Outcomes Study Sleep Scale (MOS-SS)-Quantity of Sleep/Optimal Sleep at Week 16 and 24

End point description

Sleep problems were assessed using the 12-item MOS-SS, a generic instrument designed to assess 6 dimensions of sleep: Sleep disturbance, Somnolence, SA, Snoring, Awaken short of breath or headache, QS/OS during past W4. 6 dimensions used to generate composite SPI. SA scored 0 (least SA) to 100 (better SA), positive change mean improvement. QS is scored 0 (less QS) to 24 (greater QS), positive change mean improvement. Single-item QS asks subjects to estimate average number of hours they slept each night during past 4W (0-24h) and transformed into dichotomous OS Score, reported 7 or 8h of sleep considered Optimal. OS is Yes if average hour of sleep is in range of 7-8h. Early escape rule was applied(measurement value was set as missing).FAS: subjects who were randomized, received at least one administration of study agent, analyzed as per treatment group assigned regardless treatment received. 'n': number of subjects analyzed for this endpoint at specific timepoint.

End point type

Secondary

End point timeframe

Baseline, Week (W) 16 and 24

End point values	Placebo	Ustekinumab 45mg	Ustekinumab 90mg
Number of subjects analysed	116	116	114
Units: Hours
arithmetic mean (standard deviation)
Change-W16: QS/OS(n=114,116,113)	0.15 ± 0.502	0.06 ± 0.548	0.04 ± 0.557
Change-W24: QS/OS(n=88,94,98)	0.16 ± 0.500	0.07 ± 0.626	0.12 ± 0.579

No statistical analyses for this end point

Secondary: Percentage of Subjects With at Least a 40% Improvement From Baseline in ASAS 40 Components at Week 24

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End point title

Percentage of Subjects With at Least a 40% Improvement From Baseline in ASAS 40 Components at Week 24

End point description

ASAS 40 components included Patient's global assessment (0 to 10cm; 0=very well,10=very poor),total back pain (0 to 10cm; 0=no pain,10=most severe pain), BASFI (self-assessment represented as mean (0 to 10 cm; 0=easy to 10=impossible) of 10 questions, 8 of relate to participant's functional anatomy and 2 relate to participant's ability to cope with everyday life), Inflammation (0 to 10cm;0=none,10=very severe). Percentage of Participants With at least a 40% improvement from baseline in each of the ASAS components was calculated. FAS included all subjects who were randomized and received at least one administration of study agent. Subjects analyzed based on randomized treatment group they were assigned to regardless of treatment received. Here 'n' signifies number of participants who were analyzed at each specified timepoint, for each arm, respectively.

End point type

Secondary

End point timeframe

Week 24

End point values	Placebo	Ustekinumab 45mg	Ustekinumab 90mg
Number of subjects analysed	116	116	114
Units: Percentage of subjects
number (not applicable)
Patients global assessment (n=114,115,113)	43.0	35.7	31.9
Total back pain (n=114,115,113)	42.1	42.6	38.9
Function (n=114,115,113)	32.5	33.0	35.4
Inflammation (n=114,115,113)	47.4	36.5	37.2

No statistical analyses for this end point

Secondary: Percentage of Subjects who Achieved at Least 50%, 20%, 70% and 90% Improvement From Baseline in BASDAI Through Week 24

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End point title

Percentage of Subjects who Achieved at Least 50%, 20%, 70% and 90% Improvement From Baseline in BASDAI Through Week 24

End point description

BASDAI used to measure the AS disease severity. It consists of 6 questions: fatigue, spinal pain, arthralgia (joint pain) or swelling, enthesitis (inflammation of tendons and ligaments), and morning stiffness (2 questions: duration and severity. Higher BASDAI score indicates more severe AS symptom. 20 %,50%, 70%,90% improvement in BASDAI based on imputed data using treatment failure(consider non-responders at and after treatment failure),early escape rules(consider non-responder at Week 20 and 24), NRI(missing responses at post baseline visit imputed as non-responders). FAS included subjects who were randomized and received at least one administration of study agent and analyzed based on randomized treatment group assigned regardless treatment received.

End point type

Secondary

End point timeframe

Baseline, Week 4, 8, 12, 16, 20 and 24

End point values	Placebo	Ustekinumab 45mg	Ustekinumab 90mg
Number of subjects analysed	116	116	114
Units: Percentage of subjects
number (not applicable)
Week 4 (20% improvement)	25.9	28.4	35.1
Week 8 (20% improvement)	44.8	45.7	43.0
Week 12 (20% improvement)	47.4	45.7	41.2
Week 16 (20% improvement)	49.1	46.6	48.2
Week 20 (20% improvement)	43.1	51.7	50.0
Week 24 (20% improvement)	47.4	55.2	51.8
Week 4 (50% improvement)	3.4	4.3	5.3
Week 8 (50% improvement)	12.9	12.9	14.0
Week 12 (50% improvement)	19.0	12.9	14.0
Week 16 (50% improvement)	19.8	17.2	18.4
Week 20 (50% improvement)	25.9	17.2	22.8
Week 4 (70% improvement)	0.9	0.9	1.8
Week 8 (70% improvement)	6.9	4.3	5.3
Week 12 (70% improvement)	6.9	6.9	7.9
Week 16 (70% improvement)	10.3	9.5	8.8
Week 20 (70% improvement)	11.2	6.9	10.5
Week 24 (70% improvement)	11.2	11.2	11.4
Week 4 (90% improvement)	0	0.9	0
Week 8 (90% improvement)	0.9	0	1.8
Week 12 (90% improvement)	1.7	0.9	1.8
Week 16 (90% improvement)	1.7	1.7	0.9
Week 20 (90% improvement)	2.6	0.9	1.8
Week 24 (90% improvement)	4.3	1.7	4.4

No statistical analyses for this end point

Secondary: Change From Baseline in BASDAI Total Score Through Week 24

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End point title

Change From Baseline in BASDAI Total Score Through Week 24

End point description

BASDAI used to measure the AS disease severity. It consists of 6 questions: fatigue,spinal pain,arthralgia (joint pain) or swelling, enthesitis (inflammation of tendons and ligaments), and morning stiffness (2 questions: duration and severity). Each question is easy to answer 10 cm VAS, 0 being none,10 being very severe and the last question is: 0=0 hours, 10=2 or more hours. Order to give each of 5 symptoms equal weight, mean of 2 questions about morning stiffness added to total of remaining 4 scores,final BASDAI score (ranging 0-10) is the average of the overall total score. Higher BASDAI score indicates more severe AS symptom. Early escape rule was applied (measurement value at Week 20 and Week 24 was set as missing). FAS population was included and analyzed based on randomized treatment group assigned regardless treatment received. Here 'n' signifies number of participants who were analyzed at each specified timepoint, for each arm, respectively.

End point type

Secondary

End point timeframe

Baseline, Week 4, 8, 12, 16, 20 and 24

End point values	Placebo	Ustekinumab 45mg	Ustekinumab 90mg
Number of subjects analysed	116	116	114
Units: Units on a scale
arithmetic mean (standard deviation)
Week 4 (116,116,114)	-0.83 ± 1.340	-0.92 ± 1.550	-0.87 ± 1.632
Week 8 (n=116,115,114)	-1.43 ± 1.849	-1.67 ± 1.984	-1.49 ± 2.025
Week 12 (n=116,115,112)	-1.59 ± 2.073	-1.64 ± 2.047	-1.45 ± 2.118
Week 16 (n=115,116,114)	-1.67 ± 2.271	-1.74 ± 2.300	-1.60 ± 2.276
Week 20 (n=86,92,98)	-2.35 ± 2.226	-2.39 ± 1.922	-2.20 ± 2.283
Week 24 (n=88,95,99)	-2.52 ± 2.262	-2.56 ± 2.196	-2.40 ± 2.356

No statistical analyses for this end point

Secondary: Percentage of Subjects Who Achieved ASAS 40 Response at Week 4, 8, 12, 16 and 20

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End point title

Percentage of Subjects Who Achieved ASAS 40 Response at Week 4, 8, 12, 16 and 20

End point description

ASAS 40 defined as improvement from baseline of >= 40% and with an absolute improvement from baseline of at least 2 on 0 to 10cm scale in at least 3 of following 4 domains: PGA of disease activity (0 to 10cm; 0=very well,10=very poor),TBP(0 to10cm; 0=no pain,10=most severe pain),BASFI (self-assessment represented as mean (0 to10 cm;0=easy to 10=impossible) of 10 questions, 8 of relate to subject's functional anatomy, 2 relate to subject's ability to cope with life), Inflammation (0 to 10cm;0=none,10=very severe); no worsening at all from baseline in remaining domain. ASAS40 based on imputed data using treatment failure(consider non-responders at and after treatment failure),early escape rules(consider non-responder at Week 20 and 24),non-responder[NRI] (missing responses at post baseline visit imputed as non-responder).FAS population was included and analyzed based on randomized treatment group assigned regardless treatment received.

End point type

Secondary

End point timeframe

Week 4, 8, 12, 16, and 20

End point values	Placebo	Ustekinumab 45mg	Ustekinumab 90mg
Number of subjects analysed	116	116	114
Units: Percentage of subjects
number (not applicable)
Week 4 (ASAS 40)	7.8	6.9	8.8
Week 8 (ASAS 40)	14.7	18.1	19.3
Week 12 (ASAS 40)	19.8	14.7	18.4
Week 16 (ASAS 40)	22.4	21.6	22.8
Week 20 (ASAS 40)	22.4	22.4	28.9

No statistical analyses for this end point

Secondary: Percentage of Subjects Who Achieved ASAS 20 Response at Week 4, 8, 12, 16 and 20

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End point title

Percentage of Subjects Who Achieved ASAS 20 Response at Week 4, 8, 12, 16 and 20

End point description

ASAS 20 defined as improvement from baseline of >=20% and absolute improvement of 1 on 0 to 10cm in atleast 3 of 4 domains: PGA disease activity 0 to 10cm;0=very well,10=very poor,TBP 0 to10cm; 0=no pain,10=most severe pain, BASFI(self-assessment represented as 0 to 10cm; 0=easy to10=impossible of 10 questions,8 of which relate subject's functional anatomy,2 relate to subject's ability to cope with life),Inflammation(0 to 10cm;0=none,0=very severe);absence of deterioration(>= 20%,worsening of atleast 1 on 0to10cm) from baseline in remaining domain. ASAS20 based on imputed data using treatment failure(consider non-responders at and after treatment failure),early escape rules(consider non-responder at Wk 20 and 24),non-responder[NRI] (missing responses at post baseline visit imputed as non-responder).FAS population was included and analyzed based on randomized treatment group assigned regardless treatment received.

End point type

Secondary

End point timeframe

Week 4 , 8, 12, 16 and 20

End point values	Placebo	Ustekinumab 45mg	Ustekinumab 90mg
Number of subjects analysed	116	116	114
Units: Percentage of subjects
number (not applicable)
Week 4	20.7	27.6	29.8
Week 8	33.6	41.4	42.1
Week 12	37.1	44.8	39.5
Week 16	44.0	45.7	43.9
Week 20	39.7	46.6	49.1

No statistical analyses for this end point

Secondary: Percentage of Subjects who Achieved Assessment of Spondyloarthritis international Society (ASAS) Partial Remission Through Week 24

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End point title

Percentage of Subjects who Achieved Assessment of Spondyloarthritis international Society (ASAS) Partial Remission Through Week 24

End point description

Low level of disease activity was measured by criteria for ASAS partial remission, defined as a value below 2 on a scale of 0 to 10 cm in each of the 4 ASAS domains: patient’s global assessment of disease activity, total back pain, function (BASFI), inflammation. ASAS partial remission response based on imputed data using treatment failure(consider non-responders at and after treatment failure),early escape rules(consider non-responder at Week 20 and 24),non-responder[NRI] (missing responses at post baseline visit imputed as non-responder). FAS included all subjects who were randomized and received at least one administration of study agent. Subjects analyzed based on randomized treatment group they were assigned to regardless of treatment received.

End point type

Secondary

End point timeframe

Week 4, 8, 12, 16, 20 and 24

End point values	Placebo	Ustekinumab 45mg	Ustekinumab 90mg
Number of subjects analysed	116	116	114
Units: Percentage of subjects
number (not applicable)
Week 4	1.7	0	0.9
Week 8	3.4	0.9	3.5
Week 12	4.3	4.3	3.5
Week 16	8.6	5.2	2.6
Week 20	7.8	3.4	6.1
Week 24	6.9	5.2	6.1

No statistical analyses for this end point

Secondary: Percentage of Subjects Who Achieved ASAS 5/6 Response at Week 16 and 24

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End point title

Percentage of Subjects Who Achieved ASAS 5/6 Response at Week 16 and 24

End point description

ASAS 5/6 is defined as a >=20% improvement in any 5 of the 6 domains of pain (VAS 0 to 10), patient global (VAS 0 to 10), function (BASFI score), morning stiffness (from BASDAI), hsCRP, and spine mobility (lumbar side flexion). ASAS 5/6 response is based on imputed data using treatment failure(consider non-responders at and after treatment failure),early escape rules(consider non-responder at Week 20 and 24),non-responder[NRI] (missing responses at post baseline visit imputed as non-responder). FAS included all subjects who were randomized and received at least one administration of study agent. Subjects analyzed based on randomized treatment group they were assigned to regardless of treatment received.

End point type

Secondary

End point timeframe

Week 16 and 24

End point values	Placebo	Ustekinumab 45mg	Ustekinumab 90mg
Number of subjects analysed	116	116	114
Units: Percentage of subjects
number (not applicable)
Week 16	23.3	29.3	26.3
Week 24	30.2	35.3	33.3

No statistical analyses for this end point

Secondary: Change From Baseline in Ankylosing Spondylitis Disease Activity Score ASDAS (CRP) Through Week 24

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End point title

Change From Baseline in Ankylosing Spondylitis Disease Activity Score ASDAS (CRP) Through Week 24

End point description

ASDAS includes CRP mg/L; 4 additional self-reported items (rated 0-10cm VAS or 0-10 numerical rating scale [NRS]) included are total back pain (TBP), duration of morning stiffness (DMS), peripheral pain/swelling and patient global assessment (PGA). ASDAS scores calculated as: ASDAS(CRP) = (0.121*TBP)+(0.110*PGA) + (0.073*peripheral pain(PP)/swelling)+(0.058* duration of morning stiffness) + (0.579*Ln(CRP+1)). The disease activity, TBP, and PP/swelling on a NRS(0[normal]-10[very severe]and DMS on NRS(0 to 10, 0 being none and 10 representing a duration=>2 hrs). Missing values were imputed using early escape rule (measurement value was set as missing). FAS included subjects who were randomized and received at least one administration of study agent. Subjects analyzed based on randomized treatment group assigned to regardless treatment received. Here 'n' signifies number of subjects who were analyzed at each specified timepoint, for each arm, respectively.

End point type

Secondary

End point timeframe

Baseline, Week 4, 8, 12, 16, 20 and 24

End point values	Placebo	Ustekinumab 45mg	Ustekinumab 90mg
Number of subjects analysed	116	116	114
Units: Units on a scale
arithmetic mean (standard deviation)
Change at Week 4 (n=113,116,113)	-0.41 ± 0.705	-0.52 ± 0.616	-0.55 ± 0.673
Change at Week 8 (n=114,115,114)	-0.62 ± 0.881	-0.80 ± 0.764	-0.75 ± 0.875
Change at Week 12 (n-=113,114,112)	-0.66 ± 0.957	-0.87 ± 0.800	-0.76 ± 0.881
Change at Week 16 (n=113,116,114)	-0.67 ± 1.044	-0.85 ± 0.972	-0.80 ± 0.926
Change at Week 20 (n=84,92,98)	-1.00 ± 1.033	-1.13 ± 0.844	-1.01 ± 0.982
Change at Week 24 (n=85,95,98)	-1.10 ± 1.088	-1.19 ± 0.985	-1.12 ± 1.005

No statistical analyses for this end point

Secondary: Percentage of Subjects who Achieved ASDAS (CRP) Inactive Disease (<1.3) at Week 4, 8, 12, 16 and 20

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End point title

Percentage of Subjects who Achieved ASDAS (CRP) Inactive Disease (<1.3) at Week 4, 8, 12, 16 and 20

End point description

ASDAS includes CRP mg/L; four additional self-reported items (rated on 0-10cm VAS or 0-10 NRS) included are TBP, duration of DMS, peripheral pain(PP)/swelling and PGA. ASDAS calculated:ASDAS(CRP)=(0.121*TBP)+(0.110*PGA) +(0.073*peripheral pain/swelling)+(0.058*DMS)+(0.579*Ln(CRP+1)). The disease activity, TBP,PP/swelling on NRS(0 (normal) to10 (very severe), DMS on NRS (0 to 10, with 0 being none,10 representing duration of =>2h). Clinically improvement in ASDAS defined as decrease from baseline >=1.1. ASDAS (CRP Inactive Disease (<1.3) based on imputed data using treatment failure(consider non-responders at and after treatment failure),early escape rules(consider non-responder at Week 20 and 24), NRI(missing responses at post baseline visit imputed as non-responders). FAS included subjects who were randomized and received at least one administration of study agent. Subjects analyzed based on randomized treatment group assigned to regardless treatment received.

End point type

Secondary

End point timeframe

Week 4, 8, 12, 16, and 20

End point values	Placebo	Ustekinumab 45mg	Ustekinumab 90mg
Number of subjects analysed	116	116	114
Units: Percentage of subjects
number (not applicable)
Week 4	0.9	0	0
Week 8	0.9	0.9	2.6
Week 12	1.7	0.9	0.9
Week 16	1.7	1.7	2.6
Week 20	4.3	0.9	2.6

No statistical analyses for this end point

Secondary: Percentage of Subjects With ASDAS (CRP) Major Improvement (Decrease >=2.0) Through Week 24

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End point title

Percentage of Subjects With ASDAS (CRP) Major Improvement (Decrease >=2.0) Through Week 24

End point description

ASDAS includes CRP mg/L; four additional self-reported items (rated on 0-10cm VAS or 0-10 NRS) included are TBP, duration of DMS, peripheral pain(PP)/swelling and PGA. ASDAS calculated:ASDAS(CRP)=(0.121*TBP)+(0.110*PGA) +(0.073*peripheral pain/swelling)+(0.058*DMS)+(0.579*Ln(CRP+1)). The disease activity, TBP,PP/swelling on NRS(0 (normal) to10 (very severe), DMS on NRS (0 to 10, with 0 being none,10 representing duration of =>2h). Clinically improvement in ASDAS defined as decrease from baseline >=1.1. ASDAS (CRP) major important improvement (decrease >=2.0) based on imputed data using treatment failure(consider non-responders at and after treatment failure),early escape rules(consider non-responder at Week 20 and 24), NRI(missing responses at post baseline visit imputed as non-responders). FAS included subjects who were randomized and received at least one administration of study agent. Subjects analyzed based on randomized treatment group assigned to regardless treatment received.

End point type

Secondary

End point timeframe

Baseline, Week 4, 8, 12, 16, 20 and 24

End point values	Placebo	Ustekinumab 45mg	Ustekinumab 90mg
Number of subjects analysed	116	116	114
Units: Percentage of subjects
number (not applicable)
Week 4	2.6	3.4	3.5
Week 8	6.9	8.6	12.3
Week 12	8.6	9.5	12.3
Week 16	10.3	13.8	14.0
Week 20	7.8	15.5	10.5
Week 24	13.8	16.4	14.9

No statistical analyses for this end point

Secondary: Percentage of Subjects who Achieved ASDAS (CRP) Clinically Important Improvement (Decrease >=1.1) Through Week 24

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End point title

Percentage of Subjects who Achieved ASDAS (CRP) Clinically Important Improvement (Decrease >=1.1) Through Week 24

End point description

ASDAS includes CRP mg/L; four additional self-reported items (rated on 0-10cm VAS or 0-10 NRS) included are TBP, duration of DMS, peripheral pain(PP)/swelling and PGA. ASDAS calculated:ASDAS(CRP)=(0.121*TBP)+(0.110*PGA) +(0.073*peripheral pain/swelling)+(0.058*DMS)+(0.579*Ln(CRP+1)). The disease activity, TBP,PP/swelling on NRS(0 (normal) to10 (very severe),DMS on NRS (0 to 10,with 0 being none,10 representing duration of =>2h). Clinically improvement in ASDAS defined as decrease from baseline >=1.1. ASDAS (CRP) clinical important improvement (decrease >=1.1) based on imputed data using treatment failure(consider non-responders at and after treatment failure),early escape rules(consider non-responder at Week 20 and 24), NRI(missing responses at post baseline visit imputed as non-responders). FAS included subjects who were randomized and received at least one administration of study agent. Subjects analyzed based on randomized treatment group assigned to regardless treatment received.

End point type

Secondary

End point timeframe

Baseline, Week 4, 8, 12, 16, 20 and 24

End point values	Placebo	Ustekinumab 45mg	Ustekinumab 90mg
Number of subjects analysed	116	116	114
Units: Percentage of subjects
number (not applicable)
Week 4	16.4	13.8	17.5
Week 8	26.7	31.0	30.7
Week 12	28.4	37.9	28.1
Week 16	32.8	35.3	28.1
Week 20	29.3	31.9	37.7
Week 24	37.9	40.5	37.7

No statistical analyses for this end point

Secondary: Change From Baseline in BASFI Score at Week 4, 8, 12, 16 and 20

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End point title

Change From Baseline in BASFI Score at Week 4, 8, 12, 16 and 20

End point description

The BASFI is composed with 10 questions (each question is answered with a visual analogue scale 0-10 cm) to assess the disease severity, including the first 8 questions regarding to functional anatomy related activities and the remaining 2 questions related to daily activities of AS participants. Each question is a 10cm VAS with a value between 0 (easy) and 10 (impossible). The final BASFI score is the mean of the 10 scores. The BASFI score is the average of the 10 responses and has a possible minimum value of 0 and a possible maximum value of 10. Higher BASFI score indicates more severe functional limitations of the participant due to AS. Change from baseline in BASFI score were imputed using early escape rule (measurement value at Week 20 and Week 24 was set as missing).FAS included all subjects who were randomized and received at least one administration of study agent. Subjects analyzed based on randomized treatment group they were assigned to regardless of treatment received.

End point type

Secondary

End point timeframe

Baseline , Week 4, 8, 12, 16, and 20

End point values	Placebo	Ustekinumab 45mg	Ustekinumab 90mg
Number of subjects analysed	116	116	114
Units: Units on a scale
arithmetic mean (standard deviation)
Change at Week 4(n=116,116,114)	-0.77 ± 1.635	-0.80 ± 1.359	-0.90 ± 1.524
Change at Week 8(n=116,115,114)	-1.13 ± 1.841	-1.29 ± 1.904	-1.29 ± 1.841
Change at Week 12 (n=116,115,112)	-1.09 ± 2.015	-1.22 ± 1.854	-1.34 ± 2.001
Change at Week 16(n=115,116,114)	-1.08 ± 2.179	-1.35 ± 2.113	-1.43 ± 2.125
Change at Week 20 (n=86,92,98)	-1.71 ± 2.160	-1.94 ± 1.946	-2.01 ± 2.291

No statistical analyses for this end point

Secondary: Change From Baseline in Chest Expansion at Week 16 and 24

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End point title

Change From Baseline in Chest Expansion at Week 16 and 24

End point description

Chest expansion is the difference, in centimeter (cm), between the circumference of the chest in maximal inspiration and maximal expiration. It is measured at the level of the fourth intercostal space in males, and just below the breasts in females. Change from baseline in chest expansion were imputed using early escape rule (measurement value at Week 20 and Week 24 was set as missing). FAS included all subjects who were randomized and received at least one administration of study agent. Subjects analyzed based on randomized treatment group they were assigned to regardless of treatment received. Here 'n' signifies number of subjects who were analyzed at each specified timepoint, for each arm, respectively.

End point type

Secondary

End point timeframe

Baseline , Week 16 and 24

End point values	Placebo	Ustekinumab 45mg	Ustekinumab 90mg
Number of subjects analysed	116	116	114
Units: centimeter(cm)
arithmetic mean (standard deviation)
Change at Week 16 (n=114,113,111)	0.43 ± 7.899	0.20 ± 2.209	-0.02 ± 2.240
Change at Week 24(n=87,92,97)	-0.16 ± 2.370	0.32 ± 1.939	-0.21 ± 2.232

No statistical analyses for this end point

Secondary: Change From Baseline in Total Back Pain (TBP) and Night Back Pain (NBP) Through Week 24

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End point title

Change From Baseline in Total Back Pain (TBP) and Night Back Pain (NBP) Through Week 24

End point description

The total back pain and nighttime back pain was measured on a VAS (0 to 10 cm; 0 = no pain, 10 = most severe pain). Change from baseline in TBP and NBP were imputed using early escape rule (measurement value at Week 20 and Week 24 was set as missing). FAS included all subjects who were randomized and received at least one administration of study agent. Subjects analyzed based on randomized treatment group they were assigned to regardless of treatment received. Here 'n' signifies number of subjects who were analyzed at each specified timepoint, for each arm, respectively.

End point type

Secondary

End point timeframe

Baseline, Week 4, 8, 12, 16, 20 and 24

End point values	Placebo	Ustekinumab 45mg	Ustekinumab 90mg
Number of subjects analysed	116	116	114
Units: centimeter
arithmetic mean (standard deviation)
Change -W4 in TBP (n=116,116,114)	-1.13 ± 2.019	-1.15 ± 1.911	-1.52 ± 1.895
Change -W4 in NBP (n=116,116,114)	-1.05 ± 2.270	-1.25 ± 1.835	-1.19 ± 2.082
Change -W8 in TBP (n=116,115,114)	-1.80 ± 2.190	-1.78 ± 2.294	2.20 ± 2.243
Change -W8 in NBP (n=116,115,114)	-1.69 ± 2.264	-1.85 ± 2.122	-2.01 ± 2.517
Change -W12 in TBP (n=116,115,112)	-1.81 ± 2.295	-1.70 ± 2.218	-1.84 ± 2.288
Change -W12 in NBP (n=116,115,112)	-1.61 ± 2.342	-1.79 ± 2.127	-1.76 ± 2.554
Change -W16 in TBP (n=115,116,114)	-1.80 ± 2.374	-1.87 ± 2.465	-2.07 ± 2.387
Change -W16 in NBP (n=115,116,114)	-1.76 ± 2.506	-2.02 ± 2.541	-2.05 ± 2.606
Change -W20 in TBP (n=86,92,98)	-2.73 ± 2.456	-2.74 ± 2.088	-2.69 ± 2.414
Change -W20 in NBP (n=86,92,98)	-2.67 ± 2.602	-2.73 ± 2.246	-2.83 ± 2.804
Change -W24 in TBP (n=88,95,99)	-2.80 ± 2.528	-2.90 ± 2.389	-2.77 ± 2.511
Change -W24 in NBP (n=88,94,99)	-2.75 ± 2.597	-2.79 ± 2.367	-2.68 ± 2.960

No statistical analyses for this end point

Secondary: Change From Baseline in Patients Global Assessment (PGA) Scale Score Through Week 24

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End point title

Change From Baseline in Patients Global Assessment (PGA) Scale Score Through Week 24

End point description

The Patient’s Global Assessment of Disease Activity is one of the components of ASAS 40. It is measured on a VAS (0 to 10 cm; 0 = very well, 10 = very poor). Change from baseline in PGA scale were imputed using early escape rule (The measurement value at Week 20 and Week 24 was set as missing). FAS included all subjects who were randomized and received at least one administration of study agent. Subjects analyzed based on randomized treatment group they were assigned to regardless of treatment received. Here 'n' signifies number of subjects who were analyzed at each specified timepoint, for each arm, respectively.

End point type

Secondary

End point timeframe

Baseline, Week 4, 8, 12, 16, 20 and 24

End point values	Placebo	Ustekinumab 45mg	Ustekinumab 90mg
Number of subjects analysed	116	116	114
Units: Units on a scale
arithmetic mean (standard deviation)
Change at Week 4 (n=116,116,114)	-0.99 ± 1.727	-1.01 ± 1.677	-1.21 ± 1.645
Change at Week 8 (n=116,115,114)	-1.48 ± 2.086	-1.60 ± 2.039	-1.70 ± 2.096
Change at Week 12 (n=116,115,112)	-1.52 ± 2.043	-1.53 ± 2.100	-1.77 ± 2.088
Change at Week 16 (n=115,116,114)	-1.64 ± 2.259	-1.73 ± 2.564	-1.77 ± 2.293
Change at Week 20 (n=86,92,98)	-2.10 ± 2.272	-2.17 ± 2.225	-2.36 ± 2.283
Change at Week 24 (n=88,95,99)	-2.37 ± 2.298	-2.55 ± 2.664	-2.50 ± 2.379

No statistical analyses for this end point

Secondary: Change From Baseline in EQ-5D Index at Week 16 and 24

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End point title

Change From Baseline in EQ-5D Index at Week 16 and 24

End point description

The EuroQol-5 is a five dimensional health state classification. Each dimension is assessed on a 3-point ordinal scale (1=no problems, 2=some problems, 3=extreme problems). The responses to the five EQ-5D dimensions were scored using a utility-weighted algorithm to derive an EQ-5D health status index score between 0 to 1, with 1.00 indicating "full health" and 0 representing dead. Change from baseline in EQ-5D index were imputed using early escape rule (measurement value at Week 20 and Week 24 was set as missing). FAS included all subjects who were randomized and received at least one administration of study agent. Subjects analyzed based on randomized treatment group they were assigned to regardless of treatment received. Here 'n' signifies number of subjects who were analyzed at each specified timepoint, for each arm, respectively.

End point type

Secondary

End point timeframe

Baseline, Week 16 and 24

End point values	Placebo	Ustekinumab 45mg	Ustekinumab 90mg
Number of subjects analysed	116	116	114
Units: Units on a scale
arithmetic mean (standard deviation)
Change at Week 16 (114,116,113)	0.08 ± 0.138	0.09 ± 0.154	0.10 ± 0.139
Change at Week 24 (n=87,94,98)	0.12 ± 0.137	0.12 ± 0.168	0.13 ± 0.153

No statistical analyses for this end point

Secondary: Change From Baseline in EQ-5D VAS at Week 16 and 24

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End point title

Change From Baseline in EQ-5D VAS at Week 16 and 24

End point description

European Quality of Life 5 Dimensions (EQ-5D) visual analog scale (VAS) is a 20 centimeter (cm) vertical VAS with scores ranging from 0 (worst imaginable health) to 100 (perfect health). A higher score indicates an improvement in health in the Health Status Index. Change from baseline in EQ-5D VAS were imputed using early escape rule (measurement value at Week 20 and Week 24 was set as missing). FAS included all subjects who were randomized and received at least one administration of study agent. Subjects analyzed based on randomized treatment group they were assigned to regardless of treatment received. Here 'n' signifies number of subjects who were analyzed at each specified timepoint, for each arm, respectively.

End point type

Secondary

End point timeframe

Baseline, Week 16 and 24

End point values	Placebo	Ustekinumab 45mg	Ustekinumab 90mg
Number of subjects analysed	116	116	114
Units: Units on a scale
arithmetic mean (standard deviation)
Change at Week 16 (n=114,116,113)	11.49 ± 20.328	11.26 ± 23.588	13.36 ± 22.110
Change at Week 24 (n=87,94,98)	17.57 ± 20.251	13.90 ± 26.132	16.80 ± 22.181

No statistical analyses for this end point

Secondary: Change From Baseline in Berlin Magnetic Resonance Imaging (MRI) Spine Score at Week 24

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End point title

Change From Baseline in Berlin Magnetic Resonance Imaging (MRI) Spine Score at Week 24

End point description

The study used MRI with fat-saturating techniques such as short tau inversion recovery (STIR) to look for the presence of bone marrow edema. The Berlin modification of ASspiMRI-a (ASspiMRI-a) scoring technique assesses inflammation in each of the 23 disc vertebral units (DVU), capturing edema and erosion. Scores for each DVU range from 0-3 (0=normal; 1=minor bone marrow edema [less than or equal to 25% of DVU; 3=severe bone marrow edema (more that 50% of DVU)]. The composite score ranges from 0 to 69, with higher scores indicating more severe inflammation. Population included subset of FAS with subjects who did not meet early escape criteria and have both baseline and Week 24 MRI assessments.

End point type

Secondary

End point timeframe

Baseline and Week 24

End point values	Placebo	Ustekinumab 45mg	Ustekinumab 90mg
Number of subjects analysed	23	18	26
Units: Units on a scale
arithmetic mean (standard deviation)	-0.48 ± 2.053	-0.58 ± 2.343	-1.15 ± 2.32

No statistical analyses for this end point

Secondary: Change From Baseline in Percent Work Time Missed Due to AS [Assessed by Work Productivity and Activity Impairment Questionnaire - Specific Health Problem (WPAI-SHP)] Through Week 24

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End point title

Change From Baseline in Percent Work Time Missed Due to AS [Assessed by Work Productivity and Activity Impairment Questionnaire - Specific Health Problem (WPAI-SHP)] Through Week 24

End point description

WPAI-SHP is 6-item questionnaire used to assess degree to which specified health problem (here AS) affected work attendance, work productivity (WP) and productivity in non-work regular activities. Patients are asked to consider the past 7 days prior to each questionnaire day. Questionnaire asks: current employment status, hours worked, hours missed from work for any reason other than AS, hours missed from work due to AS, degree to which AS affected WP, degree to which AS affected non-work regular activities. 4 component scores were then calculated: percent work time missed due to AS; percent impairment while working due to AS, percent overall work impairment due to AS, percent non-work activity impairment due to AS. Computed percentage range for each sub-scale was 0-100, with higher numbers indicating greater impairment, less productivity. FAS population was included. Here 'n' signifies number of participants who were analyzed at each specified timepoint, for each arm, respectively.

End point type

Secondary

End point timeframe

Baseline, Week 16 and 24

End point values	Placebo	Ustekinumab 45mg	Ustekinumab 90mg
Number of subjects analysed	116	116	114
Units: Units on a scale
arithmetic mean (standard deviation)
Change at Week 16 (67,67,70)	-3.72 ± 26.092	-2.05 ± 26.625	-2.06 ± 26.486
Change at Week 24(n=55,56,62)	-7.37 ± 16.925	-4.38 ± 22.562	-7.07 ± 22.081

No statistical analyses for this end point

Secondary: Change From Baseline in Percent Impairment While Working Due to AS (Assessed by WPAI-SHP) Through Week 24

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End point title

Change From Baseline in Percent Impairment While Working Due to AS (Assessed by WPAI-SHP) Through Week 24

End point description

End point type

Secondary

End point timeframe

Baseline, Week 16 and 24

End point values	Placebo	Ustekinumab 45mg	Ustekinumab 90mg
Number of subjects analysed	116	116	114
Units: units on a scale
arithmetic mean (standard deviation)
Change at Week 16 (n= 67, 67, 70)	-16.87 ± 25.359	-5.97 ± 21.607	-17.57 ± 20.032
Change at Week 16 (n= 55, 56, 62)	-22.00 ± 21.892	-13.57 ± 22.758	-19.68 ± 22.973

No statistical analyses for this end point

Secondary: Change From Baseline in Percent Overall Work Impairment Due to AS (Assessed by WPAI-SHP) Through Week 24

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End point title

Change From Baseline in Percent Overall Work Impairment Due to AS (Assessed by WPAI-SHP) Through Week 24

End point description

End point type

Secondary

End point timeframe

Baseline, Week 16 and 24

End point values	Placebo	Ustekinumab 45mg	Ustekinumab 90mg
Number of subjects analysed	116	116	114
Units: units on a scale
arithmetic mean (standard deviation)
Change at Week 16 (67, 67, 70)	-16.03 ± 26.281	-6.64 ± 23.976	-17.48 ± 20.811
Change at Week 16 (55, 56, 62)	-21.98 ± 21.042	-14.64 ± 24.300	-20.54 ± 24.271

No statistical analyses for this end point

Secondary: Change From Baseline in Percent non Work Activity Impairment Due to AS (Assessed by WPAI-SHP) Through Week 24

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End point title

Change From Baseline in Percent non Work Activity Impairment Due to AS (Assessed by WPAI-SHP) Through Week 24

End point description

End point type

Secondary

End point timeframe

Baseline, Week 16 and 24

End point values	Placebo	Ustekinumab 45mg	Ustekinumab 90mg
Number of subjects analysed	116	116	114
Units: Units on a scale
arithmetic mean (standard deviation)
Change at Week 16 (n= 114, 116, 113)	-14.74 ± 23.013	-13.45 ± 21.833	-17.52 ± 22.101
Change at Week 24 (n= 87, 94, 98)	-21.72 ± 23.288	-21.49 ± 23.825	-21.73 ± 22.339

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Approximately 2 years

Adverse event reporting additional description

The safety analysis set included all participants who received at least 1 (partial or complete) administration of study agent, i.e., the treated population. Adverse events were reported according to the treatment they actually received, regardless of the treatments they are randomized to.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

20.0

Reporting group title

Placebo

Reporting group description

Subjects received placebo subcutaneous (SC) injection at Weeks 0, 4, and 16. At Week 16, subjects who met EE criteria were administered open-label golimumab 50 milligram (mg) SC administrations at Week 16 and every 4 weeks (q4w) thereafter through Week 52. At Week 24 all subjects (with the exception of subjects who qualified for early escape [EE]) were re-randomized to receive either ustekinumab 45 or 90 milligram (mg) SC injection at Weeks 24 and 28 followed by every 12 weeks (q12w) dosing through Week 100.

Reporting group title

Placebo to Golimumab

Reporting group description

Subjects randomized to placebo SC who met early escape criteria and received golimumab from Week 16; adverse events are counted from early escape onward.

Reporting group title

Placebo to Ustekinumab 45mg

Reporting group description

Subjects randomized to placebo SC and then rerandomized to receive ustekinumab 45 mg at Week 24; adverse events are counted from crossover onward.

Reporting group title

Placebo to Ustekinumab 90mg

Reporting group description

Subjects randomized to placebo SC and then rerandomized to receive ustekinumab 90 mg at Week 24; adverse events are counted from crossover onward.

Reporting group title

Ustekinumab 45mg Only

Reporting group description

Reporting group title

Ustekinumab 45mg to Golimumab

Reporting group description

Subjects randomized to ustekinumab 45 mg SC who met early escape criteria and received golimumab from Week 16; adverse events are counted from early escape onward.

Reporting group title

Ustekinumab 90mg Only

Reporting group description

Reporting group title

Ustekinumab 90mg to Golimumab

Reporting group description

Subjects randomized to ustekinumab 90 mg SC who met early escape criteria and received golimumab from Week 16; adverse events are counted from early escape onward.

Serious adverse events	Placebo	Placebo to Golimumab	Placebo to Ustekinumab 45mg	Placebo to Ustekinumab 90mg	Ustekinumab 45mg Only	Ustekinumab 45mg to Golimumab	Ustekinumab 90mg Only	Ustekinumab 90mg to Golimumab
Total subjects affected by serious adverse events
subjects affected / exposed	2 / 116 (1.72%)	0 / 26 (0.00%)	2 / 44 (4.55%)	2 / 43 (4.65%)	3 / 116 (2.59%)	3 / 21 (14.29%)	2 / 114 (1.75%)	0 / 14 (0.00%)
number of deaths (all causes)	0	0	0	0	0	1	0	0
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign Salivary Gland Neoplasm
subjects affected / exposed	0 / 116 (0.00%)	0 / 26 (0.00%)	0 / 44 (0.00%)	0 / 43 (0.00%)	0 / 116 (0.00%)	1 / 21 (4.76%)	0 / 114 (0.00%)	0 / 14 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Back Injury
subjects affected / exposed	0 / 116 (0.00%)	0 / 26 (0.00%)	0 / 44 (0.00%)	0 / 43 (0.00%)	0 / 116 (0.00%)	1 / 21 (4.76%)	0 / 114 (0.00%)	0 / 14 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
Concussion
subjects affected / exposed	0 / 116 (0.00%)	0 / 26 (0.00%)	1 / 44 (2.27%)	0 / 43 (0.00%)	0 / 116 (0.00%)	0 / 21 (0.00%)	0 / 114 (0.00%)	0 / 14 (0.00%)
occurrences causally related to treatment / all	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
Ligament Sprain
subjects affected / exposed	0 / 116 (0.00%)	0 / 26 (0.00%)	1 / 44 (2.27%)	0 / 43 (0.00%)	0 / 116 (0.00%)	0 / 21 (0.00%)	0 / 114 (0.00%)	0 / 14 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Muscle Strain
subjects affected / exposed	0 / 116 (0.00%)	0 / 26 (0.00%)	1 / 44 (2.27%)	0 / 43 (0.00%)	0 / 116 (0.00%)	0 / 21 (0.00%)	0 / 114 (0.00%)	0 / 14 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Subdural Haematoma
subjects affected / exposed	0 / 116 (0.00%)	0 / 26 (0.00%)	0 / 44 (0.00%)	0 / 43 (0.00%)	0 / 116 (0.00%)	0 / 21 (0.00%)	1 / 114 (0.88%)	0 / 14 (0.00%)
occurrences causally related to treatment / all	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
Nervous system disorders
Facial Paralysis
subjects affected / exposed	0 / 116 (0.00%)	0 / 26 (0.00%)	0 / 44 (0.00%)	0 / 43 (0.00%)	1 / 116 (0.86%)	0 / 21 (0.00%)	0 / 114 (0.00%)	0 / 14 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ischaemic Stroke
subjects affected / exposed	1 / 116 (0.86%)	0 / 26 (0.00%)	0 / 44 (0.00%)	0 / 43 (0.00%)	0 / 116 (0.00%)	0 / 21 (0.00%)	0 / 114 (0.00%)	0 / 14 (0.00%)
occurrences causally related to treatment / all	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
Vertebrobasilar Insufficiency
subjects affected / exposed	1 / 116 (0.86%)	0 / 26 (0.00%)	0 / 44 (0.00%)	0 / 43 (0.00%)	0 / 116 (0.00%)	0 / 21 (0.00%)	0 / 114 (0.00%)	0 / 14 (0.00%)
occurrences causally related to treatment / all	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
Eye disorders
Ocular Hypertension
subjects affected / exposed	0 / 116 (0.00%)	0 / 26 (0.00%)	0 / 44 (0.00%)	1 / 43 (2.33%)	0 / 116 (0.00%)	0 / 21 (0.00%)	0 / 114 (0.00%)	0 / 14 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Uveitis
subjects affected / exposed	0 / 116 (0.00%)	0 / 26 (0.00%)	0 / 44 (0.00%)	0 / 43 (0.00%)	0 / 116 (0.00%)	1 / 21 (4.76%)	0 / 114 (0.00%)	0 / 14 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholelithiasis
subjects affected / exposed	0 / 116 (0.00%)	0 / 26 (0.00%)	1 / 44 (2.27%)	0 / 43 (0.00%)	0 / 116 (0.00%)	0 / 21 (0.00%)	0 / 114 (0.00%)	0 / 14 (0.00%)
occurrences causally related to treatment / all	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
Renal and urinary disorders
Calculus Urinary
subjects affected / exposed	0 / 116 (0.00%)	0 / 26 (0.00%)	0 / 44 (0.00%)	1 / 43 (2.33%)	0 / 116 (0.00%)	0 / 21 (0.00%)	0 / 114 (0.00%)	0 / 14 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Intervertebral Disc Disorder
subjects affected / exposed	0 / 116 (0.00%)	0 / 26 (0.00%)	0 / 44 (0.00%)	0 / 43 (0.00%)	1 / 116 (0.86%)	0 / 21 (0.00%)	0 / 114 (0.00%)	0 / 14 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	0 / 116 (0.00%)	0 / 26 (0.00%)	0 / 44 (0.00%)	0 / 43 (0.00%)	1 / 116 (0.86%)	0 / 21 (0.00%)	0 / 114 (0.00%)	0 / 14 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Appendicitis
subjects affected / exposed	0 / 116 (0.00%)	0 / 26 (0.00%)	1 / 44 (2.27%)	0 / 43 (0.00%)	0 / 116 (0.00%)	0 / 21 (0.00%)	0 / 114 (0.00%)	0 / 14 (0.00%)
occurrences causally related to treatment / all	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
Cellulitis
subjects affected / exposed	0 / 116 (0.00%)	0 / 26 (0.00%)	0 / 44 (0.00%)	0 / 43 (0.00%)	0 / 116 (0.00%)	0 / 21 (0.00%)	1 / 114 (0.88%)	0 / 14 (0.00%)
occurrences causally related to treatment / all	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

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

Non-serious adverse events	Placebo	Placebo to Golimumab	Placebo to Ustekinumab 45mg	Placebo to Ustekinumab 90mg	Ustekinumab 45mg Only	Ustekinumab 45mg to Golimumab	Ustekinumab 90mg Only	Ustekinumab 90mg to Golimumab
Total subjects affected by non serious adverse events
subjects affected / exposed	15 / 116 (12.93%)	4 / 26 (15.38%)	3 / 44 (6.82%)	0 / 43 (0.00%)	24 / 116 (20.69%)	7 / 21 (33.33%)	26 / 114 (22.81%)	4 / 14 (28.57%)
Investigations
Alanine Aminotransferase Increased
subjects affected / exposed	6 / 116 (5.17%)	2 / 26 (7.69%)	1 / 44 (2.27%)	0 / 43 (0.00%)	8 / 116 (6.90%)	2 / 21 (9.52%)	6 / 114 (5.26%)	0 / 14 (0.00%)
occurrences all number	6	2	1	0	8	2	6	0
Aspartate Aminotransferase Increased
subjects affected / exposed	3 / 116 (2.59%)	2 / 26 (7.69%)	0 / 44 (0.00%)	0 / 43 (0.00%)	8 / 116 (6.90%)	3 / 21 (14.29%)	3 / 114 (2.63%)	0 / 14 (0.00%)
occurrences all number	4	2	0	0	8	3	3	0
Musculoskeletal and connective tissue disorders
Ankylosing Spondylitis
subjects affected / exposed	0 / 116 (0.00%)	0 / 26 (0.00%)	1 / 44 (2.27%)	0 / 43 (0.00%)	0 / 116 (0.00%)	0 / 21 (0.00%)	0 / 114 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	1	0	0	0	0	1
Fasciitis
subjects affected / exposed	0 / 116 (0.00%)	0 / 26 (0.00%)	0 / 44 (0.00%)	0 / 43 (0.00%)	0 / 116 (0.00%)	0 / 21 (0.00%)	0 / 114 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	1
Infections and infestations
Acute Sinusitis
subjects affected / exposed	0 / 116 (0.00%)	0 / 26 (0.00%)	0 / 44 (0.00%)	0 / 43 (0.00%)	0 / 116 (0.00%)	0 / 21 (0.00%)	1 / 114 (0.88%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	1	1
Influenza
subjects affected / exposed	1 / 116 (0.86%)	0 / 26 (0.00%)	0 / 44 (0.00%)	0 / 43 (0.00%)	2 / 116 (1.72%)	0 / 21 (0.00%)	0 / 114 (0.00%)	1 / 14 (7.14%)
occurrences all number	1	0	0	0	2	0	0	1
Respiratory Tract Infection Viral
subjects affected / exposed	2 / 116 (1.72%)	0 / 26 (0.00%)	0 / 44 (0.00%)	0 / 43 (0.00%)	0 / 116 (0.00%)	0 / 21 (0.00%)	6 / 114 (5.26%)	0 / 14 (0.00%)
occurrences all number	2	0	0	0	0	0	6	0
Upper Respiratory Tract Infection
subjects affected / exposed	2 / 116 (1.72%)	1 / 26 (3.85%)	0 / 44 (0.00%)	0 / 43 (0.00%)	3 / 116 (2.59%)	2 / 21 (9.52%)	4 / 114 (3.51%)	0 / 14 (0.00%)
occurrences all number	2	1	0	0	6	2	4	0
Viral Upper Respiratory Tract Infection
subjects affected / exposed	5 / 116 (4.31%)	1 / 26 (3.85%)	1 / 44 (2.27%)	0 / 43 (0.00%)	9 / 116 (7.76%)	2 / 21 (9.52%)	11 / 114 (9.65%)	0 / 14 (0.00%)
occurrences all number	6	1	1	0	9	2	14	0
Metabolism and nutrition disorders
Hyperglycaemia
subjects affected / exposed	0 / 116 (0.00%)	0 / 26 (0.00%)	0 / 44 (0.00%)	0 / 43 (0.00%)	3 / 116 (2.59%)	0 / 21 (0.00%)	1 / 114 (0.88%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	3	0	1	1

More information

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Were there any global substantial amendments to the protocol? Yes

04 Aug 2015

The main reason of this amendment was to included the following changes: a subset of subjects was to be enrolled in an MRI substudy to explore changes in the Berlin MRI spine score during treatment, an additional chemistry assessment at Week 28 was added, clarification on the informed consents for the microbiome and MRI substudies were made, only subjects participating in the MRI substudy were to undergo MRI assessments, and some minor editorial changes. The Sponsor intended to enroll up to 10% of the study population with total spinal ankyloses.

16 Feb 2016

The main reason of this amendment was to included the following changes: radiographic progression was added as an efficacy related secondary objective for the study, change in length of the study from Week 64 to Week 112 for subjects who did not meet EE criteria and continued treatment. Subjects who reached Week 64 had the opportunity to decide their participation in the study extension. The added radiographic evaluations (x-ray of cervical and lumbar spine) were to be conducted during the study at baseline and at Week 100, and minor editorial changes.

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.

The study was discontinued since neither dose achieved the study's primary or major secondary endpoints.

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Clinical trials

Clinical Trial Results: A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Ustekinumab in the Treatment of Anti-TNFα Naïve Subjects With Active Radiographic Axial Spondyloarthritis

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Subjects Who Achieved an Assessment of Spondyloarthritis international Society (ASAS) 40 Response at Week 24

Primary: Percentage of Subjects Who Achieved an Assessment of Spondyloarthritis international Society (ASAS) 40 Response at Week 24

Secondary: Percentage of Subjects Who Achieved an ASAS 20 Response at Week 24

Secondary: Percentage of Subjects Who Achieved an ASAS 20 Response at Week 24

Secondary: Percentage of Subjects who Achieved at Least a 50 Percent (%) Improvement From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 24

Secondary: Percentage of Subjects who Achieved at Least a 50 Percent (%) Improvement From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 24

Secondary: Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) Total Score at Week 24

Secondary: Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) Total Score at Week 24

Secondary: Percentage of Subjects who Achieved Ankylosing Spondylitis Disease Activity Score-C Reactive Protein (ASDAS-CRP) Inactive Disease (<1.3) at Week 24

Secondary: Percentage of Subjects who Achieved Ankylosing Spondylitis Disease Activity Score-C Reactive Protein (ASDAS-CRP) Inactive Disease (<1.3) at Week 24

Secondary: Change From Baseline in hsCRP Through Week 24

Secondary: Change From Baseline in hsCRP Through Week 24

Secondary: Change From Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) at Week 16 and 24

Secondary: Change From Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) at Week 16 and 24

Secondary: Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Week 16 and 24

Secondary: Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Week 16 and 24

Secondary: Change from Baseline in Ankylosing Spondylitis Quality of Life questionnaire (ASQoL) Score at Week 16 and 24

Secondary: Change from Baseline in Ankylosing Spondylitis Quality of Life questionnaire (ASQoL) Score at Week 16 and 24

Secondary: Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Week 16 and 24

Secondary: Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Week 16 and 24

Secondary: Change From Baseline in Norm-Based SF-36 Physical Component Summary (PCS) and SF-36 Mental Component Summary (MCS) at Week 16 and 24

Secondary: Change From Baseline in Norm-Based SF-36 Physical Component Summary (PCS) and SF-36 Mental Component Summary (MCS) at Week 16 and 24

Secondary: Change From Baseline in BASDAI Inflammation Score Through Week 24

Secondary: Change From Baseline in BASDAI Inflammation Score Through Week 24

Secondary: Change From Baseline in Composite and Domain Scores of Medical Outcomes Study Sleep Scale (MOS-SS) at Week 16 and 24

Secondary: Change From Baseline in Composite and Domain Scores of Medical Outcomes Study Sleep Scale (MOS-SS) at Week 16 and 24

Secondary: Change From Baseline in Composite and Domain Scores of Medical Outcomes Study Sleep Scale (MOS-SS)-Quantity of Sleep/Optimal Sleep at Week 16 and 24

Secondary: Change From Baseline in Composite and Domain Scores of Medical Outcomes Study Sleep Scale (MOS-SS)-Quantity of Sleep/Optimal Sleep at Week 16 and 24

Secondary: Percentage of Subjects With at Least a 40% Improvement From Baseline in ASAS 40 Components at Week 24

Secondary: Percentage of Subjects With at Least a 40% Improvement From Baseline in ASAS 40 Components at Week 24

Secondary: Percentage of Subjects who Achieved at Least 50%, 20%, 70% and 90% Improvement From Baseline in BASDAI Through Week 24

Secondary: Percentage of Subjects who Achieved at Least 50%, 20%, 70% and 90% Improvement From Baseline in BASDAI Through Week 24

Secondary: Change From Baseline in BASDAI Total Score Through Week 24

Secondary: Change From Baseline in BASDAI Total Score Through Week 24

Secondary: Percentage of Subjects Who Achieved ASAS 40 Response at Week 4, 8, 12, 16 and 20

Secondary: Percentage of Subjects Who Achieved ASAS 40 Response at Week 4, 8, 12, 16 and 20

Secondary: Percentage of Subjects Who Achieved ASAS 20 Response at Week 4, 8, 12, 16 and 20

Secondary: Percentage of Subjects Who Achieved ASAS 20 Response at Week 4, 8, 12, 16 and 20

Secondary: Percentage of Subjects who Achieved Assessment of Spondyloarthritis international Society (ASAS) Partial Remission Through Week 24

Secondary: Percentage of Subjects who Achieved Assessment of Spondyloarthritis international Society (ASAS) Partial Remission Through Week 24

Secondary: Percentage of Subjects Who Achieved ASAS 5/6 Response at Week 16 and 24

Secondary: Percentage of Subjects Who Achieved ASAS 5/6 Response at Week 16 and 24

Secondary: Change From Baseline in Ankylosing Spondylitis Disease Activity Score ASDAS (CRP) Through Week 24

Secondary: Change From Baseline in Ankylosing Spondylitis Disease Activity Score ASDAS (CRP) Through Week 24

Secondary: Percentage of Subjects who Achieved ASDAS (CRP) Inactive Disease (<1.3) at Week 4, 8, 12, 16 and 20

Secondary: Percentage of Subjects who Achieved ASDAS (CRP) Inactive Disease (<1.3) at Week 4, 8, 12, 16 and 20

Secondary: Percentage of Subjects With ASDAS (CRP) Major Improvement (Decrease >=2.0) Through Week 24

Secondary: Percentage of Subjects With ASDAS (CRP) Major Improvement (Decrease >=2.0) Through Week 24

Secondary: Percentage of Subjects who Achieved ASDAS (CRP) Clinically Important Improvement (Decrease >=1.1) Through Week 24

Secondary: Percentage of Subjects who Achieved ASDAS (CRP) Clinically Important Improvement (Decrease >=1.1) Through Week 24

Secondary: Change From Baseline in BASFI Score at Week 4, 8, 12, 16 and 20

Secondary: Change From Baseline in BASFI Score at Week 4, 8, 12, 16 and 20

Secondary: Change From Baseline in Chest Expansion at Week 16 and 24

Secondary: Change From Baseline in Chest Expansion at Week 16 and 24

Secondary: Change From Baseline in Total Back Pain (TBP) and Night Back Pain (NBP) Through Week 24

Secondary: Change From Baseline in Total Back Pain (TBP) and Night Back Pain (NBP) Through Week 24

Secondary: Change From Baseline in Patients Global Assessment (PGA) Scale Score Through Week 24

Secondary: Change From Baseline in Patients Global Assessment (PGA) Scale Score Through Week 24

Secondary: Change From Baseline in EQ-5D Index at Week 16 and 24

Secondary: Change From Baseline in EQ-5D Index at Week 16 and 24

Secondary: Change From Baseline in EQ-5D VAS at Week 16 and 24

Secondary: Change From Baseline in EQ-5D VAS at Week 16 and 24

Secondary: Change From Baseline in Berlin Magnetic Resonance Imaging (MRI) Spine Score at Week 24

Secondary: Change From Baseline in Berlin Magnetic Resonance Imaging (MRI) Spine Score at Week 24

Secondary: Change From Baseline in Percent Work Time Missed Due to AS [Assessed by Work Productivity and Activity Impairment Questionnaire - Specific Health Problem (WPAI-SHP)] Through Week 24

Secondary: Change From Baseline in Percent Work Time Missed Due to AS [Assessed by Work Productivity and Activity Impairment Questionnaire - Specific Health Problem (WPAI-SHP)] Through Week 24

Secondary: Change From Baseline in Percent Impairment While Working Due to AS (Assessed by WPAI-SHP) Through Week 24

Secondary: Change From Baseline in Percent Impairment While Working Due to AS (Assessed by WPAI-SHP) Through Week 24

Secondary: Change From Baseline in Percent Overall Work Impairment Due to AS (Assessed by WPAI-SHP) Through Week 24

Secondary: Change From Baseline in Percent Overall Work Impairment Due to AS (Assessed by WPAI-SHP) Through Week 24

Clinical Trial Results:
A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Ustekinumab in the Treatment of Anti-TNFα Naïve Subjects With Active Radiographic Axial Spondyloarthritis