Multicenter Study Evaluating Certolizumab Pegol Compared to Placebo in Subjects With axSpA Without X-ray Evidence of AS (C-AXSPAND)

• ClinicalTrials.gov Identifier: NCT02552212
• Recruitment Status: Completed
• First Posted: September 17, 2015
• Results First Posted: August 17, 2020
• Last Update Posted: August 18, 2022
• Sponsor: UCB BIOSCIENCES GmbH
• Information provided by (Responsible Party): UCB Pharma ( UCB BIOSCIENCES GmbH )

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Conditions: Axial Spondyloarthritis; Nonradiographic Axial Spondyloarthritis; Nr-axSpA
• Interventions: Biological: Certolizumab Pegol; Other: Placebo
• Enrollment: 317

Participant Flow

Recruitment Details	This study started to enroll participants in September 2015. The study included a Screening Period, up to 6 weeks before Baseline, a Double-Blind (DB) Period from Baseline (Week 0) to Week 52, that included the open label CZP (OL-CZP) treatment and other treatment (OT) and an Open Label Safety Follow-up Extension (SFE) Period, up to Week 156.
Pre-assignment Details	The Participant Flow refers to the Randomized Set (RS).

Arm/Group Title	Placebo	CZP 200 mg Q2W	SFE OL CZP 200 mg Q2W
Arm/Group Description	Matching placebo to certolizumab pegol (CZP) injections were administered every 2 weeks from Week 0 onwards.	Certolizumab pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards.	Subjects who completed Double-Blind Period received CZP 200 mg at Week 52, 54 and 56 to maintain the blinding and who completed the Week 52 Visit on placebo treatment received loading doses of CZP 400 mg at these visits. Subjects who completed the Week 52 Visit on CZP treatment received 1 injection of CZP 200 mg and 1 injection of placebo at these visits to continue their previous CZP treatment regimen and subjects who discontinued from Double-Blind Period and entered OL CZP treatment continued their OL CZP treatment regimen during Safety Follow-Up Extension (SFE) Period. Subjects received CZP 200 mg Q2W for up to 2 years during the SFE Period. An additional signed informed consent for the SFE was a pre-requisite For the additional milestone one (Received OL CZP; Completed Week 52 without starting SFE) reported in Double-Blind Period (Week 0 -52).
Period Title: Double-Blind Period (Week 0 - 52)
Started	158	159	0
Received OL CZP	96	20	0
Completed Week 52 Without Starting SFE	20	22	0
Completed	143	142	0
Not Completed	15	17	0
Reason Not Completed
Adverse Event	6	3	0
Lack of Efficacy	2	2	0
Protocol Violation	1	1	0
Lost to Follow-up	1	0	0
Withdrawal by Subject	3	7	0
Study non-compliance	1	1	0
Patient's decision	0	1	0
As per suggestion	0	1	0
Not eligible	0	1	0
Missing/Unspecified	1	0	0
Period Title: SFE Period (Week 52 - 156)
Started	0	0	243 [1]
Completed	0	0	206
Not Completed	0	0	37
Reason Not Completed
Adverse Event	0	0	5
Lack of Efficacy	0	0	4
Lost to Follow-up	0	0	2
Withdrawal by Subject	0	0	18
Return to standard-of-care /OL CZP	0	0	1
Patient's personal reason	0	0	1
Investigator decision	0	0	1
Subject withdrew consent due to traveling to site	0	0	1
Compassionate access	0	0	2
Patient travelling for study unable to continue	0	0	1
Decision of Patient	0	0	1
[1] 123 subjects from Placebo arm and 120 subjects from CZP 200 mg Q2W arm

Baseline Characteristics

Arm/Group Title		Placebo	CZP 200 mg Q2W	Total Title
Arm/Group Description		Matching placebo to certolizumab pegol (CZP) injections were administered every 2 weeks from Week 0 onwards.	Certolizumab pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards.	[Not Specified]
Overall Number of Baseline Participants		158	159	317
Baseline Analysis Population Description		Baseline Characteristics refer to the Randomized Set witch consisted of all subjects randomized into the study.
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	158 participants	159 participants	317 participants
	<=18 years	3 1.9%	1 0.6%	4 1.3%
	Between 18 and 65 years	154 97.5%	156 98.1%	310 97.8%
	>=65 years	1 0.6%	2 1.3%	3 0.9%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	158 participants	159 participants	317 participants
		37.4 (10.8)	37.3 (10.5)	37.3 (10.6)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	158 participants	159 participants	317 participants
	Female	82 51.9%	81 50.9%	163 51.4%
	Male	76 48.1%	78 49.1%	154 48.6%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	158 participants	159 participants	317 participants
	Asian	8 5.1%	5 3.1%	13 4.1%
	Black	1 0.6%	0 0.0%	1 0.3%
	White	148 93.7%	152 95.6%	300 94.6%
	Other/mixed	1 0.6%	2 1.3%	3 0.9%

Outcome Measures

1. Primary Outcome

Title	Percentage of Subjects With Ankylosing Spondylitis Disease Activity Score Major Improvement (ASDAS-MI) Response Criteria Response at Week 52
Description	This variable was considered as primary in all countries except for Canada (and any other country where applicable or where requested by Regulatory Authorities) where it was considered as secondary variable. ASDAS-MI was achieved when there was a reduction (improvement) >= 2.0 in the ASDAS relative to Baseline, or when the lowest possible ASDAS score (0.6) was reached. The ASDAS was calculated as the sum of the following components: 0.121 × Back pain (BASDAI Q2 result) 0.058 × Duration of morning stiffness (BASDAI Q6 result) 0.110 × Patient's Global Assessment of Disease Activity (PGADA) 0.073 × Peripheral pain/swelling (BASDAI Q3 result) 0.579 × (natural logarithm [ln] of the (CRP [mg/L] + 1)) Back pain, PGADA, duration of morning stiffness, peripheral pain/swelling and fatigue were all assessed on a numerical scale (0 to 10 units, where 0 is "not active" and 10 is "very active").
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

The FAS consisted of all subjects in the RS who have received at least 1 dose of study medication.

Arm/Group Title	Placebo (FAS)	CZP 200 mg Q2W (FAS)
Arm/Group Description:	Matching placebo to certolizumab pegol (CZP) injections were administered every 2 weeks from Week 0 onwards. Subjects formed the Full Analysis Set (FAS).	Certolizumab pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. Subjects formed the FAS.
Overall Number of Participants Analyzed	158	159
Measure Type: Number; Unit of Measure: percentage of subjects
	7.0	47.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), CZP 200 mg Q2W (FAS)
	Comments	Odds ratio: CZP/Placebo and p-value were calculated using logistic regression with factors for treatment, region and Magnetic Resonance Imaging/C- Reactive Protein (MRI/CRP) classification.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	15.231
	Confidence Interval	(2-Sided) 95%; 7.336 to 31.623
	Estimation Comments	[Not Specified]

2. Primary Outcome

Title	Percentage of Subjects With Axial SpondyloArthritis International Society 40% Response Criteria (ASAS40) Response at Week 12
Description	This variable was considered as primary for Canada (and any other country where applicable or where requested by Regulatory Authorities) and as secondary variable in all other countries. The ASAS40 response was defined as relative improvements of at least 40 % and absolute improvement of at least 2 units on a 0 to 10 Numeric Rating Scale (NRS), where 0 is "not active" and 10 is "very active" in at least 3 of the 4 domains: Patient's Global Assessment of Disease Activity (PGADA), Pain assessment (total spinal pain NRS scores), Function (Bath Ankylosing Spondylitis Functional Index (BASFI), Inflammation (mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)) questions 5 and 6 concerning morning stiffness intensity and duration) and no worsening at all in the remaining domain.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

The FAS consisted of all subjects in the RS who have received at least 1 dose of study medication.

Arm/Group Title	Placebo (FAS)	CZP 200 mg Q2W (FAS)
Arm/Group Description:	Matching placebo to certolizumab pegol (CZP) injections were administered every 2 weeks from Week 0 onwards. Subjects formed the Full Analysis Set (FAS).	Certolizumab pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. Subjects formed the FAS.
Overall Number of Participants Analyzed	158	159
Measure Type: Number; Unit of Measure: percentage of subjects
	11.4	47.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), CZP 200 mg Q2W (FAS)
	Comments	Odds ratio: CZP/Placebo and p-value were calculated using logistic regression with factors for treatment, region and MRI/CRP classification.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	7.436
	Confidence Interval	(2-Sided) 95%; 4.127 to 13.401
	Estimation Comments	[Not Specified]

3. Primary Outcome

Title	Certolizumab Pegol Plasma Concentration at Baseline
Description	Certolizumab pegol plasma concentration was measured at Baseline in micrograms per millilitre (µg/mL).
Time Frame	Baseline (Week 0)

Outcome Measure Data

Analysis Population Description

The Safety Set (SS) consisted of all subjects who have received at least 1 dose of study medication. Note: None of the Safety Set subjects had Pharmacokinetic (PK) concentrations above the lower limit of quantification.

Arm/Group Title	Placebo (SS)	CZP 200 mg Q2W (SS)
Arm/Group Description:	Matching placebo to certolizumab pegol (CZP) injections were administered every 2 weeks from Week 0 onwards. Subjects formed the Safety Set (SS).	Certolizumab pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. Subjects formed the SS.
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

4. Primary Outcome

Title	Certolizumab Pegol Plasma Concentration at Week 1
Description	Certolizumab pegol plasma concentration was measured at Week 1, in µg/mL.
Time Frame	Week 1

Outcome Measure Data

Analysis Population Description

The SS consisted of all subjects who received at least 1 dose of study treatment. Note: No samples taken at Week 1 for the Placebo->OL CZP.

Arm/Group Title	CZP 200 mg Q2W (SS)	Placebo->OL CZP (SS)
Arm/Group Description:	Certolizumab pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. Subjects formed the SS.	Subset of subjects from the Placebo group, who discontinued the CZP double-blind treatment and entered the open-label CZP treatment. The subjects were included in the SS for safety analysis.
Overall Number of Participants Analyzed	148	0
Geometric Mean (95% Confidence Interval); Unit of Measure: µg/mL
	50.5; (48.0 to 53.0)

5. Primary Outcome

Title	Certolizumab Pegol Plasma Concentration at Week 2
Description	Certolizumab pegol plasma concentration was measured at Week 2, in µg/mL.
Time Frame	Week 2

Outcome Measure Data

Analysis Population Description

The SS consisted of all subjects who received at least 1 dose of study treatment. Note: No samples taken at Week 2 for the Placebo->OL CZP.

Arm/Group Title	CZP 200 mg Q2W (SS)	Placebo->OL CZP (SS)
Arm/Group Description:	Certolizumab pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. Subjects formed the SS.	Subset of subjects from the Placebo group, who discontinued the CZP double-blind treatment and entered the open-label CZP treatment. The subjects were included in the SS for safety analysis.
Overall Number of Participants Analyzed	153	0
Geometric Mean (95% Confidence Interval); Unit of Measure: µg/mL
	36.4; (33.0 to 40.1)

6. Primary Outcome

Title	Certolizumab Pegol Plasma Concentration at Week 4
Description	Certolizumab pegol plasma concentration was measured at Week 4, in µg/mL.
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

The SS consisted of all subjects who received at least 1 dose of study treatment.

Arm/Group Title	CZP 200 mg Q2W (SS)	Placebo->OL CZP (SS)
Arm/Group Description:	Certolizumab pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. Subjects formed the SS.	Subset of subjects from the Placebo group, who discontinued the CZP double-blind treatment and entered the open-label CZP treatment. The subjects were included in the SS for safety analysis.
Overall Number of Participants Analyzed	155	93
Geometric Mean (95% Confidence Interval); Unit of Measure: µg/mL
	54.6; (51.4 to 58.0)	48.8; (42.2 to 56.4)

7. Primary Outcome

Title	Certolizumab Pegol Plasma Concentration at Week 12
Description	Certolizumab pegol plasma concentration was measured at Week 12, in µg/mL.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

The SS consisted of all subjects who received at least 1 dose of study treatment.

Arm/Group Title	CZP 200 mg Q2W (SS)	Placebo->OL CZP (SS)
Arm/Group Description:	Certolizumab pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. Subjects formed the SS.	Subset of subjects from the Placebo group, who discontinued the CZP double-blind treatment and entered the open-label CZP treatment. The subjects were included in the SS for safety analysis.
Overall Number of Participants Analyzed	143	93
Geometric Mean (95% Confidence Interval); Unit of Measure: µg/mL
	29.1; (24.0 to 35.2)	30.5; (26.4 to 35.3)

8. Primary Outcome

Title	Certolizumab Pegol Plasma Concentration at Week 24
Description	Certolizumab pegol plasma concentration was measured at Week 24, in µg/mL.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

The SS consisted of all subjects who received at least 1 dose of study treatment.

Arm/Group Title	CZP 200 mg Q2W (SS)	Placebo->OL CZP (SS)
Arm/Group Description:	Certolizumab pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. Subjects formed the SS.	Subset of subjects from the Placebo group, who discontinued the CZP double-blind treatment and entered the open-label CZP treatment. The subjects were included in the SS for safety analysis.
Overall Number of Participants Analyzed	135	86
Geometric Mean (95% Confidence Interval); Unit of Measure: µg/mL
	23.5; (18.5 to 29.7)	24.8; (20.6 to 29.9)

9. Primary Outcome

Title	Certolizumab Pegol Plasma Concentration at Week 36
Description	Certolizumab pegol plasma concentration was measured at Week 36, in µg/mL.
Time Frame	Week 36

Outcome Measure Data

Analysis Population Description

The SS consisted of all subjects who received at least 1 dose of study treatment.

Arm/Group Title	CZP 200 mg Q2W (SS)	Placebo->OL CZP (SS)
Arm/Group Description:	Certolizumab pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. Subjects formed the SS.	Subset of subjects from the Placebo group, who discontinued the CZP double-blind treatment and entered the open-label CZP treatment. The subjects were included in the SS for safety analysis.
Overall Number of Participants Analyzed	123	65
Geometric Mean (95% Confidence Interval); Unit of Measure: µg/mL
	24.0; (19.0 to 30.4)	22.9; (18.3 to 28.7)

10. Primary Outcome

Title	Certolizumab Pegol Plasma Concentration at Week 52
Description	Certolizumab pegol plasma concentration was measured at Week 52, in µg/mL.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

The SS consisted of all subjects who received at least 1 dose of study treatment. Note: No samples taken at OL Week 52 for the Placebo->OL CZP.

Arm/Group Title	CZP 200 mg Q2W (SS)	Placebo->OL CZP (SS)
Arm/Group Description:	Certolizumab pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. Subjects formed the SS.	Subset of subjects from the Placebo group, who discontinued the CZP double-blind treatment and entered the open-label CZP treatment. The subjects were included in the SS for safety analysis.
Overall Number of Participants Analyzed	123	0
Geometric Mean (95% Confidence Interval); Unit of Measure: µg/mL
	22.6; (17.8 to 28.6)

11. Primary Outcome

Title	Certolizumab Pegol Plasma Concentration at Follow-Up (FU) Visit
Description	Certolizumab pegol plasma concentration was measured at the Follow-Up Visit, in µg/mL. Follow-Up Visit was defined as 8 weeks after Week 52 or Withdrawal (WD) visit for subjects not participating in the Safety Follow-Up Extension (SFE) Period.
Time Frame	Follow-up Visit (up to Week 60)

Outcome Measure Data

Analysis Population Description

The SS consisted of all subjects who received at least 1 dose of study treatment. Only participants included, who had a SFU Visit at 8 weeks after Week 52/WD visit for those not participating in the SFE period.

Arm/Group Title	CZP 200 mg Q2W (SS)	Placebo->OL CZP (SS)
Arm/Group Description:	Certolizumab pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. Subjects formed the SS.	Subset of subjects from the Placebo group, who discontinued the CZP double-blind treatment and entered the open-label CZP treatment. The subjects were included in the SS for safety analysis.
Overall Number of Participants Analyzed	17	10
Geometric Mean (95% Confidence Interval); Unit of Measure: µg/mL
	0.2; (0.1 to 0.7)	NA [1]; (NA to NA)

[1]

Values were below the level of quantification.

12. Secondary Outcome

Title	Percentage of Subjects With Axial SpondyloArthritis International Society 40% Response Criteria (ASAS40) Response at Week 52
Description	The ASAS40 response was defined as relative improvements of at least 40% and absolute improvement of at least 2 units on a 0 to 10 Numeric Rating Scale (NRS), where 0 is "not active" and 10 is "very active" in at least 3 of the 4 domains: Patient's Global Assessment of Disease Activity (PGADA), Pain assessment (total spinal pain NRS scores), Function (Bath Ankylosing Spondylitis Functional Index (BASFI)), Inflammation (mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)) questions 5 and 6 concerning morning stiffness intensity and duration) and no worsening at all in the remaining domain.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

The FAS consisted of all subjects in the RS who have received at least 1 dose of study medication.

Arm/Group Title	Placebo (FAS)	CZP 200 mg Q2W (FAS)
Arm/Group Description:	Matching placebo to certolizumab pegol (CZP) injections were administered every 2 weeks from Week 0 onwards. Subjects formed the Full Analysis Set (FAS).	Certolizumab pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. Subjects formed the FAS.
Overall Number of Participants Analyzed	158	159
Measure Type: Number; Unit of Measure: percentage of subjects
	15.8	56.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), CZP 200 mg Q2W (FAS)
	Comments	Odds ratio: CZP/Placebo and p-value were calculated using logistic regression with factors for treatment, region MRI/CRP classification.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	7.359
	Confidence Interval	(2-Sided) 95%; 4.286 to 12.636
	Estimation Comments	[Not Specified]

13. Secondary Outcome

Title	Change From Baseline to Week 12 in the Bath Ankylosing Spondylitis Functional Index (BASFI)
Description	The BASFI is a validated disease-specific instrument for assessing physical function. The BASFI comprises 10 items relating to the past week. The BASFI is the mean of the 10 scores such that the total score ranges from 0 (Easy) to 10 (Impossible), with lower scores indicating better physical function. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Time Frame	From Baseline to Week 12

Outcome Measure Data

Analysis Population Description

The FAS consisted of all subjects in the RS who have received at least 1 dose of study medication.

Arm/Group Title	Placebo (FAS)	CZP 200 mg Q2W (FAS)
Arm/Group Description:	Matching placebo to certolizumab pegol (CZP) injections were administered every 2 weeks from Week 0 onwards. Subjects formed the Full Analysis Set (FAS).	Certolizumab pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. Subjects formed the FAS.
Overall Number of Participants Analyzed	158	159
Least Squares Mean (Standard Error); Unit of Measure: scores on a scale
	-0.38 (0.21)	-2.07 (0.20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), CZP 200 mg Q2W (FAS)
	Comments	From an ANCOVA model including scores at Baseline, treatment group, region and MRI/CRP classification.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-1.696
	Confidence Interval	(2-Sided) 95%; -2.110 to -1.282
	Estimation Comments	[Not Specified]

14. Secondary Outcome

Title	Change From Baseline to Week 52 in the Bath Ankylosing Spondylitis Functional Index (BASFI)
Description	The BASFI is a validated disease-specific instrument for assessing physical function. The BASFI comprises 10 items relating to the past week. The BASFI is the mean of the 10 scores such that the total score ranges from 0 (Easy) to 10 (Impossible), with lower scores indicating better physical function. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Time Frame	From Baseline to Week 52

Outcome Measure Data

Analysis Population Description

The FAS consisted of all subjects in the RS who have received at least 1 dose of study medication.

Arm/Group Title	Placebo (FAS)	CZP 200 mg Q2W (FAS)
Arm/Group Description:	Matching placebo to certolizumab pegol (CZP) injections were administered every 2 weeks from Week 0 onwards. Subjects formed the Full Analysis Set (FAS).	Certolizumab pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. Subjects formed the FAS.
Overall Number of Participants Analyzed	158	159
Least Squares Mean (Standard Error); Unit of Measure: scores on a scale
	-1.44 (0.30)	-3.03 (0.24)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), CZP 200 mg Q2W (FAS)
	Comments	From an ANCOVA model including scores at Baseline, treatment group, region and MRI/CRP classification.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-1.585
	Confidence Interval	(2-Sided) 95%; -2.132 to -1.038
	Estimation Comments	[Not Specified]

15. Secondary Outcome

Title	Change From Baseline to Week 12 in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
Description	The BASDAI is a validated self-reported instrument, which consists of six 10 unit horizontal Numeric Rating Scales to measure the disease activity of ankylosing spondylitis (AS) from the subject's perspective. It measures the severity of fatigue, spinal and peripheral joint pain and swelling, enthesitis, and morning stiffness (both severity and duration) over the last week. The final BASDAI scores ranges from 0 (not active) to 10 (very active), with lower scores indicating lower disease activity. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Time Frame	From Baseline to Week 12

Outcome Measure Data

Analysis Population Description

The FAS consisted of all subjects in the RS who have received at least 1 dose of study medication.

Arm/Group Title	Placebo (FAS)	CZP 200 mg Q2W (FAS)
Arm/Group Description:	Matching placebo to certolizumab pegol (CZP) injections were administered every 2 weeks from Week 0 onwards. Subjects formed the Full Analysis Set (FAS).	Certolizumab pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. Subjects formed the FAS.
Overall Number of Participants Analyzed	158	159
Least Squares Mean (Standard Error); Unit of Measure: scores on a scale
	-0.91 (0.22)	-2.73 (0.21)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), CZP 200 mg Q2W (FAS)
	Comments	From an ANCOVA model including scores at Baseline, treatment group, region and MRI/CRP classification.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-1.819
	Confidence Interval	(2-Sided) 95%; -2.250 to -1.388
	Estimation Comments	[Not Specified]

16. Secondary Outcome

Title	Change From Baseline to Week 52 in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
Description	The BASDAI is a validated self-reported instrument, which consists of six 10 unit horizontal Numeric Rating Scales to measure the disease activity of ankylosing spondylitis (AS) from the subject's perspective. It measures the severity of fatigue, spinal and peripheral joint pain and swelling, enthesitis, and morning stiffness (both severity and duration) over the last week. The final BASDAI scores ranges from 0 (not active) to 10 (very active), with lower scores indicating lower disease activity. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Time Frame	From Baseline to Week 52

Outcome Measure Data

Analysis Population Description

The FAS consisted of all subjects in the RS who have received at least 1 dose of study medication.

Arm/Group Title	Placebo (FAS)	CZP 200 mg Q2W (FAS)
Arm/Group Description:	Matching placebo to certolizumab pegol (CZP) injections were administered every 2 weeks from Week 0 onwards. Subjects formed the Full Analysis Set (FAS).	Certolizumab pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. Subjects formed the FAS.
Overall Number of Participants Analyzed	158	159
Least Squares Mean (Standard Error); Unit of Measure: scores on a scale
	-2.59 (0.37)	-3.88 (0.27)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), CZP 200 mg Q2W (FAS)
	Comments	From an ANCOVA model including scores at Baseline, treatment group, region and MRI/CRP classification.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-1.290
	Confidence Interval	(2-Sided) 95%; -1.909 to -0.672
	Estimation Comments	[Not Specified]

17. Secondary Outcome

Title	Change From Baseline to Week 12 in Sacroiliac Spondyloarthritis Research Consortium of Canada (SI-SPARCC) Score
Description	The Spondyloarthritis Research Consortium of Canada (SPARCC) scoring method for lesions found on the Magnetic Resonance Imaging (MRI) is based on an abnormal increased signal on the Short-Tau-Inversion Recovery (STIR) sequence, representing bone marrow edema. Total Sacroiliac (SI) joint SPARCC score can range from 0 to 72 with higher scores indicating higher joint inflammation. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Time Frame	From Baseline to Week 12

Outcome Measure Data

Analysis Population Description

The FAS consisted of all subjects in the RS who have received at least 1 dose of study medication.

Arm/Group Title	Placebo (FAS)	CZP 200 mg Q2W (FAS)
Arm/Group Description:	Matching placebo to certolizumab pegol (CZP) injections were administered every 2 weeks from Week 0 onwards. Subjects formed the Full Analysis Set (FAS).	Certolizumab pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. Subjects formed the FAS.
Overall Number of Participants Analyzed	158	159
Least Squares Mean (Standard Error); Unit of Measure: scores on a scale
	0.200 (0.772)	-4.669 (0.770)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), CZP 200 mg Q2W (FAS)
	Comments	From an ANCOVA model including scores at Baseline, treatment group, region and MRI/CRP classification.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-4.8687
	Confidence Interval	(2-Sided) 95%; -6.4014 to -3.3360
	Estimation Comments	[Not Specified]

18. Secondary Outcome

Title	Number of Subjects Without Relevant Changes to Background Medication From Baseline to Week 52
Description	The number of subjects who did not have relevant changes to background medications during the study treatment period. A subject is without relevant changes to background medication if they do not have: the addition of a new disease-modifying antirheumatic drug (DMARD) or the change from one DMAR to another; the addition of an nonsteroidal anti-inflammatory drug (NSAID) or the change from one NSAID to another; an increased dose of chronic corticosteroids; the addition of a new chronic analgesic medication or increased dose in chronic analgesic medication; and they complete double-blind study treatment to Week 52.
Time Frame	From Baseline to Week 52

Outcome Measure Data

Analysis Population Description

The FAS consisted of all subjects in the RS who have received at least 1 dose of study medication.

Arm/Group Title	Placebo (FAS)	CZP 200 mg Q2W (FAS)
Arm/Group Description:	Matching placebo to certolizumab pegol (CZP) injections were administered every 2 weeks from Week 0 onwards. Subjects formed the Full Analysis Set (FAS).	Certolizumab pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. Subjects formed the FAS.
Overall Number of Participants Analyzed	158	159
Measure Type: Count of Participants; Unit of Measure: Participants
	48 30.4%	115 72.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), CZP 200 mg Q2W (FAS)
	Comments	Odds ratio: CZP/Placebo and p-value were calculated using logistic regression with factors for treatment, region and MRI/CRP classification.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	6.223
	Confidence Interval	(2-Sided) 95%; 3.800 to 10.191
	Estimation Comments	[Not Specified]

19. Secondary Outcome

Title	Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) at Week 52
Description	The ASQoL score ranged from 0 to 18 with higher score indicating worse Health-Related Quality of Life (HRQoL) and 0 indicating good HRQoL. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Time Frame	From Baseline to Week 52

Outcome Measure Data

Analysis Population Description

The FAS consisted of all subjects in the RS who have received at least 1 dose of study medication.

Arm/Group Title	Placebo (FAS)	CZP 200 mg Q2W (FAS)
Arm/Group Description:	Matching placebo to certolizumab pegol (CZP) injections were administered every 2 weeks from Week 0 onwards. Subjects formed the Full Analysis Set (FAS).	Certolizumab pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. Subjects formed the FAS.
Overall Number of Participants Analyzed	158	159
Least Squares Mean (Standard Error); Unit of Measure: scores on a scale
	-0.18 (0.04)	-0.36 (0.03)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), CZP 200 mg Q2W (FAS)
	Comments	From an ANCOVA model including scores at Baseline, treatment group, region and MRI/CRP classification.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-0.183
	Confidence Interval	(2-Sided) 95%; -0.250 to -0.117
	Estimation Comments	[Not Specified]

20. Secondary Outcome

Title	Change From Baseline in ASQoL at Week 1
Description	The ASQoL score ranged from 0 to 18 with higher score indicating worse Health-Related Quality of Life (HRQoL) and 0 indicating good HRQoL. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Time Frame	From Baseline to Week 1

Outcome Measure Data

Analysis Population Description

The FAS consisted of all subjects in the RS who have received at least 1 dose of study medication.

Arm/Group Title	Placebo (FAS)	CZP 200 mg Q2W (FAS)
Arm/Group Description:	Matching placebo to certolizumab pegol (CZP) injections were administered every 2 weeks from Week 0 onwards. Subjects formed the Full Analysis Set (FAS).	Certolizumab pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. Subjects formed the FAS.
Overall Number of Participants Analyzed	150	147
Mean (Standard Deviation); Unit of Measure: scores on a scale
	-0.03 (0.14)	-0.11 (0.21)

21. Secondary Outcome

Title	Change From Baseline in ASQoL at Week 2
Description	The ASQoL score ranged from 0 to 18 with higher score indicating worse Health-Related Quality of Life (HRQoL) and 0 indicating good HRQoL. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Time Frame	From Baseline to Week 2

Outcome Measure Data

Analysis Population Description

The FAS consisted of all subjects in the RS who have received at least 1 dose of study medication.

Arm/Group Title	Placebo (FAS)	CZP 200 mg Q2W (FAS)
Arm/Group Description:	Matching placebo to certolizumab pegol (CZP) injections were administered every 2 weeks from Week 0 onwards. Subjects formed the Full Analysis Set (FAS).	Certolizumab pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. Subjects formed the FAS.
Overall Number of Participants Analyzed	158	156
Mean (Standard Deviation); Unit of Measure: scores on a scale
	-0.03 (0.15)	-0.16 (0.23)

22. Secondary Outcome

Title	Change From Baseline in ASQoL at Week 4
Description	The ASQoL score ranged from 0 to 18 with higher score indicating worse Health-Related Quality of Life (HRQoL) and 0 indicating good HRQoL. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Time Frame	From Baseline to Week 4

Outcome Measure Data

Analysis Population Description

The FAS consisted of all subjects in the RS who have received at least 1 dose of study medication.

Arm/Group Title	Placebo (FAS)	CZP 200 mg Q2W (FAS)
Arm/Group Description:	Matching placebo to certolizumab pegol (CZP) injections were administered every 2 weeks from Week 0 onwards. Subjects formed the Full Analysis Set (FAS).	Certolizumab pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. Subjects formed the FAS.
Overall Number of Participants Analyzed	158	156
Mean (Standard Deviation); Unit of Measure: scores on a scale
	-0.06 (0.19)	-0.18 (0.23)

23. Secondary Outcome

Title	Change From Baseline in ASQoL at Week 12
Description	The ASQoL score ranged from 0 to 18 with higher score indicating worse Health-Related Quality of Life (HRQoL) and 0 indicating good HRQoL. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Time Frame	From Baseline to Week 12

Outcome Measure Data

Analysis Population Description

The FAS consisted of all subjects in the RS who have received at least 1 dose of study medication.

Arm/Group Title	Placebo (FAS)	CZP 200 mg Q2W (FAS)
Arm/Group Description:	Matching placebo to certolizumab pegol (CZP) injections were administered every 2 weeks from Week 0 onwards. Subjects formed the Full Analysis Set (FAS).	Certolizumab pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. Subjects formed the FAS.
Overall Number of Participants Analyzed	158	156
Mean (Standard Deviation); Unit of Measure: scores on a scale
	-0.08 (0.22)	-0.28 (0.26)

24. Secondary Outcome

Title	Change From Baseline in ASQoL at Week 24
Description	The ASQoL score ranged from 0 to 18 with higher score indicating worse Health-Related Quality of Life (HRQoL) and 0 indicating good HRQoL. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Time Frame	From Baseline to Week 24

Outcome Measure Data

Analysis Population Description

The FAS consisted of all subjects in the RS who have received at least 1 dose of study medication.

Arm/Group Title	Placebo (FAS)	CZP 200 mg Q2W (FAS)
Arm/Group Description:	Matching placebo to certolizumab pegol (CZP) injections were administered every 2 weeks from Week 0 onwards. Subjects formed the Full Analysis Set (FAS).	Certolizumab pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. Subjects formed the FAS.
Overall Number of Participants Analyzed	158	156
Mean (Standard Deviation); Unit of Measure: scores on a scale
	-0.09 (0.23)	-0.31 (0.27)

25. Secondary Outcome

Title	Change From Baseline in ASQoL at Week 36
Description	The ASQoL score ranged from 0 to 18 with higher score indicating worse Health-Related Quality of Life (HRQoL) and 0 indicating good HRQoL. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Time Frame	From Baseline to Week 36

Outcome Measure Data

Analysis Population Description

The FAS consisted of all subjects in the RS who have received at least 1 dose of study medication.

Arm/Group Title	Placebo (FAS)	CZP 200 mg Q2W (FAS)
Arm/Group Description:	Matching placebo to certolizumab pegol (CZP) injections were administered every 2 weeks from Week 0 onwards. Subjects formed the Full Analysis Set (FAS).	Certolizumab pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. Subjects formed the FAS.
Overall Number of Participants Analyzed	158	156
Mean (Standard Deviation); Unit of Measure: scores on a scale
	-0.11 (0.23)	-0.33 (0.29)

26. Secondary Outcome

Title	Change From Baseline in ASQoL at Week 48
Description	The ASQoL score ranged from 0 to 18 with higher score indicating worse Health-Related Quality of Life (HRQoL) and 0 indicating good HRQoL. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Time Frame	From Baseline to Week 48

Outcome Measure Data

Analysis Population Description

The FAS consisted of all subjects in the RS who have received at least 1 dose of study medication.

Arm/Group Title	Placebo (FAS)	CZP 200 mg Q2W (FAS)
Arm/Group Description:	Matching placebo to certolizumab pegol (CZP) injections were administered every 2 weeks from Week 0 onwards. Subjects formed the Full Analysis Set (FAS).	Certolizumab pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. Subjects formed the FAS.
Overall Number of Participants Analyzed	158	156
Mean (Standard Deviation); Unit of Measure: scores on a scale
	-0.10 (0.24)	-0.34 (0.30)

27. Secondary Outcome

Title	Change From Baseline in Nocturnal Spinal Pain Numerical Rating Scale (NRS) at Week 52
Description	The nocturnal spinal pain experienced by subjects due to AS was measured by following question 'How much pain of your spine due to spondylitis do you have at night?'. The NRS ranged from 0 to 10, where 0 represented 'no pain' and 10 represented 'most severe pain'. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Time Frame	From Baseline to Week 52

Outcome Measure Data

Analysis Population Description

The FAS consisted of all subjects in the RS who have received at least 1 dose of study medication.

Arm/Group Title	Placebo (FAS)	CZP 200 mg Q2W (FAS)
Arm/Group Description:	Matching placebo to certolizumab pegol (CZP) injections were administered every 2 weeks from Week 0 onwards. Subjects formed the Full Analysis Set (FAS).	Certolizumab pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. Subjects formed the FAS.
Overall Number of Participants Analyzed	158	159
Least Squares Mean (Standard Error); Unit of Measure: scores on a scale
	-2.1 (0.5)	-4.0 (0.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), CZP 200 mg Q2W (FAS)
	Comments	From an ANCOVA model including scores at Baseline, treatment group, region and MRI/CRP classification.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-1.90
	Confidence Interval	(2-Sided) 95%; -2.62 to -1.18
	Estimation Comments	[Not Specified]

28. Secondary Outcome

Title	Number of Subjects With Anterior Uveitis (AU) or New AU Flares Through Week 52
Description	The number of subjects with AU or new AU flares during the study treatment period.
Time Frame	Throughout the study conduct (up to Week 52)

Outcome Measure Data

Analysis Population Description

The FAS consisted of all subjects in the RS who have received at least 1 dose of study medication.

Arm/Group Title	Placebo (FAS)	CZP 200 mg Q2W (FAS)
Arm/Group Description:	Matching placebo to certolizumab pegol (CZP) injections were administered every 2 weeks from Week 0 onwards. Subjects formed the Full Analysis Set (FAS).	Certolizumab pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. Subjects formed the FAS.
Overall Number of Participants Analyzed	158	159
Measure Type: Count of Participants; Unit of Measure: Participants
	8 5.1%	4 2.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), CZP 200 mg Q2W (FAS)
	Comments	Odds ratio: CZP/PBO and p-value were calculated using logistic regression with factors for treatment, region and MRI/CRP classification.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	=0.247
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.484
	Confidence Interval	(2-Sided) 95%; 0.142 to 1.653
	Estimation Comments	[Not Specified]

29. Secondary Outcome

Title	Percentage of Subjects With Treatment-Emergent Adverse Events (TEAEs) During the Study
Description	An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Time Frame	From Baseline up to the End of Safety Follow-up Extension Period (up to Week 156)

Outcome Measure Data

Analysis Population Description

The SS consisted of all subjects who received at least 1 dose of study treatment.

Arm/Group Title	Placebo (SS)	CZP 200 mg Q2W (SS)	Placebo->OL CZP (SS)	CZP->OL CZP (SS)	SFE OL CZP 200 mg Q2W (SS)
Arm/Group Description:	Matching placebo to certolizumab pegol (CZP) injections were administered every 2 weeks from Week 0 onwards. Subjects formed the Safety Set (SS).	Certolizumab pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. Subjects formed the SS.	Subset of subjects from the Placebo group, who discontinued the CZP double-blind treatment and entered the open-label CZP treatment. The subjects were included in the SS for safety analysis.	Subset of subjects from the CZP 200 mg Q2W group, who discontinued the CZP double-blind treatment and entered the CZP open-label treatment. The subjects were included in the SS for safety analysis.	Subjects who completed Double-Blind Period received CZP 200 mg at Week 52, 54 and 56 to maintain the blinding and who completed the Week 52 Visit on placebo treatment received loading doses of CZP 400 mg at these visits. Subjects who completed the Week 52 Visit on CZP treatment received 1 injection of CZP 200 mg and 1 injection of placebo at these visits to continue their previous CZP treatment regimen and subjects who discontinued from Double-Blind Period and entered OL CZP treatment continued their OL CZP treatment regimen during SFE Period. The subjects were included in the SS for safety analysis. Subjects received CZP 200 mg Q2W for up to 2 years during the SFE Period. An additional signed informed consent for the SFE was a pre-requisite For the additional milestone one (Received OL CZP; Completed Week 52 without starting SFE) reported in Double-Blind Period (Week 0 -52).
Overall Number of Participants Analyzed	158	159	96	20	243
Measure Type: Number; Unit of Measure: percentage of subjects
	63.9	75.5	59.4	65.0	61.3

30. Secondary Outcome

Title	Percentage of Subjects With Serious Adverse Events (SAEs) During the Study
Description	A serious adverse event (SAE) is any untoward medical occurrence that at any dose: Results in death; Is life-threatening; Requires in patient hospitalization or prolongation of existing hospitalization; Is a congenital anomaly or birth defect; Is an infection that requires treatment parenteral antibiotics; Other important medical events which based on medical or scientific judgement may jeopardize the patients, or may require medical or surgical intervention to prevent any of the above.
Time Frame	From Baseline up to the End of Safety Follow-up Extension Period (up to Week 156)

Outcome Measure Data

Analysis Population Description

The SS consisted of all subjects who received at least 1 dose of study treatment.

Arm/Group Title	Placebo (SS)	CZP 200 mg Q2W (SS)	Placebo->OL CZP (SS)	CZP->OL CZP (SS)	SFE OL CZP 200 mg Q2W (SS)
Arm/Group Description:	Matching placebo to certolizumab pegol (CZP) injections were administered every 2 weeks from Week 0 onwards. Subjects formed the Safety Set (SS).	Certolizumab pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. Subjects formed the SS.	Subset of subjects from the Placebo group, who discontinued the CZP double-blind treatment and entered the open-label CZP treatment. The subjects were included in the SS for safety analysis.	Subset of subjects from the CZP 200 mg Q2W group, who discontinued the CZP double-blind treatment and entered the CZP open-label treatment. The subjects were included in the SS for safety analysis.	Subjects who completed Double-Blind Period received CZP 200 mg at Week 52, 54 and 56 to maintain the blinding and who completed the Week 52 Visit on placebo treatment received loading doses of CZP 400 mg at these visits. Subjects who completed the Week 52 Visit on CZP treatment received 1 injection of CZP 200 mg and 1 injection of placebo at these visits to continue their previous CZP treatment regimen and subjects who discontinued from Double-Blind Period and entered OL CZP treatment continued their OL CZP treatment regimen during SFE Period. The subjects were included in the SS for safety analysis. Subjects received CZP 200 mg Q2W for up to 2 years during the SFE Period. An additional signed informed consent for the SFE was a pre-requisite For the additional milestone one (Received OL CZP; Completed Week 52 without starting SFE) reported in Double-Blind Period (Week 0 -52).
Overall Number of Participants Analyzed	158	159	96	20	243
Measure Type: Number; Unit of Measure: percentage of subjects
	2.5	5.0	3.1	5.0	6.2

31. Secondary Outcome

Title	Percentage of Subjects With Adverse Events Leading to Withdrawal From Investigational Medicinal Product (IMP) During the Study
Description	An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Time Frame	From Baseline up to the End of Safety Follow-up Extension Period (up to Week 156)

Outcome Measure Data

Analysis Population Description

The SS consisted of all subjects who received at least 1 dose of study treatment.

Arm/Group Title	Placebo (SS)	CZP 200 mg Q2W (SS)	Placebo->OL CZP (SS)	CZP->OL CZP (SS)	SFE OL CZP 200 mg Q2W (SS)
Arm/Group Description:	Matching placebo to certolizumab pegol (CZP) injections were administered every 2 weeks from Week 0 onwards. Subjects formed the Safety Set (SS).	Certolizumab pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. Subjects formed the SS.	Subset of subjects from the Placebo group, who discontinued the CZP double-blind treatment and entered the open-label CZP treatment. The subjects were included in the SS for safety analysis.	Subset of subjects from the CZP 200 mg Q2W group, who discontinued the CZP double-blind treatment and entered the CZP open-label treatment. The subjects were included in the SS for safety analysis.	Subjects who completed Double-Blind Period received CZP 200 mg at Week 52, 54 and 56 to maintain the blinding and who completed the Week 52 Visit on placebo treatment received loading doses of CZP 400 mg at these visits. Subjects who completed the Week 52 Visit on CZP treatment received 1 injection of CZP 200 mg and 1 injection of placebo at these visits to continue their previous CZP treatment regimen and subjects who discontinued from Double-Blind Period and entered OL CZP treatment continued their OL CZP treatment regimen during SFE Period. The subjects were included in the SS for safety analysis. Subjects received CZP 200 mg Q2W for up to 2 years during the SFE Period. An additional signed informed consent for the SFE was a pre-requisite For the additional milestone one (Received OL CZP; Completed Week 52 without starting SFE) reported in Double-Blind Period (Week 0 -52).
Overall Number of Participants Analyzed	158	159	96	20	243
Measure Type: Number; Unit of Measure: percentage of subjects
	1.9	1.9	3.1	0	2.5

Adverse Events

Time Frame	From Baseline up to the End of Safety Follow-up Extension Period (up to Week 156)
Adverse Event Reporting Description	Adverse events were recorded for all subjects, including those who discontinued the blinded treatment and entered the open-label treatment with CZP (OL). Based on this the following groups were generated: Placebo, Placebo-> OL CZP, CZP, CZP->OL CZP and OL CZP during SFE Period for all subjects entering the SFE Period.
Arm/Group Title	Placebo (SS)		CZP 200 mg Q2W (SS)		Placebo->OL CZP (SS)		CZP->OL CZP (SS)		SFE OL CZP 200 mg Q2W (SS)
Arm/Group Description	Matching placebo to certolizumab pegol (CZP) injections were administered every 2 weeks from Week 0 onwards. Subjects formed the Safety Set (SS).		Certolizumab pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. Subjects formed the SS.		Subset of subjects from the Placebo group, who discontinued the CZP double-blind treatment and entered the open-label CZP treatment. The subjects were included in the SS for safety analysis.		Subset of subjects from the CZP 200 mg Q2W group, who discontinued the CZP double-blind treatment and entered the CZP open-label treatment. The subjects were included in the SS for safety analysis.		Subjects who completed Double-Blind Period received CZP 200 mg at Week 52, 54 and 56 to maintain the blinding and who completed the Week 52 Visit on placebo treatment received loading doses of CZP 400 mg at these visits. Subjects who completed the Week 52 Visit on CZP treatment received 1 injection of CZP 200 mg and 1 injection of placebo at these visits to continue their previous CZP treatment regimen and subjects who discontinued from Double-Blind Period and entered OL CZP treatment continued their OL CZP treatment regimen during SFE Period. The subjects were included in the SS for safety analysis. Subjects received CZP 200 mg Q2W for up to 2 years during the SFE Period. An additional signed informed consent for the SFE was a pre-requisite For the additional milestone one (Received OL CZP; Completed Week 52 without starting SFE) reported in Double-Blind Period (Week 0 -52).
All-Cause Mortality
	Placebo (SS)		CZP 200 mg Q2W (SS)		Placebo->OL CZP (SS)		CZP->OL CZP (SS)		SFE OL CZP 200 mg Q2W (SS)
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	0/158 (0.00%)		0/159 (0.00%)		0/96 (0.00%)		0/20 (0.00%)		0/243 (0.00%)
Serious Adverse Events
	Placebo (SS)		CZP 200 mg Q2W (SS)		Placebo->OL CZP (SS)		CZP->OL CZP (SS)		SFE OL CZP 200 mg Q2W (SS)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/158 (2.53%)		8/159 (5.03%)		3/96 (3.13%)		1/20 (5.00%)		15/243 (6.17%)
Eye disorders
Glaucoma * 1	0/158 (0.00%)	0	1/159 (0.63%)	1	0/96 (0.00%)	0	0/20 (0.00%)	0	0/243 (0.00%)	0
Iridocyclitis * 1	0/158 (0.00%)	0	0/159 (0.00%)	0	0/96 (0.00%)	0	0/20 (0.00%)	0	1/243 (0.41%)	1
Uveitis * 1	0/158 (0.00%)	0	0/159 (0.00%)	0	0/96 (0.00%)	0	0/20 (0.00%)	0	1/243 (0.41%)	1
Gastrointestinal disorders
Pancreatitis * 1	0/158 (0.00%)	0	0/159 (0.00%)	0	0/96 (0.00%)	0	0/20 (0.00%)	0	1/243 (0.41%)	1
Diarrhoea * 1	0/158 (0.00%)	0	1/159 (0.63%)	1	0/96 (0.00%)	0	0/20 (0.00%)	0	0/243 (0.00%)	0
Constipation * 1	0/158 (0.00%)	0	0/159 (0.00%)	0	0/96 (0.00%)	0	1/20 (5.00%)	1	0/243 (0.00%)	0
Gastrointestinal obstruction * 1	0/158 (0.00%)	0	0/159 (0.00%)	0	0/96 (0.00%)	0	0/20 (0.00%)	0	1/243 (0.41%)	1
Inguinal hernia * 1	0/158 (0.00%)	0	0/159 (0.00%)	0	0/96 (0.00%)	0	0/20 (0.00%)	0	1/243 (0.41%)	1
Hepatobiliary disorders
Cholelithiasis * 1	0/158 (0.00%)	0	0/159 (0.00%)	0	0/96 (0.00%)	0	0/20 (0.00%)	0	1/243 (0.41%)	2
Immune system disorders
Sarcoidosis * 1	1/158 (0.63%)	1	0/159 (0.00%)	0	0/96 (0.00%)	0	0/20 (0.00%)	0	0/243 (0.00%)	0
Infections and infestations
Neuroborreliosis * 1	0/158 (0.00%)	0	1/159 (0.63%)	1	0/96 (0.00%)	0	0/20 (0.00%)	0	0/243 (0.00%)	0
Encephalitis * 1	0/158 (0.00%)	0	0/159 (0.00%)	0	0/96 (0.00%)	0	0/20 (0.00%)	0	1/243 (0.41%)	1
Gastroenteritis rotavirus * 1	0/158 (0.00%)	0	0/159 (0.00%)	0	0/96 (0.00%)	0	0/20 (0.00%)	0	1/243 (0.41%)	1
Tuberculosis * 1	0/158 (0.00%)	0	0/159 (0.00%)	0	0/96 (0.00%)	0	0/20 (0.00%)	0	1/243 (0.41%)	1
Chronic tonsillitis * 1	0/158 (0.00%)	0	0/159 (0.00%)	0	0/96 (0.00%)	0	0/20 (0.00%)	0	1/243 (0.41%)	1
Metabolism and nutrition disorders
Obesity * 1	0/158 (0.00%)	0	0/159 (0.00%)	0	0/96 (0.00%)	0	0/20 (0.00%)	0	1/243 (0.41%)	1
Musculoskeletal and connective tissue disorders
Spinal pain * 1	0/158 (0.00%)	0	0/159 (0.00%)	0	0/96 (0.00%)	0	0/20 (0.00%)	0	1/243 (0.41%)	1
Rotator cuff syndrome * 1	0/158 (0.00%)	0	0/159 (0.00%)	0	1/96 (1.04%)	1	0/20 (0.00%)	0	0/243 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma * 1	0/158 (0.00%)	0	1/159 (0.63%)	1	0/96 (0.00%)	0	0/20 (0.00%)	0	0/243 (0.00%)	0
Malignant melanoma stage I * 1	1/158 (0.63%)	1	0/159 (0.00%)	0	0/96 (0.00%)	0	0/20 (0.00%)	0	0/243 (0.00%)	0
Uterine leiomyoma * 1	1/158 (0.63%)	1	0/159 (0.00%)	0	0/96 (0.00%)	0	0/20 (0.00%)	0	1/243 (0.41%)	1
Nervous system disorders
Cervicobrachial syndrome * 1	0/158 (0.00%)	0	0/159 (0.00%)	0	1/96 (1.04%)	1	0/20 (0.00%)	0	0/243 (0.00%)	0
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous * 1	1/158 (0.63%)	1	0/159 (0.00%)	0	0/96 (0.00%)	0	0/20 (0.00%)	0	0/243 (0.00%)	0
Renal and urinary disorders
Renal colic * 1	0/158 (0.00%)	0	0/159 (0.00%)	0	1/96 (1.04%)	1	0/20 (0.00%)	0	0/243 (0.00%)	0
Reproductive system and breast disorders
Cervix neoplasms * 1	0/158 (0.00%)	0	0/159 (0.00%)	0	0/96 (0.00%)	0	0/20 (0.00%)	0	1/243 (0.41%)	1
Cervical polyp * 1	0/158 (0.00%)	0	0/159 (0.00%)	0	0/96 (0.00%)	0	0/20 (0.00%)	0	1/243 (0.41%)	1
Ovarian cyst ruptured * 1	0/158 (0.00%)	0	1/159 (0.63%)	1	0/96 (0.00%)	0	0/20 (0.00%)	0	0/243 (0.00%)	0
Hydrosalpinx * 1	0/158 (0.00%)	0	0/159 (0.00%)	0	1/96 (1.04%)	1	0/20 (0.00%)	0	0/243 (0.00%)	0
Ovarian enlargement * 1	0/158 (0.00%)	0	1/159 (0.63%)	1	0/96 (0.00%)	0	0/20 (0.00%)	0	0/243 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Pharyngeal oedema * 1	0/158 (0.00%)	0	1/159 (0.63%)	1	0/96 (0.00%)	0	0/20 (0.00%)	0	0/243 (0.00%)	0
Skin and subcutaneous tissue disorders
Erythema multiforme * 1	0/158 (0.00%)	0	0/159 (0.00%)	0	0/96 (0.00%)	0	0/20 (0.00%)	0	1/243 (0.41%)	1
Hypersensitivity vasculitis * 1	0/158 (0.00%)	0	0/159 (0.00%)	0	0/96 (0.00%)	0	0/20 (0.00%)	0	1/243 (0.41%)	1
Surgical and medical procedures
Cholecystectomy * 1	0/158 (0.00%)	0	0/159 (0.00%)	0	0/96 (0.00%)	0	0/20 (0.00%)	0	1/243 (0.41%)	1
Tooth extraction * 1	0/158 (0.00%)	0	1/159 (0.63%)	1	0/96 (0.00%)	0	0/20 (0.00%)	0	0/243 (0.00%)	0
Vascular disorders
Deep vein thrombosis * 1	0/158 (0.00%)	0	1/159 (0.63%)	1	0/96 (0.00%)	0	0/20 (0.00%)	0	0/243 (0.00%)	0
Hypertension * 1	0/158 (0.00%)	0	0/159 (0.00%)	0	0/96 (0.00%)	0	0/20 (0.00%)	0	1/243 (0.41%)	1
1 Term from vocabulary, MedDRA19.0; * Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo (SS)		CZP 200 mg Q2W (SS)		Placebo->OL CZP (SS)		CZP->OL CZP (SS)		SFE OL CZP 200 mg Q2W (SS)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	59/158 (37.34%)		75/159 (47.17%)		27/96 (28.13%)		7/20 (35.00%)		69/243 (28.40%)
Gastrointestinal disorders
Diarrhoea * 1	10/158 (6.33%)	10	8/159 (5.03%)	11	1/96 (1.04%)	1	0/20 (0.00%)	0	4/243 (1.65%)	4
Infections and infestations
Upper respiratory tract infection * 1	16/158 (10.13%)	23	30/159 (18.87%)	38	10/96 (10.42%)	14	4/20 (20.00%)	5	21/243 (8.64%)	31
Nasopharyngitis * 1	13/158 (8.23%)	17	21/159 (13.21%)	24	10/96 (10.42%)	13	0/20 (0.00%)	0	26/243 (10.70%)	33
Bronchitis * 1	5/158 (3.16%)	5	8/159 (5.03%)	9	5/96 (5.21%)	5	0/20 (0.00%)	0	10/243 (4.12%)	11
Investigations
Blood creatine phosphokinase increased * 1	4/158 (2.53%)	4	8/159 (5.03%)	9	1/96 (1.04%)	1	1/20 (5.00%)	1	3/243 (1.23%)	3
Musculoskeletal and connective tissue disorders
Arthralgia * 1	10/158 (6.33%)	12	9/159 (5.66%)	12	2/96 (2.08%)	2	2/20 (10.00%)	2	6/243 (2.47%)	6
Axial spondyloarthritis * 1	12/158 (7.59%)	13	11/159 (6.92%)	13	0/96 (0.00%)	0	0/20 (0.00%)	0	5/243 (2.06%)	5
Nervous system disorders
Headache * 1	7/158 (4.43%)	9	11/159 (6.92%)	15	0/96 (0.00%)	0	3/20 (15.00%)	3	9/243 (3.70%)	11
Respiratory, thoracic and mediastinal disorders
Cough * 1	8/158 (5.06%)	10	6/159 (3.77%)	6	2/96 (2.08%)	2	0/20 (0.00%)	0	3/243 (1.23%)	3
1 Term from vocabulary, MedDRA19.0; * Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: UCB
• Organization: Cares
• Phone: +1844 599 ext 2273
• EMail: UCBCares@ucb.com

Publications of Results:

van der Heijde D, Gensler LS, Maksymowych WP, Landewe R, Rudwaleit M, Bauer L, Kumke T, Kim M, Auteri SE, Hoepken B, Deodhar A. Long-term safety and clinical outcomes of certolizumab pegol treatment in patients with active non-radiographic axial spondyloarthritis: 3-year results from the phase 3 C-axSpAnd study. RMD Open. 2022 Mar;8(1):e002138. doi: 10.1136/rmdopen-2021-002138.

Robinson PC, Maksymowych WP, Gensler LS, Hall S, Rudwaleit M, Hoepken B, Bauer L, Kumke T, Kim M, de Peyrecave N, Deodhar A. Certolizumab Pegol Efficacy in Patients With Non-Radiographic Axial Spondyloarthritis Stratified by Baseline MRI and C-Reactive Protein Status: An Analysis From the C-axSpAnd Study. ACR Open Rheumatol. 2022 Sep;4(9):794-801. doi: 10.1002/acr2.11469. Epub 2022 Jun 22.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Maksymowych WP, Kumke T, Auteri SE, Hoepken B, Bauer L, Rudwaleit M. Predictors of long-term clinical response in patients with non-radiographic axial spondyloarthritis receiving certolizumab pegol. Arthritis Res Ther. 2021 Oct 29;23(1):274. doi: 10.1186/s13075-021-02650-4.

Deodhar A, Gensler LS, Kay J, Maksymowych WP, Haroon N, Landewe R, Rudwaleit M, Hall S, Bauer L, Hoepken B, de Peyrecave N, Kilgallen B, van der Heijde D. A Fifty-Two-Week, Randomized, Placebo-Controlled Trial of Certolizumab Pegol in Nonradiographic Axial Spondyloarthritis. Arthritis Rheumatol. 2019 Jul;71(7):1101-1111. doi: 10.1002/art.40866. Epub 2019 May 28.

• Responsible Party: UCB Pharma ( UCB BIOSCIENCES GmbH )
• ClinicalTrials.gov Identifier: NCT02552212
• Other Study ID Numbers: AS0006; 2015-001894-41 ( EudraCT Number )
• First Submitted: September 15, 2015
• First Posted: September 17, 2015
• Results First Submitted: April 27, 2019
• Results First Posted: August 17, 2020
• Last Update Posted: August 18, 2022