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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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:
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
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
Hide 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
Arm/Group Title Placebo CZP 200 mg Q2W Total Title
Hide 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
Hide 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%
1.Primary Outcome
Title Percentage of Subjects With Ankylosing Spondylitis Disease Activity Score Major Improvement (ASDAS-MI) Response Criteria Response at Week 52
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide 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
Hide Description Certolizumab pegol plasma concentration was measured at Baseline in micrograms per millilitre (µg/mL).
Time Frame Baseline (Week 0)
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide Description Certolizumab pegol plasma concentration was measured at Week 1, in µg/mL.
Time Frame Week 1
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide Description Certolizumab pegol plasma concentration was measured at Week 2, in µg/mL.
Time Frame Week 2
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide Description Certolizumab pegol plasma concentration was measured at Week 4, in µg/mL.
Time Frame Week 4
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide Description Certolizumab pegol plasma concentration was measured at Week 12, in µg/mL.
Time Frame Week 12
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide Description Certolizumab pegol plasma concentration was measured at Week 24, in µg/mL.
Time Frame Week 24
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide Description Certolizumab pegol plasma concentration was measured at Week 36, in µg/mL.
Time Frame Week 36
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide Description Certolizumab pegol plasma concentration was measured at Week 52, in µg/mL.
Time Frame Week 52
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide 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)
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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)
Hide 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)
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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)
Hide 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)
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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)
Hide 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)
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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)
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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)
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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%
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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)
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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)
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide 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)
Hide 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%
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide 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)
Hide 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
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)
Hide 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%)    
Hide 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
Hide 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
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
Layout table for Results Point of Contact information
Name/Title: UCB
Organization: Cares
Phone: +1844 599 ext 2273
EMail: UCBCares@ucb.com
Layout table for additonal information
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