A Study to Test the Efficacy and Safety of Certolizumab Pegol in Japanese Subjects With Moderate to Severe Chronic Psoriasis

• Sponsor: UCB Biopharma S.P.R.L. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03051217
• Collaborator: (none)
• Enrollment: 127
• Locations: 33
• Arms: 3
• Actual Duration (Months): 22.8
• Patients Per Site: 3.8
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to demonstrate the efficacy and safety of Certolizumab Pegol (CZP) in the treatment of moderate to severe chronic plaque Psoriasis (PSO) in Japanese subjects.

Condition or Disease	Intervention/Treatment	Phase
Moderate to Severe Psoriasis; Generalized Pustular Psoriasis and Erythrodermic Psoriasis	Other: Placebo; Drug: Certolizumab Pegol	Phase 2/Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 127 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Phase 2/3, Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study To Evaluate the Efficacy and Safety of Certolizumab Pegol in Japanese Subjects With Moderate to Severe Chronic Psoriasis
• Actual Study Start Date: Feb 21, 2017
• Actual Primary Completion Date: Nov 19, 2018
• Actual Study Completion Date: Jan 16, 2019

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Placebo subcutaneous (sc) injection every two weeks (Q2W)	Other: Placebo; Pharmaceutical Form: Solution for injection in pre-filled syringe Concentration: 0.9 % saline Route of Administration: Subcutaneous use Q2W; Other Names: PBO
Experimental: CZP 200 mg Certolizumab Pegol subcutaneous (sc) injection 400 mg at Weeks 0, 2, 4, followed by Certolizumab Pegol subcutaneous (sc) injection 200 mg every two weeks (Q2W) with PBO administered to maintain the blind, starting at Week 6	Other: Placebo; Pharmaceutical Form: Solution for injection in pre-filled syringe Concentration: 0.9 % saline Route of Administration: Subcutaneous use Q2W; Other Names: PBO ; Drug: Certolizumab Pegol; Pharmaceutical Form: Solution for injection in pre-filled syringe Concentration: 200 mg/mL Route of Administration: Subcutaneous use; Other Names: Cimzia CDP870 CZP
Experimental: CZP 400 mg Certolizumab Pegol subcutaneous (sc) injection 400 mg every two weeks (Q2W).	Drug: Certolizumab Pegol; Pharmaceutical Form: Solution for injection in pre-filled syringe Concentration: 200 mg/mL Route of Administration: Subcutaneous use; Other Names: Cimzia CDP870 CZP

Outcome Measures

Primary Outcome Measures

1. Percentage of Subjects Achieving a 75 % or Higher Improvement in Psoriasis Area and Severity Index (PASI) Score at Week 16 [Week 16]

   The PASI75 response assessments were based on at least 75 % improvement in the PASI score from Baseline. This is a scoring system that averages the redness, thickness, and scaliness of the psoriatic lesions (on a 0-4 scale), and weights the resulting score by the area of skin involved. Body divided into 4 areas: head, arms, trunk to groin, and legs to top of buttocks. Assignment of an average score for the redness, thickness, and scaling for each of the 4 body areas with a score of 0 (clear) to 4 (very marked). Determining the percentage of skin covered with PSO for each of the body areas and converting to a 0 to 6 scale. Final PASI= average redness, thickness, and scaliness of the psoriatic skin lesions, multiplied by the involved psoriasis area score of the respective section, and weighted by the percentage of the person's affected skin for the respective section. The minimum possible PASI score is 0= no disease, the maximum score is 72= maximal disease.

Secondary Outcome Measures

1. Percentage of Subjects Who Achieve a Physician's Global Assessment (PGA) Clear or Almost Clear Response (With at Least 2-category Improvement) at Week 16 [Week 16]

   This Outcome Measure applied to participants with moderate to severe chronic plaque Psoriasis (PSO). The Investigator assessed the overall severity of Psoriasis (PSO) using the following 5-point scale: 0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe.

2. Percentage of Subjects Achieving a 90 % or Higher Improvement in Psoriasis Area and Severity Index (PASI) Score at Week 16 [Week 16]

   The PASI90 response assessments were based on at least 90 % improvement in the PASI score from Baseline. This is a scoring system that averages the redness, thickness, and scaliness of the psoriatic lesions (on a 0-4 scale), and weights the resulting score by the area of skin involved. Body divided into 4 areas: head, arms, trunk to groin, and legs to top of buttocks. Assignment of an average score for the redness, thickness, and scaling for each of the 4 body areas with a score of 0 (clear) to 4 (very marked). Determining the percentage of skin covered with PSO for each of the body areas and converting to a 0 to 6 scale. Final PASI= average redness, thickness, and scaliness of the psoriatic skin lesions, multiplied by the involved psoriasis area score of the respective section, and weighted by the percentage of the person's affected skin for the respective section. The minimum possible PASI score is 0= no disease, the maximum score is 72= maximal disease.

3. Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16 [Baseline and Week 16]

   This Outcome Measure applied to participants with moderate to severe chronic plaque Psoriasis (PSO). The DLQI is a subject-reported questionnaire designed for use in adult participants with PSO. The DLQI is a skin disease-specific questionnaire aimed at the evaluation of how symptoms and treatment affect patients' health related quality of life (HRQoL). This instrument asked participants about symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. It has been shown to be valid and reproducible in PSO patients. The DLQI score ranges from 0 to 30 with higher scores indicating lower HRQoL. A higher than or equal to (>=) 4-point change in the DLQI score (DLQI response) has been reported to be meaningful for the patient (within-patient minimal important difference Basra et al, 2015) a DLQI absolute score of lower than or equal to (=<) 1 indicates DLQI remission (i.e., no or small impact of the disease on HRQoL).

4. Change From Baseline in Itch Numeric Rating Scale at Week 16 [Baseline and Week 16]

   This Outcome Measure applied to participants with moderate to severe chronic plaque Psoriasis (PSO). The Itch Numeric Rating Scale (NRS) has been developed as a simple, single item instrument to assess the patient-reported severity of itch at its most intense during the past 24h period. Participants indicate itch severity by circling the integer that best describes the worst level of itching due to PSO in the past 24h period on an 11-point scale anchored at 0, representing "no itching" and 10, representing "worst itch imaginable" (Kimball et al, 2016).

5. Plasma Concentration of Certolizumab Pegol (CZP) [Blood samples were collected at Baseline (Week 0) and at Weeks 2, 4, 6, 8, 12, 16, 24, 32, 40, 52, 60]

   Plasma concentration was expressed in micrograms per milliliter (μg/mL). Values below Lower Limit of Quantification (LLOQ) were set to half the LLOQ to present summaries. The geometric mean and geometric coefficient of variation were only displayed if at least 2/3 of the data were above the LLOQ.

6. Percentage of Participants With Positive Anti-Certolizumab Pegol-antibody Levels in Plasma [Blood samples will be collected at Baseline (Week 0) and at Weeks 2, 4, 6, 8, 12, 16, 24, 32, 40, 52, 60]

   A pre-anti-drug (CZP) antibody (ADA) positive subject was defined as having a confirmed positive sample at Baseline. A pre-ADA negative subject was defined as having a Screening below the cut point (BCP) sample, or a screening above the cut point (ACP) sample, but not confirmed positive at Baseline. A treatment-emergent ADA positive subject was defined as either 1) pre-ADA negative subjects having at least 1 ADA confirmed positive sample or 2) pre-ADA positive subjects with at least 1 sample with greater then or equal to (>=) 1.67-fold increase from Baseline on CZP treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subject is male or female, >= 20 years of age.

• Institutional Review Board-approved written informed consent form is signed and dated by the subject.

• Other protocol-defined inclusion criteria may apply.

For subjects with moderate to severe chronic plaque psoriasis (PSO)

• Chronic plaque psoriasis for at least 6 months.

• Baseline Psoriasis Activity and Severity Index (PASI) >=12 and Body Surface Area (BSA) affected by PSO >=10% and Physician's Global Assessment (PGA) score of 3 or higher.

• Candidates for systemic PSO therapy and/or phototherapy and/or chemophototherapy.

For subjects with generalized pustular PSO or erythrodermic PSO

• Diagnosis of generalized pustular PSO or erythrodermic PSO at Screening.

• History of plaque-type PSO if subjects have a diagnosis of erythrodermic PSO.

• Baseline BSA affected by PSO >=80% if subjects have a diagnosis of erythrodermic PSO.

Exclusion Criteria:

• Female subject who is breastfeeding, pregnant, or plans to become pregnant during the study or within 5 months following last dose of study drug. Male subject who is planning a partner pregnancy during the study or within 5 months following the last dose of study drug.

• Subject has guttate psoriasis or drug-induced psoriasis. For subjects with moderate to severe plaque psoriasis, erythrodermic or pustular forms of psoriasis also are excluded.

• History of current, chronic, or recurrent infections of viral, bacterial, or fungal origin as described in the protocol. Also, subjects with a high risk of infection in the Investigator's opinion.

• History of a lymphoproliferative disorder including lymphoma or current signs and symptoms suggestive of lymphoproliferative disease.

• History of other malignancy or concurrent malignancy as described in the protocol.

• Class III or IV congestive heart failure

• History of, or suspected, demyelinating disease of the central nervous system (e.g., multiple sclerosis or optic neuritis).

• Subject has any other condition which, in the Investigator's judgment, would make the subject unsuitable for inclusion in the study.

• Concurrent medication restrictions as described in the protocol.

• Subject with known tuberculosis (TB) infection, at high risk of acquiring TB infection, or with untreated latent tuberculosis infection (LTBI) or current or history of nontuberculous mycobacterial (NTMB) infection.

• Subject has any protocol defined clinically significant laboratory abnormalities at the screening

• Other protocol-defined exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ps0017 024	Asahikawa		Japan
2	Ps0017 012	Bunkyo-Ku		Japan
3	Ps0017 010	Chiyoda-Ku		Japan
4	Ps0017 007	Chūōku		Japan
5	Ps0017 004	Fukuoka		Japan
6	Ps0017 039	Fukushima		Japan
7	Ps0017 028	Gifu		Japan
8	Ps0017 040	Hamamatsu		Japan
9	Ps0017 013	Itabashi-Ku		Japan
10	Ps0017 022	Kobe		Japan
11	Ps0017 032	Kumamoto		Japan
12	Ps0017 031	Kurume		Japan
13	Ps0017 021	Kyoto		Japan
14	Ps0017 041	Matsumoto		Japan
15	Ps0017 009	Minatoku		Japan
16	Ps0017 033	Miyazaki		Japan
17	Ps0017 016	Nagoya		Japan
18	Ps0017 029	Nankoku		Japan
19	Ps0017 005	Obihiro		Japan
20	Ps0017 037	Osaka-Sayama		Japan
21	Ps0017 017	Osaka		Japan
22	Ps0017 042	Osaka		Japan
23	Ps0017 001	Sapporo		Japan
24	Ps0017 027	Sendai		Japan
25	Ps0017 015	Shimotsuke		Japan
26	Ps0017 008	Shinagawa-Ku		Japan
27	Ps0017 002	Shinjuku		Japan
28	Ps0017 003	Shinjuku		Japan
29	Ps0017 011	Shinjuku		Japan
30	Ps0017 014	Shinjuku		Japan
31	Ps0017 034	Sumida		Japan
32	Ps0017 038	Takaoka		Japan
33	Ps0017 025	Tsu		Japan

Sponsors and Collaborators

• UCB Biopharma S.P.R.L.

Investigators

• Study Director: UCB Cares, UCB ([phone])

Study Documents (Full-Text)

• Study Protocol - Jan 25, 2018
• Statistical Analysis Plan - Dec 20, 2018

More Information

Additional Information:

• Product Information
• FDA Safety Alerts and Recalls

Publications

None provided.

• Responsible Party: UCB Biopharma S.P.R.L.
• ClinicalTrials.gov Identifier: NCT03051217
• Other Study ID Numbers: PS0017
• First Posted: Feb 13, 2017
• Last Update Posted: Jan 4, 2022
• Last Verified: Nov 1, 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by UCB Biopharma S.P.R.L.: Psoriasis; PSO; Chronic plaque psoriasis; Certolizumb Pegol; Cimzia; Generalized pustular psoriasis and erythrodermic psoriasis
• Additional relevant MeSH terms: Psoriasis; Certolizumab Pegol

Study Results

Participant Flow

Recruitment Details	The study started to enroll patients in February 2017 and concluded in January 2019.
Pre-assignment Detail	The study included a 5 Week Screening Period, an Initial Period up to Week 16, a Maintenance Period up to Week 52 and a Safety Follow-up Period up to Week 60. Participant Flow refers to the Randomized Set (RS)

Arm/Group Title	Placebo	CZP 200 mg Q2W	CZP 400 mg Q2W	Placebo/Placebo	CZP 400 mg Q2W/CZP 400 mg Q2W	CZP 200 mg Q2W/CZP 200 mg Q2W	CZP 200 mg Q2W/CZP 400 mg Q4W
Arm/Group Description	This arm consisted of participants who received Placebo subcutaneous (sc) injection every two weeks (Q2W) during the Initial Period.	This arm consisted of participants who received Certolizumab Pegol (CZP) subcutaneous (sc) injection 400 mg at Weeks 0, 2, 4, followed by Certolizumab Pegol subcutaneous (sc) injection 200 mg every two weeks (Q2W) starting at Week 6 during the Initial Period.	This arm consisted of participants who received Certolizumab Pegol (CZP) subcutaneous (sc) injection 400 mg every two weeks (Q2W) during the Initial Period.	This arm consisted of participants who were initially randomized to Placebo during the Initial Period, who achieved a PASI50 response at Week 16 and continued to receive Placebo during the Maintenance Period. Participants who did not achieve a PASI50 response at Week 16 escaped from the double-blind treatment and received open-label CZP 400 mg Q2W as 3 loading doses followed by CZP 200 mg Q2W.	This arm consisted of participants who were initially randomized to CZP 400 mg Q2W during the Initial Period, who achieved a PASI50 response at Week 16 and continued to receive CZP 400 mg Q2W during the Maintenance Period. Participants who did not achieve a PASI50 response at Week 16 escaped from the double-blind treatment and received open-label CZP 400 mg Q2W as 3 loading doses followed by CZP 200 mg Q2W.	This arm consisted of participants who were initially randomized to CZP 200 mg Q2W during the Initial Period, who achieved a PASI50 response at Week 16 and were re-randomized to receive CZP 200 mg Q2W during the Maintenance Period. Participants who did not achieve a PASI50 response at Week 16 escaped from the double-blind treatment and received open-label CZP 400 mg Q2W as 3 loading doses followed by CZP 200 mg Q2W.	This arm consisted of participants who were initially randomized to CZP 200 mg Q2W during the Initial Period, who achieved a PASI50 response at Week 16 and were re-randomized to receive CZP 400 mg Q4W, with Placebo administered on alternate dosing weeks to maintain the blind, during the Maintenance Period. Participants who did not achieve a PASI50 response at Week 16 escaped from the double-blind treatment and received open-label CZP 400 mg Q2W as 3 loading doses followed by CZP 200 mg Q2W.
Period Title: Initial Period (Week 0 to Week 16)
STARTED	26	48	53	0	0	0	0
COMPLETED	23	46	51	0	0	0	0
NOT COMPLETED	3	2	2	0	0	0	0
Period Title: Initial Period (Week 0 to Week 16)
STARTED	0	0	0	23	51	26	20
Received Escape Treatment	0	0	0	21	3	7	3
COMPLETED	0	0	0	20	48	24	19
NOT COMPLETED	0	0	0	3	3	2	1

Baseline Characteristics

Arm/Group Title	Placebo	CZP 200 mg Q2W	CZP 400 mg Q2W	Total Title
Arm/Group Description	This arm consisted of participants who received Placebo subcutaneous (sc) injection every two weeks (Q2W) during the Initial Period.	This arm consisted of participants who received Certolizumab Pegol (CZP) subcutaneous (sc) injection 400 mg at Weeks 0, 2, 4, followed by Certolizumab Pegol subcutaneous (sc) injection 200 mg every two weeks (Q2W) starting at Week 6 during the Initial Period.	This arm consisted of participants who received Certolizumab Pegol (CZP) subcutaneous (sc) injection 400 mg every two weeks (Q2W) during the Initial Period.
Overall Participants	26	48	53	127
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	24 92.3%	40 83.3%	49 92.5%	113 89%
>=65 years	2 7.7%	8 16.7%	4 7.5%	14 11%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.93 (11.37)	48.43 (13.47)	52.43 (11.59)	50.00 (12.37)
Sex: Female, Male (Count of Participants)
Female	5 19.2%	12 25%	11 20.8%	28 22%
Male	21 80.8%	36 75%	42 79.2%	99 78%
Race/Ethnicity, Customized (Count of Participants)
Asian (Japanese only)	26 100%	48 100%	53 100%	127 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Subjects Achieving a 75 % or Higher Improvement in Psoriasis Area and Severity Index (PASI) Score at Week 16
Description	The PASI75 response assessments were based on at least 75 % improvement in the PASI score from Baseline. This is a scoring system that averages the redness, thickness, and scaliness of the psoriatic lesions (on a 0-4 scale), and weights the resulting score by the area of skin involved. Body divided into 4 areas: head, arms, trunk to groin, and legs to top of buttocks. Assignment of an average score for the redness, thickness, and scaling for each of the 4 body areas with a score of 0 (clear) to 4 (very marked). Determining the percentage of skin covered with PSO for each of the body areas and converting to a 0 to 6 scale. Final PASI= average redness, thickness, and scaliness of the psoriatic skin lesions, multiplied by the involved psoriasis area score of the respective section, and weighted by the percentage of the person's affected skin for the respective section. The minimum possible PASI score is 0= no disease, the maximum score is 72= maximal disease.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all participants in the Randomized Set (RS) who received at least 1 dose of the study medication and had valid efficacy assessments for Baseline and for at least 1 post-Baseline visit. Missing data were handled using the Markov Chain Monte Carlo (MCMC) method for multiple imputation.

Arm/Group Title	Placebo (FAS)	CZP 200 mg Q2W (FAS)	CZP 400 mg Q2W (FAS)
Arm/Group Description	This arm consisted of participants who received Placebo subcutaneous (sc) injection every two weeks (Q2W) during the Initial Period. Participants formed the Full Analysis Set (FAS).	This arm consisted of participants who received Certolizumab Pegol (CZP) subcutaneous (sc) injection 400 mg at Weeks 0, 2, 4, followed by Certolizumab Pegol subcutaneous (sc) injection 200 mg every two weeks (Q2W) starting at Week 6 during the Initial Period. Participants formed the FAS.	This arm consisted of participants who received Certolizumab Pegol (CZP) subcutaneous (sc) injection 400 mg every two weeks (Q2W) during the Initial Period. Participants formed the FAS.
Measure Participants	26	48	53
Number [percentage of participants]	7.9 30.4%	73.0 152.1%	87.1 164.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), CZP 200 mg Q2W (FAS)
	Comments	The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimated difference in responder rate
	Estimated Value	65.1
	Confidence Interval	(2-Sided) 95%; 48.22 to 81.90
	Parameter Dispersion	Type: Value:
	Estimation Comments	If there is a group without a responder, in this case the biological exposure will be excluded from the model, an exact logistic regression applied.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), CZP 400 mg Q2W (FAS)
	Comments	The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimated difference in responder rate
	Estimated Value	79.1
	Confidence Interval	(2-Sided) 95%; 65.10 to 93.17
	Parameter Dispersion	Type: Value:
	Estimation Comments	If there is a group without a responder, in this case the biological exposure will be excluded from the model, an exact logistic regression applied.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), CZP 200 mg Q2W (FAS)
	Comments	The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	The p-value for the primary analysis was evaluated at a 2-sided significance level of 0.025 for each CZP dose vs PBO.
	Method	Regression, Logistic
	Comments	If there is a group without a responder, in this case the biological exposure will be excluded from the model, an exact logistic regression applied.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	31.695
	Confidence Interval	(2-Sided) 97.5%; 5.129 to 195.877
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), CZP 400 mg Q2W (FAS)
	Comments	The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	The p-value for the primary analysis was evaluated at a 2-sided significance level of 0.025 for each CZP dose vs PBO.
	Method	Regression, Logistic
	Comments	If there is a group without a responder, in this case the biological exposure will be excluded from the model, an exact logistic regression applied.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	79.112
	Confidence Interval	(2-Sided) 97.5%; 11.739 to 533.168
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Subjects Who Achieve a Physician's Global Assessment (PGA) Clear or Almost Clear Response (With at Least 2-category Improvement) at Week 16
Description	This Outcome Measure applied to participants with moderate to severe chronic plaque Psoriasis (PSO). The Investigator assessed the overall severity of Psoriasis (PSO) using the following 5-point scale: 0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all participants in the RS who received at least 1 dose of the study medication and had valid efficacy assessments for Baseline and for at least 1 post-Baseline visit. Missing data were handled using the Markov Chain Monte Carlo (MCMC) method for multiple imputation.

Arm/Group Title	Placebo (FAS)	CZP 200 mg Q2W (FAS)	CZP 400 mg Q2W (FAS)
Arm/Group Description	This arm consisted of participants who received Placebo subcutaneous (sc) injection every two weeks (Q2W) during the Initial Period. Participants formed the Full Analysis Set (FAS).	This arm consisted of participants who received Certolizumab Pegol (CZP) subcutaneous (sc) injection 400 mg at Weeks 0, 2, 4, followed by Certolizumab Pegol subcutaneous (sc) injection 200 mg every two weeks (Q2W) starting at Week 6 during the Initial Period. Participants formed the FAS.	This arm consisted of participants who received Certolizumab Pegol (CZP) subcutaneous (sc) injection 400 mg every two weeks (Q2W) during the Initial Period. Participants formed the FAS.
Measure Participants	26	48	53
Number [percentage of participants]	0.0 0%	52.7 109.8%	66.7 125.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), CZP 200 mg Q2W (FAS)
	Comments	The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimated difference in responder rate
	Estimated Value	52.7
	Confidence Interval	(2-Sided) 95%; 29.95 to 75.39
	Parameter Dispersion	Type: Value:
	Estimation Comments	If there is a group without a responder, in this case the biological exposure will be excluded from the model, an exact logistic regression applied.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), CZP 400 mg Q2W (FAS)
	Comments	The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimated difference in responder rate
	Estimated Value	66.7
	Confidence Interval	(2-Sided) 95%; 43.34 to 90.15
	Parameter Dispersion	Type: Value:
	Estimation Comments	If there is a group without a responder, in this case the biological exposure will be excluded from the model, an exact logistic regression applied.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), CZP 200 mg Q2W (FAS)
	Comments	The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	The p-value for the primary analysis was evaluated at a 2-sided significance level of 0.025 for each CZP dose vs PBO.
	Method	Regression, Logistic
	Comments	If there is a group without a responder, in this case the biological exposure will be excluded from the model, an exact logistic regression applied.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	38.193
	Confidence Interval	(2-Sided) 97.5%; 6.113 to 238.619
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), CZP 400 mg Q2W (FAS)
	Comments	The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	The p-value for the primary analysis was evaluated at a 2-sided significance level of 0.025 for each CZP dose vs PBO.
	Method	Regression, Logistic
	Comments	If there is a group without a responder, in this case the biological exposure will be excluded from the model, an exact logistic regression applied.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	69.580
	Confidence Interval	(2-Sided) 97.5%; 11.138 to 434.659
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Subjects Achieving a 90 % or Higher Improvement in Psoriasis Area and Severity Index (PASI) Score at Week 16
Description	The PASI90 response assessments were based on at least 90 % improvement in the PASI score from Baseline. This is a scoring system that averages the redness, thickness, and scaliness of the psoriatic lesions (on a 0-4 scale), and weights the resulting score by the area of skin involved. Body divided into 4 areas: head, arms, trunk to groin, and legs to top of buttocks. Assignment of an average score for the redness, thickness, and scaling for each of the 4 body areas with a score of 0 (clear) to 4 (very marked). Determining the percentage of skin covered with PSO for each of the body areas and converting to a 0 to 6 scale. Final PASI= average redness, thickness, and scaliness of the psoriatic skin lesions, multiplied by the involved psoriasis area score of the respective section, and weighted by the percentage of the person's affected skin for the respective section. The minimum possible PASI score is 0= no disease, the maximum score is 72= maximal disease.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all participants in the RS who received at least 1 dose of the study medication and had valid efficacy assessments for Baseline and for at least 1 post-Baseline visit. Missing data were handled using the Markov Chain Monte Carlo (MCMC) method for multiple imputation.

Arm/Group Title	Placebo (FAS)	CZP 200 mg Q2W (FAS)	CZP 400 mg Q2W (FAS)
Arm/Group Description	This arm consisted of participants who received Placebo subcutaneous (sc) injection every two weeks (Q2W) during the Initial Period. Participants formed the Full Analysis Set (FAS).	This arm consisted of participants who received Certolizumab Pegol (CZP) subcutaneous (sc) injection 400 mg at Weeks 0, 2, 4, followed by Certolizumab Pegol subcutaneous (sc) injection 200 mg every two weeks (Q2W) starting at Week 6 during the Initial Period. Participants formed the FAS.	This arm consisted of participants who received Certolizumab Pegol (CZP) subcutaneous (sc) injection 400 mg every two weeks (Q2W) during the Initial Period. Participants formed the FAS.
Measure Participants	26	48	53
Number [percentage of participants]	0.2 0.8%	53.8 112.1%	75.7 142.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), CZP 200 mg Q2W (FAS)
	Comments	The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimated difference in responder rate
	Estimated Value	53.6
	Confidence Interval	(2-Sided) 95%; 30.67 to 76.47
	Parameter Dispersion	Type: Value:
	Estimation Comments	If there is a group without a responder, in this case the biological exposure will be excluded from the model, an exact logistic regression applied.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), CZP 400 mg Q2W (FAS)
	Comments	The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimated difference in responder rate
	Estimated Value	75.5
	Confidence Interval	(2-Sided) 95%; 51.95 to 99.04
	Parameter Dispersion	Type: Value:
	Estimation Comments	If there is a group without a responder, in this case the biological exposure will be excluded from the model, an exact logistic regression applied.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), CZP 200 mg Q2W (FAS)
	Comments	The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	The p-value for the primary analysis was evaluated at a 2-sided significance level of 0.025 for each CZP dose vs PBO.
	Method	Regression, Logistic
	Comments	If there is a group without a responder, in this case the biological exposure will be excluded from the model, an exact logistic regression applied.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	38.696
	Confidence Interval	(2-Sided) 97.5%; 6.047 to 247.634
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), CZP 400 mg Q2W (FAS)
	Comments	The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	The p-value for the primary analysis was evaluated at a 2-sided significance level of 0.025 for each CZP dose vs PBO.
	Method	Regression, Logistic
	Comments	If there is a group without a responder, in this case the biological exposure will be excluded from the model, an exact logistic regression applied.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	100.459
	Confidence Interval	(2-Sided) 97.5%; 15.540 to 649.437
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16
Description	This Outcome Measure applied to participants with moderate to severe chronic plaque Psoriasis (PSO). The DLQI is a subject-reported questionnaire designed for use in adult participants with PSO. The DLQI is a skin disease-specific questionnaire aimed at the evaluation of how symptoms and treatment affect patients' health related quality of life (HRQoL). This instrument asked participants about symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. It has been shown to be valid and reproducible in PSO patients. The DLQI score ranges from 0 to 30 with higher scores indicating lower HRQoL. A higher than or equal to (>=) 4-point change in the DLQI score (DLQI response) has been reported to be meaningful for the patient (within-patient minimal important difference Basra et al, 2015) a DLQI absolute score of lower than or equal to (=<) 1 indicates DLQI remission (i.e., no or small impact of the disease on HRQoL).
Time Frame	Baseline and Week 16

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all participants in the RS who received at least 1 dose of the study medication and had valid efficacy assessments for Baseline and for at least 1 post-Baseline visit. Missing data were handled using the last observation carried forward (LOCF) method for the DLQI.

Arm/Group Title	Placebo (FAS)	CZP 200 mg Q2W (FAS)	CZP 400 mg Q2W (FAS)
Arm/Group Description	This arm consisted of participants who received Placebo subcutaneous (sc) injection every two weeks (Q2W) during the Initial Period. Participants formed the Full Analysis Set (FAS).	This arm consisted of participants who received Certolizumab Pegol (CZP) subcutaneous (sc) injection 400 mg at Weeks 0, 2, 4, followed by Certolizumab Pegol subcutaneous (sc) injection 200 mg every two weeks (Q2W) starting at Week 6 during the Initial Period. Participants formed the FAS.	This arm consisted of participants who received Certolizumab Pegol (CZP) subcutaneous (sc) injection 400 mg every two weeks (Q2W) during the Initial Period. Participants formed the FAS.
Measure Participants	26	48	53
Least Squares Mean (Standard Error) [Scores on a scale]	-0.3 (1.0)	-6.8 (0.7)	-6.8 (0.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), CZP 200 mg Q2W (FAS)
	Comments	The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	p-value obtained for each treatment group comparison tested at a significance level of 0.025 in the fixed sequence testing procedure.
	Method	ANCOVA
	Comments	ANCOVA model of change from Baseline DLQI score with treatment group and prior biologic exposure as factors and Baseline DLQI score as a covariate.
Method of Estimation	Estimation Parameter	Adjusted Mean Treatment Difference
	Estimated Value	-6.5
	Confidence Interval	(2-Sided) 97.5%; -9.100 to -3.844
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), CZP 400 mg Q2W (FAS)
	Comments	The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	p-value obtained for each treatment group comparison tested at a significance level of 0.025 in the fixed sequence testing procedure.
	Method	ANCOVA
	Comments	ANCOVA model of change from Baseline DLQI score with treatment group and prior biologic exposure as factors and Baseline DLQI score as a covariate.
Method of Estimation	Estimation Parameter	Adjusted Mean Treatment Difference
	Estimated Value	-6.5
	Confidence Interval	(2-Sided) 97.5%; -9.099 to -3.910
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in Itch Numeric Rating Scale at Week 16
Description	This Outcome Measure applied to participants with moderate to severe chronic plaque Psoriasis (PSO). The Itch Numeric Rating Scale (NRS) has been developed as a simple, single item instrument to assess the patient-reported severity of itch at its most intense during the past 24h period. Participants indicate itch severity by circling the integer that best describes the worst level of itching due to PSO in the past 24h period on an 11-point scale anchored at 0, representing "no itching" and 10, representing "worst itch imaginable" (Kimball et al, 2016).
Time Frame	Baseline and Week 16

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all participants in the RS who received at least 1 dose of the study medication and had valid efficacy assessments for Baseline and for at least 1 post-Baseline visit. Missing data were handled using the last observation carried forward (LOCF) method for the Itch Numeric Rating Scale.

Arm/Group Title	Placebo (FAS)	CZP 200 mg Q2W (FAS)	CZP 400 mg Q2W (FAS)
Arm/Group Description	This arm consisted of participants who received Placebo subcutaneous (sc) injection every two weeks (Q2W) during the Initial Period. Participants formed the Full Analysis Set (FAS).	This arm consisted of participants who received Certolizumab Pegol (CZP) subcutaneous (sc) injection 400 mg at Weeks 0, 2, 4, followed by Certolizumab Pegol subcutaneous (sc) injection 200 mg every two weeks (Q2W) starting at Week 6 during the Initial Period. Participants formed the FAS.	This arm consisted of participants who received Certolizumab Pegol (CZP) subcutaneous (sc) injection 400 mg every two weeks (Q2W) during the Initial Period. Participants formed the FAS.
Measure Participants	26	48	53
Least Squares Mean (Standard Error) [Scores on a scale]	0.2 (0.5)	-2.9 (0.4)	-4.0 (0.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), CZP 200 mg Q2W (FAS)
	Comments	The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	p-value obtained for each treatment group comparison tested at a significance level of 0.025 in the fixed sequence testing procedure.
	Method	ANCOVA
	Comments	ANCOVA model of change from Baseline Itch NRS with treatment group and prior biologic exposure as factors and Baseline Itch NRS as a covariate.
Method of Estimation	Estimation Parameter	Adjusted Mean Treatment Difference
	Estimated Value	-3.1
	Confidence Interval	(2-Sided) 95%; -4.265 to -2.002
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), CZP 400 mg Q2W (FAS)
	Comments	The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	p-value obtained for each treatment group comparison tested at a significance level of 0.025 in the fixed sequence testing procedure.
	Method	ANCOVA
	Comments	ANCOVA model of change from Baseline Itch NRS with treatment group and prior biologic exposure as factors and Baseline Itch NRS as a covariate.
Method of Estimation	Estimation Parameter	Adjusted Mean Treatment Difference
	Estimated Value	-4.2
	Confidence Interval	(2-Sided) 95%; -5.295 to -3.069
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Plasma Concentration of Certolizumab Pegol (CZP)
Description	Plasma concentration was expressed in micrograms per milliliter (μg/mL). Values below Lower Limit of Quantification (LLOQ) were set to half the LLOQ to present summaries. The geometric mean and geometric coefficient of variation were only displayed if at least 2/3 of the data were above the LLOQ.
Time Frame	Blood samples were collected at Baseline (Week 0) and at Weeks 2, 4, 6, 8, 12, 16, 24, 32, 40, 52, 60

Outcome Measure Data

Analysis Population Description

The Pharmacokinetics Per-Protocol Set (PK-PPS) consisted of all participants in the RS who took at least 1 dose of the study medication and provided at least 1 quantifiable CZP plasma concentration.

Arm/Group Title	CZP 200 mg Q2W/CZP 200 mg Q2W (PK-PPS)	CZP 400 mg Q2W/CZP 400 mg Q2W (PK-PPS)	CZP 200 mg Q2W/CZP 400 mg Q4W (PK-PPS)
Arm/Group Description	This arm consisted of participants who were initially randomized to CZP 200 mg Q2W during the Initial Period, who achieved a PASI50 response at Week 16 and were re-randomized to receive CZP 200 mg Q2W during the Maintenance Period. Participants who did not achieve a PASI50 response at Week 16 escaped from the double-blind treatment and received open-label CZP 400 mg Q2W as 3 loading doses followed by CZP 200 mg Q2W. Participants formed the Pharmacokinetics Per-Protocol Set (PK-PPS).	This arm consisted of participants who were initially randomized to CZP 400 mg Q2W during the Initial Period, who achieved a PASI50 response at Week 16 and continued to receive CZP 400 mg Q2W during the Maintenance Period. Participants who did not achieve a PASI50 response at Week 16 escaped from the double-blind treatment and received open-label CZP 400 mg Q2W as 3 loading doses followed by CZP 200 mg Q2W. Participants formed the PK-PPS.	This arm consisted of participants who were initially randomized to CZP 200 mg Q2W during the Initial Period, who achieved a PASI50 response at Week 16 and were re-randomized to receive CZP 400 mg Q4W, with Placebo administered on alternate dosing weeks to maintain the blind, during the Maintenance Period. Participants who did not achieve a PASI50 response at Week 16 escaped from the double-blind treatment and received open-label CZP 400 mg Q2W as 3 loading doses followed by CZP 200 mg Q2W. Participants formed the PK-PPS.
Measure Participants	28	53	20
Baseline	NA (NA)	NA (NA)	NA (NA)
Week 2	34.6417 (28.3)	35.2588 (25.2)	33.2026 (26.0)
Week 4	47.9241 (45.6)	47.0462 (35.7)	48.3634 (21.3)
Week 6	36.3003 (286.7)	41.2410 (183.0)	52.4876 (38.0)
Week 8	21.9292 (621.4)	39.9282 (243.7)	33.4139 (69.0)
Week 12	16.1907 (300.7)	46.9934 (189.3)	23.8437 (105.9)
Week 16	14.5995 (405.5)	48.3156 (183.8)	18.1204 (381.8)
Week 24	26.2596 (52.8)	51.6911 (118.2)	7.7206 (1747.5)
Week 32	26.9398 (48.8)	44.5749 (177.2)	8.4148 (1245.6)
Week 40	22.2790 (68.3)	50.9685 (53.3)	16.7013 (231.1)
Week 52	20.4541 (90.8)	54.1341 (43.4)	15.9290 (149.1)
Early Withdrawal	0.8342 (5520.7)	0.6115 (49802.8)
Safety Follow-Up	0.1739 (757.5)	0.3760 (1460.3)	0.1407 (714.5)

7. Secondary Outcome

Title	Percentage of Participants With Positive Anti-Certolizumab Pegol-antibody Levels in Plasma
Description	A pre-anti-drug (CZP) antibody (ADA) positive subject was defined as having a confirmed positive sample at Baseline. A pre-ADA negative subject was defined as having a Screening below the cut point (BCP) sample, or a screening above the cut point (ACP) sample, but not confirmed positive at Baseline. A treatment-emergent ADA positive subject was defined as either 1) pre-ADA negative subjects having at least 1 ADA confirmed positive sample or 2) pre-ADA positive subjects with at least 1 sample with greater then or equal to (>=) 1.67-fold increase from Baseline on CZP treatment.
Time Frame	Blood samples will be collected at Baseline (Week 0) and at Weeks 2, 4, 6, 8, 12, 16, 24, 32, 40, 52, 60

Outcome Measure Data

Analysis Population Description

The Pharmacokinetics Per-Protocol Set (PK-PPS) consisted of all participants in the RS who took at least 1 dose of the study medication and provided at least 1 quantifiable CZP plasma concentration.

Arm/Group Title	CZP 200 mg Q2W/CZP 200 mg Q2W (PK-PPS)	CZP 400 mg Q2W/CZP 400 mg Q2W (PK-PPS)	CZP 200 mg Q2W/CZP 400 mg Q4W (PK-PPS)
Arm/Group Description	This arm consisted of participants who were initially randomized to CZP 200 mg Q2W during the Initial Period, who achieved a PASI50 response at Week 16 and were re-randomized to receive CZP 200 mg Q2W during the Maintenance Period. Participants who did not achieve a PASI50 response at Week 16 escaped from the double-blind treatment and received open-label CZP 400 mg Q2W as 3 loading doses followed by CZP 200 mg Q2W. Participants formed the Pharmacokinetics Per-Protocol Set (PK-PPS).	This arm consisted of participants who were initially randomized to CZP 400 mg Q2W during the Initial Period, who achieved a PASI50 response at Week 16 and continued to receive CZP 400 mg Q2W during the Maintenance Period. Participants who did not achieve a PASI50 response at Week 16 escaped from the double-blind treatment and received open-label CZP 400 mg Q2W as 3 loading doses followed by CZP 200 mg Q2W. Participants formed the PK-PPS.	This arm consisted of participants who were initially randomized to CZP 200 mg Q2W during the Initial Period, who achieved a PASI50 response at Week 16 and were re-randomized to receive CZP 400 mg Q4W, with Placebo administered on alternate dosing weeks to maintain the blind, during the Maintenance Period. Participants who did not achieve a PASI50 response at Week 16 escaped from the double-blind treatment and received open-label CZP 400 mg Q2W as 3 loading doses followed by CZP 200 mg Q2W. Participants formed the PK-PPS.
Measure Participants	28	53	20
Number [percentage of participants]	100 384.6%	96.2 200.4%	90.0 169.8%

Adverse Events

Time Frame	Adverse Events (AEs) were collected from Baseline (Week 0) until the Safety Follow-up Visit (Week 60).
Adverse Event Reporting Description	Until Week 16 (Initial Period), there were 26 pts of PBO, 48 pts of CZP 200 mg, 53 pts of CZP 400 mg, but the safety set up to Week 52 was Escape Arm after Week 16, and CZP was administered. Therefore, Combined Initial and Maintenance Period is evaluated by the number of pts actually administered according to the dose of CZP.
Arm/Group Title	Placebo (SS)		CZP 200mg Q2W (SS)		CZP 400mg Q4W (SS)		CZP 200 mg Q2W + CZP 400 mg Q4W (SS)		CZP 400 mg Q2W (SS)		All CZP (SS)
Arm/Group Description	This arm consisted of participants who received at least one dose of Placebo subcutaneous (sc) injection every two weeks (Q2W) during the study. Participants formed the Safety Set (SS).		This arm consisted of participants who received at least one dose of Certolizumab Pegol (CZP) subcutaneous (sc) injection 200 mg every two weeks (Q2W) during the study. Participants formed the SS.		This arm consisted of participants who received at least one dose of Certolizumab Pegol (CZP) subcutaneous (sc) injection 400 mg every four weeks (Q4W) during the study. Participants formed the SS.		This arm consisted of participants who received at least one dose of Certolizumab Pegol (CZP) subcutaneous (sc) injection 200 mg every two weeks (Q2W) and at least one dose of Certolizumab Pegol (CZP) subcutaneous (sc) injection 400 mg every four weeks (Q4W) during the study. Participants formed the SS.		This arm consisted of participants who received at least one dose of Certolizumab Pegol (CZP) subcutaneous (sc) injection 400 mg every two weeks (Q2W) during the study. Participants formed the SS.		This arm consisted of participants who received at least one dose of Certolizumab Pegol (CZP) subcutaneous (sc) injection regardless of the dose during the study. Participants formed the SS.
All Cause Mortality
	Placebo (SS)		CZP 200mg Q2W (SS)		CZP 400mg Q4W (SS)		CZP 200 mg Q2W + CZP 400 mg Q4W (SS)		CZP 400 mg Q2W (SS)		All CZP (SS)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/26 (0%)		0/72 (0%)		0/20 (0%)		0/72 (0%)		0/64 (0%)		0/122 (0%)
Serious Adverse Events
	Placebo (SS)		CZP 200mg Q2W (SS)		CZP 400mg Q4W (SS)		CZP 200 mg Q2W + CZP 400 mg Q4W (SS)		CZP 400 mg Q2W (SS)		All CZP (SS)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/26 (3.8%)		2/72 (2.8%)		0/20 (0%)		2/72 (2.8%)		6/64 (9.4%)		8/122 (6.6%)
Blood and lymphatic system disorders
Neutropenia	0/26 (0%)	0	1/72 (1.4%)	1	0/20 (0%)	0	1/72 (1.4%)	1	0/64 (0%)	0	1/122 (0.8%)	1
Thrombocytopenia	0/26 (0%)	0	0/72 (0%)	0	0/20 (0%)	0	0/72 (0%)	0	1/64 (1.6%)	1	1/122 (0.8%)	1
Eye disorders
Eyelid ptosis	0/26 (0%)	0	0/72 (0%)	0	0/20 (0%)	0	0/72 (0%)	0	1/64 (1.6%)	1	1/122 (0.8%)	1
Gastrointestinal disorders
Large intestine polyp	1/26 (3.8%)	1	0/72 (0%)	0	0/20 (0%)	0	0/72 (0%)	0	1/64 (1.6%)	1	1/122 (0.8%)	1
Dental cyst	1/26 (3.8%)	1	0/72 (0%)	0	0/20 (0%)	0	0/72 (0%)	0	0/64 (0%)	0	0/122 (0%)	0
Immune system disorders
Sarcoidosis	0/26 (0%)	0	1/72 (1.4%)	1	0/20 (0%)	0	1/72 (1.4%)	1	0/64 (0%)	0	1/122 (0.8%)	1
Infections and infestations
Herpes zoster	0/26 (0%)	0	0/72 (0%)	0	0/20 (0%)	0	0/72 (0%)	0	1/64 (1.6%)	1	1/122 (0.8%)	1
Latent tuberculosis	0/26 (0%)	0	0/72 (0%)	0	0/20 (0%)	0	0/72 (0%)	0	2/64 (3.1%)	2	2/122 (1.6%)	2
Skin and subcutaneous tissue disorders
Henoch-Schonlein purpura	0/26 (0%)	0	0/72 (0%)	0	0/20 (0%)	0	0/72 (0%)	0	1/64 (1.6%)	1	1/122 (0.8%)	1
Other (Not Including Serious) Adverse Events
	Placebo (SS)		CZP 200mg Q2W (SS)		CZP 400mg Q4W (SS)		CZP 200 mg Q2W + CZP 400 mg Q4W (SS)		CZP 400 mg Q2W (SS)		All CZP (SS)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/26 (65.4%)		41/72 (56.9%)		15/20 (75%)		48/72 (66.7%)		45/64 (70.3%)		91/122 (74.6%)
Cardiac disorders
Aortic valve incompetence	0/26 (0%)	0	0/72 (0%)	0	1/20 (5%)	1	1/72 (1.4%)	1	0/64 (0%)	0	1/122 (0.8%)	1
Arrhythmia	0/26 (0%)	0	0/72 (0%)	0	1/20 (5%)	1	1/72 (1.4%)	1	0/64 (0%)	0	1/122 (0.8%)	1
Gastrointestinal disorders
Dental caries	0/26 (0%)	0	2/72 (2.8%)	2	2/20 (10%)	2	4/72 (5.6%)	4	1/64 (1.6%)	1	5/122 (4.1%)	5
Abdominal pain upper	0/26 (0%)	0	0/72 (0%)	0	1/20 (5%)	1	1/72 (1.4%)	1	0/64 (0%)	0	1/122 (0.8%)	1
Constipation	0/26 (0%)	0	0/72 (0%)	0	1/20 (5%)	1	1/72 (1.4%)	1	0/64 (0%)	0	1/122 (0.8%)	1
Abdominal discomfort	0/26 (0%)	0	0/72 (0%)	0	1/20 (5%)	1	1/72 (1.4%)	1	0/64 (0%)	0	1/122 (0.8%)	1
Infections and infestations
Gastroenteritis	0/26 (0%)	0	2/72 (2.8%)	2	1/20 (5%)	1	3/72 (4.2%)	3	1/64 (1.6%)	1	4/122 (3.3%)	4
Folliculitis	0/26 (0%)	0	2/72 (2.8%)	2	1/20 (5%)	1	3/72 (4.2%)	3	3/64 (4.7%)	4	6/122 (4.9%)	7
Myringitis	0/26 (0%)	0	0/72 (0%)	0	1/20 (5%)	1	1/72 (1.4%)	1	0/64 (0%)	0	1/122 (0.8%)	1
Influenza	3/26 (11.5%)	4	1/72 (1.4%)	1	1/20 (5%)	1	2/72 (2.8%)	2	2/64 (3.1%)	2	4/122 (3.3%)	4
Dermatophytosis of nail	0/26 (0%)	0	1/72 (1.4%)	1	0/20 (0%)	0	1/72 (1.4%)	1	4/64 (6.3%)	4	5/122 (4.1%)	5
Body tinea	0/26 (0%)	0	0/72 (0%)	0	1/20 (5%)	1	1/72 (1.4%)	1	0/64 (0%)	0	1/122 (0.8%)	1
Tinea versicolour	0/26 (0%)	0	0/72 (0%)	0	1/20 (5%)	1	1/72 (1.4%)	1	0/64 (0%)	0	1/122 (0.8%)	1
Nasopharyngitis	6/26 (23.1%)	8	23/72 (31.9%)	24	6/20 (30%)	6	25/72 (34.7%)	30	28/64 (43.8%)	48	53/122 (43.4%)	78
Injury, poisoning and procedural complications
Meniscus injury	0/26 (0%)	0	0/72 (0%)	0	1/20 (5%)	1	1/72 (1.4%)	1	0/64 (0%)	0	1/122 (0.8%)	1
Ligament sprain	2/26 (7.7%)	2	0/72 (0%)	0	0/20 (0%)	0	0/72 (0%)	0	0/64 (0%)	0	0/122 (0%)	0
Limb injury	0/26 (0%)	0	0/72 (0%)	0	1/20 (5%)	1	1/72 (1.4%)	1	0/64 (0%)	0	1/122 (0.8%)	1
Investigations
Cell marker increased	0/26 (0%)	0	0/72 (0%)	0	1/20 (5%)	1	1/72 (1.4%)	1	1/64 (1.6%)	1	2/122 (1.6%)	2
Metabolism and nutrition disorders
Type 2 diabetes mellitus	0/26 (0%)	0	0/72 (0%)	0	1/20 (5%)	1	1/72 (1.4%)	1	0/64 (0%)	0	1/122 (0.8%)	1
Musculoskeletal and connective tissue disorders
Arthritis	0/26 (0%)	0	0/72 (0%)	0	1/20 (5%)	1	1/72 (1.4%)	1	0/64 (0%)	0	1/122 (0.8%)	1
Temporomandibular joint syndrome	0/26 (0%)	0	0/72 (0%)	0	1/20 (5%)	1	1/72 (1.4%)	1	0/64 (0%)	0	1/122 (0.8%)	1
Back pain	0/26 (0%)	0	2/72 (2.8%)	3	2/20 (10%)	2	4/72 (5.6%)	5	3/64 (4.7%)	4	7/122 (5.7%)	9
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma	2/26 (7.7%)	2	1/72 (1.4%)	1	0/20 (0%)	0	1/72 (1.4%)	1	1/64 (1.6%)	1	2/122 (1.6%)	2
Nervous system disorders
Headache	0/26 (0%)	0	2/72 (2.8%)	2	2/20 (10%)	2	4/72 (5.6%)	4	4/64 (6.3%)	6	7/122 (5.7%)	10
Dizziness	0/26 (0%)	0	2/72 (2.8%)	2	1/20 (5%)	1	3/72 (4.2%)	3	0/64 (0%)	0	3/122 (2.5%)	3
Psychiatric disorders
Insomnia	0/26 (0%)	0	0/72 (0%)	0	1/20 (5%)	1	1/72 (1.4%)	1	1/64 (1.6%)	1	2/122 (1.6%)	2
Respiratory, thoracic and mediastinal disorders
Cough	4/26 (15.4%)	4	4/72 (5.6%)	5	0/20 (0%)	0	4/72 (5.6%)	5	3/64 (4.7%)	4	7/122 (5.7%)	9
Sputum increased	0/26 (0%)	0	0/72 (0%)	0	1/20 (5%)	1	1/72 (1.4%)	1	0/64 (0%)	0	1/122 (0.8%)	1
Skin and subcutaneous tissue disorders
Eczema	0/26 (0%)	0	5/72 (6.9%)	7	0/20 (0%)	0	5/72 (6.9%)	7	4/64 (6.3%)	4	9/122 (7.4%)	11
Dermatitis contact	0/26 (0%)	0	1/72 (1.4%)	1	1/20 (5%)	1	2/72 (2.8%)	2	4/64 (6.3%)	4	6/122 (4.9%)	6
Dyshidrotic eczema	0/26 (0%)	0	1/72 (1.4%)	1	1/20 (5%)	1	2/72 (2.8%)	2	2/64 (3.1%)	2	4/122 (3.3%)	4
Pruritus	2/26 (7.7%)	2	2/72 (2.8%)	3	0/20 (0%)	0	2/72 (2.8%)	3	1/64 (1.6%)	1	3/122 (2.5%)	4
Psoriasis	6/26 (23.1%)	6	8/72 (11.1%)	8	0/20 (0%)	0	8/72 (11.1%)	8	5/64 (7.8%)	5	13/122 (10.7%)	13
Vascular disorders
Essential hypertension	0/26 (0%)	0	0/72 (0%)	0	1/20 (5%)	1	1/72 (1.4%)	1	0/64 (0%)	0	1/122 (0.8%)	1
Orthostatic hypotension	0/26 (0%)	0	0/72 (0%)	0	1/20 (5%)	1	1/72 (1.4%)	1	0/64 (0%)	0	1/122 (0.8%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.