A Study to Test the Efficacy and Safety of Certolizumab P... | NCT03051217 | Trialant
NCT03051217
Sponsor
UCB Biopharma S.P.R.L.
Status
Completed
Last Update Posted
Jan 4, 2022Actual
Enrollment
127Actual
Phase
Phase 2Phase 3
Conditions
Moderate to Severe Psoriasis
Generalized Pustular Psoriasis and Erythrodermic Psoriasis
Interventions
Placebo
Certolizumab Pegol
Countries
Japan
Protocol Section
Identification Module
NCT ID
NCT03051217
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
PS0017
Secondary IDs
Not provided
Brief Title
A Study to Test the Efficacy and Safety of Certolizumab Pegol in Japanese Subjects With Moderate to Severe Chronic Psoriasis
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
Acronym
Not provided
Organization
UCB PharmaINDUSTRY
Status Module
Record Verification Date
Nov 2020
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Feb 21, 2017Actual
Primary Completion Date
Nov 19, 2018Actual
Completion Date
Jan 16, 2019Actual
First Submitted Date
Feb 9, 2017
First Submission Date that Met QC Criteria
Feb 9, 2017
First Posted Date
Feb 13, 2017Actual
Results Waived
Not provided
Results First Submitted Date
Nov 19, 2019
Results First Submitted that Met QC Criteria
Nov 19, 2019
Results First Posted Date
Dec 11, 2019Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Dec 13, 2021
Last Update Posted Date
Jan 4, 2022Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
UCB Biopharma S.P.R.L.INDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
No
Is FDA Regulated Drug
No
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
No
FDAAA801 Violation
Not provided
Description Module
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.
Detailed Description
Not provided
Conditions Module
Conditions
Moderate to Severe Psoriasis
Generalized Pustular Psoriasis and Erythrodermic Psoriasis
Keywords
Psoriasis
PSO
Chronic plaque psoriasis
Certolizumb Pegol
Cimzia
Generalized pustular psoriasis and erythrodermic psoriasis
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2Phase 3
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
127Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Placebo
Placebo Comparator
Placebo subcutaneous (sc) injection every two weeks (Q2W)
Other: Placebo
CZP 200 mg
Experimental
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
Drug: Certolizumab Pegol
CZP 400 mg
Experimental
Certolizumab Pegol subcutaneous (sc) injection 400 mg every two weeks (Q2W).
Drug: Certolizumab Pegol
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Placebo
Other
Pharmaceutical Form: Solution for injection in pre-filled syringe
Concentration: 0.9 % saline
Route of Administration: Subcutaneous use Q2W
CZP 200 mg
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Percentage of Subjects Achieving a 75 % or Higher Improvement in Psoriasis Area and Severity Index (PASI) Score at 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.
Week 16
Secondary Outcomes
Measure
Description
Time Frame
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
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.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
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.
Imafuku S, Tada Y, Umezawa Y, Sakurai S, Hoshii N, Nakagawa H. Certolizumab Pegol in Japanese Patients with Moderate to Severe Plaque Psoriasis: Effect of Demographics and Baseline Disease Characteristics on Efficacy. Dermatol Ther (Heidelb). 2022 Jan;12(1):121-135. doi: 10.1007/s13555-021-00645-2. Epub 2021 Nov 26.
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)
Recruitment Details
The study started to enroll patients in February 2017 and concluded in January 2019.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Placebo
This arm consisted of participants who received Placebo subcutaneous (sc) injection every two weeks (Q2W) during the Initial Period.
FG001
CZP 200 mg Q2W
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.
Pharmaceutical Form: Solution for injection in pre-filled syringe
Concentration: 200 mg/mL
Route of Administration: Subcutaneous use
CZP 200 mg
CZP 400 mg
Cimzia
CDP870
CZP
Week 16
Percentage of Subjects Achieving a 90 % or Higher Improvement in Psoriasis Area and Severity Index (PASI) Score at 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.
Week 16
Change From Baseline in Dermatology Life Quality Index (DLQI) at 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).
Baseline and Week 16
Change From Baseline in Itch Numeric Rating Scale at 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).
Baseline and Week 16
Plasma Concentration of Certolizumab Pegol (CZP)
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.
Blood samples were collected at Baseline (Week 0) and at Weeks 2, 4, 6, 8, 12, 16, 24, 32, 40, 52, 60
Percentage of Participants With Positive Anti-Certolizumab Pegol-antibody Levels in Plasma
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.
Blood samples will be collected at Baseline (Week 0) and at Weeks 2, 4, 6, 8, 12, 16, 24, 32, 40, 52, 60
Bunkyō City
Japan
Ps0017 010
Chiyoda-Ku
Japan
Ps0017 007
Chūōku
Japan
Ps0017 004
Fukuoka
Japan
Ps0017 039
Fukushima
Japan
Ps0017 028
Gifu
Japan
Ps0017 040
Hamamatsu
Japan
Ps0017 013
Itabashi-Ku
Japan
Ps0017 022
Kobe
Japan
Ps0017 032
Kumamoto
Japan
Ps0017 031
Kurume
Japan
Ps0017 021
Kyoto
Japan
Ps0017 041
Matsumoto
Japan
Ps0017 009
Minatoku
Japan
Ps0017 033
Miyazaki
Japan
Ps0017 016
Nagoya
Japan
Ps0017 029
Nankoku
Japan
Ps0017 005
Obihiro
Japan
Ps0017 017
Osaka
Japan
Ps0017 042
Osaka
Japan
Ps0017 037
Ōsaka-sayama
Japan
Ps0017 001
Sapporo
Japan
Ps0017 027
Sendai
Japan
Ps0017 015
Shimotsuke
Japan
Ps0017 008
Shinagawa-Ku
Japan
Ps0017 002
Shinjuku
Japan
Ps0017 003
Shinjuku
Japan
Ps0017 011
Shinjuku
Japan
Ps0017 014
Shinjuku
Japan
Ps0017 034
Sumida City
Japan
Ps0017 038
Takaoka
Japan
Ps0017 025
Tsu
Japan
Okubo Y, Umezawa Y, Sakurai S, Hoshii N, Nakagawa H. Efficacy and Safety of Certolizumab Pegol in Japanese Patients with Generalized Pustular Psoriasis and Erythrodermic Psoriasis: 52-Week Results. Dermatol Ther (Heidelb). 2022 Jun;12(6):1397-1415. doi: 10.1007/s13555-022-00741-x. Epub 2022 May 27.
Umezawa Y, Asahina A, Imafuku S, Tada Y, Sano S, Morita A, Sakurai S, Hoshii N, Tilt N, Nakagawa H. Efficacy and Safety of Certolizumab Pegol in Japanese Patients with Moderate to Severe Plaque Psoriasis: 52-Week Results. Dermatol Ther (Heidelb). 2021 Jun;11(3):943-960. doi: 10.1007/s13555-021-00520-0. Epub 2021 Apr 22.
Umezawa Y, Sakurai S, Hoshii N, Nakagawa H; PS0017 Study Group. Certolizumab Pegol for the Treatment of Moderate to Severe Plaque Psoriasis: 16-Week Results from a Phase 2/3 Japanese Study. Dermatol Ther (Heidelb). 2021 Apr;11(2):513-528. doi: 10.1007/s13555-021-00494-z. Epub 2021 Feb 19.
FG002
CZP 400 mg Q2W
This arm consisted of participants who received Certolizumab Pegol (CZP) subcutaneous (sc) injection 400 mg every two weeks (Q2W) during the Initial Period.
FG003
Placebo/Placebo
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.
FG004
CZP 400 mg Q2W/CZP 400 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.
FG005
CZP 200 mg Q2W/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.
FG006
CZP 200 mg Q2W/CZP 400 mg Q4W
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.
FG00026 subjects
FG00148 subjects
FG00253 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
COMPLETED
FG00023 subjects
FG00146 subjects
FG00251 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
NOT COMPLETED
FG0003 subjects
FG0012 subjects
FG0022 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
Type
Comment
Reasons
Adverse Event
FG0002 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
Protocol Violation
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG004
Withdrawal by Subject
FG0001 subjects
FG0011 subjects
FG0021 subjects
FG0030 subjects
FG004
Maintenance Period (Week 16 to Week 52)
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG00323 subjects
FG00451 subjects
FG00526 subjects
FG00620 subjects
Received Escape Treatment
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG00321 subjects
FG004
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG00320 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0033 subjects
FG004
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Baseline Characteristics refer to the Safety Set which consisted of all participants in the Randomized Set (RS) who received at least 1 dose of study medication.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Placebo
This arm consisted of participants who received Placebo subcutaneous (sc) injection every two weeks (Q2W) during the Initial Period.
BG001
CZP 200 mg Q2W
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.
BG002
CZP 400 mg Q2W
This arm consisted of participants who received Certolizumab Pegol (CZP) subcutaneous (sc) injection 400 mg every two weeks (Q2W) during the Initial Period.
BG003
Total Title
Denominators
Units
Counts
Participants
BG00026
BG00148
BG00253
BG003127
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Categorical
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
<=18 years
BG0000
BG0010
BG0020
BG003
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00047.93± 11.37
BG00148.43± 13.47
BG002
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0005
BG00112
BG002
Race/Ethnicity, Customized
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Asian (Japanese only)
BG00026
BG00148
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Percentage of Subjects Achieving a 75 % or Higher Improvement in Psoriasis Area and Severity Index (PASI) Score at 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.
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.
Posted
Number
percentage of participants
Week 16
ID
Title
Description
OG000
Placebo (FAS)
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).
OG001
CZP 200 mg Q2W (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.
OG002
CZP 400 mg Q2W (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.
Units
Counts
Participants
OG00026
OG00148
OG00253
Title
Denominators
Categories
Title
Measurements
OG0007.9
OG00173.0
OG00287.1
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.
Regression, Logistic
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.
Estimated difference in responder rate
65.1
2-Sided
95
48.22
81.90
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.
Superiority
Secondary
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
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.
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.
Posted
Number
percentage of participants
Week 16
ID
Title
Description
OG000
Placebo (FAS)
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).
OG001
CZP 200 mg Q2W (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.
OG002
Secondary
Percentage of Subjects Achieving a 90 % or Higher Improvement in Psoriasis Area and Severity Index (PASI) Score at 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.
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.
Posted
Number
percentage of participants
Week 16
ID
Title
Description
OG000
Placebo (FAS)
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).
Secondary
Change From Baseline in Dermatology Life Quality Index (DLQI) at 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).
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.
Posted
Least Squares Mean
Standard Error
Scores on a scale
Baseline and Week 16
ID
Title
Description
OG000
Placebo (FAS)
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).
Secondary
Change From Baseline in Itch Numeric Rating Scale at 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).
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.
Posted
Least Squares Mean
Standard Error
Scores on a scale
Baseline and Week 16
ID
Title
Description
OG000
Placebo (FAS)
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).
OG001
CZP 200 mg Q2W (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.
Secondary
Plasma Concentration of Certolizumab Pegol (CZP)
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.
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.
Posted
Geometric Mean
Geometric Coefficient of Variation
µg/mL
Blood samples were collected at Baseline (Week 0) and at Weeks 2, 4, 6, 8, 12, 16, 24, 32, 40, 52, 60
ID
Title
Description
OG000
CZP 200 mg Q2W/CZP 200 mg Q2W (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 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).
OG001
CZP 400 mg Q2W/CZP 400 mg Q2W (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.
Secondary
Percentage of Participants With Positive Anti-Certolizumab Pegol-antibody Levels in Plasma
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.
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.
Posted
Number
percentage of participants
Blood samples will be collected at Baseline (Week 0) and at Weeks 2, 4, 6, 8, 12, 16, 24, 32, 40, 52, 60
ID
Title
Description
OG000
CZP 200 mg Q2W/CZP 200 mg Q2W (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 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).
OG001
Time Frame
Adverse Events (AEs) were collected from Baseline (Week 0) until the Safety Follow-up Visit (Week 60).
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.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Placebo (SS)
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).
0
26
1
26
17
26
EG001
CZP 200mg Q2W (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.
0
72
2
72
41
72
EG002
CZP 400mg Q4W (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.
0
20
0
20
15
20
EG003
CZP 200 mg Q2W + CZP 400 mg Q4W (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.
0
72
2
72
48
72
EG004
CZP 400 mg Q2W (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.
0
64
6
64
45
64
EG005
All CZP (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.
0
122
8
122
91
122
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Neutropenia
Blood and lymphatic system disorders
MedDRA18.1
Non-systematic Assessment
EG0000 events0 affected26 at risk
EG0011 events1 affected72 at risk
EG0020 events0 affected20 at risk
EG0031 events1 affected72 at risk
EG0040 events0 affected64 at risk
EG0051 events1 affected122 at risk
Thrombocytopenia
Blood and lymphatic system disorders
MedDRA18.1
Non-systematic Assessment
EG0000 events0 affected26 at risk
EG0010 events0 affected72 at risk
EG0020 events0 affected20 at risk
EG003
Eyelid ptosis
Eye disorders
MedDRA18.1
Non-systematic Assessment
EG0000 events0 affected26 at risk
EG0010 events0 affected72 at risk
EG0020 events0 affected20 at risk
EG003
Large intestine polyp
Gastrointestinal disorders
MedDRA18.1
Non-systematic Assessment
EG0001 events1 affected26 at risk
EG0010 events0 affected72 at risk
EG0020 events0 affected20 at risk
EG003
Dental cyst
Gastrointestinal disorders
MedDRA18.1
Non-systematic Assessment
EG0001 events1 affected26 at risk
EG0010 events0 affected72 at risk
EG0020 events0 affected20 at risk
EG003
Sarcoidosis
Immune system disorders
MedDRA18.1
Non-systematic Assessment
EG0000 events0 affected26 at risk
EG0011 events1 affected72 at risk
EG0020 events0 affected20 at risk
EG003
Herpes zoster
Infections and infestations
MedDRA18.1
Non-systematic Assessment
EG0000 events0 affected26 at risk
EG0010 events0 affected72 at risk
EG0020 events0 affected20 at risk
EG003
Latent tuberculosis
Infections and infestations
MedDRA18.1
Non-systematic Assessment
EG0000 events0 affected26 at risk
EG0010 events0 affected72 at risk
EG0020 events0 affected20 at risk
EG003
Henoch-Schonlein purpura
Skin and subcutaneous tissue disorders
MedDRA18.1
Non-systematic Assessment
EG0000 events0 affected26 at risk
EG0010 events0 affected72 at risk
EG0020 events0 affected20 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Aortic valve incompetence
Cardiac disorders
MedDRA18.1
Non-systematic Assessment
EG0000 events0 affected26 at risk
EG0010 events0 affected72 at risk
EG0021 events1 affected20 at risk
EG0031 events1 affected72 at risk
EG0040 events0 affected64 at risk
EG0051 events1 affected122 at risk
Arrhythmia
Cardiac disorders
MedDRA18.1
Non-systematic Assessment
EG0000 events0 affected26 at risk
EG0010 events0 affected72 at risk
EG0021 events1 affected20 at risk
EG003
Dental caries
Gastrointestinal disorders
MedDRA18.1
Non-systematic Assessment
EG0000 events0 affected26 at risk
EG0012 events2 affected72 at risk
EG0022 events2 affected20 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA18.1
Non-systematic Assessment
EG0000 events0 affected26 at risk
EG0010 events0 affected72 at risk
EG0021 events1 affected20 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA18.1
Non-systematic Assessment
EG0000 events0 affected26 at risk
EG0010 events0 affected72 at risk
EG0021 events1 affected20 at risk
EG003
Abdominal discomfort
Gastrointestinal disorders
MedDRA18.1
Non-systematic Assessment
EG0000 events0 affected26 at risk
EG0010 events0 affected72 at risk
EG0021 events1 affected20 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA18.1
Non-systematic Assessment
EG0000 events0 affected26 at risk
EG0012 events2 affected72 at risk
EG0021 events1 affected20 at risk
EG003
Folliculitis
Infections and infestations
MedDRA18.1
Non-systematic Assessment
EG0000 events0 affected26 at risk
EG0012 events2 affected72 at risk
EG0021 events1 affected20 at risk
EG003
Myringitis
Infections and infestations
MedDRA18.1
Non-systematic Assessment
EG0000 events0 affected26 at risk
EG0010 events0 affected72 at risk
EG0021 events1 affected20 at risk
EG003
Influenza
Infections and infestations
MedDRA18.1
Non-systematic Assessment
EG0004 events3 affected26 at risk
EG0011 events1 affected72 at risk
EG0021 events1 affected20 at risk
EG003
Dermatophytosis of nail
Infections and infestations
MedDRA18.1
Non-systematic Assessment
EG0000 events0 affected26 at risk
EG0011 events1 affected72 at risk
EG0020 events0 affected20 at risk
EG003
Body tinea
Infections and infestations
MedDRA18.1
Non-systematic Assessment
EG0000 events0 affected26 at risk
EG0010 events0 affected72 at risk
EG0021 events1 affected20 at risk
EG003
Tinea versicolour
Infections and infestations
MedDRA18.1
Non-systematic Assessment
EG0000 events0 affected26 at risk
EG0010 events0 affected72 at risk
EG0021 events1 affected20 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA18.1
Non-systematic Assessment
EG0008 events6 affected26 at risk
EG00124 events23 affected72 at risk
EG0026 events6 affected20 at risk
EG003
Meniscus injury
Injury, poisoning and procedural complications
MedDRA18.1
Non-systematic Assessment
EG0000 events0 affected26 at risk
EG0010 events0 affected72 at risk
EG0021 events1 affected20 at risk
EG003
Ligament sprain
Injury, poisoning and procedural complications
MedDRA18.1
Non-systematic Assessment
EG0002 events2 affected26 at risk
EG0010 events0 affected72 at risk
EG0020 events0 affected20 at risk
EG003
Limb injury
Injury, poisoning and procedural complications
MedDRA18.1
Non-systematic Assessment
EG0000 events0 affected26 at risk
EG0010 events0 affected72 at risk
EG0021 events1 affected20 at risk
EG003
Cell marker increased
Investigations
MedDRA18.1
Non-systematic Assessment
EG0000 events0 affected26 at risk
EG0010 events0 affected72 at risk
EG0021 events1 affected20 at risk
EG003
Type 2 diabetes mellitus
Metabolism and nutrition disorders
MedDRA18.1
Non-systematic Assessment
EG0000 events0 affected26 at risk
EG0010 events0 affected72 at risk
EG0021 events1 affected20 at risk
EG003
Arthritis
Musculoskeletal and connective tissue disorders
MedDRA18.1
Non-systematic Assessment
EG0000 events0 affected26 at risk
EG0010 events0 affected72 at risk
EG0021 events1 affected20 at risk
EG003
Temporomandibular joint syndrome
Musculoskeletal and connective tissue disorders
MedDRA18.1
Non-systematic Assessment
EG0000 events0 affected26 at risk
EG0010 events0 affected72 at risk
EG0021 events1 affected20 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA18.1
Non-systematic Assessment
EG0000 events0 affected26 at risk
EG0013 events2 affected72 at risk
EG0022 events2 affected20 at risk
EG003
Skin papilloma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.
Regression, Logistic
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.
Estimated difference in responder rate
79.1
2-Sided
95
65.10
93.17
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.
Superiority
OG000
OG001
The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.
Regression, Logistic
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.
<0.0001
The p-value for the primary analysis was evaluated at a 2-sided significance level of 0.025 for each CZP dose vs PBO.
Odds Ratio (OR)
31.695
2-Sided
97.5
5.129
195.877
Superiority
OG000
OG002
The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.
Regression, Logistic
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.
<0.0001
The p-value for the primary analysis was evaluated at a 2-sided significance level of 0.025 for each CZP dose vs PBO.
Odds Ratio (OR)
79.112
2-Sided
97.5
11.739
533.168
Superiority
CZP 400 mg Q2W (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.
Units
Counts
Participants
OG00026
OG00148
OG00253
Title
Denominators
Categories
Title
Measurements
OG0000.0
OG00152.7
OG00266.7
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.
Regression, Logistic
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.
Estimated difference in responder rate
52.7
2-Sided
95
29.95
75.39
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.
Superiority
OG000
OG002
The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.
Regression, Logistic
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.
Estimated difference in responder rate
66.7
2-Sided
95
43.34
90.15
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.
Superiority
OG000
OG001
The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.
Regression, Logistic
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.
<0.0001
The p-value for the primary analysis was evaluated at a 2-sided significance level of 0.025 for each CZP dose vs PBO.
Odds Ratio (OR)
38.193
2-Sided
97.5
6.113
238.619
Superiority
OG000
OG002
The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.
Regression, Logistic
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.
<0.0001
The p-value for the primary analysis was evaluated at a 2-sided significance level of 0.025 for each CZP dose vs PBO.
Odds Ratio (OR)
69.580
2-Sided
97.5
11.138
434.659
Superiority
OG001
CZP 200 mg Q2W (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.
OG002
CZP 400 mg Q2W (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.
Units
Counts
Participants
OG00026
OG00148
OG00253
Title
Denominators
Categories
Title
Measurements
OG0000.2
OG00153.8
OG00275.7
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.
Regression, Logistic
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.
Estimated difference in responder rate
53.6
2-Sided
95
30.67
76.47
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.
Superiority
OG000
OG002
The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.
Regression, Logistic
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.
Estimated difference in responder rate
75.5
2-Sided
95
51.95
99.04
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.
Superiority
OG000
OG001
The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.
Regression, Logistic
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.
<0.0001
The p-value for the primary analysis was evaluated at a 2-sided significance level of 0.025 for each CZP dose vs PBO.
Odds Ratio (OR)
38.696
2-Sided
97.5
6.047
247.634
Superiority
OG000
OG002
The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.
Regression, Logistic
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.
<0.0001
The p-value for the primary analysis was evaluated at a 2-sided significance level of 0.025 for each CZP dose vs PBO.
Odds Ratio (OR)
100.459
2-Sided
97.5
15.540
649.437
Superiority
OG001
CZP 200 mg Q2W (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.
OG002
CZP 400 mg Q2W (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.
Units
Counts
Participants
OG00026
OG00148
OG00253
Title
Denominators
Categories
Title
Measurements
OG000-0.3± 1.0
OG001-6.8± 0.7
OG002-6.8± 0.7
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.
ANCOVA
ANCOVA model of change from Baseline DLQI score with treatment group and prior biologic exposure as factors and Baseline DLQI score as a covariate.
<0.0001
p-value obtained for each treatment group comparison tested at a significance level of 0.025 in the fixed sequence testing procedure.
Adjusted Mean Treatment Difference
-6.5
2-Sided
97.5
-9.100
-3.844
Superiority
OG000
OG002
The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.
ANCOVA
ANCOVA model of change from Baseline DLQI score with treatment group and prior biologic exposure as factors and Baseline DLQI score as a covariate.
<0.0001
p-value obtained for each treatment group comparison tested at a significance level of 0.025 in the fixed sequence testing procedure.
Adjusted Mean Treatment Difference
-6.5
2-Sided
97.5
-9.099
-3.910
Superiority
OG002
CZP 400 mg Q2W (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.
Units
Counts
Participants
OG00026
OG00148
OG00253
Title
Denominators
Categories
Title
Measurements
OG0000.2± 0.5
OG001-2.9± 0.4
OG002-4.0± 0.3
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.
ANCOVA
ANCOVA model of change from Baseline Itch NRS with treatment group and prior biologic exposure as factors and Baseline Itch NRS as a covariate.
<0.0001
p-value obtained for each treatment group comparison tested at a significance level of 0.025 in the fixed sequence testing procedure.
Adjusted Mean Treatment Difference
-3.1
2-Sided
95
-4.265
-2.002
Superiority
OG000
OG002
The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.
ANCOVA
ANCOVA model of change from Baseline Itch NRS with treatment group and prior biologic exposure as factors and Baseline Itch NRS as a covariate.
<0.0001
p-value obtained for each treatment group comparison tested at a significance level of 0.025 in the fixed sequence testing procedure.
Adjusted Mean Treatment Difference
-4.2
2-Sided
95
-5.295
-3.069
Superiority
OG002
CZP 200 mg Q2W/CZP 400 mg Q4W (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.
Units
Counts
Participants
OG00028
OG00153
OG00220
Title
Denominators
Categories
Baseline
ParticipantsOG00028
ParticipantsOG00153
ParticipantsOG00220
Title
Measurements
OG000NA± NAValues were below the level of detection.
OG001NA± NAValues were below the level of detection.
OG002NA± NAValues were below the level of detection.
Week 2
ParticipantsOG00028
ParticipantsOG00153
ParticipantsOG00220
Title
Measurements
OG000
Week 4
ParticipantsOG00028
ParticipantsOG00152
ParticipantsOG00220
Title
Measurements
OG000
Week 6
ParticipantsOG00028
ParticipantsOG00152
ParticipantsOG00220
Title
Measurements
OG000
Week 8
ParticipantsOG00028
ParticipantsOG00152
ParticipantsOG00220
Title
Measurements
OG000
Week 12
ParticipantsOG00026
ParticipantsOG00150
ParticipantsOG00220
Title
Measurements
OG000
Week 16
ParticipantsOG00026
ParticipantsOG00151
ParticipantsOG00220
Title
Measurements
OG000
Week 24
ParticipantsOG00021
ParticipantsOG00149
ParticipantsOG00220
Title
Measurements
OG000
Week 32
ParticipantsOG00020
ParticipantsOG00149
ParticipantsOG00219
Title
Measurements
OG000
Week 40
ParticipantsOG00019
ParticipantsOG00148
ParticipantsOG00217
Title
Measurements
OG000
Week 52
ParticipantsOG00019
ParticipantsOG00145
ParticipantsOG00217
Title
Measurements
OG000
Early Withdrawal
ParticipantsOG0004
ParticipantsOG0016
ParticipantsOG0020
Title
Measurements
OG000
Safety Follow-Up
ParticipantsOG00027
ParticipantsOG00153
ParticipantsOG00220
Title
Measurements
OG000
CZP 400 mg Q2W/CZP 400 mg Q2W (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.
OG002
CZP 200 mg Q2W/CZP 400 mg Q4W (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.