Plaque Psoriasis, Psoriasis
Conditions
Keywords
Certolizumab Pegol, Cimzia, Psoriasis
Brief summary
The purpose of this study is to investigate the efficacy and safety of two dose levels of certolizumab pegol compared to active comparator and placebo in adults with moderate to severe chronic plaque psoriasis.
Detailed description
This study consists of the following Periods: * Initial Treatment Period from Week 0 to Week 16 * Maintenance Treatment Period from Week 16 to Week 48 * Open-label Extension Treatment Period (96 weeks) * Safety Follow-Up (10 weeks)
Interventions
BIOLOGICALCertolizumab Pegol
* Active Substance: Certolizumab Pegol * Pharmaceutical Form: Solution for injection in pre-filled syringe * Concentration: 200 mg/ mL * Route of Administration: Subcutaneous use
BIOLOGICALEtanercept
* Active Substance: Etanercept * Pharmaceutical Form: Solution for injection in pre-filled syringe * Concentration: 50 mg / mL * Route of Administration: Subcutaneous use
OTHERPlacebo
* Active Substance: Placebo * Pharmaceutical Form: Solution for injection in pre-filled syringe * Concentration: 0.9 % saline * Route of Administration: Subcutaneous use
Sponsors
UCB Biopharma S.P.R.L.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Provided informed consent * Adult men or women \>= 18 years * Chronic plaque psoriasis for at least 6 months * Baseline psoriasis activity and severity index \>= 12 and body surface area \>= 10 % and Physician's Global Assessments score \>= 3 * Candidate for systemic psoriasis therapy and/or phototherapy and/or chemophototherapy * Other protocol-defined inclusion criteria may apply
Exclusion criteria
* Erythrodermic, guttate, generalized pustular form of psoriasis * History of current, chronic, or recurrent infections of viral, bacterial, or fungal origin as described in the protocol * Congestive heart failure * History of a lymphoproliferative disorder including lymphoma or current signs and symptoms suggestive of lymphoproliferative disease * Concurrent malignancy or a history of malignancy as described in the protocol * History of, or suspected, demyelinating disease of the central nervous system (e.g., multiple sclerosis or optic neuritis) * Female subjects who are breastfeeding, pregnant, or plan to become pregnant during the study or within 5 months following last dose of study drug in the UK, Czech Republic, Germany, and France, and within 3 months for all other countries. Male subjects who are planning a partner pregnancy during the study or within 5 months following the last dose in France and within 10 weeks in all other countries * Any other condition which, in the Investigator's judgment, would make the subject unsuitable for participation in the study * Other protocol-defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI75) Response at Week 12 | Week 12 | The PASI75 response assessments are 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
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI90) Response at Week 12 | Week 12 | The PASI90 response assessments are 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. |
| Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI75) Response at Week 16 | Week 16 | The PASI75 response assessments are 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. |
| Proportion of Subjects Who Achieve a Physician's Global Assessment (PGA) Clear or Almost Clear Response (With at Least 2 Category Improvement) at Week 12 | Week 12 | 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. |
| Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI90) Response at Week 16 | Week 16 | The PASI90 response assessments are 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. |
| Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI75) Response at Week 48 for Those Achieving PASI75 at Week 16 | Week 48 | The PASI75 response assessments are 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. |
| Proportion 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 | 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. |
Countries
Bulgaria, Czechia, France, Germany, Hungary, Netherlands, Poland, United Kingdom, United States
Participant flow
Recruitment details
This study started to enroll participants in February 2015, from multiple sites in Europe and United States and concluded in December 2018. 559 participants are included in the Randomized Set (RS) shown in the Participant Flow.
Pre-assignment details
The study included a Screening Period, an Initial Treatment Period up to Week 16, a Maintenance Treatment Period up to Week 48, an Open-Label Extension Treatment Period up to Week 144 and a Safety Follow-up Period up to Week 157. The Participants Flow refers to the Randomized Set, the Maintenance Set and the Open Label Set.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Q2W Placebo subcutaneous (sc) injections every 2 weeks (Q2W) through Week 14. Treatment received from Week 16-48 is based on initial treatment and response to treatment:
•PASI75 responders at Week 16 continued to receive blinded Placebo. PASI75 non-responders at Week 16 were removed from blinded study medication and escaped to Certolizumab pegol (CZP) 400 mg Q2W. Participants who received unblinded CZP 400 mg Q2W for 16 weeks and did not achieve a PASI50 response were withdrawn from the study.
Participants could enter a 96-week open-label extension period after completing the Maintenance Period (Weeks 16-48) and receive CZP under certain conditions. | 57 |
| Etanercept Etanercept (ETN) 50 mg subcutaneous (sc) injections twice per week throughout Week 11.5.
•PASI75 responders at Week 16 were re-randomized to either CZP (loading dose of 400 mg at Weeks 16, 18, and 20 followed by 200 mg Q2W) or Placebo Q2W. Participants who did not achieve a PASI75 response at Week 16 escaped to CZP 400 mg Q2W.
Participants who received unblinded CZP 400 mg Q2W for 16 weeks and did not achieve a PASI50 response were withdrawn from the study. Participants could enter a 96-week open-label extension period after completing the Maintenance Period and receive CZP under certain conditions. | 170 |
| CZP 200 mg Q2W CZP 400 mg injections at Weeks 0, 2, 4, followed by CZP 200 mg every 2 weeks (Q2W) from Week 6 to Week 14. Treatment received from Week 16-48 is based on initial treatment and response to treatment:
•PASI75 responders at Week 16 were re-randomized to receive either CZP 200 mg Q2W or CZP 400 mg every 4 weeks (Q4W); with Placebo administered on alternate dosing weeks to maintain the blind) Or Placebo Q2W. Participants who did not achieve a PASI75 response at Week 16 were removed from blinded study medication and escaped to CZP 400 mg Q2W.
Participants who received unblinded CZP 400 mg Q2W for 16 weeks and did not achieve a PASI50 response were withdrawn from the study. Participants could enter a 96-week open-label extension period after completing the Maintenance Period and receive CZP under certain conditions. | 165 |
| CZP 400 mg Q2W CZP 400 mg injections every 2 weeks (Q2W) through Week 14. Treatment received from Week 16-48 is based on initial treatment and response to treatment:
•PASI75 responders at Week 16 were re-randomized to CZP 200 mg Q2W or CZP 400 mg Q2W or Placebo Q2W. Participants who did not achieve a PASI75 response at Week 16 were removed from blinded study medication and escaped to CZP 400 mg Q2W.
Participants who received unblinded CZP 400 mg Q2W for 16 weeks and did not achieve a PASI50 response were withdrawn from the study. Participants could enter a 96-week open-label extension period after completing the Maintenance Period and receive CZP under certain conditions. | 167 |
| Total Title | 559 |
| Total | 1,118 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 | FG017 | FG018 | FG019 | FG020 | FG021 | FG022 | FG023 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Initial Period (Baseline to Week 16) | Adverse Event | 0 | 4 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Initial Period (Baseline to Week 16) | Lack of Efficacy | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Initial Period (Baseline to Week 16) | Lost to Follow-up | 1 | 2 | 1 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Initial Period (Baseline to Week 16) | Non-compliance | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Initial Period (Baseline to Week 16) | Protocol Violation | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Initial Period (Baseline to Week 16) | Subject missed 3 visits | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Initial Period (Baseline to Week 16) | Withdrawal by Subject | 1 | 2 | 3 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Maintenance Period (Week 16 to Week 48) | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 0 | 0 | 0 | 0 | 1 | 4 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Maintenance Period (Week 16 to Week 48) | Adverse events and alcohol problem | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Maintenance Period (Week 16 to Week 48) | Did not achieve PASI50 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 3 | 8 | 4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Maintenance Period (Week 16 to Week 48) | Lack of Efficacy | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Maintenance Period (Week 16 to Week 48) | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Maintenance Period (Week 16 to Week 48) | Moved out of state | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Maintenance Period (Week 16 to Week 48) | Patient request due to non-compliance | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Maintenance Period (Week 16 to Week 48) | Patient's decisions | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Maintenance Period (Week 16 to Week 48) | Sponsor decision due to non-compliance | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Maintenance Period (Week 16 to Week 48) | Unavailability due to business trip | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Maintenance Period (Week 16 to Week 48) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 0 | 1 | 2 | 0 | 2 | 5 | 2 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Maintenance Period (Week 16 to Week 48) | Withdrawn by Sponsor | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Open-Label Period (Week 48 to Week 144) | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 6 | 2 | 3 | 13 | 3 | 3 |
| Open-Label Period (Week 48 to Week 144) | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 1 | 0 | 0 |
| Open-Label Period (Week 48 to Week 144) | Lack of Efficacy | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 |
| Open-Label Period (Week 48 to Week 144) | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 2 | 3 | 0 | 1 | 1 | 1 |
| Open-Label Period (Week 48 to Week 144) | No efficacy of study medication | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Open-Label Period (Week 48 to Week 144) | No PASI50 response | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 4 | 2 | 3 |
| Open-Label Period (Week 48 to Week 144) | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Open-Label Period (Week 48 to Week 144) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 1 | 0 | 10 | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo Q2W | Etanercept | CZP 200 mg Q2W | CZP 400 mg Q2W | Total Title |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 3 Participants |
| Age, Categorical >=65 years | 4 Participants | 13 Participants | 12 Participants | 11 Participants | 40 Participants |
| Age, Categorical Between 18 and 65 years | 53 Participants | 156 Participants | 153 Participants | 154 Participants | 516 Participants |
| Age, Continuous | 46.5 years STANDARD_DEVIATION 12.5 | 44.6 years STANDARD_DEVIATION 14.1 | 46.7 years STANDARD_DEVIATION 13.5 | 45.4 years STANDARD_DEVIATION 12.4 | 45.7 years STANDARD_DEVIATION 13.3 |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 3 Participants | 3 Participants | 7 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 3 Participants | 2 Participants | 2 Participants | 7 Participants |
| Race/Ethnicity, Customized Other/mixed | 0 Participants | 3 Participants | 2 Participants | 0 Participants | 5 Participants |
| Race/Ethnicity, Customized White | 57 Participants | 163 Participants | 158 Participants | 162 Participants | 540 Participants |
| Sex: Female, Male Female | 23 Participants | 43 Participants | 52 Participants | 60 Participants | 178 Participants |
| Sex: Female, Male Male | 34 Participants | 127 Participants | 113 Participants | 107 Participants | 381 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 128 | 0 / 168 | 2 / 373 | 1 / 412 | 0 / 44 |
| other Total, other adverse events | 42 / 128 | 37 / 168 | 139 / 373 | 158 / 412 | 11 / 44 |
| serious Total, serious adverse events | 8 / 128 | 1 / 168 | 34 / 373 | 51 / 412 | 5 / 44 |
Outcome results
Primary
Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI75) Response at Week 12
The PASI75 response assessments are 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 12
Population: The Randomized Set (RS) consisted of all participants randomized into the study.~Missing data were handled using the Markov Chain Monte Carlo (MCMC) method for multiple imputation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Q2W (RS) | Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI75) Response at Week 12 | 5.0 percentage of participants |
| Etanercept (RS) | Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI75) Response at Week 12 | 53.3 percentage of participants |
| CZP 200 mg Q2W (RS) | Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI75) Response at Week 12 | 61.3 percentage of participants |
| CZP 400 mg Q2W (RS) | Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI75) Response at Week 12 | 66.7 percentage of participants |
Comparison: The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.95% CI: [52.1, 71.2]Regression, Logistic
Comparison: The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.95% CI: [46.4, 66]Regression, Logistic
Comparison: The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.p-value: <0.000195% CI: [11.312, 127.576]Regression, Logistic
Comparison: The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.p-value: <0.000195% CI: [8.971, 100.481]Regression, Logistic
Comparison: The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.95% CI: [2.7, 24.1]Regression, Logistic
Comparison: The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.95% CI: [-2.9, 18.9]Regression, Logistic
Comparison: The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.p-value: =0.015295% CI: [1.114, 2.768]Regression, Logistic
Comparison: The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.p-value: =0.152395% CI: [0.886, 2.175]Regression, Logistic
Secondary
Proportion of Subjects Who Achieve a Physician's Global Assessment (PGA) Clear or Almost Clear Response (With at Least 2 Category Improvement) at Week 12
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 12
Population: The Randomized Set (RS) consisted of all participants randomized into the study.~Missing data were handled using the Markov Chain Monte Carlo (MCMC) method for multiple imputation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Q2W (RS) | Proportion of Subjects Who Achieve a Physician's Global Assessment (PGA) Clear or Almost Clear Response (With at Least 2 Category Improvement) at Week 12 | 1.9 percentage of participants |
| Etanercept (RS) | Proportion of Subjects Who Achieve a Physician's Global Assessment (PGA) Clear or Almost Clear Response (With at Least 2 Category Improvement) at Week 12 | 39.2 percentage of participants |
| CZP 200 mg Q2W (RS) | Proportion of Subjects Who Achieve a Physician's Global Assessment (PGA) Clear or Almost Clear Response (With at Least 2 Category Improvement) at Week 12 | 39.8 percentage of participants |
| CZP 400 mg Q2W (RS) | Proportion of Subjects Who Achieve a Physician's Global Assessment (PGA) Clear or Almost Clear Response (With at Least 2 Category Improvement) at Week 12 | 50.3 percentage of participants |
Comparison: The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.95% CI: [39.33, 57.63]Regression, Logistic
Comparison: The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.95% CI: [28.88, 46.96]Regression, Logistic
Comparison: The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.p-value: <0.000195% CI: [7.787, 404.555]Regression, Logistic
Comparison: The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.p-value: =0.000495% CI: [5.061, 264.196]Regression, Logistic
Secondary
Proportion of Subjects Who Achieve a Physician's Global Assessment (PGA) Clear or Almost Clear Response (With at Least 2 Category Improvement) at Week 16
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
Population: The Randomized Set (RS) consisted of all participants randomized into the study.~Missing data were handled using the Markov Chain Monte Carlo (MCMC) method for multiple imputation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Q2W (RS) | Proportion of Subjects Who Achieve a Physician's Global Assessment (PGA) Clear or Almost Clear Response (With at Least 2 Category Improvement) at Week 16 | 3.4 percentage of participants |
| Etanercept (RS) | Proportion of Subjects Who Achieve a Physician's Global Assessment (PGA) Clear or Almost Clear Response (With at Least 2 Category Improvement) at Week 16 | 48.3 percentage of participants |
| CZP 200 mg Q2W (RS) | Proportion of Subjects Who Achieve a Physician's Global Assessment (PGA) Clear or Almost Clear Response (With at Least 2 Category Improvement) at Week 16 | 58.4 percentage of participants |
Comparison: The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.95% CI: [45.59, 64.35]Regression, Logistic
Comparison: The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.95% CI: [35.39, 54.49]Regression, Logistic
Comparison: The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.p-value: <0.000195% CI: [9.741, 170.198]Regression, Logistic
Comparison: The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.p-value: <0.000195% CI: [6.504, 113.453]Regression, Logistic
Secondary
Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI75) Response at Week 16
The PASI75 response assessments are 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
Population: The Randomized Set (RS) consisted of all participants randomized into the study.~Missing data were handled using the Markov Chain Monte Carlo (MCMC) method for multiple imputation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Q2W (RS) | Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI75) Response at Week 16 | 3.8 percentage of participants |
| Etanercept (RS) | Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI75) Response at Week 16 | 68.2 percentage of participants |
| CZP 200 mg Q2W (RS) | Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI75) Response at Week 16 | 74.7 percentage of participants |
Comparison: The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.95% CI: [62.15, 79.59]Regression, Logistic
Comparison: The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.95% CI: [55.12, 73.63]Regression, Logistic
Comparison: The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.p-value: <0.000195% CI: [17.952, 324.094]Regression, Logistic
Comparison: The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.p-value: <0.000195% CI: [13.135, 233.782]Regression, Logistic
Secondary
Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI75) Response at Week 48 for Those Achieving PASI75 at Week 16
The PASI75 response assessments are 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 48
Population: The Week 16 Randomized Set (WK16RS) consisted of all participants who achieved a PASI75 response at Week 16 and were re-randomized into the double-blind, placebo-controlled Maintenance Treatment Period.~Missing data were handled using non-response imputation (NRI) methods.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Q2W (RS) | Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI75) Response at Week 48 for Those Achieving PASI75 at Week 16 | 100 percentage of participants |
| Etanercept (RS) | Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI75) Response at Week 48 for Those Achieving PASI75 at Week 16 | 8.3 percentage of participants |
| CZP 200 mg Q2W (RS) | Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI75) Response at Week 48 for Those Achieving PASI75 at Week 16 | 82.0 percentage of participants |
| CZP 400 mg Q2W (RS) | Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI75) Response at Week 48 for Those Achieving PASI75 at Week 16 | 45.5 percentage of participants |
| CZP 200 mg Q2W/CZP 200 mg Q2W (WK16RS) | Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI75) Response at Week 48 for Those Achieving PASI75 at Week 16 | 79.5 percentage of participants |
| CZP 200 mg Q2W/CZP 400 mg Q4W (WK16RS) | Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI75) Response at Week 48 for Those Achieving PASI75 at Week 16 | 88.6 percentage of participants |
| CZP 400 mg Q2W/Placebo Q2W (WK16RS) | Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI75) Response at Week 48 for Those Achieving PASI75 at Week 16 | 36.0 percentage of participants |
| CZP 400 mg Q2W/CZP 200 mg Q2W (WK16RS) | Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI75) Response at Week 48 for Those Achieving PASI75 at Week 16 | 80.0 percentage of participants |
| CZP 400 mg Q2W/CZP 400 mg Q2W (WK16RS) | Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI75) Response at Week 48 for Those Achieving PASI75 at Week 16 | 98.0 percentage of participants |
Secondary
Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI90) Response at Week 12
The PASI90 response assessments are 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 12
Population: The Randomized Set (RS) consisted of all participants randomized into the study.~Missing data were handled using the Markov Chain Monte Carlo (MCMC) method for multiple imputation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Q2W (RS) | Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI90) Response at Week 12 | 0.2 percentage of participants |
| Etanercept (RS) | Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI90) Response at Week 12 | 27.1 percentage of participants |
| CZP 200 mg Q2W (RS) | Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI90) Response at Week 12 | 31.2 percentage of participants |
| CZP 400 mg Q2W (RS) | Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI90) Response at Week 12 | 34.0 percentage of participants |
Comparison: The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.95% CI: [20.68, 46.98]Regression, Logistic
Comparison: The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.95% CI: [18.18, 43.8]Regression, Logistic
Comparison: The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.p-value: <0.000195% CI: [8.407, 189.828]Regression, Logistic
Comparison: The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.p-value: <0.000195% CI: [7.363, 167.179]Regression, Logistic
Secondary
Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI90) Response at Week 16
The PASI90 response assessments are 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
Population: The Randomized Set (RS) consisted of all participants randomized into the study.~Missing data were handled using the Markov Chain Monte Carlo (MCMC) method for multiple imputation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Q2W (RS) | Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI90) Response at Week 16 | 0.3 percentage of participants |
| Etanercept (RS) | Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI90) Response at Week 16 | 39.8 percentage of participants |
| CZP 200 mg Q2W (RS) | Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI90) Response at Week 16 | 49.1 percentage of participants |
Comparison: The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.95% CI: [34.22, 63.41]Regression, Logistic
Comparison: The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.95% CI: [25.58, 53.38]Regression, Logistic
Comparison: The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.p-value: <0.000195% CI: [14.65, 356.602]Regression, Logistic
Comparison: The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.p-value: <0.000195% CI: [10.002, 245.256]Regression, Logistic