Generalized Pustular Psoriasis and Erythrodermic Psoriasis, Moderate to Severe Psoriasis
Conditions
Keywords
Psoriasis, PSO, Chronic plaque psoriasis, Certolizumb Pegol, Cimzia, Generalized pustular psoriasis and erythrodermic psoriasis
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.
Interventions
OTHERPlacebo
* Pharmaceutical Form: Solution for injection in pre-filled syringe * Concentration: 0.9 % saline * Route of Administration: Subcutaneous use Q2W
DRUGCertolizumab Pegol
* Pharmaceutical Form: Solution for injection in pre-filled syringe * Concentration: 200 mg/mL * 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
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject is male or female, \>= 20 years of age. * Institutional Review Board-approved written informed consent form is signed and dated by the subject. * Other protocol-defined inclusion criteria may apply. For subjects with moderate to severe chronic plaque psoriasis (PSO) * Chronic plaque psoriasis for at least 6 months. * Baseline Psoriasis Activity and Severity Index (PASI) \>=12 and Body Surface Area (BSA) affected by PSO \>=10% and Physician's Global Assessment (PGA) score of 3 or higher. * Candidates for systemic PSO therapy and/or phototherapy and/or chemophototherapy. For subjects with generalized pustular PSO or erythrodermic PSO * Diagnosis of generalized pustular PSO or erythrodermic PSO at Screening. * History of plaque-type PSO if subjects have a diagnosis of erythrodermic PSO. * Baseline BSA affected by PSO \>=80% if subjects have a diagnosis of erythrodermic PSO.
Exclusion criteria
* Female subject who is breastfeeding, pregnant, or plans to become pregnant during the study or within 5 months following last dose of study drug. Male subject who is planning a partner pregnancy during the study or within 5 months following the last dose of study drug. * Subject has guttate psoriasis or drug-induced psoriasis. For subjects with moderate to severe plaque psoriasis, erythrodermic or pustular forms of psoriasis also are excluded. * History of current, chronic, or recurrent infections of viral, bacterial, or fungal origin as described in the protocol. Also, subjects with a high risk of infection in the Investigator's opinion. * History of a lymphoproliferative disorder including lymphoma or current signs and symptoms suggestive of lymphoproliferative disease. * History of other malignancy or concurrent malignancy as described in the protocol. * Class III or IV congestive heart failure * History of, or suspected, demyelinating disease of the central nervous system (e.g., multiple sclerosis or optic neuritis). * Subject has any other condition which, in the Investigator's judgment, would make the subject unsuitable for inclusion in the study. * Concurrent medication restrictions as described in the protocol. * Subject with known tuberculosis (TB) infection, at high risk of acquiring TB infection, or with untreated latent tuberculosis infection (LTBI) or current or history of nontuberculous mycobacterial (NTMB) infection. * Subject has any protocol defined clinically significant laboratory abnormalities at the screening * Other protocol-defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Achieving a 75 % or Higher Improvement in Psoriasis Area and Severity Index (PASI) Score at Week 16 | Week 16 | The PASI75 response assessments were based on at least 75 % improvement in the PASI score from Baseline. This is a scoring system that averages the redness, thickness, and scaliness of the psoriatic lesions (on a 0-4 scale), and weights the resulting score by the area of skin involved. Body divided into 4 areas: head, arms, trunk to groin, and legs to top of buttocks. Assignment of an average score for the redness, thickness, and scaling for each of the 4 body areas with a score of 0 (clear) to 4 (very marked). Determining the percentage of skin covered with PSO for each of the body areas and converting to a 0 to 6 scale. Final PASI= average redness, thickness, and scaliness of the psoriatic skin lesions, multiplied by the involved psoriasis area score of the respective section, and weighted by the percentage of the person's affected skin for the respective section. The minimum possible PASI score is 0= no disease, the maximum score is 72= maximal disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Achieving a 90 % or Higher Improvement in Psoriasis Area and Severity Index (PASI) Score at Week 16 | Week 16 | The PASI90 response assessments were based on at least 90 % improvement in the PASI score from Baseline. This is a scoring system that averages the redness, thickness, and scaliness of the psoriatic lesions (on a 0-4 scale), and weights the resulting score by the area of skin involved. Body divided into 4 areas: head, arms, trunk to groin, and legs to top of buttocks. Assignment of an average score for the redness, thickness, and scaling for each of the 4 body areas with a score of 0 (clear) to 4 (very marked). Determining the percentage of skin covered with PSO for each of the body areas and converting to a 0 to 6 scale. Final PASI= average redness, thickness, and scaliness of the psoriatic skin lesions, multiplied by the involved psoriasis area score of the respective section, and weighted by the percentage of the person's affected skin for the respective section. The minimum possible PASI score is 0= no disease, the maximum score is 72= maximal disease. |
| Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16 | Baseline and Week 16 | This Outcome Measure applied to participants with moderate to severe chronic plaque Psoriasis (PSO). The DLQI is a subject-reported questionnaire designed for use in adult participants with PSO. The DLQI is a skin disease-specific questionnaire aimed at the evaluation of how symptoms and treatment affect patients' health related quality of life (HRQoL). This instrument asked participants about symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. It has been shown to be valid and reproducible in PSO patients. The DLQI score ranges from 0 to 30 with higher scores indicating lower HRQoL. A higher than or equal to (\>=) 4-point change in the DLQI score (DLQI response) has been reported to be meaningful for the patient (within-patient minimal important difference Basra et al, 2015) a DLQI absolute score of lower than or equal to (=\<) 1 indicates DLQI remission (i.e., no or small impact of the disease on HRQoL). |
| Percentage of Subjects Who Achieve a Physician's Global Assessment (PGA) Clear or Almost Clear Response (With at Least 2-category Improvement) at Week 16 | Week 16 | This Outcome Measure applied to participants with moderate to severe chronic plaque Psoriasis (PSO). The Investigator assessed the overall severity of Psoriasis (PSO) using the following 5-point scale: 0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe. |
| Plasma Concentration of Certolizumab Pegol (CZP) | Blood samples were collected at Baseline (Week 0) and at Weeks 2, 4, 6, 8, 12, 16, 24, 32, 40, 52, 60 | Plasma concentration was expressed in micrograms per milliliter (μg/mL). Values below Lower Limit of Quantification (LLOQ) were set to half the LLOQ to present summaries. The geometric mean and geometric coefficient of variation were only displayed if at least 2/3 of the data were above the LLOQ. |
| Percentage of Participants With Positive Anti-Certolizumab Pegol-antibody Levels in Plasma | Blood samples will be collected at Baseline (Week 0) and at Weeks 2, 4, 6, 8, 12, 16, 24, 32, 40, 52, 60 | A pre-anti-drug (CZP) antibody (ADA) positive subject was defined as having a confirmed positive sample at Baseline. A pre-ADA negative subject was defined as having a Screening below the cut point (BCP) sample, or a screening above the cut point (ACP) sample, but not confirmed positive at Baseline. A treatment-emergent ADA positive subject was defined as either 1) pre-ADA negative subjects having at least 1 ADA confirmed positive sample or 2) pre-ADA positive subjects with at least 1 sample with greater then or equal to (\>=) 1.67-fold increase from Baseline on CZP treatment. |
| Change From Baseline in Itch Numeric Rating Scale at Week 16 | Baseline and Week 16 | This Outcome Measure applied to participants with moderate to severe chronic plaque Psoriasis (PSO). The Itch Numeric Rating Scale (NRS) has been developed as a simple, single item instrument to assess the patient-reported severity of itch at its most intense during the past 24h period. Participants indicate itch severity by circling the integer that best describes the worst level of itching due to PSO in the past 24h period on an 11-point scale anchored at 0, representing no itching and 10, representing worst itch imaginable (Kimball et al, 2016). |
Countries
Japan
Participant flow
Recruitment details
The study started to enroll patients in February 2017 and concluded in January 2019.
Pre-assignment details
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)
Participants by arm
| Arm | Count |
|---|---|
| Placebo This arm consisted of participants who received Placebo subcutaneous (sc) injection every two weeks (Q2W) during the Initial Period. | 26 |
| 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. | 48 |
| 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. | 53 |
| Total Title | 127 |
| Total | 254 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Initial Period (Week 0 to Week 16) | Adverse Event | 2 | 0 | 1 | 0 | 0 | 0 | 0 |
| Initial Period (Week 0 to Week 16) | Protocol Violation | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Initial Period (Week 0 to Week 16) | Withdrawal by Subject | 1 | 1 | 1 | 0 | 0 | 0 | 0 |
| Maintenance Period (Week 16 to Week 52) | Adverse Event | 0 | 0 | 0 | 1 | 2 | 1 | 1 |
| Maintenance Period (Week 16 to Week 52) | Difficulty in going to hospital | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Maintenance Period (Week 16 to Week 52) | Lack of Efficacy | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Maintenance Period (Week 16 to Week 52) | Protocol Violation | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Maintenance Period (Week 16 to Week 52) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | CZP 200 mg Q2W | CZP 400 mg Q2W | Placebo | Total Title |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 8 Participants | 4 Participants | 2 Participants | 14 Participants |
| Age, Categorical Between 18 and 65 years | 40 Participants | 49 Participants | 24 Participants | 113 Participants |
| Age, Continuous | 48.43 years STANDARD_DEVIATION 13.47 | 52.43 years STANDARD_DEVIATION 11.59 | 47.93 years STANDARD_DEVIATION 11.37 | 50.00 years STANDARD_DEVIATION 12.37 |
| Race/Ethnicity, Customized Asian (Japanese only) | 48 Participants | 53 Participants | 26 Participants | 127 Participants |
| Sex: Female, Male Female | 12 Participants | 11 Participants | 5 Participants | 28 Participants |
| Sex: Female, Male Male | 36 Participants | 42 Participants | 21 Participants | 99 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 | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 0 / 72 | 0 / 20 | 0 / 72 | 0 / 64 | 0 / 122 |
| other Total, other adverse events | 17 / 26 | 41 / 72 | 15 / 20 | 48 / 72 | 45 / 64 | 91 / 122 |
| serious Total, serious adverse events | 1 / 26 | 2 / 72 | 0 / 20 | 2 / 72 | 6 / 64 | 8 / 122 |
Outcome results
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.
Time frame: Week 16
Population: The Full Analysis Set (FAS) consisted of all participants in the Randomized Set (RS) who received at least 1 dose of the study medication and had valid efficacy assessments for Baseline and for at least 1 post-Baseline visit.~Missing data were handled using the Markov Chain Monte Carlo (MCMC) method for multiple imputation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (FAS) | Percentage of Subjects Achieving a 75 % or Higher Improvement in Psoriasis Area and Severity Index (PASI) Score at Week 16 | 7.9 percentage of participants |
| CZP 200 mg Q2W (FAS) | Percentage of Subjects Achieving a 75 % or Higher Improvement in Psoriasis Area and Severity Index (PASI) Score at Week 16 | 73.0 percentage of participants |
| CZP 400 mg Q2W (FAS) | Percentage of Subjects Achieving a 75 % or Higher Improvement in Psoriasis Area and Severity Index (PASI) Score at Week 16 | 87.1 percentage of participants |
Comparison: The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.95% CI: [48.22, 81.9]Regression, Logistic
Comparison: The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.95% CI: [65.1, 93.17]Regression, Logistic
Comparison: The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.p-value: <0.000197.5% CI: [5.129, 195.877]Regression, Logistic
Comparison: The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.p-value: <0.000197.5% CI: [11.739, 533.168]Regression, Logistic
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).
Time frame: Baseline and Week 16
Population: The Full Analysis Set (FAS) consisted of all participants in the RS who received at least 1 dose of the study medication and had valid efficacy assessments for Baseline and for at least 1 post-Baseline visit.~Missing data were handled using the last observation carried forward (LOCF) method for the DLQI.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (FAS) | Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16 | -0.3 Scores on a scale | Standard Error 1 |
| CZP 200 mg Q2W (FAS) | Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16 | -6.8 Scores on a scale | Standard Error 0.7 |
| CZP 400 mg Q2W (FAS) | Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16 | -6.8 Scores on a scale | Standard Error 0.7 |
Comparison: The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.p-value: <0.000197.5% CI: [-9.1, -3.844]ANCOVA
Comparison: The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.p-value: <0.000197.5% CI: [-9.099, -3.91]ANCOVA
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).
Time frame: Baseline and Week 16
Population: The Full Analysis Set (FAS) consisted of all participants in the RS who received at least 1 dose of the study medication and had valid efficacy assessments for Baseline and for at least 1 post-Baseline visit.~Missing data were handled using the last observation carried forward (LOCF) method for the Itch Numeric Rating Scale.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (FAS) | Change From Baseline in Itch Numeric Rating Scale at Week 16 | 0.2 Scores on a scale | Standard Error 0.5 |
| CZP 200 mg Q2W (FAS) | Change From Baseline in Itch Numeric Rating Scale at Week 16 | -2.9 Scores on a scale | Standard Error 0.4 |
| CZP 400 mg Q2W (FAS) | Change From Baseline in Itch Numeric Rating Scale at Week 16 | -4.0 Scores on a scale | Standard Error 0.3 |
Comparison: The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.p-value: <0.000195% CI: [-4.265, -2.002]ANCOVA
Comparison: The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.p-value: <0.000195% CI: [-5.295, -3.069]ANCOVA
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.
Time frame: Blood samples will be collected at Baseline (Week 0) and at Weeks 2, 4, 6, 8, 12, 16, 24, 32, 40, 52, 60
Population: The Pharmacokinetics Per-Protocol Set (PK-PPS) consisted of all participants in the RS who took at least 1 dose of the study medication and provided at least 1 quantifiable CZP plasma concentration.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (FAS) | Percentage of Participants With Positive Anti-Certolizumab Pegol-antibody Levels in Plasma | 100 percentage of participants |
| CZP 200 mg Q2W (FAS) | Percentage of Participants With Positive Anti-Certolizumab Pegol-antibody Levels in Plasma | 96.2 percentage of participants |
| CZP 400 mg Q2W (FAS) | Percentage of Participants With Positive Anti-Certolizumab Pegol-antibody Levels in Plasma | 90.0 percentage of participants |
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.
Time frame: Week 16
Population: The Full Analysis Set (FAS) consisted of all participants in the RS who received at least 1 dose of the study medication and had valid efficacy assessments for Baseline and for at least 1 post-Baseline visit.~Missing data were handled using the Markov Chain Monte Carlo (MCMC) method for multiple imputation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (FAS) | Percentage of Subjects Achieving a 90 % or Higher Improvement in Psoriasis Area and Severity Index (PASI) Score at Week 16 | 0.2 percentage of participants |
| CZP 200 mg Q2W (FAS) | Percentage of Subjects Achieving a 90 % or Higher Improvement in Psoriasis Area and Severity Index (PASI) Score at Week 16 | 53.8 percentage of participants |
| CZP 400 mg Q2W (FAS) | Percentage of Subjects Achieving a 90 % or Higher Improvement in Psoriasis Area and Severity Index (PASI) Score at Week 16 | 75.7 percentage of participants |
Comparison: The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.p-value: <0.000197.5% CI: [6.047, 247.634]Regression, Logistic
Comparison: The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.95% CI: [30.67, 76.47]Regression, Logistic
Comparison: The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.95% CI: [51.95, 99.04]Regression, Logistic
Comparison: The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.p-value: <0.000197.5% CI: [15.54, 649.437]Regression, Logistic
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.
Time frame: Week 16
Population: The Full Analysis Set (FAS) consisted of all participants in the RS who received at least 1 dose of the study medication and had valid efficacy assessments for Baseline and for at least 1 post-Baseline visit.~Missing data were handled using the Markov Chain Monte Carlo (MCMC) method for multiple imputation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (FAS) | 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 | 0.0 percentage of participants |
| CZP 200 mg Q2W (FAS) | 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 | 52.7 percentage of participants |
| CZP 400 mg Q2W (FAS) | 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 | 66.7 percentage of participants |
Comparison: The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.95% CI: [29.95, 75.39]Regression, Logistic
Comparison: The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.95% CI: [43.34, 90.15]Regression, Logistic
Comparison: The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.p-value: <0.000197.5% CI: [6.113, 238.619]Regression, Logistic
Comparison: The primary and secondary efficacy endpoints were evaluated using a fixed-sequence testing procedure to account for multiplicity.p-value: <0.000197.5% CI: [11.138, 434.659]Regression, Logistic
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.
Time frame: Blood samples were collected at Baseline (Week 0) and at Weeks 2, 4, 6, 8, 12, 16, 24, 32, 40, 52, 60
Population: The Pharmacokinetics Per-Protocol Set (PK-PPS) consisted of all participants in the RS who took at least 1 dose of the study medication and provided at least 1 quantifiable CZP plasma concentration.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (FAS) | Plasma Concentration of Certolizumab Pegol (CZP) | Safety Follow-Up | 0.1739 µg/mL | Geometric Coefficient of Variation 757.5 |
| Placebo (FAS) | Plasma Concentration of Certolizumab Pegol (CZP) | Week 16 | 14.5995 µg/mL | Geometric Coefficient of Variation 405.5 |
| Placebo (FAS) | Plasma Concentration of Certolizumab Pegol (CZP) | Week 32 | 26.9398 µg/mL | Geometric Coefficient of Variation 48.8 |
| Placebo (FAS) | Plasma Concentration of Certolizumab Pegol (CZP) | Week 40 | 22.2790 µg/mL | Geometric Coefficient of Variation 68.3 |
| Placebo (FAS) | Plasma Concentration of Certolizumab Pegol (CZP) | Week 52 | 20.4541 µg/mL | Geometric Coefficient of Variation 90.8 |
| Placebo (FAS) | Plasma Concentration of Certolizumab Pegol (CZP) | Week 2 | 34.6417 µg/mL | Geometric Coefficient of Variation 28.3 |
| Placebo (FAS) | Plasma Concentration of Certolizumab Pegol (CZP) | Week 4 | 47.9241 µg/mL | Geometric Coefficient of Variation 45.6 |
| Placebo (FAS) | Plasma Concentration of Certolizumab Pegol (CZP) | Week 6 | 36.3003 µg/mL | Geometric Coefficient of Variation 286.7 |
| Placebo (FAS) | Plasma Concentration of Certolizumab Pegol (CZP) | Week 8 | 21.9292 µg/mL | Geometric Coefficient of Variation 621.4 |
| Placebo (FAS) | Plasma Concentration of Certolizumab Pegol (CZP) | Week 12 | 16.1907 µg/mL | Geometric Coefficient of Variation 300.7 |
| Placebo (FAS) | Plasma Concentration of Certolizumab Pegol (CZP) | Week 24 | 26.2596 µg/mL | Geometric Coefficient of Variation 52.8 |
| Placebo (FAS) | Plasma Concentration of Certolizumab Pegol (CZP) | Early Withdrawal | 0.8342 µg/mL | Geometric Coefficient of Variation 5520.7 |
| Placebo (FAS) | Plasma Concentration of Certolizumab Pegol (CZP) | Baseline | NA µg/mL | — |
| CZP 200 mg Q2W (FAS) | Plasma Concentration of Certolizumab Pegol (CZP) | Safety Follow-Up | 0.3760 µg/mL | Geometric Coefficient of Variation 1460.3 |
| CZP 200 mg Q2W (FAS) | Plasma Concentration of Certolizumab Pegol (CZP) | Baseline | NA µg/mL | — |
| CZP 200 mg Q2W (FAS) | Plasma Concentration of Certolizumab Pegol (CZP) | Early Withdrawal | 0.6115 µg/mL | Geometric Coefficient of Variation 49802.8 |
| CZP 200 mg Q2W (FAS) | Plasma Concentration of Certolizumab Pegol (CZP) | Week 2 | 35.2588 µg/mL | Geometric Coefficient of Variation 25.2 |
| CZP 200 mg Q2W (FAS) | Plasma Concentration of Certolizumab Pegol (CZP) | Week 24 | 51.6911 µg/mL | Geometric Coefficient of Variation 118.2 |
| CZP 200 mg Q2W (FAS) | Plasma Concentration of Certolizumab Pegol (CZP) | Week 4 | 47.0462 µg/mL | Geometric Coefficient of Variation 35.7 |
| CZP 200 mg Q2W (FAS) | Plasma Concentration of Certolizumab Pegol (CZP) | Week 6 | 41.2410 µg/mL | Geometric Coefficient of Variation 183 |
| CZP 200 mg Q2W (FAS) | Plasma Concentration of Certolizumab Pegol (CZP) | Week 52 | 54.1341 µg/mL | Geometric Coefficient of Variation 43.4 |
| CZP 200 mg Q2W (FAS) | Plasma Concentration of Certolizumab Pegol (CZP) | Week 8 | 39.9282 µg/mL | Geometric Coefficient of Variation 243.7 |
| CZP 200 mg Q2W (FAS) | Plasma Concentration of Certolizumab Pegol (CZP) | Week 12 | 46.9934 µg/mL | Geometric Coefficient of Variation 189.3 |
| CZP 200 mg Q2W (FAS) | Plasma Concentration of Certolizumab Pegol (CZP) | Week 32 | 44.5749 µg/mL | Geometric Coefficient of Variation 177.2 |
| CZP 200 mg Q2W (FAS) | Plasma Concentration of Certolizumab Pegol (CZP) | Week 16 | 48.3156 µg/mL | Geometric Coefficient of Variation 183.8 |
| CZP 200 mg Q2W (FAS) | Plasma Concentration of Certolizumab Pegol (CZP) | Week 40 | 50.9685 µg/mL | Geometric Coefficient of Variation 53.3 |
| CZP 400 mg Q2W (FAS) | Plasma Concentration of Certolizumab Pegol (CZP) | Week 4 | 48.3634 µg/mL | Geometric Coefficient of Variation 21.3 |
| CZP 400 mg Q2W (FAS) | Plasma Concentration of Certolizumab Pegol (CZP) | Baseline | NA µg/mL | — |
| CZP 400 mg Q2W (FAS) | Plasma Concentration of Certolizumab Pegol (CZP) | Safety Follow-Up | 0.1407 µg/mL | Geometric Coefficient of Variation 714.5 |
| CZP 400 mg Q2W (FAS) | Plasma Concentration of Certolizumab Pegol (CZP) | Week 12 | 23.8437 µg/mL | Geometric Coefficient of Variation 105.9 |
| CZP 400 mg Q2W (FAS) | Plasma Concentration of Certolizumab Pegol (CZP) | Week 2 | 33.2026 µg/mL | Geometric Coefficient of Variation 26 |
| CZP 400 mg Q2W (FAS) | Plasma Concentration of Certolizumab Pegol (CZP) | Week 8 | 33.4139 µg/mL | Geometric Coefficient of Variation 69 |
| CZP 400 mg Q2W (FAS) | Plasma Concentration of Certolizumab Pegol (CZP) | Week 52 | 15.9290 µg/mL | Geometric Coefficient of Variation 149.1 |
| CZP 400 mg Q2W (FAS) | Plasma Concentration of Certolizumab Pegol (CZP) | Week 24 | 7.7206 µg/mL | Geometric Coefficient of Variation 1747.5 |
| CZP 400 mg Q2W (FAS) | Plasma Concentration of Certolizumab Pegol (CZP) | Week 40 | 16.7013 µg/mL | Geometric Coefficient of Variation 231.1 |
| CZP 400 mg Q2W (FAS) | Plasma Concentration of Certolizumab Pegol (CZP) | Week 6 | 52.4876 µg/mL | Geometric Coefficient of Variation 38 |
| CZP 400 mg Q2W (FAS) | Plasma Concentration of Certolizumab Pegol (CZP) | Week 32 | 8.4148 µg/mL | Geometric Coefficient of Variation 1245.6 |
| CZP 400 mg Q2W (FAS) | Plasma Concentration of Certolizumab Pegol (CZP) | Week 16 | 18.1204 µg/mL | Geometric Coefficient of Variation 381.8 |