Chronic Plaque Psoriasis
Conditions
Keywords
chronic plaque psoriasis, anti TNFα, CDP870, Cimzia
Brief summary
A study to assess the safety and efficacy of 2 different doses of CDP870 versus placebo, administered during 12 weeks, to patients suffering from moderate to severe chronic plaque psoriasis, extended by a 12 to 24 week follow-up.
Interventions
DRUGCertolizumab Pegol
* Pharmaceutical Form: solution for injection in pre-filled syringe * Route of Administration: subcutaneous use
OTHERPlacebo
Matching Placebo to Certolizumab Pegol
Sponsors
UCB Pharma
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
* Adult men and women \> 18 years * Subjects with chronic plaque psoriasis stable for at least 3 months and moderate to severe for at least 6 months * Subjects with Psoriasis Area and Severity Index (PASI) ≥ 12 and Body Surface Area (BSA) ≥ 10 % * Subjects were candidates for systemic psoriasis therapy and/or phototherapy and/or photochemotherapy
Exclusion criteria
* Subjects with an erythrodermic, guttate, palmar or plantar, generalized pustular form of psoriasis * A history of chronic infection, recent serious or life-threatening infection (within six months, including herpes zoster), or any current sign or symptom that may indicate an infection (e.g. fever, cough); * White blood cell counts less than 4000/mm\^3 or more than 20000/mm\^3 * Suspected or diagnosed demyelinating disease of the central nervous system (e.g. multiple sclerosis or optic neuritis) * Systemic Lupus * Non respect of adequate wash out periods for treatments that might have an impact on the disease * Any associated disease that could be impacted by the study treatment intake * Any other condition, which in the Investigator's judgment would make the subject unsuitable for inclusion in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Achievement of Psoriasis Activity and Severity Index (PASI75) Response at Week 12 | Week 12 | Determining the PASI score involves the evaluation of erythema, infiltration, and desquamation and body surface area involvement over 4 body regions. These regions are the head, trunk, upper and lower extremities. PASI75 response at Week 12 is defined as a decrease in PASI score at Week 12 from Baseline of at least 75 %. |
| Achievement of a Physician's Global Assessment (PGA) of Clear or Almost Clear at Week 12 | Week 12 | The overall severity of the disease was evaluated using the following 6-point scale: 5 = Severe: Very marked plaque elevation, scaling, and/or erythema. 4 = Moderate to severe: Marked plaque elevation, scaling, and/or erythema. 3 = Moderate: Moderate plaque elevation, scaling, and/or erythema. 2 = Mild: Slight plaque elevation, scaling, and/or erythema 1 = Almost clear: Intermediate between mild and clear 0 = Clear: No signs of psoriasis (post-inflammatory hyperpigmentation may be present) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Relapse | During the 12-weeks Treatment Period | Time to relapse is defined as the time elapsed between the last dose and when maximal improvement in PASI from Baseline was reduced by \> 50 %. This variable is defined only for those patients who have achieved PASI75 at the end of the Treatment Period (Week 12). |
| Achievement of a Psoriasis Activity and Severity Index (PASI50) Response at Week 12 | Week 12 | Determining the PASI score involves the evaluation of erythema, infiltration, and desquamation and body surface area involvement over 4 body regions. These regions are the head, trunk, upper and lower extremities. PASI50 response at Week 12 is defined as a decrease in PASI score at Week 12 from Baseline of at least 50 %. |
| Achievement of a Psoriasis Activity and Severity Index (PASI90) Response at Week 12 | Week 12 | Determining the PASI score involves the evaluation of erythema, infiltration, and desquamation and body surface area involvement over 4 body regions. These regions are the head, trunk, upper and lower extremities. PASI90 response at Week 12 is defined as a decrease in PASI score at Week 12 from Baseline of at least 90 %. |
| Time to Psoriasis Activity and Severity Index 50 (PASI50) | During the 12-weeks Treatment Period | Time to PASI50 is defined as the time elapsed between the start of the Treatment Period (Week 0) and the first occurrence of PASI50 during the Treatment Period. This variable is defined only for those patients who have achieved PASI75 at the end of the Treatment Period (Week 12). |
| Percent of Body Surface Area (BSA) Affected by Psoriasis at Week 12 | Week 12 | Two methods were used for the evaluation of BSA: 1. The area of one side of a subject's flat closed hand was used to represent 1 % to the total body surface area (BSA) to estimate the extent of skin involvement in subjects with psoriasis 2. The rule of nines method assumed that the total BSA comprises head (9 %), anterior trunk (upper, 9 %; lower, 9 %), posterior trunk (upper, 9 %; lower, 9 %), each leg (anterior, 9 %; posterior, 9 %), each arm (9 %) and genitalia (1 %) |
| Absolute Change From Baseline in the Body Surface Area (BSA) Affected by Psoriasis at Week 12 | Baseline up to Week 12 | Two methods were used for the evaluation of BSA: 1. The area of one side of a subject's flat closed hand was used to represent 1 % to the total body surface area (BSA) to estimate the extent of skin involvement in subjects with psoriasis 2. The rule of nines method assumed that the total BSA comprises head (9 %), anterior trunk (upper, 9 %; lower, 9 %), posterior trunk (upper, 9 %; lower, 9 %), each leg (anterior, 9 %; posterior, 9 %), each arm (9 %) and genitalia (1 %) A positive value in Change from Baseline indicates an improvement from Baseline. The higher the positive value, the higher the change. |
| Time to Discontinuation From the Treatment Period Due to Lack of Efficacy or Worsening of Psoriasis | During the 12-week Treatment Period | — |
| Experience of a Rebound Effect Within 2 Months After Stopping Therapy | Within 2 months of stopping therapy | Rebound is defined as worsening of psoriasis over baseline value with more than 125 % or new pustular, erythrodermic or more inflammatory psoriasis within 2 months of stopping therapy. |
| Time to Psoriasis Activity and Severity Index 75 (PASI75) | During the 12-weeks Treatment Period | Time to PASI75 is defined as the time elapsed between the start of the Treatment Period (Week 0) and the first occurrence of PASI75 during the Treatment Period. This variable is defined only for those patients who have achieved PASI75 at the end of the Treatment Period (Week 12). |
Countries
France, Germany
Participant flow
Recruitment details
The study started to enroll patients in October 2005 and concluded in November 2006.
Pre-assignment details
The study included a 12-week Treatment Period and a 12 to 24-week Follow-up Period. Participant Flow refers to the Intention-to-treat Set.
Participants by arm
| Arm | Count |
|---|---|
| Placebo (ITT) Subcutaneous injections of Placebo every 2 weeks | 59 |
| Certolizumab Pegol 200 mg (ITT) Subcutaneous injections of 400 mg initial dose at week 0 with 200 mg every 2 weeks thereafter | 59 |
| Certolizumab Pegol 400 mg (ITT) Subcutaneous injections of 400 mg every 2 weeks | 58 |
| Total Title | 176 |
| Total | 352 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 0 |
| Overall Study | Lack of Efficacy | 14 | 7 | 0 |
| Overall Study | Lost to Follow-up | 1 | 2 | 0 |
| Overall Study | Other | 13 | 4 | 4 |
| Overall Study | Other reason | 2 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 3 |
Baseline characteristics
| Characteristic | Placebo (ITT) | Certolizumab Pegol 200 mg (ITT) | Certolizumab Pegol 400 mg (ITT) | Total Title |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 2 Participants | 3 Participants | 10 Participants |
| Age, Categorical Between 18 and 65 years | 54 Participants | 57 Participants | 55 Participants | 166 Participants |
| Age, Continuous | 43.30 years STANDARD_DEVIATION 12.78 | 43.26 years STANDARD_DEVIATION 10.12 | 43.64 years STANDARD_DEVIATION 12.36 | 43.40 years STANDARD_DEVIATION 11.74 |
| Sex: Female, Male Female | 22 Participants | 15 Participants | 16 Participants | 53 Participants |
| Sex: Female, Male Male | 37 Participants | 44 Participants | 42 Participants | 123 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 58 | 0 / 60 | 0 / 57 |
| other Total, other adverse events | 34 / 58 | 32 / 60 | 27 / 57 |
| serious Total, serious adverse events | 1 / 58 | 2 / 60 | 5 / 57 |
Outcome results
Primary
Achievement of a Physician's Global Assessment (PGA) of Clear or Almost Clear at Week 12
The overall severity of the disease was evaluated using the following 6-point scale: 5 = Severe: Very marked plaque elevation, scaling, and/or erythema. 4 = Moderate to severe: Marked plaque elevation, scaling, and/or erythema. 3 = Moderate: Moderate plaque elevation, scaling, and/or erythema. 2 = Mild: Slight plaque elevation, scaling, and/or erythema 1 = Almost clear: Intermediate between mild and clear 0 = Clear: No signs of psoriasis (post-inflammatory hyperpigmentation may be present)
Time frame: Week 12
Population: Intention-To-Treat (ITT) population consisting of all randomized subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (ITT) | Achievement of a Physician's Global Assessment (PGA) of Clear or Almost Clear at Week 12 | 1.7 percentage of subjects |
| Certolizumab Pegol 200 mg (ITT) | Achievement of a Physician's Global Assessment (PGA) of Clear or Almost Clear at Week 12 | 52.5 percentage of subjects |
| Certolizumab Pegol 400 mg (ITT) | Achievement of a Physician's Global Assessment (PGA) of Clear or Almost Clear at Week 12 | 72.4 percentage of subjects |
p-value: <0.00195% CI: [12.7, 1169.1]Regression, Logistic
p-value: <0.00195% CI: [31.4, 2999.2]Regression, Logistic
Primary
Achievement of Psoriasis Activity and Severity Index (PASI75) Response at Week 12
Determining the PASI score involves the evaluation of erythema, infiltration, and desquamation and body surface area involvement over 4 body regions. These regions are the head, trunk, upper and lower extremities. PASI75 response at Week 12 is defined as a decrease in PASI score at Week 12 from Baseline of at least 75 %.
Time frame: Week 12
Population: Intention-To-Treat (ITT) population consisting of all randomized subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (ITT) | Achievement of Psoriasis Activity and Severity Index (PASI75) Response at Week 12 | 6.8 percentage of subjects |
| Certolizumab Pegol 200 mg (ITT) | Achievement of Psoriasis Activity and Severity Index (PASI75) Response at Week 12 | 74.6 percentage of subjects |
| Certolizumab Pegol 400 mg (ITT) | Achievement of Psoriasis Activity and Severity Index (PASI75) Response at Week 12 | 82.8 percentage of subjects |
p-value: <0.00195% CI: [13.7, 150.3]Regression, Logistic
p-value: <0.00195% CI: [23.5, 292.6]Regression, Logistic
Secondary
Absolute Change From Baseline in the Body Surface Area (BSA) Affected by Psoriasis at Week 12
Two methods were used for the evaluation of BSA: 1. The area of one side of a subject's flat closed hand was used to represent 1 % to the total body surface area (BSA) to estimate the extent of skin involvement in subjects with psoriasis 2. The rule of nines method assumed that the total BSA comprises head (9 %), anterior trunk (upper, 9 %; lower, 9 %), posterior trunk (upper, 9 %; lower, 9 %), each leg (anterior, 9 %; posterior, 9 %), each arm (9 %) and genitalia (1 %) A positive value in Change from Baseline indicates an improvement from Baseline. The higher the positive value, the higher the change.
Time frame: Baseline up to Week 12
Population: ITT population consisting of all randomized subjects. The analysis was performed for week 12 using observed case data (i.e., no imputation was performed for missing data). By week 12, there were 29 patients who had prematurely discontinued the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (ITT) | Absolute Change From Baseline in the Body Surface Area (BSA) Affected by Psoriasis at Week 12 | 3.2 Percent of total Body surface area | Standard Deviation 11.9 |
| Certolizumab Pegol 200 mg (ITT) | Absolute Change From Baseline in the Body Surface Area (BSA) Affected by Psoriasis at Week 12 | 18.3 Percent of total Body surface area | Standard Deviation 15.1 |
| Certolizumab Pegol 400 mg (ITT) | Absolute Change From Baseline in the Body Surface Area (BSA) Affected by Psoriasis at Week 12 | 22.6 Percent of total Body surface area | Standard Deviation 15.7 |
Secondary
Achievement of a Psoriasis Activity and Severity Index (PASI50) Response at Week 12
Determining the PASI score involves the evaluation of erythema, infiltration, and desquamation and body surface area involvement over 4 body regions. These regions are the head, trunk, upper and lower extremities. PASI50 response at Week 12 is defined as a decrease in PASI score at Week 12 from Baseline of at least 50 %.
Time frame: Week 12
Population: Intention-To-Treat (ITT) population consisting of all randomized subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (ITT) | Achievement of a Psoriasis Activity and Severity Index (PASI50) Response at Week 12 | 11.9 percentage of subjects |
| Certolizumab Pegol 200 mg (ITT) | Achievement of a Psoriasis Activity and Severity Index (PASI50) Response at Week 12 | 86.4 percentage of subjects |
| Certolizumab Pegol 400 mg (ITT) | Achievement of a Psoriasis Activity and Severity Index (PASI50) Response at Week 12 | 93.1 percentage of subjects |
Secondary
Achievement of a Psoriasis Activity and Severity Index (PASI90) Response at Week 12
Determining the PASI score involves the evaluation of erythema, infiltration, and desquamation and body surface area involvement over 4 body regions. These regions are the head, trunk, upper and lower extremities. PASI90 response at Week 12 is defined as a decrease in PASI score at Week 12 from Baseline of at least 90 %.
Time frame: Week 12
Population: Intention-To-Treat (ITT) population consisting of all randomized subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (ITT) | Achievement of a Psoriasis Activity and Severity Index (PASI90) Response at Week 12 | 1.7 percentage of subjects |
| Certolizumab Pegol 200 mg (ITT) | Achievement of a Psoriasis Activity and Severity Index (PASI90) Response at Week 12 | 39.0 percentage of subjects |
| Certolizumab Pegol 400 mg (ITT) | Achievement of a Psoriasis Activity and Severity Index (PASI90) Response at Week 12 | 46.6 percentage of subjects |
Secondary
Experience of a Rebound Effect Within 2 Months After Stopping Therapy
Rebound is defined as worsening of psoriasis over baseline value with more than 125 % or new pustular, erythrodermic or more inflammatory psoriasis within 2 months of stopping therapy.
Time frame: Within 2 months of stopping therapy
Population: Intention-To-Treat (ITT) population consisting of all randomized subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (ITT) | Experience of a Rebound Effect Within 2 Months After Stopping Therapy | 15.3 percentage of subjects |
| Certolizumab Pegol 200 mg (ITT) | Experience of a Rebound Effect Within 2 Months After Stopping Therapy | 1.7 percentage of subjects |
| Certolizumab Pegol 400 mg (ITT) | Experience of a Rebound Effect Within 2 Months After Stopping Therapy | 1.7 percentage of subjects |
Secondary
Percent of Body Surface Area (BSA) Affected by Psoriasis at Week 12
Two methods were used for the evaluation of BSA: 1. The area of one side of a subject's flat closed hand was used to represent 1 % to the total body surface area (BSA) to estimate the extent of skin involvement in subjects with psoriasis 2. The rule of nines method assumed that the total BSA comprises head (9 %), anterior trunk (upper, 9 %; lower, 9 %), posterior trunk (upper, 9 %; lower, 9 %), each leg (anterior, 9 %; posterior, 9 %), each arm (9 %) and genitalia (1 %)
Time frame: Week 12
Population: ITT population consisting of all randomized subjects. The analysis was performed for week 12 using observed case data (i.e., no imputation was performed for missing data). By week 12, there were 29 patients who had prematurely discontinued the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (ITT) | Percent of Body Surface Area (BSA) Affected by Psoriasis at Week 12 | 28.8 percentage of affected Body Surface Area | Standard Deviation 17.2 |
| Certolizumab Pegol 200 mg (ITT) | Percent of Body Surface Area (BSA) Affected by Psoriasis at Week 12 | 7.1 percentage of affected Body Surface Area | Standard Deviation 9.3 |
| Certolizumab Pegol 400 mg (ITT) | Percent of Body Surface Area (BSA) Affected by Psoriasis at Week 12 | 5.6 percentage of affected Body Surface Area | Standard Deviation 6.5 |
Secondary
Time to Discontinuation From the Treatment Period Due to Lack of Efficacy or Worsening of Psoriasis
Time frame: During the 12-week Treatment Period
Population: Intention-To-Treat (ITT) population consisting of all randomized subjects.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (ITT) | Time to Discontinuation From the Treatment Period Due to Lack of Efficacy or Worsening of Psoriasis | 42.0 days |
| Certolizumab Pegol 200 mg (ITT) | Time to Discontinuation From the Treatment Period Due to Lack of Efficacy or Worsening of Psoriasis | 59.5 days |
| Certolizumab Pegol 400 mg (ITT) | Time to Discontinuation From the Treatment Period Due to Lack of Efficacy or Worsening of Psoriasis | 49.0 days |
Secondary
Time to Psoriasis Activity and Severity Index 50 (PASI50)
Time to PASI50 is defined as the time elapsed between the start of the Treatment Period (Week 0) and the first occurrence of PASI50 during the Treatment Period. This variable is defined only for those patients who have achieved PASI75 at the end of the Treatment Period (Week 12).
Time frame: During the 12-weeks Treatment Period
Population: Only those subjects from the Intention-To-Treat (ITT) population who are PASI75 responder at Week 12 are included in the analysis of this variable.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (ITT) | Time to Psoriasis Activity and Severity Index 50 (PASI50) | 56.50 days |
| Certolizumab Pegol 200 mg (ITT) | Time to Psoriasis Activity and Severity Index 50 (PASI50) | 21.00 days |
| Certolizumab Pegol 400 mg (ITT) | Time to Psoriasis Activity and Severity Index 50 (PASI50) | 22.00 days |
Secondary
Time to Psoriasis Activity and Severity Index 75 (PASI75)
Time to PASI75 is defined as the time elapsed between the start of the Treatment Period (Week 0) and the first occurrence of PASI75 during the Treatment Period. This variable is defined only for those patients who have achieved PASI75 at the end of the Treatment Period (Week 12).
Time frame: During the 12-weeks Treatment Period
Population: Only those subjects from the Intention-To-Treat (ITT) population who are PASI75 responder at Week 12 are included in the analysis of this variable.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (ITT) | Time to Psoriasis Activity and Severity Index 75 (PASI75) | 77.50 days |
| Certolizumab Pegol 200 mg (ITT) | Time to Psoriasis Activity and Severity Index 75 (PASI75) | 42.50 days |
| Certolizumab Pegol 400 mg (ITT) | Time to Psoriasis Activity and Severity Index 75 (PASI75) | 55.50 days |
Secondary
Time to Relapse
Time to relapse is defined as the time elapsed between the last dose and when maximal improvement in PASI from Baseline was reduced by \> 50 %. This variable is defined only for those patients who have achieved PASI75 at the end of the Treatment Period (Week 12).
Time frame: During the 12-weeks Treatment Period
Population: Only those subjects from the Intention-To-Treat (ITT) population who are PASI75 responder at Week 12 are included in the analysis of this variable.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (ITT) | Time to Relapse | NA weeks |
| Certolizumab Pegol 200 mg (ITT) | Time to Relapse | 22.14 weeks |
| Certolizumab Pegol 400 mg (ITT) | Time to Relapse | 20.14 weeks |