Plaque Psoriasis
Conditions
Keywords
plaque psoriasis, alefacept, Amevive, narrow band ultraviolet B, phototherapy
Brief summary
Assess the efficacy and safety of alefacept with nbUVB compared to alefacept alone in chronic plaque psoriasis subjects. Combination therapy may improve the clinical response to psoriatic subjects as both modalities have an effect on T cells
Interventions
DRUGalefacept
IM
PROCEDURENarrow Band UVB Phototherapy
UVB Phototherapy
Sponsors
Astellas Pharma Canada, Inc.
Astellas Pharma Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject has given written informed consent * Subject has a diagnosis of moderate to severe chronic plaque psoriasis involving \>=10% with a Psoriasis Area and Severity Index (PASI) score \>=10 at Baseline * Subject has CD4+ T lymphocyte (CD4) count at or above the lower limit of normal * Male and female subjects must use an adequate means of contraception from screening to end of study.
Exclusion criteria
* Subject who received alefacept in the past * Subject who has shown no improvement following an adequate course of nbUVB in the past * Subject who has been treated in the past with either therapy or cyclosporine * Subject with any active cancer, including skin cancer at Baseline * Subject with erythrodermic, pustular or predominantly guttate psoriasis * Subject who has used treatment for psoriasis prior to Baseline as follows: * Topical treatment within 14 days * Oral treatment within 28 days * Broad band UVB (bbUVB) or nbUVB treatment within 56 days * Biological treatment within 84 days * Serious local infection or serious systemic infection within the 3 months prior to the first dose of study drug * Subject with a history of drug or alcohol abuse within the past 2 years * Subject that is known to be infected with the AIDS virus * Subject with any other skin disease or other disease that might interfere with psoriasis status assessments * Female subject who is nursing, pregnant or planning to become pregnant while in this study * Subject who is currently enrolled in any other investigational drug or device study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Who Achieve Psoriasis Area and Severity Index (PASI) 75 at Week 16 | Week 16 | The PASI score is a tool that allows investigators to assign an objective number to the degree of severity of a person's psoriasis, and considers: redness, scaling and thickness. Values for PASI score range from 0 (least) to 72 (worst). PASI 75 was defined as an improvement of at least 75% in PASI as compared to Baseline. The Last Observation Carry Forward (LOCF) method was used to impute missing data. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Reaching PASI 75 Over the Entire Course of the Study | Week 36 | The PASI score is a tool that allows investigators to assign an objective number to the degree of severity of a person's psoriasis, and considers: redness, scaling and thickness. Values for PASI score range from 0 (least) to 72 (worst). PASI 75 was defined as an improvement of at least 75% in PASI as compared to Baseline. The Last Observation Carry Forward (LOCF) method was used to impute missing data. |
| Change in Body Surface Area (BSA) Covered With Psoriasis at Week 16 | Baseline and Week 16 | A negative change from Baseline represents improvement. Change is calculated as Week 16- Baseline. The Last Observation Carry Forward (LOCF) method was used to impute missing data. |
| Change in Body Surface Area (BSA) Covered With Psoriasis Over the Entire Course of the Study | Baseline and Week 36 | A negative change from Baseline represents improvement. Change is calculated as Week 36- Baseline. The Last Observation Carry Forward (LOCF) method was used to impute missing data. |
| Percentage of Subjects Who Achieved Physical Global Assessment (PGA) of Clear or Almost Clear at Week 16 | Week 16 | The PGA scale is a tool used to evaluate the degree of overall lesion severity. The scale ranges from 0 (clear) to 5 (very severe). Clear is defined as a score of 0; Almost Clear is defined as a score of 1. Subjects who achieved PGA of clear or almost clear at any visit during the study were assigned to the YES category for their respective groups. The Last Observation Carry Forward (LOCF) method was used to impute missing data. |
| Percentage of Subjects Who Achieved Physical Global Assessment (PGA) of Clear or Almost Clear Over the Entire Course of the Study | Week 36 | The PGA scale is a tool used to evaluate the degree of overall lesion severity. The scale ranges from 0 (clear) to 5 (very severe). Clear is defined as a score of 0; Almost Clear is defined as a score of 1. Subjects who achieved PGA of clear or almost clear at any visit during the study were assigned to the YES category for their respective groups. The Last Observation Carry Forward (LOCF) method was used to impute missing data. |
| Percentage of Subjects Who Achieve PASI 90 at Week 16 | Week 16 | The PASI score is a tool that allows investigators to assign an objective number to the degree of severity of a person's psoriasis, and considers: redness, scaling and thickness. Values for PASI score range from 0 (least) to 72 (worst). PASI 90 was defined as an improvement of at least 90% in PASI as compared to Baseline. The Last Observation Carry Forward (LOCF) method was used to impute missing data. |
| Time to Relapse | Week 36 | The analysis only included subjects who achieved a 75% improvement in PASI and then relapsed. Relapse is defined by a loss of 50% of improvement in PASI. |
| Time for 50% Decrease in PASI | Week 36 | The PASI score is a tool that allows investigators to assign an objective number to the degree of severity of a person's psoriasis, and considers: redness, scaling and thickness. Values for PASI score range from 0 (least) to 72 (worst). Only subjects who experienced 50% decrease in PASI were included in the analysis. |
| Time for a 75% Decrease in PASI | Week 36 | The PASI score is a tool that allows investigators to assign an objective number to the degree of severity of a person's psoriasis, and considers: redness, scaling and thickness. Values for PASI score range from 0 (least) to 72 (worst). Only subjects who experienced 75% decrease in PASI were included in the analysis. |
| Change in Dermatology Life Quality Index (DLQI) | Baseline and Week 36 | The DLQI questionnaire is intended to measure how much a subject's skin problem affects the subject's life. Subjects provide answers considering the past week. The scale of the DQLI ranges from 0 (best) to 30 (worst). A negative change from Baseline represents improvement. Change is calculated as Week 36- Baseline. The Last Observation Carry Forward (LOCF) method was used to impute missing data. |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Alefacept Alone 15 mg alefacept intramuscularly (IM) once weekly for 12 weeks | 49 |
| Alefacept + nbUVB 15 mg alefacept intramuscularly once weekly and narrow band Ultraviolet B (nbUVB) phototherapy 3 times per week for 12 weeks | 49 |
| Total | 98 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 |
| Overall Study | Lack of Compliance | 0 | 3 |
| Overall Study | Lack of Efficacy | 6 | 3 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Withdrawal by Subject | 7 | 16 |
Baseline characteristics
| Characteristic | Alefacept Alone | Alefacept + nbUVB | Total |
|---|---|---|---|
| Age Continuous | 48.2 years STANDARD_DEVIATION 13.8 | 47.1 years STANDARD_DEVIATION 14.2 | 47.7 years STANDARD_DEVIATION 14 |
| BSA Score | 21.9 Percentage of BSA STANDARD_DEVIATION 13 | 20.0 Percentage of BSA STANDARD_DEVIATION 9.4 | 21.0 Percentage of BSA STANDARD_DEVIATION 11.3 |
| DLQI Score | 6.1 Score STANDARD_DEVIATION 10 | 5.9 Score STANDARD_DEVIATION 7 | 6.1 Score STANDARD_DEVIATION 9 |
| PASI Score | 17.8 Score STANDARD_DEVIATION 6 | 17.5 Score STANDARD_DEVIATION 5.2 | 17.7 Score STANDARD_DEVIATION 5.6 |
| PGA Score | 3.3 Score STANDARD_DEVIATION 0.7 | 3.4 Score STANDARD_DEVIATION 0.6 | 3.3 Score STANDARD_DEVIATION 0.6 |
| Race/Ethnicity, Customized Asian | 5 participants | 6 participants | 11 participants |
| Race/Ethnicity, Customized Black | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Caucasian | 43 participants | 42 participants | 85 participants |
| Race/Ethnicity, Customized Other | 1 participants | 0 participants | 1 participants |
| Sex: Female, Male Female | 12 Participants | 17 Participants | 29 Participants |
| Sex: Female, Male Male | 37 Participants | 32 Participants | 69 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 49 | 40 / 49 |
| serious Total, serious adverse events | 0 / 49 | 2 / 49 |
Outcome results
Primary
Percentage of Subjects Who Achieve Psoriasis Area and Severity Index (PASI) 75 at Week 16
The PASI score is a tool that allows investigators to assign an objective number to the degree of severity of a person's psoriasis, and considers: redness, scaling and thickness. Values for PASI score range from 0 (least) to 72 (worst). PASI 75 was defined as an improvement of at least 75% in PASI as compared to Baseline. The Last Observation Carry Forward (LOCF) method was used to impute missing data.
Time frame: Week 16
Population: The number of participants analyzed per arm represents the ITT-Efficacy Population, which consisted of all subjects randomized into the study who received at least one dose of study drug (alefacept).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alefacept Alone | Percentage of Subjects Who Achieve Psoriasis Area and Severity Index (PASI) 75 at Week 16 | 22.4 Percentage of Subjects |
| Alefacept + nbUVB | Percentage of Subjects Who Achieve Psoriasis Area and Severity Index (PASI) 75 at Week 16 | 44.9 Percentage of Subjects |
p-value: 0.032Fisher Exact
Secondary
Change in Body Surface Area (BSA) Covered With Psoriasis at Week 16
A negative change from Baseline represents improvement. Change is calculated as Week 16- Baseline. The Last Observation Carry Forward (LOCF) method was used to impute missing data.
Time frame: Baseline and Week 16
Population: The number of participants analyzed per arm represents the ITT-Efficacy Population, which consisted of all subjects randomized into the study who received at least one dose of study drug (alefacept).~The number of participants per arm is consistent for all categories / rows of the data table.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alefacept Alone | Change in Body Surface Area (BSA) Covered With Psoriasis at Week 16 | Baseline | 21.9 Percentage of BSA | Standard Deviation 13 |
| Alefacept Alone | Change in Body Surface Area (BSA) Covered With Psoriasis at Week 16 | Week 16 | 13.9 Percentage of BSA | Standard Deviation 10.8 |
| Alefacept Alone | Change in Body Surface Area (BSA) Covered With Psoriasis at Week 16 | Change from Baseline | -8.0 Percentage of BSA | Standard Deviation 14.7 |
| Alefacept + nbUVB | Change in Body Surface Area (BSA) Covered With Psoriasis at Week 16 | Baseline | 20.0 Percentage of BSA | Standard Deviation 9.4 |
| Alefacept + nbUVB | Change in Body Surface Area (BSA) Covered With Psoriasis at Week 16 | Week 16 | 6.6 Percentage of BSA | Standard Deviation 8 |
| Alefacept + nbUVB | Change in Body Surface Area (BSA) Covered With Psoriasis at Week 16 | Change from Baseline | -13.4 Percentage of BSA | Standard Deviation 9.2 |
Comparison: Statistical Analysis applies to 'Change from Baseline'p-value: 0.001Wilcoxon (Mann-Whitney)
Secondary
Change in Body Surface Area (BSA) Covered With Psoriasis Over the Entire Course of the Study
A negative change from Baseline represents improvement. Change is calculated as Week 36- Baseline. The Last Observation Carry Forward (LOCF) method was used to impute missing data.
Time frame: Baseline and Week 36
Population: The number of participants analyzed per arm represents the ITT-Efficacy Population, which consisted of all subjects randomized into the study who received at least one dose of study drug (alefacept).~The number of participants per arm is consistent for all categories / rows of the data table.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alefacept Alone | Change in Body Surface Area (BSA) Covered With Psoriasis Over the Entire Course of the Study | Baseline | 21.9 Percentage of BSA | Standard Deviation 13 |
| Alefacept Alone | Change in Body Surface Area (BSA) Covered With Psoriasis Over the Entire Course of the Study | Week 36 | 14.4 Percentage of BSA | Standard Deviation 14.1 |
| Alefacept Alone | Change in Body Surface Area (BSA) Covered With Psoriasis Over the Entire Course of the Study | Change from Baseline | -7.5 Percentage of BSA | Standard Deviation 14.7 |
| Alefacept + nbUVB | Change in Body Surface Area (BSA) Covered With Psoriasis Over the Entire Course of the Study | Week 36 | 8.2 Percentage of BSA | Standard Deviation 8.8 |
| Alefacept + nbUVB | Change in Body Surface Area (BSA) Covered With Psoriasis Over the Entire Course of the Study | Baseline | 20.0 Percentage of BSA | Standard Deviation 9.4 |
| Alefacept + nbUVB | Change in Body Surface Area (BSA) Covered With Psoriasis Over the Entire Course of the Study | Change from Baseline | -11.9 Percentage of BSA | Standard Deviation 9.7 |
Comparison: Statistical Analysis applies to 'Change from Baseline'p-value: 0.382ANOVA
Secondary
Change in Dermatology Life Quality Index (DLQI)
The DLQI questionnaire is intended to measure how much a subject's skin problem affects the subject's life. Subjects provide answers considering the past week. The scale of the DQLI ranges from 0 (best) to 30 (worst). A negative change from Baseline represents improvement. Change is calculated as Week 36- Baseline. The Last Observation Carry Forward (LOCF) method was used to impute missing data.
Time frame: Baseline and Week 36
Population: The number of participants analyzed per arm represents the ITT-Efficacy Population, which consisted of all subjects randomized into the study who received at least one dose of study drug (alefacept).~The number of participants per arm is consistent for all categories / rows of the data table.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alefacept Alone | Change in Dermatology Life Quality Index (DLQI) | Baseline | 11.0 DLQI Score | Standard Deviation 6.1 |
| Alefacept Alone | Change in Dermatology Life Quality Index (DLQI) | Week 36 | 8.2 DLQI Score | Standard Deviation 7.6 |
| Alefacept Alone | Change in Dermatology Life Quality Index (DLQI) | Change from Baseline | -2.7 DLQI Score | Standard Deviation 6.5 |
| Alefacept + nbUVB | Change in Dermatology Life Quality Index (DLQI) | Baseline | 9.1 DLQI Score | Standard Deviation 5.9 |
| Alefacept + nbUVB | Change in Dermatology Life Quality Index (DLQI) | Week 36 | 5.6 DLQI Score | Standard Deviation 6.7 |
| Alefacept + nbUVB | Change in Dermatology Life Quality Index (DLQI) | Change from Baseline | -3.5 DLQI Score | Standard Deviation 6.4 |
Comparison: Statistical Analysis applies to 'Change from Baseline'p-value: 0.539ANOVA
Secondary
Percentage of Subjects Reaching PASI 75 Over the Entire Course of the Study
The PASI score is a tool that allows investigators to assign an objective number to the degree of severity of a person's psoriasis, and considers: redness, scaling and thickness. Values for PASI score range from 0 (least) to 72 (worst). PASI 75 was defined as an improvement of at least 75% in PASI as compared to Baseline. The Last Observation Carry Forward (LOCF) method was used to impute missing data.
Time frame: Week 36
Population: The number of participants analyzed per arm represents the ITT-Efficacy Population, which consisted of all subjects randomized into the study who received at least one dose of study drug (alefacept).~Only subjects who completed follow-up were included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alefacept Alone | Percentage of Subjects Reaching PASI 75 Over the Entire Course of the Study | 26.5 Percentage of Subjects |
| Alefacept + nbUVB | Percentage of Subjects Reaching PASI 75 Over the Entire Course of the Study | 36.7 Percentage of Subjects |
p-value: 0.037Wilcoxon (Mann-Whitney)
Secondary
Percentage of Subjects Who Achieved Physical Global Assessment (PGA) of Clear or Almost Clear at Week 16
The PGA scale is a tool used to evaluate the degree of overall lesion severity. The scale ranges from 0 (clear) to 5 (very severe). Clear is defined as a score of 0; Almost Clear is defined as a score of 1. Subjects who achieved PGA of clear or almost clear at any visit during the study were assigned to the YES category for their respective groups. The Last Observation Carry Forward (LOCF) method was used to impute missing data.
Time frame: Week 16
Population: The number of participants analyzed per arm represents the ITT-Efficacy Population, which consisted of all subjects randomized into the study who received at least one dose of study drug (alefacept).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alefacept Alone | Percentage of Subjects Who Achieved Physical Global Assessment (PGA) of Clear or Almost Clear at Week 16 | PGA Clear or Almost Clear = Yes | 22.5 Percentage of Subjects |
| Alefacept Alone | Percentage of Subjects Who Achieved Physical Global Assessment (PGA) of Clear or Almost Clear at Week 16 | PGA Clear or Almost Clear = No | 77.6 Percentage of Subjects |
| Alefacept + nbUVB | Percentage of Subjects Who Achieved Physical Global Assessment (PGA) of Clear or Almost Clear at Week 16 | PGA Clear or Almost Clear = Yes | 42.9 Percentage of Subjects |
| Alefacept + nbUVB | Percentage of Subjects Who Achieved Physical Global Assessment (PGA) of Clear or Almost Clear at Week 16 | PGA Clear or Almost Clear = No | 57.1 Percentage of Subjects |
Comparison: Statistical Analysis applies to 'Clear or Almost Clear = Yes'p-value: 0.052Fisher Exact
Secondary
Percentage of Subjects Who Achieved Physical Global Assessment (PGA) of Clear or Almost Clear Over the Entire Course of the Study
The PGA scale is a tool used to evaluate the degree of overall lesion severity. The scale ranges from 0 (clear) to 5 (very severe). Clear is defined as a score of 0; Almost Clear is defined as a score of 1. Subjects who achieved PGA of clear or almost clear at any visit during the study were assigned to the YES category for their respective groups. The Last Observation Carry Forward (LOCF) method was used to impute missing data.
Time frame: Week 36
Population: The number of participants analyzed per arm represents the ITT-Efficacy Population, which consisted of all subjects randomized into the study who received at least one dose of study drug (alefacept).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alefacept Alone | Percentage of Subjects Who Achieved Physical Global Assessment (PGA) of Clear or Almost Clear Over the Entire Course of the Study | PGA of Clear or Almost Clear = Yes | 34.7 Percentage of Subjects |
| Alefacept Alone | Percentage of Subjects Who Achieved Physical Global Assessment (PGA) of Clear or Almost Clear Over the Entire Course of the Study | PGA of Clear or Almost Clear = No | 65.3 Percentage of Subjects |
| Alefacept + nbUVB | Percentage of Subjects Who Achieved Physical Global Assessment (PGA) of Clear or Almost Clear Over the Entire Course of the Study | PGA of Clear or Almost Clear = Yes | 59.2 Percentage of Subjects |
| Alefacept + nbUVB | Percentage of Subjects Who Achieved Physical Global Assessment (PGA) of Clear or Almost Clear Over the Entire Course of the Study | PGA of Clear or Almost Clear = No | 40.8 Percentage of Subjects |
Comparison: Statistical Analysis applies to 'Clear or Almost Clear = Yes'p-value: 0.026Fisher Exact
Secondary
Percentage of Subjects Who Achieve PASI 90 at Week 16
The PASI score is a tool that allows investigators to assign an objective number to the degree of severity of a person's psoriasis, and considers: redness, scaling and thickness. Values for PASI score range from 0 (least) to 72 (worst). PASI 90 was defined as an improvement of at least 90% in PASI as compared to Baseline. The Last Observation Carry Forward (LOCF) method was used to impute missing data.
Time frame: Week 16
Population: The number of participants analyzed per arm represents the ITT-Efficacy Population, which consisted of all subjects randomized into the study who received at least one dose of study drug (alefacept).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alefacept Alone | Percentage of Subjects Who Achieve PASI 90 at Week 16 | PASI 90 = Yes | 8.2 Percentage of Subjects |
| Alefacept Alone | Percentage of Subjects Who Achieve PASI 90 at Week 16 | PASI 90 = No | 91.8 Percentage of Subjects |
| Alefacept + nbUVB | Percentage of Subjects Who Achieve PASI 90 at Week 16 | PASI 90 = Yes | 20.4 Percentage of Subjects |
| Alefacept + nbUVB | Percentage of Subjects Who Achieve PASI 90 at Week 16 | PASI 90 = No | 79.6 Percentage of Subjects |
Comparison: Statistical Analysis applies to 'PASI 90 = Yes'p-value: 0.147Fisher Exact
Secondary
Time for 50% Decrease in PASI
The PASI score is a tool that allows investigators to assign an objective number to the degree of severity of a person's psoriasis, and considers: redness, scaling and thickness. Values for PASI score range from 0 (least) to 72 (worst). Only subjects who experienced 50% decrease in PASI were included in the analysis.
Time frame: Week 36
Population: The number of participants analyzed per arm represents the ITT-Efficacy Population, which consisted of all subjects randomized into the study who received at least one dose of study drug (alefacept).~Only subjects who experienced a 50% decrease in PASI were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Alefacept Alone | Time for 50% Decrease in PASI | 84.0 Days |
| Alefacept + nbUVB | Time for 50% Decrease in PASI | 56.0 Days |
p-value: 0.001Log Rank
Secondary
Time for a 75% Decrease in PASI
The PASI score is a tool that allows investigators to assign an objective number to the degree of severity of a person's psoriasis, and considers: redness, scaling and thickness. Values for PASI score range from 0 (least) to 72 (worst). Only subjects who experienced 75% decrease in PASI were included in the analysis.
Time frame: Week 36
Population: The number of participants analyzed per arm represents the ITT-Efficacy Population, which consisted of all subjects randomized into the study who received at least one dose of study drug (alefacept).~Only subjects who experienced a 75% decrease in PASI were included in the analysis.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Alefacept Alone | Time for a 75% Decrease in PASI | 99.5 Days |
| Alefacept + nbUVB | Time for a 75% Decrease in PASI | 84.0 Days |
p-value: 0.007Log Rank
Secondary
Time to Relapse
The analysis only included subjects who achieved a 75% improvement in PASI and then relapsed. Relapse is defined by a loss of 50% of improvement in PASI.
Time frame: Week 36
Population: The number of participants analyzed per arm represents the ITT-Efficacy Population, which consisted of all subjects randomized into the study who received at least one dose of study drug (alefacept).~Only subjects who achieved a 75% improvement in PASI and then relapsed were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alefacept Alone | Time to Relapse | 98.0 Days | Standard Deviation 19.8 |
| Alefacept + nbUVB | Time to Relapse | 119.0 Days | Standard Deviation 29.7 |
p-value: 0.566Log Rank