Plaque Psoriasis
Conditions
Keywords
cyclosporine A
Brief summary
The purpose of this study was to assess the efficacy and safety of secukinumab at Week 16 based on psoriasis area and severity index (PASI) 75 in subjects who had inadequate response to cyclosporine A.
Interventions
Secukinumab was supplied as 150 mg doses, provided in 1 mL prefilled syringes.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Plaque psoriasis diagnosed for at least 6 months before baseline - Treated with cyclosporine A for at least 12 weeks prior to baseline * Currently treated with cyclosporine A at baseline for psoriasis but is a primary or secondary inadequate response as defined at baseline by: * PASI score of 10 or greater and * IGA mod 2011 score of 2 or greater (based on a scale of 0 to 4)
Exclusion criteria
* Forms of psoriasis other than plaque (e.g., pustular, erythrodermic and guttate psoriasis). -Drug-induced psoriasis (i.e., new onset or current exacerbation from beta-blockers, calcium channel blockers or lithium). * Patients who have to discontinue cyclosporine A treatment due to side effects like renal impairment (serum creatinine exceeding 176.8 μmol/L \[2.0 mg/dL\]) and hypertension at screening. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved ≥ 75% Psoriasis Area and Severity Index (PASI 75) | Week 16 | PASI is a combined assessment of a lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). The body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for a final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area \* area score weight of section (head: 0.1, arms: 0.2, body: 0.3, legs: 0.4). PASI 75 was defined as participants achieving \>= 75% improvement from baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percent Change From Baseline in PASI Score | Week 4 | PASI is a combined assessment of a lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). The body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for a final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area \* area score weight of section (head: 0.1, arms: 0.2, body: 0.3, legs: 0.4). A negative change from baseline indicates improvement. |
| Percentage of Participants Achieving PASI 50 or PASI 75 | Week 4 | PASI is a combined assessment of a lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). The body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for a final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area \* area score weight of section (head: 0.1, arms: 0.2, body: 0.3, legs: 0.4). PASI 50 and PASI 75 were defined as participants achieving \>= 50% or \>= 75% improvement from baseline, respectively. |
| Percentage of Participants Achieving PASI 90 and Investigator's Global Assessment (IGA) of 0 or 1 Response | Week 16 | PASI is a combined assessment of a lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). The body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for a final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area \* area score weight of section (head: 0.1, arms: 0.2, body: 0.3, legs: 0.4). PASI 90 was defined as participants achieving \>= 90% improvement from baseline. The IGA scale is static, i.e. it referred exclusively to the participant's disease at the time of assessment and did not compare with any of the participant's previous disease states at previous visits. The scores are: 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe. |
| Mean Percent Change From Baseline in Dermatology Life Quality Index (DLQI) Score | Week 16 | The DLQI is a ten item general dermatology disability index designed to assess health-related quality of life in adult participants with skin diseases such as eczema, psoriasis, acne and viral warts. It is a self-administered questionnaire which includes domains of daily activity, leisure, personal relationships, symptoms and feelings, treatment and school/work activities. Each domain has 4 response categories ranging from 0 (not at all) to 3 (very much). Not relevant is a valid score also and is scored as 0. The DLQI total score is a sum of all 10 responses. Scores range from 0 to 30 with higher scores indicating greater health-related quality of life impairment. A negative mean percentage change from baseline indicates improvement. |
| Percentage of Participants Achieving DLQI 0 or 1 | Week 16 | The DLQI is a ten item general dermatology disability index designed to assess health-related quality of life in adult participants with skin diseases such as eczema, psoriasis, acne and viral warts. It is a self-administered questionnaire which includes domains of daily activity, leisure, personal relationships, symptoms and feelings, treatment and school/work activities. Each domain has 4 response categories ranging from 0 (not at all) to 3 (very much). Not relevant is a valid score also and is scored as 0. The DLQI total score is a sum of all 10 responses. Scores range from 0 to 30 with higher scores indicating greater health-related quality of life impairment. |
Countries
Japan
Participant flow
Pre-assignment details
The overall treatment period consisted of a 4 week induction period (Day 1 and weeks 1, 2, 3 and 4) and a 12 week maintenance period (weeks 8 and 12). All participants entered and completed both periods.
Participants by arm
| Arm | Count |
|---|---|
| Secukinumab (AIN457) 300 mg Participants received secukinumab 300 mg subcutaneously (s.c.) (two 150 mg injections) on Day 1 and at Weeks 1, 2, 3, 4, 8 and 12. | 34 |
| Total | 34 |
Baseline characteristics
| Characteristic | Secukinumab (AIN457) 300 mg |
|---|---|
| Age, Continuous | 51.5 Years STANDARD_DEVIATION 12.08 |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 24 / 34 | 10 / 34 |
| serious Total, serious adverse events | 0 / 34 | 0 / 34 |
Outcome results
Primary
Percentage of Participants Who Achieved ≥ 75% Psoriasis Area and Severity Index (PASI 75)
PASI is a combined assessment of a lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). The body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for a final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area \* area score weight of section (head: 0.1, arms: 0.2, body: 0.3, legs: 0.4). PASI 75 was defined as participants achieving \>= 75% improvement from baseline.
Time frame: Week 16
Population: The full analysis set, which included all participants who received at least one dose of study drug, was analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Secukinumab (AIN457) 300 mg | Percentage of Participants Who Achieved ≥ 75% Psoriasis Area and Severity Index (PASI 75) | 82.4 Percentage of participants |
Secondary
Mean Percent Change From Baseline in Dermatology Life Quality Index (DLQI) Score
The DLQI is a ten item general dermatology disability index designed to assess health-related quality of life in adult participants with skin diseases such as eczema, psoriasis, acne and viral warts. It is a self-administered questionnaire which includes domains of daily activity, leisure, personal relationships, symptoms and feelings, treatment and school/work activities. Each domain has 4 response categories ranging from 0 (not at all) to 3 (very much). Not relevant is a valid score also and is scored as 0. The DLQI total score is a sum of all 10 responses. Scores range from 0 to 30 with higher scores indicating greater health-related quality of life impairment. A negative mean percentage change from baseline indicates improvement.
Time frame: Week 16
Population: The full analysis set was considered for the analysis. Only participants who had both baseline and week 16 values were included in the analysis. The full analysis set included all participants who received at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Secukinumab (AIN457) 300 mg | Mean Percent Change From Baseline in Dermatology Life Quality Index (DLQI) Score | -63.07 Percent change | Standard Deviation 59.192 |
Secondary
Mean Percent Change From Baseline in PASI Score
PASI is a combined assessment of a lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). The body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for a final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area \* area score weight of section (head: 0.1, arms: 0.2, body: 0.3, legs: 0.4). A negative change from baseline indicates improvement.
Time frame: Week 4
Population: The full analysis set, which included all participants who received at least one dose of study drug, was analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Secukinumab (AIN457) 300 mg | Mean Percent Change From Baseline in PASI Score | -65.64 Percent change | Standard Deviation 37.2 |
Secondary
Percentage of Participants Achieving DLQI 0 or 1
The DLQI is a ten item general dermatology disability index designed to assess health-related quality of life in adult participants with skin diseases such as eczema, psoriasis, acne and viral warts. It is a self-administered questionnaire which includes domains of daily activity, leisure, personal relationships, symptoms and feelings, treatment and school/work activities. Each domain has 4 response categories ranging from 0 (not at all) to 3 (very much). Not relevant is a valid score also and is scored as 0. The DLQI total score is a sum of all 10 responses. Scores range from 0 to 30 with higher scores indicating greater health-related quality of life impairment.
Time frame: Week 16
Population: The full analysis set, which included all participants who received at least one dose of study drug, was analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Secukinumab (AIN457) 300 mg | Percentage of Participants Achieving DLQI 0 or 1 | 76.5 Percentage of participants |
Secondary
Percentage of Participants Achieving PASI 50 or PASI 75
PASI is a combined assessment of a lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). The body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for a final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area \* area score weight of section (head: 0.1, arms: 0.2, body: 0.3, legs: 0.4). PASI 50 and PASI 75 were defined as participants achieving \>= 50% or \>= 75% improvement from baseline, respectively.
Time frame: Week 4
Population: The full analysis set, which included all participants who received at least one dose of study drug, was analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Secukinumab (AIN457) 300 mg | Percentage of Participants Achieving PASI 50 or PASI 75 | PASI 50 | 76.5 Percentage of participants |
| Secukinumab (AIN457) 300 mg | Percentage of Participants Achieving PASI 50 or PASI 75 | PASI 75 | 44.1 Percentage of participants |
Secondary
Percentage of Participants Achieving PASI 90 and Investigator's Global Assessment (IGA) of 0 or 1 Response
PASI is a combined assessment of a lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). The body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for a final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area \* area score weight of section (head: 0.1, arms: 0.2, body: 0.3, legs: 0.4). PASI 90 was defined as participants achieving \>= 90% improvement from baseline. The IGA scale is static, i.e. it referred exclusively to the participant's disease at the time of assessment and did not compare with any of the participant's previous disease states at previous visits. The scores are: 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe.
Time frame: Week 16
Population: The full analysis set, which included all participants who received at least one dose of study drug, was analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Secukinumab (AIN457) 300 mg | Percentage of Participants Achieving PASI 90 and Investigator's Global Assessment (IGA) of 0 or 1 Response | PASI 90 | 64.7 Percentage of participants |
| Secukinumab (AIN457) 300 mg | Percentage of Participants Achieving PASI 90 and Investigator's Global Assessment (IGA) of 0 or 1 Response | IGA 0/1 | 70.6 Percentage of participants |