Psoriasis
Conditions
Keywords
Plaque Psoriasis
Brief summary
The main objective of this study is to evaluate the efficacy and safety of risankizumab compared with secukinumab for the treatment of adult subjects with moderate to severe plaque psoriasis who are candidates for systemic therapy.
Interventions
DRUGrisankizumab
Subcutaneous (SC) injection
DRUGsecukinumab
Subcutaneous (SC) injection
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of chronic plaque psoriasis with or without psoriatic arthritis for at least 6 months before the Baseline Visit * Subject has stable moderate to severe chronic plaque psoriasis with or without psoriatic arthritis * Subject must be a candidate for systemic therapy as assessed by the investigator; * Subject must be an acceptable candidate to receive secukinumab according to the local label for this compound.
Exclusion criteria
* History of erythrodermic psoriasis, generalized or localized pustular psoriasis, medication-induced or medication-exacerbated psoriasis, or new onset guttate psoriasis; or active skin disease other than psoriasis that could interfere with the assessment of psoriasis; * Chronic infections including HIV, viral hepatitis (hepatitis B, hepatitis C), and/ or active tuberculosis. Subjects with a positive QuantiFERON®-TB/purified protein derivative (PPD) test result may participate in the study if further work up (according to local practice/guidelines) establishes conclusively that the subject has no evidence of active tuberculosis. If presence of latent tuberculosis is established, then treatment must have been initiated and maintained according to local country guidelines. * Active systemic infection during the last 2 weeks prior to Baseline Visit (exception: common cold) * History of any documented active or suspected malignancy or history of any malignancy within the last 5 years except for successfully treated non-melanoma skin cancer (NMSC) or localized carcinoma in situ of the cervix * Previous exposure to risankizumab * Previous exposure to secukinumab
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a 90% Reduction From Baseline Psoriasis Area and Severity Index (PASI 90) at Week 16 | Week 16 | The Psoriasis Area and Severity Index (PASI) is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI 90 is defined as at least a 90% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline \* 100. Non-responder imputation (NRI) was used for missing data. |
| Percentage of Participants With a PASI 90 at Week 52 | Week 52 | The PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI 90 is defined as at least a 90% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline \* 100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a 100% Reduction From Baseline Psoriasis Area and Severity Index (PASI 100) at Week 52 | Week 52 | PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI 100 is defined as 100% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline \* 100. |
| Percentage of Participants Achieving Static Physician Global Assessment (sPGA) of Clear or Almost Clear at Week 52 | Week 52 | The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema, induration, and scaling of psoriatic lesions are scored on a 5-point scale ranging from 0 (none) to 4 (severe). The sPGA ranges from 0 to 4, and is calculated as Clear (0) = 0 for all 3; Almost clear (1) = mean \> 0, \< 1.5; Mild (2) = mean ≥ 1.5, \< 2.5; Moderate (3) = mean ≥ 2.5, \< 3.5; and Severe (4) = mean ≥ 3.5. |
| Percentage of Participants With a 75% Reduction From Baseline Psoriasis Area and Severity Index (PASI 75) at Week 52 | Week 52 | The PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI 75 is defined as at least a 75% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline \* 100. |
Countries
Canada, France, Germany, Italy, Netherlands, Poland, Spain, United Kingdom, United States
Participant flow
Recruitment details
A total of 327 participants were randomized from 53 sites across 9 countries including Canada, France, Germany, Italy, The Netherlands, Poland, Spain, the United Kingdom, and the United States.
Pre-assignment details
Eligible participants were randomized to receive risankizumab or secukinumab in a 1:1 ratio. The randomization was stratified by weight (≤ 100 kg vs. \> 100 kg) and prior systemic biologic for psoriasis (0 vs. ≥ 1).
Participants by arm
| Arm | Count |
|---|---|
| Secukinumab Participants randomized to secukinumab received 2 injections of active secukinumab (300 mg total dosage) subcutaneously (SC) at Weeks 0, 1, 2, 3, and 4, and then every 4 weeks (q4w) thereafter until the last dose at Week 48. | 163 |
| Risankizumab Participants randomized to risankizumab received 2 injections of active risankizumab (150 mg total dosage) SC at Weeks 0 and 4, and then every 12 weeks (q12w) thereafter until the last dose at Week 40 (Week 64 for participants in France). | 164 |
| Total | 327 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 1 |
| Overall Study | Lack of Efficacy | 7 | 1 |
| Overall Study | Lost to Follow-up | 9 | 5 |
| Overall Study | Other, Not Specified | 3 | 0 |
| Overall Study | Protocol Violation | 3 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 6 |
Baseline characteristics
| Characteristic | Secukinumab | Risankizumab | Total |
|---|---|---|---|
| Age, Customized 40 to < 65 years | 81 Participants | 99 Participants | 180 Participants |
| Age, Customized < 40 years | 60 Participants | 50 Participants | 110 Participants |
| Age, Customized >/= 65 years | 22 Participants | 15 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 34 Participants | 37 Participants | 71 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 129 Participants | 127 Participants | 256 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 11 Participants | 6 Participants | 17 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 6 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 144 Participants | 151 Participants | 295 Participants |
| Sex: Female, Male Female | 62 Participants | 52 Participants | 114 Participants |
| Sex: Female, Male Male | 101 Participants | 112 Participants | 213 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 163 | 0 / 164 |
| other Total, other adverse events | 71 / 163 | 66 / 164 |
| serious Total, serious adverse events | 6 / 163 | 9 / 164 |
Outcome results
Primary
Percentage of Participants With a 90% Reduction From Baseline Psoriasis Area and Severity Index (PASI 90) at Week 16
The Psoriasis Area and Severity Index (PASI) is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI 90 is defined as at least a 90% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline \* 100. Non-responder imputation (NRI) was used for missing data.
Time frame: Week 16
Population: Intent to Treat (ITT) analysis set: all participants who were randomized at Baseline. Non-responder imputation (NRI) was used for missing data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Secukinumab | Percentage of Participants With a 90% Reduction From Baseline Psoriasis Area and Severity Index (PASI 90) at Week 16 | 65.6 percentage of participants |
| Risankizumab | Percentage of Participants With a 90% Reduction From Baseline Psoriasis Area and Severity Index (PASI 90) at Week 16 | 73.8 percentage of participants |
96.25% CI: [-2.2, 18.6]
Primary
Percentage of Participants With a PASI 90 at Week 52
The PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI 90 is defined as at least a 90% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline \* 100.
Time frame: Week 52
Population: ITT analysis set: all participants who were randomized at Baseline. NRI was used for missing data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Secukinumab | Percentage of Participants With a PASI 90 at Week 52 | 57.1 percentage of participants |
| Risankizumab | Percentage of Participants With a PASI 90 at Week 52 | 86.6 percentage of participants |
p-value: <0.00195% CI: [20.8, 38.8]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving Static Physician Global Assessment (sPGA) of Clear or Almost Clear at Week 52
The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema, induration, and scaling of psoriatic lesions are scored on a 5-point scale ranging from 0 (none) to 4 (severe). The sPGA ranges from 0 to 4, and is calculated as Clear (0) = 0 for all 3; Almost clear (1) = mean \> 0, \< 1.5; Mild (2) = mean ≥ 1.5, \< 2.5; Moderate (3) = mean ≥ 2.5, \< 3.5; and Severe (4) = mean ≥ 3.5.
Time frame: Week 52
Population: ITT analysis set: all participants who were randomized at Baseline. NRI was used for missing data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Secukinumab | Percentage of Participants Achieving Static Physician Global Assessment (sPGA) of Clear or Almost Clear at Week 52 | 58.3 percentage of participants |
| Risankizumab | Percentage of Participants Achieving Static Physician Global Assessment (sPGA) of Clear or Almost Clear at Week 52 | 87.8 percentage of participants |
p-value: <0.00195% CI: [20.9, 38.8]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With a 100% Reduction From Baseline Psoriasis Area and Severity Index (PASI 100) at Week 52
PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI 100 is defined as 100% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline \* 100.
Time frame: Week 52
Population: ITT analysis set: all participants who were randomized at Baseline. NRI was used for missing data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Secukinumab | Percentage of Participants With a 100% Reduction From Baseline Psoriasis Area and Severity Index (PASI 100) at Week 52 | 39.9 percentage of participants |
| Risankizumab | Percentage of Participants With a 100% Reduction From Baseline Psoriasis Area and Severity Index (PASI 100) at Week 52 | 65.9 percentage of participants |
p-value: <0.00195% CI: [15.9, 36.5]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With a 75% Reduction From Baseline Psoriasis Area and Severity Index (PASI 75) at Week 52
The PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI 75 is defined as at least a 75% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline \* 100.
Time frame: Week 52
Population: ITT analysis set: all participants who were randomized at Baseline. NRI was used for missing data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Secukinumab | Percentage of Participants With a 75% Reduction From Baseline Psoriasis Area and Severity Index (PASI 75) at Week 52 | 69.9 percentage of participants |
| Risankizumab | Percentage of Participants With a 75% Reduction From Baseline Psoriasis Area and Severity Index (PASI 75) at Week 52 | 89.6 percentage of participants |
p-value: <0.00195% CI: [11.7, 28.3]Cochran-Mantel-Haenszel