Psoriasis
Conditions
Keywords
Psoriasis, Skin Diseases, Skin Diseases, Papulosquamous, ustekinumab, Dermatologic Agents, ABBV-066, BI 655066, risankizumab
Brief summary
The purpose of this study is to assess the safety and efficacy of BI 655066/ABBV-066 (risankizumab) for the treatment of moderate to severe chronic plaque psoriasis in adult patients.
Detailed description
Participants were randomized to receive either placebo, ustekinumab, or risankizumab in Part A. All participants received 2 sets of injections to maintain the blind: the placebo arm received placebo for risankizumab and placebo for ustekinumab), the risankizumab arm received risankizumab and placebo for ustekinumab, and the ustekinumab arm received ustekinumab and placebo for risankizumab. Participants who received placebo in Part A switched to risankizumab in Part B; participants who received ustekinumab or risankizumab in Part A continued to receive the same treatment (ustekinumab or risankizumab) in Part B.
Interventions
DRUGrisankizumab
Risankizumab administered by subcutaneous (SC) injection
Placebo for risankizumab administered by subcutaneous (SC) injection
DRUGustekinumab
Ustekinumab administered by subcutaneous (SC) injection
Placebo for ustekinumab administered by subcutaneous (SC) injection
Sponsors
Boehringer Ingelheim
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female patients with age ≥18 years at screening. * Have a diagnosis of chronic plaque psoriasis (with or without psoriatic arthritis) for at least 6 months before the first administration of study drug. * Have stable moderate to severe chronic plaque psoriasis with or without psoriatic arthritis at both Screening and Baseline (Randomisation): 1. Have an involved body surface area (BSA) ≥10% and 2. Have a Psoriasis Area and Severity Index (PASI) score ≥12 and 3. Have a static Physician Global Assessment (sPGA) score of ≥3. * Must be candidates for systemic therapy or phototherapy for psoriasis treatment, as assessed by the investigator. * Must be a candidate for treatment with Stelara® (ustekinumab) according to local label.
Exclusion criteria
* Patients with: 1. non-plaque forms of psoriasis (including guttate, erythrodermic, or pustular) 2. current drug-induced psoriasis (including an exacerbation of psoriasis from beta blockers, calcium channel blockers, or lithium) 3. active ongoing inflammatory diseases other than psoriasis and psoriatic arthritis that might confound trial evaluations according to investigator's judgment * Previous exposure to BI 655066. * Previous exposure to ustekinumab (Stelara®).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving 90% Improvement in Psoriasis Area and Severity Index (PASI) Score (PASI90) at Week 16 in Participants Who Received Risankizumab Compared With Placebo (Part A) | Week 16 | 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 severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI90 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. Nonresponder imputation (NRI) was used for missing data. |
| Percentage of Participants Achieving Static Physician Global Assessment (sPGA) Score of Clear or Almost Clear at Week 16 in Participants Who Received Risankizumab Compared With Placebo (Part A) | Week 16 | The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) 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 three; 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. NRI was used for missing data. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Dermatology Life Quality Index (DLQI) Score of 0 or 1 at Week 16 in Participants Who Received Risankizumab Compared With Placebo (Part A) | Week 16 | DLQI is a 10-question questionnaire that asks the participant to evaluate the degree that psoriasis has affected their quality of life in the last week and includes 6 domains (symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment). Responses to each domain are not relevant (0), not at all (0), a little (1), a lot (2), and very much (3). The DLQI is calculated by summing the scores of the questions and ranges from 0 to 30, where 0-1 = no effect on patient's life, 2-5 = small effect, 6-10 = moderate effect, 11-20 = very large effect, and 21-30 = extremely large effect on patient's life. The higher the score, the more the quality of life is impaired.). A 5-point change from baseline is considered a clinically important difference. NRI was used for missing data. |
| Percentage of Participants Achieving Psoriasis Symptoms Scale (PSS) Total Score of 0 at Week 16 in Participants Who Received Risankizumab Compared With Placebo (Part A) | Week 16 | The PSS asks the participant to rate the severity of symptoms of psoriasis in the last 24 hours (pain, redness, itching, and burning) using a 5-point Likert -type scale ranging from 0 (none) to 4 (very severe). The PSS total score is calculated by summing the scores of the questions and ranges from 0 to 16, where the higher the score, the greater the severity of psoriasis symptoms. NRI was used for missing data. |
| Percentage of Participants Achieving PASI90 at Week 16 in Participants Who Received Risankizumab Compared With Ustekinumab (Part A) | Week 16 | 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 severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI90 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. Nonresponder imputation (NRI) was used for missing data. |
| Percentage of Participants Achieving sPGA Score of Clear or Almost Clear at Week 16 in Participants Who Received Risankizumab Compared With Ustekinumab (Part A) | Week 16 | The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) 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 three; 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. NRI was used for missing data. |
| Percentage of Participants Achieving PASI100 at Week 16 in Participants Who Received Risankizumab Compared With Ustekinumab (Part A) | Week 16 | 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 severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI100 is defined as a 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. NRI was used for missing data. |
| Percentage of Participants Achieving sPGA Score of Clear at Week 16 in Participants Who Received Risankizumab Compared With Ustekinumab (Part A) | Week 16 | The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) 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 three; 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. NRI was used for missing data. |
| Percentage of Participants Achieving sPGA Score of Clear at Week 16 in Participants Who Received Risankizumab Compared With Placebo (Part A) | Week 16 | The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) 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 three; 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. NRI was used for missing data. |
| Percentage of Participants Achieving PASI100 at Week 52 in Participants Who Received Risankizumab Compared With Ustekinumab (Part B) | 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 severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI100 is defined as a 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. Nonresponder imputation (NRI) was used for missing data. |
| Percentage of Participants Achieving sPGA Score of Clear at Week 52 in Participants Who Received Risankizumab Compared With Ustekinumab (Part B) | Week 52 | The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) 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 three; 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. NRI was used for missing data. |
| Percentage of Participants Achieving PASI75 at Week 12 in Participants Who Received Risankizumab Compared With Ustekinumab (Part A) | Week 12 | 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 severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI75 is defined as at least a 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. NRI was used for missing data. |
| Percentage of Participants Achieving sPGA Score of Clear or Almost Clear at Week 12 in Participants Who Received Risankizumab Compared With Ustekinumab (Part A) | Week 12 | The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) 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 three; 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. NRI was used for missing data. |
| Percentage of Participants Achieving DLQI Score of 0 or 1 at Week 16 in Participants Who Received Risankizumab Compared With Ustekinumab (Part A) | Week 16 | DLQI is a 10-question questionnaire that asks the participant to evaluate the degree that psoriasis has affected their quality of life in the last week and includes 6 domains (symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment). Responses to each domain are not relevant (0), not at all (0), a little (1), a lot (2), and very much (3). The DLQI is calculated by summing the scores of the questions and ranges from 0 to 30, where 0-1 = no effect on patient's life, 2-5 = small effect, 6-10 = moderate effect, 11-20 = very large effect, and 21-30 = extremely large effect on patient's life. The higher the score, the more the quality of life is impaired.). A 5-point change from baseline is considered a clinically important difference. NRI was used for missing data. |
| PSS Total Score: Change From Baseline to Week 16 in Participants Who Received Risankizumab Compared With Placebo (Part A) | Baseline, Week 16 | The PSS asks the participant to rate the severity of symptoms of psoriasis in the last 24 hours (pain, redness, itching, and burning) using a 5-point Likert -type scale ranging from 0 (none) to 4 (very severe). The PSS total score is calculated by summing the scores of the questions and ranges from 0 to 16, where the higher the score, the greater the severity of psoriasis symptoms. A negative change from Baseline indicates improvement. Last observation carried forward (LOCF) imputation was used for missing data. |
| Percentage of Participants Achieving PASI90 at Week 52 in Participants Who Received Risankizumab Compared With Ustekinumab (Part B) | 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 severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI90 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. Nonresponder imputation (NRI) was used for missing data. |
| Percentage of Participants Achieving PASI100 at Week 16 in Participants Who Received Risankizumab Compared With Placebo (Part A) | Week 16 | 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 severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI100 is defined as a 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. NRI was used for missing data. |
Participant flow
Pre-assignment details
A total of 560 subjects were enrolled; 54 subjects failed screening and are excluded from the analyses.
Participants by arm
| Arm | Count |
|---|---|
| Placebo (Part A) Participants randomized to receive double-blind (DB) placebo by subcutaneous (SC) injection at Weeks 0 and 4 (Part A). | 102 |
| Ustekinumab (Part A) Participants randomized to receive double-blind (DB) ustekinumab 45 mg or 90 mg (based on screening weight) by subcutaneous (SC) injection at Weeks 0 and 4 (Part A). | 100 |
| Risankizumab (Part A) Participants randomized to receive double-blind (DB) risankizumab 150 mg by subcutaneous (SC) injection at Weeks 0 and 4 (Part A). | 304 |
| Total | 506 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Part A | Adverse Event | 2 | 0 | 1 | 0 | 0 | 0 |
| Part A | Lost to Follow-up | 1 | 1 | 0 | 0 | 0 | 0 |
| Part A | Other | 0 | 0 | 1 | 0 | 0 | 0 |
| Part A | Subject Withdrawal | 1 | 0 | 3 | 0 | 0 | 0 |
| Part B | Adverse Event | 0 | 0 | 0 | 0 | 2 | 1 |
| Part B | Lost to Follow-up | 0 | 0 | 0 | 1 | 2 | 5 |
| Part B | Subject Withdrawal | 0 | 0 | 0 | 1 | 1 | 2 |
Baseline characteristics
| Characteristic | Placebo (Part A) | Ustekinumab (Part A) | Risankizumab (Part A) | Total |
|---|---|---|---|---|
| Age, Continuous | 49.3 years STANDARD_DEVIATION 13.63 | 46.5 years STANDARD_DEVIATION 13.42 | 48.3 years STANDARD_DEVIATION 13.39 | 48.1 years STANDARD_DEVIATION 13.45 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 12 Participants | 23 Participants | 47 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 90 Participants | 88 Participants | 281 Participants | 459 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 2 Participants | 7 Participants | 11 Participants |
| Race (NIH/OMB) Asian | 28 Participants | 22 Participants | 86 Participants | 136 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 10 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 71 Participants | 74 Participants | 200 Participants | 345 Participants |
| Sex: Female, Male Female | 23 Participants | 30 Participants | 92 Participants | 145 Participants |
| Sex: Female, Male Male | 79 Participants | 70 Participants | 212 Participants | 361 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 / 102 | 0 / 100 | 0 / 304 | 0 / 97 | 0 / 99 | 0 / 297 |
| other Total, other adverse events | 16 / 102 | 16 / 100 | 45 / 304 | 25 / 97 | 36 / 99 | 75 / 297 |
| serious Total, serious adverse events | 3 / 102 | 8 / 100 | 7 / 304 | 3 / 97 | 4 / 99 | 16 / 297 |
Outcome results
Primary
Percentage of Participants Achieving 90% Improvement in Psoriasis Area and Severity Index (PASI) Score (PASI90) at Week 16 in Participants Who Received Risankizumab Compared With Placebo (Part A)
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 severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI90 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. Nonresponder imputation (NRI) was used for missing data.
Time frame: Week 16
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Part A) | Percentage of Participants Achieving 90% Improvement in Psoriasis Area and Severity Index (PASI) Score (PASI90) at Week 16 in Participants Who Received Risankizumab Compared With Placebo (Part A) | 4.9 percentage of participants |
| Risankizumab (Part A) | Percentage of Participants Achieving 90% Improvement in Psoriasis Area and Severity Index (PASI) Score (PASI90) at Week 16 in Participants Who Received Risankizumab Compared With Placebo (Part A) | 75.3 percentage of participants |
p-value: <0.00195% CI: [64, 76.7]Cochran-Mantel-Haenszel
Primary
Percentage of Participants Achieving Static Physician Global Assessment (sPGA) Score of Clear or Almost Clear at Week 16 in Participants Who Received Risankizumab Compared With Placebo (Part A)
The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) 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 three; 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. NRI was used for missing data.
Time frame: Week 16
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Part A) | Percentage of Participants Achieving Static Physician Global Assessment (sPGA) Score of Clear or Almost Clear at Week 16 in Participants Who Received Risankizumab Compared With Placebo (Part A) | 7.8 percentage of participants |
| Risankizumab (Part A) | Percentage of Participants Achieving Static Physician Global Assessment (sPGA) Score of Clear or Almost Clear at Week 16 in Participants Who Received Risankizumab Compared With Placebo (Part A) | 87.8 percentage of participants |
p-value: <0.00195% CI: [73.5, 86.3]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving Dermatology Life Quality Index (DLQI) Score of 0 or 1 at Week 16 in Participants Who Received Risankizumab Compared With Placebo (Part A)
DLQI is a 10-question questionnaire that asks the participant to evaluate the degree that psoriasis has affected their quality of life in the last week and includes 6 domains (symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment). Responses to each domain are not relevant (0), not at all (0), a little (1), a lot (2), and very much (3). The DLQI is calculated by summing the scores of the questions and ranges from 0 to 30, where 0-1 = no effect on patient's life, 2-5 = small effect, 6-10 = moderate effect, 11-20 = very large effect, and 21-30 = extremely large effect on patient's life. The higher the score, the more the quality of life is impaired.). A 5-point change from baseline is considered a clinically important difference. NRI was used for missing data.
Time frame: Week 16
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Part A) | Percentage of Participants Achieving Dermatology Life Quality Index (DLQI) Score of 0 or 1 at Week 16 in Participants Who Received Risankizumab Compared With Placebo (Part A) | 7.8 percentage of participants |
| Risankizumab (Part A) | Percentage of Participants Achieving Dermatology Life Quality Index (DLQI) Score of 0 or 1 at Week 16 in Participants Who Received Risankizumab Compared With Placebo (Part A) | 65.8 percentage of participants |
p-value: <0.00195% CI: [50.4, 65.3]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving DLQI Score of 0 or 1 at Week 16 in Participants Who Received Risankizumab Compared With Ustekinumab (Part A)
DLQI is a 10-question questionnaire that asks the participant to evaluate the degree that psoriasis has affected their quality of life in the last week and includes 6 domains (symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment). Responses to each domain are not relevant (0), not at all (0), a little (1), a lot (2), and very much (3). The DLQI is calculated by summing the scores of the questions and ranges from 0 to 30, where 0-1 = no effect on patient's life, 2-5 = small effect, 6-10 = moderate effect, 11-20 = very large effect, and 21-30 = extremely large effect on patient's life. The higher the score, the more the quality of life is impaired.). A 5-point change from baseline is considered a clinically important difference. NRI was used for missing data.
Time frame: Week 16
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Part A) | Percentage of Participants Achieving DLQI Score of 0 or 1 at Week 16 in Participants Who Received Risankizumab Compared With Ustekinumab (Part A) | 43.0 percentage of participants |
| Risankizumab (Part A) | Percentage of Participants Achieving DLQI Score of 0 or 1 at Week 16 in Participants Who Received Risankizumab Compared With Ustekinumab (Part A) | 65.8 percentage of participants |
p-value: <0.00195% CI: [11.9, 34]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving PASI100 at Week 16 in Participants Who Received Risankizumab Compared With Placebo (Part A)
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 severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI100 is defined as a 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. NRI was used for missing data.
Time frame: Week 16
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Part A) | Percentage of Participants Achieving PASI100 at Week 16 in Participants Who Received Risankizumab Compared With Placebo (Part A) | 0 percentage of participants |
| Risankizumab (Part A) | Percentage of Participants Achieving PASI100 at Week 16 in Participants Who Received Risankizumab Compared With Placebo (Part A) | 35.9 percentage of participants |
p-value: <0.00195% CI: [30, 41]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving PASI100 at Week 16 in Participants Who Received Risankizumab Compared With Ustekinumab (Part A)
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 severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI100 is defined as a 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. NRI was used for missing data.
Time frame: Week 16
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Part A) | Percentage of Participants Achieving PASI100 at Week 16 in Participants Who Received Risankizumab Compared With Ustekinumab (Part A) | 12.0 percentage of participants |
| Risankizumab (Part A) | Percentage of Participants Achieving PASI100 at Week 16 in Participants Who Received Risankizumab Compared With Ustekinumab (Part A) | 35.9 percentage of participants |
p-value: <0.00195% CI: [15.5, 32.1]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving PASI100 at Week 52 in Participants Who Received Risankizumab Compared With Ustekinumab (Part B)
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 severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI100 is defined as a 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. Nonresponder imputation (NRI) was used for missing data.
Time frame: Week 52
Population: ITT population. Non-responder imputation. Analysis performed on all participants randomized to ustekinumab or risankizumab treatment in Part A.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Part A) | Percentage of Participants Achieving PASI100 at Week 52 in Participants Who Received Risankizumab Compared With Ustekinumab (Part B) | 21.0 percentage of participants |
| Risankizumab (Part A) | Percentage of Participants Achieving PASI100 at Week 52 in Participants Who Received Risankizumab Compared With Ustekinumab (Part B) | 56.3 percentage of participants |
p-value: <0.00195% CI: [25.7, 44.6]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving PASI75 at Week 12 in Participants Who Received Risankizumab Compared With Ustekinumab (Part A)
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 severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI75 is defined as at least a 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. NRI was used for missing data.
Time frame: Week 12
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Part A) | Percentage of Participants Achieving PASI75 at Week 12 in Participants Who Received Risankizumab Compared With Ustekinumab (Part A) | 70.0 percentage of participants |
| Risankizumab (Part A) | Percentage of Participants Achieving PASI75 at Week 12 in Participants Who Received Risankizumab Compared With Ustekinumab (Part A) | 86.8 percentage of participants |
p-value: <0.00195% CI: [7.4, 26.6]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving PASI90 at Week 16 in Participants Who Received Risankizumab Compared With Ustekinumab (Part A)
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 severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI90 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. Nonresponder imputation (NRI) was used for missing data.
Time frame: Week 16
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Part A) | Percentage of Participants Achieving PASI90 at Week 16 in Participants Who Received Risankizumab Compared With Ustekinumab (Part A) | 42.0 percentage of participants |
| Risankizumab (Part A) | Percentage of Participants Achieving PASI90 at Week 16 in Participants Who Received Risankizumab Compared With Ustekinumab (Part A) | 75.3 percentage of participants |
p-value: <0.00195% CI: [22.7, 44.3]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving PASI90 at Week 52 in Participants Who Received Risankizumab Compared With Ustekinumab (Part B)
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 severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI90 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. Nonresponder imputation (NRI) was used for missing data.
Time frame: Week 52
Population: ITT population. Non-responder imputation. Analysis performed on all participants randomized to ustekinumab or risankizumab treatment in Part A.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Part A) | Percentage of Participants Achieving PASI90 at Week 52 in Participants Who Received Risankizumab Compared With Ustekinumab (Part B) | 44.0 percentage of participants |
| Risankizumab (Part A) | Percentage of Participants Achieving PASI90 at Week 52 in Participants Who Received Risankizumab Compared With Ustekinumab (Part B) | 81.9 percentage of participants |
Comparison: P-value calculated according to the Cochran-Mantel-Haenszel test adjusted for baseline weight (≤100 kg vs \>100 kg) and prior exposure to TNF antagonists (0 vs ≥1).p-value: <0.00195% CI: [27.9, 48.6]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving Psoriasis Symptoms Scale (PSS) Total Score of 0 at Week 16 in Participants Who Received Risankizumab Compared With Placebo (Part A)
The PSS asks the participant to rate the severity of symptoms of psoriasis in the last 24 hours (pain, redness, itching, and burning) using a 5-point Likert -type scale ranging from 0 (none) to 4 (very severe). The PSS total score is calculated by summing the scores of the questions and ranges from 0 to 16, where the higher the score, the greater the severity of psoriasis symptoms. NRI was used for missing data.
Time frame: Week 16
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Part A) | Percentage of Participants Achieving Psoriasis Symptoms Scale (PSS) Total Score of 0 at Week 16 in Participants Who Received Risankizumab Compared With Placebo (Part A) | 2.0 percentage of participants |
| Risankizumab (Part A) | Percentage of Participants Achieving Psoriasis Symptoms Scale (PSS) Total Score of 0 at Week 16 in Participants Who Received Risankizumab Compared With Placebo (Part A) | 29.3 percentage of participants |
p-value: <0.00195% CI: [21.2, 32.9]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving sPGA Score of Clear at Week 16 in Participants Who Received Risankizumab Compared With Placebo (Part A)
The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) 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 three; 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. NRI was used for missing data.
Time frame: Week 16
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Part A) | Percentage of Participants Achieving sPGA Score of Clear at Week 16 in Participants Who Received Risankizumab Compared With Placebo (Part A) | 2.0 percentage of participants |
| Risankizumab (Part A) | Percentage of Participants Achieving sPGA Score of Clear at Week 16 in Participants Who Received Risankizumab Compared With Placebo (Part A) | 36.8 percentage of participants |
p-value: <0.00195% CI: [28.6, 40.8]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving sPGA Score of Clear at Week 16 in Participants Who Received Risankizumab Compared With Ustekinumab (Part A)
The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) 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 three; 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. NRI was used for missing data.
Time frame: Week 16
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Part A) | Percentage of Participants Achieving sPGA Score of Clear at Week 16 in Participants Who Received Risankizumab Compared With Ustekinumab (Part A) | 14.0 percentage of participants |
| Risankizumab (Part A) | Percentage of Participants Achieving sPGA Score of Clear at Week 16 in Participants Who Received Risankizumab Compared With Ustekinumab (Part A) | 36.8 percentage of participants |
p-value: <0.00195% CI: [14.3, 31.6]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving sPGA Score of Clear at Week 52 in Participants Who Received Risankizumab Compared With Ustekinumab (Part B)
The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) 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 three; 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. NRI was used for missing data.
Time frame: Week 52
Population: ITT population. Non-responder imputation. Analysis performed on all participants randomized to ustekinumab or risankizumab treatment in Part A.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Part A) | Percentage of Participants Achieving sPGA Score of Clear at Week 52 in Participants Who Received Risankizumab Compared With Ustekinumab (Part B) | 21.0 percentage of participants |
| Risankizumab (Part A) | Percentage of Participants Achieving sPGA Score of Clear at Week 52 in Participants Who Received Risankizumab Compared With Ustekinumab (Part B) | 57.6 percentage of participants |
p-value: <0.00195% CI: [27, 45.9]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving sPGA Score of Clear or Almost Clear at Week 12 in Participants Who Received Risankizumab Compared With Ustekinumab (Part A)
The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) 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 three; 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. NRI was used for missing data.
Time frame: Week 12
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Part A) | Percentage of Participants Achieving sPGA Score of Clear or Almost Clear at Week 12 in Participants Who Received Risankizumab Compared With Ustekinumab (Part A) | 65.0 percentage of participants |
| Risankizumab (Part A) | Percentage of Participants Achieving sPGA Score of Clear or Almost Clear at Week 12 in Participants Who Received Risankizumab Compared With Ustekinumab (Part A) | 82.2 percentage of participants |
p-value: <0.00195% CI: [7.3, 27.3]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving sPGA Score of Clear or Almost Clear at Week 16 in Participants Who Received Risankizumab Compared With Ustekinumab (Part A)
The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) 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 three; 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. NRI was used for missing data.
Time frame: Week 16
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Part A) | Percentage of Participants Achieving sPGA Score of Clear or Almost Clear at Week 16 in Participants Who Received Risankizumab Compared With Ustekinumab (Part A) | 63.0 percentage of participants |
| Risankizumab (Part A) | Percentage of Participants Achieving sPGA Score of Clear or Almost Clear at Week 16 in Participants Who Received Risankizumab Compared With Ustekinumab (Part A) | 87.8 percentage of participants |
p-value: <0.00195% CI: [15.2, 35]Cochran-Mantel-Haenszel
Secondary
PSS Total Score: Change From Baseline to Week 16 in Participants Who Received Risankizumab Compared With Placebo (Part A)
The PSS asks the participant to rate the severity of symptoms of psoriasis in the last 24 hours (pain, redness, itching, and burning) using a 5-point Likert -type scale ranging from 0 (none) to 4 (very severe). The PSS total score is calculated by summing the scores of the questions and ranges from 0 to 16, where the higher the score, the greater the severity of psoriasis symptoms. A negative change from Baseline indicates improvement. Last observation carried forward (LOCF) imputation was used for missing data.
Time frame: Baseline, Week 16
Population: ITT population. Last observation carried forward. Participants randomized to placebo or risankizumab with an observed baseline PSS and at least one post-baseline PSS observation on or prior to Week 16.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Part A) | PSS Total Score: Change From Baseline to Week 16 in Participants Who Received Risankizumab Compared With Placebo (Part A) | 0.157 units on a scale | Standard Error 0.3476 |
| Risankizumab (Part A) | PSS Total Score: Change From Baseline to Week 16 in Participants Who Received Risankizumab Compared With Placebo (Part A) | -5.608 units on a scale | Standard Error 0.2254 |
Comparison: P-value calculated by the van Elteren test stratified for baseline weight (≤100 kg vs \>100 kg) and prior exposure to TNF antagonists (0 vs ≥1).p-value: <0.00195% CI: [-6.496, -5.035]van Elteren test