BI 655066 (Risankizumab) Compared to Placebo and Active Comparator (Ustekinumab) in Patients With Moderate to Severe Chronic Plaque Psoriasis

Study Overview
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Brief Summary
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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
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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.

Official Title
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BI 655066/ABBV-066 (Risankizumab) Versus Ustekinumab and Placebo Comparators in a Randomized Double Blind trIal for Maintenance Use in Moderate to Severe Plaque Type Psoriasis (UltIMMa-1)

Conditions
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Psoriasis

Intervention / Treatment
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* Drug: risankizumab
* Drug: placebo for risankizumab
* Drug: ustekinumab
* Drug: placebo for ustekinumab


Participation Criteria
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Eligibility Criteria
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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): Have an involved body surface area (BSA) ≥10% and Have a Psoriasis Area and Severity Index (PASI) score ≥12 and 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: non-plaque forms of psoriasis (including guttate, erythrodermic, or pustular) current drug-induced psoriasis (including an exacerbation of psoriasis from beta blockers, calcium channel blockers, or lithium) 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®).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo (Part A)<br>Participants randomized to receive double-blind (DB) placebo by subcutaneous (SC) injection at Weeks 0 and 4 (Part A). | Drug: placebo for risankizumab<br>* Placebo for risankizumab administered by subcutaneous (SC) injection<br>Drug: placebo for ustekinumab<br>* Placebo for ustekinumab administered by subcutaneous (SC) injection<br>|
| Active Comparator: Ustekinumab (Part A)<br>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). | Drug: placebo for risankizumab<br>* Placebo for risankizumab administered by subcutaneous (SC) injection<br>Drug: ustekinumab<br>* Ustekinumab administered by subcutaneous (SC) injection<br>|
| Experimental: Risankizumab (Part A)<br>Participants randomized to receive double-blind (DB) risankizumab 150 mg by subcutaneous (SC) injection at Weeks 0 and 4 (Part A). | Drug: risankizumab<br>* Risankizumab administered by subcutaneous (SC) injection<br>* Other names: SKYRIZI;Drug: placebo for ustekinumab<br>* Placebo for ustekinumab administered by subcutaneous (SC) injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Week 16 | 
| 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. | Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Week 16 | 
| 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. | Week 16 | 
| 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. | Week 16 | 
| 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. | Week 16 | 
| 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. | Week 16 | 
| 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. | Week 16 | 
| 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. | Week 16 | 
| 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. | Week 16 | 
| 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. | Week 52 | 
| 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. | Week 52 | 
| 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. | Week 52 | 
| 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. | Week 12 | 
| 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. | Week 12 | 
| 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. | Week 16 | 
| 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. | Baseline, Week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Psoriasis, Skin Diseases, Skin Diseases, Papulosquamous, ustekinumab, Dermatologic Agents, ABBV-066, BI 655066, risankizumab