BI 655066/ABBV-066 (Risankizumab) Compared to Active Comparator (Adalimumab) in Patients With Moderate to Severe Chronic Plaque Psoriasis

Study Overview
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Brief Summary
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This is a randomized double blind, double dummy, active comparator controlled, parallel design study that is performed to assess the safety and efficacy of BI 655066/ABBV-066 (risankizumab) compared to adalimumab to support registration for the treatment of moderate to severe chronic plaque psoriasis in adult patients.

Detailed Description
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This study consists of 2 parts (Part A and Part B). Part A: Participants were randomized to receive either risankizumab or adalimumab. Part B: Participants who received risankizumab in Part A continued to receive risankizumab in Part B Adalimumab nonresponders (<PASI 50 at Week 16) switched to risankizumab in Part B; Adalimumab responders (PASI 90 at Week 16) continued to received adalimumab in Part B; Adalimumab inadequate responders (PASI 50 to <PASI 90) were rerandomized to receive either risankizumab or adalimumab in Part B.

Official Title
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BI 655066/ABBV-066 (Risankizumab) Versus Adalimumab in a Randomized, Double Blind, Parallel Group Trial in Moderate to Severe Plaque Psoriasis to Assess Safety and Efficacy After 16 Weeks of Treatment and After Inadequate Adalimumab Treatment Response (IMMvent)

Conditions
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Psoriasis

Intervention / Treatment
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* Drug: risankizumab
* Biological: adalimumab
* Drug: placebo for risankizumab
* Biological: placebo for adalimumab


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Male or female patients. Women of childbearing potential* must be ready and able to use highly effective methods of birth control per ICH M3(R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information. *Women of childbearing potential are defined as: having experienced menarche and not postmenopausal (12 months with no menses without an alternative medical cause) and not permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral oophorectomy or bilateral salpingectomy). 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. Duration of diagnosis may be reported by the patient. Have stable moderate to severe chronic plaque psoriasis with or without psoriatic arthritis at both Screening and Baseline (Randomization): 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 candidates for treatment with adalimumab (Humira®) according to local label as confirmed by the investigator. Signed and dated written informed consent prior to admission to the study in accordance with GCP and local legislation 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 that might confound trial evaluations according to investigator's judgment Previous exposure to ABBV-066 Previous exposure to adalimumab (Humira®) Currently enrolled in another investigational study or less than 30 days or more from screening since completing another investigational drug or device study. Use of any restricted medication or any drug considered likely to interfere with the safe conduct of the study. Major surgery performed within 12 weeks prior to randomization or planned within 12 months after screening (e.g. hip replacement, removal aneurysm, stomach ligation). Known chronic or relevant acute infections, such as active tuberculosis (TB), human immunodeficiency virus (HIV) or viral hepatitis; QuantiFERON® TB test or purified protein derivative (PPD) skin test will be performed according to local labelling for Humira®. If the result is positive, patients may participate in the study if further work up (according to local practice/guidelines) establishes conclusively that the patient has no evidence of active TB. If presence of latent TB is established, then treatment should have been initiated and maintained according to local country guidelines. Any documented active or suspected malignancy or history of malignancy within 5 years prior to screening, except appropriately treated basal cell or squamous cell carcinoma of the skin or in situ carcinoma of uterine cervix. Evidence of a current or previous disease, medical condition (including chronic alcohol or drug abuse) other than psoriasis, surgical procedure (i.e., organ transplant), medical examination finding (including vital signs and electrocardiogram [ECG]), or laboratory value at the Screening Visit outside the reference range that in the opinion of the investigator is clinically significant and would make the study participant unreliable to adhere to the protocol or to complete the trial, compromise the safety of the patient, or compromise the quality of the data. History of allergy/hypersensitivity to a systemically administered biologic agent or its excipients Women who are pregnant, nursing, or who plan to become pregnant while in the trial Previous enrolment in this trial

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Adalimumab (Part A)<br>Participants randomized to receive double-blind (DB) adalimumab 80 mg by subcutaneous (SC) injection at Week 0, then 40 mg at Week 1 and every 2 weeks for 15 weeks (Part A). | Biological: adalimumab<br>* Adalimumab pre-filled syringe, administered by subcutaneous (SC) injection<br>* Other names: ABT-D2E7;Drug: placebo for risankizumab<br>* Placebo risankizumab administered by subcutaneous (SC) injection<br>|
| Experimental: Risankizumab (Part A)<br>Participants randomized to receive risankizumab at Weeks 0 and 4 (Part A). | Drug: risankizumab<br>* Risankizumab administered by subcutaneous (SC) injection<br>* Other names: SKYRIZI;Biological: placebo for adalimumab<br>* Placebo for adalimumab pre-filled syringe, 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 (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 (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 Who Were Re-Randomized to Receive Either Adalimumab or Risankizumab in Part B Achieving PASI90 at Week 44 (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. NRI was used for missing data. | Week 44 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving PASI75 at Week 16 (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 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. NRI was used for missing data. | Week 16 | 
| Percentage of Participants Achieving PASI100 at Week 16 (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 Who Were Rerandomized to Receive Either Adalimumab or Risankizumab in Part B Achieving PASI100 at Week 44 (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. NRI was used for missing data. | Week 44 | 
| Percentage of Participants Who Were ReRandomized to Receive Either Adalimumab or Risankizumab in Part B Achieving sPGA Score of Clear at Week 44 (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 44 | 

 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, Adalimumab, Anti-Inflammatory Agents, ABBV-066, BI 655066, Risankizumab