BI 655066/ABBV-066/Risankizumab Compared to Placebo in Patients With Active Psoriatic Arthritis

Study Overview
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Brief Summary
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The overall purpose of this trial is to assess clinical efficacy and safety of different subcutaneous doses of BI 655066/ABBV-066/risankizumab in adult patients with psoriatic arthritis in order to select doses for further clinical trials.

Official Title
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A Randomised, Double-blind, Placebo-controlled, Proof-of-concept, Dose-ranging Study of BI 655066/ABBV-066/Risankizumab in Patients With Active Psoriatic Arthritis

Conditions
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Arthritis, Psoriatic

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


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Have psoriatic arthritis (PsA) symptoms for ≥ 6 months prior to screening, as assessed by the investigator Have PsA on the basis of the Classification Criteria for Psoriatic Arthritis (CASPAR) with peripheral symptoms at screening visit, as assessed by the investigator Have ≥ 5 tender joints and ≥ 5 swollen joints at screening and randomisation visits, as assessed by the investigator At least one psoriasis (PsO) lesion or a documented personal history of PsO at screening, as assessed by the investigator If patients receive concurrent PsA treatments, these need to be on stable doses Active PsA that has been inadequately controlled by standard doses of non-steroidal anti-inflammatory drugs (NSAIDs) administered for ≥ 4 weeks, or traditional disease-modifying anti-rheumatic drugs (DMARDs) (including sulfasalazine) administered for ≥ 3 months, or tumor necrosis factor inhibitor (TNFi) agents, or subjects are intolerant to NSAIDs or DMARDs or tumor necrosis factor inhibitor (TNFi) agents, as assessed by the investigator Exclusion criteria: Major chronic inflammatory or connective tissue disease other than PsA (e.g. rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, Lyme disease, gout) and fibromyalgia, as assessed by the investigator Has received any therapeutic agent directly targeted to interleukin 12/23 (IL-12/23) (including ustekinumab), IL-23 or IL-17 (including secukinumab) Prior use of more than two different TNFi agents Use of the following treatments: TNFi agents within 12 weeks, etanercept within 8 weeks, leflunomide without cholestyramine wash-out within 8 weeks, systemic non-biologic medications for psoriatic arthritis or psoriasis and photochemotherapy within 4 weeks, intraarticular injections (including steroids) and intramuscular or intravenous corticosteroid treatment within 4 weeks, topical psoriasis medications and phototherapy within 2 weeks, low and high potency opioid analgesics within 2 weeks prior to randomisation Plans for administration of live vaccines during the study period or within 6 weeks prior to randomisation History of allergy/hypersensitivity to a systemically administered biologic agent or its excipients Active systemic infections during the last 2 weeks (exception: common cold) prior to randomisation, as assessed by the investigator Chronic or relevant acute infections including HIV, viral hepatitis and (or) active tuberculosis (TB). Patients with a positive QuantiFERON TB or purified protein derivate (PPD) test 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. Any documented active or suspected malignancy or history of malignancy within 5 years prior to screening, except appropriately treated basal or squamous cell carcinoma of the skin or in situ carcinoma of uterine cervix Major surgery performed within 12 weeks prior to randomisation or planned within 32 weeks after randomisation (e.g. hip replacement, aneurysm removal, stomach ligation), as assessed by the investigator Total white blood count (WBC) < 3,000/µL, or platelets < 100,000/µL or neutrophils < 1,500/µL, or hemoglobin < 8.5 g/dL at screening Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2x the upper limit of normal, or serum direct bilirubin ≥ 1.5 mg/dL at screening Positive rheumatoid factor or anti-cyclic-citrullinated peptide (anti-CCP) antibodies at screening

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 |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants randomized to receive double-blind (DB) placebo for risankizumab by subcutaneous (SC) injection every 4 weeks for 16 weeks. | Drug: placebo for risankizumab<br>* Placebo for risankizumab administered by SC injection<br>|
| Experimental: Risankizumab 150 mg Every 4 Weeks<br>Participants randomized to receive double-blind (DB) risankizumab 150 mg by subcutaneous (SC) injection every 4 weeks for 16 weeks. | Drug: risankizumab<br>* Risankizumab administered by SC injection<br>* Other names: SKYRIZI;|
| Experimental: Risankizumab 150 mg Weeks 0, 4, and 16<br>Participants randomized to receive double-blind (DB) risankizumab 150 mg by subcutaneous (SC) injection at Weeks 0, 4, and 16. | Drug: risankizumab<br>* Risankizumab administered by SC injection<br>* Other names: SKYRIZI;|
| Experimental: Risankizumab 150 mg Weeks 0 and 12<br>Participants randomized to receive double-blind (DB) risankizumab 150 mg by subcutaneous (SC) injection at Weeks 0 and 12. | Drug: risankizumab<br>* Risankizumab administered by SC injection<br>* Other names: SKYRIZI;|
| Experimental: Risankizumab 75 mg Week 0<br>Participants randomized to receive double-blind (DB) risankizumab 75 mg by subcutaneous (SC) injection at Week 0. | Drug: risankizumab<br>* Risankizumab administered by SC injection<br>* Other names: SKYRIZI;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 16 | Response defined by ACR20 criteria (improvement from baseline) at Week 16: ≥ 20% improvement in tender joint count; ≥ 20% improvement in swollen joint count; and ≥ 20% improvement in at least 3 of the 5 following parameters: Patient assessment of pain Patient global assessment of disease activity Investigator's global assessment of disease activity Health Assessment Questionnaire Disability Index (HAQ-DI) Acute phase reactant value (C-reactive protein). Nonresponder imputation (NRI) was used for missing data. | Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Week 16 | Response defined by ACR50 criteria (improvement from baseline) at Week 16: ≥ 50% improvement in tender joint count; ≥ 50% improvement in swollen joint count; and ≥ 50% improvement in at least 3 of the 5 following parameters: Patient assessment of pain Patient global assessment of disease activity Investigator's global assessment of disease activity HAQ-DI Acute phase reactant value (C-reactive protein). NRI was used for missing data. | Week 16 | 
| Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response at Week 16 | Response defined by ACR70 criteria (improvement from baseline) at Week 16: ≥ 70% improvement in tender joint count; ≥ 70% improvement in swollen joint count; and ≥ 70% improvement in at least 3 of the 5 following parameters: Patient assessment of pain Patient global assessment of disease activity Investigator's global assessment of disease activity HAQ-DI Acute phase reactant value (C-reactive protein). NRI was used for missing data. | Week 16 | 
| Tender Joint Count (TJC68): Change From Baseline to Week 16 | Sixty-eight joints were assessed and classified as either tender (1) or not tender (0). A negative change represents a decrease in the number of tender joints. | Baseline, Week 16 | 
| Swollen Joint Count (SJC): Change From Baseline to Week 16 | Sixty-six joints were assessed and classified as either swollen (1) or not swollen (0). A negative change represents a decrease in the number of tender joints. | Baseline, Week 16 | 
| Health Assessment Questionnaire Disability Index (HAQ-DI) Score: Change From Baseline to Week 16 | The HAQ-DI is a patient-reported questionnaire specific for rheumatoid arthritis that consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where 0 represents no disability and 3 very severe, high-dependency disability. HAQ remission indicating normal physical function is defined by HAQ-DI score of < 0.5. A negative change from Baseline indicates improvement. | Baseline, Week 16 | 
| Short Form-36 Health Status Survey (SF-36) Physical Component: Change From Baseline to Week 16 | The SF-36 determined participant's overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 comprise the physical component of the SF-36. Scores on each item were summed and averaged (range = 0-100); a positive change from Baseline indicates improvement. | Baseline, Week 16 | 
| SF-36 Mental Component: Change From Baseline to Week 16 | The SF-36 determined participant's overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 5-8 comprise the mental component of the SF-36. Scores on each item were summed and averaged (range = 0-100); a positive change from Baseline indicates improvement. | Baseline, Week 16 | 
| Dactylitis Count: Change From Baseline to Week 16 in Participants With Dactylitis at Baseline | The number of fingers and toes with dactylitis (ranging from 0 to 20). A negative change represents a decrease in the number of fingers and toes affected by dactylitis. | Baseline, Week 16 | 
| Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index: Change From Baseline to Week 16 in Participants With Enthesitis at Baseline | Assessment of enthesitis was performed in the following 16 domains: left and right (L/R) medial epicondyle; L/R lateral epicondyle; L/R supraspinatus insertion into the greater tuberosity of humerus; L/R greater trochanter; L/R quadriceps insertion into superior border of patella; L/R patellar ligament insertion into inferior pole of patella or tibial tubercle; L/R Achilles tendon insertion into calcaneum; L/R plantar fascia insertion into calcaneum. Tenderness at each site was classified as either absent (0) or present (1) to yield total SPARCC scores ranging from 0 (0 sites with tenderness) to 16 (16 sites with tenderness). A negative change from Baseline indicates improvement. | Baseline, Week 16 | 
| Modified Nail Psoriasis Severity Index (mNAPSI): Change From Baseline to Week 16 | mNAPSI grades each fingernail for onycholysis (separation of the nail plate from the nail bed) and oil-drop (salmon patch) dyschromia (reddish-brown discoloration under the nail plate) on a scale of 0 (none present) to 3 (>30% of the nail); pitting (small, sharply defined depressions in the nail surface) on a scale of 0 (0 pits present) to 3 (>50 pits present); nail plate crumbling on a scale of 0 (no crumbling) to 3 (>50% of nail has crumbling); and presence (1) or absence (0) of leukonychia (white spots), splinter hemorrhages, nail bed hyperkeratosis, and red spots in the lunula. mNAPSI is calculated as the sum of all the components for all of the participants fingernails, for a minimal - maximal total score of 0 to 130. A negative change from Baseline indicates improvement. | Baseline, Week 16 | 
| Percentage of Participants Achieving 90% Improvement in Psoriasis Area and Severity Index (PASI) Score (PASI90) at 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. The percentage of participants achieving PASI90 at Week 16 are provided. NRI was used for missing data. | Week 16 |