BI 655066 Dose Ranging in Psoriasis, Active Comparator Ustekinumab

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 in adult patients with chronic plaque psoriasis in order to select doses for further clinical trials.

Official Title
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A 48 Weeks Study of Three Different Dose Regimens of BI 655066 Administered Subcutaneously in Patients With Moderate to Severe Chronic Plaque Psoriasis (Randomised, Dose-ranging, Active-comparator-controlled (Ustekinumab), Double-blind Within Dose Groups of BI 655066)

Conditions
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Psoriasis

Intervention / Treatment
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* Drug: BI 655066
* Drug: BI 655066
* Drug: Ustekinumab
* Drug: BI 655066


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Body Mass Index (BMI) >/= 18.5 and < 40 kg/m² Patients with stable moderate to severe chronic plaque-type psoriasis with or without psoriatic arthritis involving >/= 10% body surface area, with disease severity PASI >/= 12 and sPGA score of moderate and above (score of at least 3) at screening visit and visit 2 (randomisation), as assessed by the investigator Psoriasis disease duration of at least 6 months prior to screening, as assessed by the investigator Patients must be candidates for systemic psoriasis treatment or phototherapy, as assessed by the investigator Patients must be suitable candidates for ustekinumab (Stelara®) therapy as given in the local labelling Patient must give informed consent and sign an approved consent form prior to any study procedures in accordance with GCP and local legislation Exclusion criteria: Patients with guttate, erythrodermic, or pustular psoriasis and patients with drug-induced psoriasis, as diagnosed by the investigator Evidence of current or previous clinically significant disease, medical condition other than psoriasis, or finding of the medical examination (including vital signs and ECG), that in the opinion of the investigator, would compromise the safety of the patient or the quality of the data. This criterion provides an opportunity for the investigator to exclude patients based on clinical judgment, even if other eligibility criteria are satisfied. (Psoriatic arthritis is not considered an exclusion criterion) Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders, diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders, or history of orthostatic hypotension, fainting spells or blackouts, that in the investigator's judgement, could jeopardize the safe conduct of the study. Clinically important acute or chronic infections including hepatitis and HIV. With regards to tuberculosis the following applies: Have signs or symptoms suggestive of current active or latent TB upon medical history, physical examination and/or a chest radiograph (both posterior-anterior and lateral views, taken within 3 months prior to the first administration of study drug and read by a qualified radiologist). Have history of latent or active TB prior to screening, except for patients who have documentation of having completed an adequate treatment regimen at least 6 months prior to the first administration of study agent. Have positive IGRA testing (QuantiFERON-TB Gold) within 2 months prior to or during screening, in which active TB has not been ruled out, except for patients with history of latent TB and documentation of having completed an adequate treatment regimen at least 6 months prior to the first administration of study agent. Have had a live vaccination </= 12 weeks prior to randomisation (visit 2). Patients must agree not to receive a live vaccination during the study. No BCG vaccines should be given for one year prior to randomisation (visit 2), during the study and for one year after last administration of study drug (according to the Stelara® SPC). History of clinically significant hypersensitivity to a systemically administered biologic agent or its excipients History of malignancy in the past 5 years or suspicion of active malignant disease except treated cutaneous squamous cell or basal cell carcinoma Has received any therapeutic agent directly targeted to IL-12, IL-23 (including ustekinumab (Stelara®)) Use of biologic agents within 12 weeks (infliximab, etanercept, adalimumab, other biologics) prior to treatment, systemic anti-psoriatic medications or phototherapy within 4 weeks prior to treatment, or topical anti-psoriasis medications within 2 weeks prior to treatment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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 |
| --- | --- |
| Experimental: Arm 1<br>BI 655066 s.c. | Drug: BI 655066<br>* Low dose<br>|
| Experimental: Arm 2<br>BI 655066 s.c. | Drug: BI 655066<br>* Medium dose<br>|
| Experimental: Arm 3<br>BI 655066 s.c. | Drug: BI 655066<br>* High dose<br>|
| Active Comparator: Arm 4<br>Ustekinumab s.c. | Drug: Ustekinumab<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Achievement of ≥90% Reduction From Baseline PASI Score (PASI90) at Week 12 | Percentage of participants who achieved ≥90% reduction from baseline in Psoriasis Area and Severity Index score (PASI90) at Week 12. PASI score ranges from 0 (best) to 72 (worst). | Baseline and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Achievement of ≥75% Reduction From Baseline in PASI Score (PASI75) at Weeks 12 and 24 | Percentage of participants who achieved ≥75% reduction from baseline in Psoriasis Area and Severity Index score (PASI75) at Weeks 12 and 24. PASI score ranges from 0 (best) to 72 (worst). | Baseline, Week 12 and Week 24 | 
| Achievement of 100% Reduction From Baseline in PASI Score (PASI100) at Week 12 | Percentage of participants who achieved 100% reduction from baseline in Psoriasis Area and Severity Index score (PASI100) at Week 12. PASI score ranges from 0 (best) to 72 (worst). | Baseline and Week 12 | 
| Achievement of ≥50% Reduction From Baseline in PASI Score (PASI50) at Week 12 | Percentage of participants who achieved ≥50% reduction from baseline in Psoriasis Area and Severity Index score (PASI50) at Week 12. PASI score ranges from 0 (best) to 72 (worst). | Baseline and Week 12 | 
| Achievement of PASI90 at Week 24 | Percentage of participants who achieved PASI90 at Week 24. PASI score ranges from 0 (best) to 72 (worst). | Week 24 | 
| Percentage Change in PASI Score From Baseline at Week 12 | Percentage change in Psoriasis Area and Severity Index (PASI) from baseline at Week 12. PASI score ranges from 0 (best) to 72 (worst). | Baseline and Week 12 | 
| Achievement of sPGA Clear or Almost Clear at Week 12 | Percentage of participants who achieved static Physician Global Assessment (sPGA) clear or almost clear at Week 12. sPGA is assessed on a six-point scale from 0 (clear) to 5 (severe). | Week 12 | 
| Time to Loss of PASI50 Response | Time to loss of PASI50 response. | From first drug administration until end of follow-up period, up to 48 weeks |