This Study is Done in Patients With Plaque Psoriasis and Tests How Well They Tolerate BI 730357 and How Effective it is

Study Overview
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Brief Summary
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The primary objective is based on Week 12 co-primary endpoints of PASI (Psoriasis Area and Severity Index) 75 and sPGA (Static Physician's Global Assessment) 0/1, and overall safety Secondary objectives of Part 1 are to evaluate the efficacy and safety of BI 730357 through 24 weeks of treatment

Official Title
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Phase II Evaluation of Safety, Tolerability, and Efficacy of BI 730357 in Patients With Moderate-to-severe Plaque Psoriasis

Conditions
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Psoriasis

Intervention / Treatment
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* Drug: Placebo (fasted)
* Drug: BI 25 mg (fasted)
* Drug: BI 50 mg (fasted)
* Drug: BI 100 mg (fasted)
* Drug: BI 200 mg (fasted)
* Drug: Placebo (fed)
* Drug: BI 400 mg once daily (fed)
* Drug: BI 200 mg twice daily, 400 mg total (fed)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients. Woman Of Childbearing Potential (WoCBP) must be ready and able to use highly effective methods of birth control per International Conference on Harmonisation (ICH) M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly from date of screening until 4 weeks after last treatment in this trial. A list of contraception methods meeting these criteria is provided in the patient information. Age 18 to 75 years (both inclusive) at screening BMI < 35 kg/m2 at screening 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 Patients must be candidates for systemic PsO therapy.Moderate-to-severe plaque psoriasis: BSA ≥10% and PASI ≥12 and sPGA moderate or severe Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial Exclusion Criteria: Nonplaque forms of PsO (including guttate, erythrodermic, or pustular), current druginduced PsO (including a new onset or exacerbation of PsO from, e.g., beta blockers, calcium channel blockers, lithium), active ongoing inflammatory diseases (including but not limited to Inflammatory bowel disease (IBD)) other than PsO that might confound trial evaluations Previous enrolment in this trial or previous exposure to BI 730357. Current enrollment in another investigational device or drug trial, or is less than 30 days (from randomisation) since ending another investigational device or drug trial(s), or receipt of other investigational treatment(s). Use of any biologic agent within 12 weeks, or any anti IL-23 biologic agent within 24 weeks prior to randomisation, or systemic anti-psoriatic medications or phototherapy within 4 weeks prior to randomisation, or topical anti-psoriasis medications within 2 weeks prior to randomisation Receipt of a live vaccination within 12 weeks prior to randomisation (visit 2), or any plan to receive a live vaccination during the conduct of this trial Patients who must or wish to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial Patients not expected to comply with the protocol requirements or not expected to complete the trial as scheduled. Chronic alcohol or drug abuse or any condition that, in the investigator's opinion, makes the patient an unreliable trial participant or unlikely to complete the trial. Major surgery (major according to the investigator's assessment) performed within 12 weeks prior to randomisation or planned within 12 months after screening, e.g., hip replacement Women who are pregnant, nursing, or who plan to become pregnant while in the trial Any documented active or suspected malignancy or history of malignancy within 5 years prior to screening, except appropriately treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ carcinoma of uterine cervix Relevant chronic or acute infections including human immunodeficiency virus (HIV), viral hepatitis, candidiasis and tuberculosis. A patient can be re-screened if the patient was treated and is cured from the acute infection. Evidence of a current or previous disease (including known or suspected IBD, and cardiovascular disease), or medical finding 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. Any suicidal ideation, including grade 4 or 5 in the Columbia Suicide Severity Rating Scale (CSSRS) in the past 3 months (i.e., active suicidal thought with intent but without specific plan, or active suicidal thought with plan and intent). Unwillingness to adhere to the rules of UV-light protection Further exclusion criteria apply

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 |
| --- | --- |
| Placebo Comparator: Part I - Placebo (fasted)<br>Part I - Placebo matching BI 730357 taken orally once daily as a film-coated tablet in the morning while fasted for 12 weeks in period 1 followed by the same treatment for 12 weeks in period 2 (total treatment period of 24 weeks). Participants who failed to achieve a Psoriasis Area Severity Index score (PASI) 75 response at Week 12 were switched to a 200 mg dose, participants switching dose were imputed as failure for records after week 12, under original randomized treatment arm. | Drug: Placebo (fasted)<br>* Placebo matching BI 730357 taken orally once daily as a film-coated tablet in the morning while fasted for 12 weeks in period 1 followed by the same treatment for 12 weeks in period 2 (total treatment period of 24 weeks).<br>|
| Experimental: Part I - BI 25 mg (fasted)<br>Part I - 25 milligram (mg) BI 730357 taken orally once daily as a film-coated tablet in the morning while fasted for 12 weeks in period 1 followed by the same treatment for 12 weeks in period 2 (total treatment period of 24 weeks). Participants who failed to achieve a Psoriasis Area Severity Index score (PASI) 50 response at Week 12 were switched to a 50 mg dose, participants switching dose were imputed as failure for records after week 12, under original randomized treatment arm. | Drug: BI 25 mg (fasted)<br>* 25 milligram (mg) BI 730357 taken orally once daily as a film-coated tablet in the morning while fasted for 12 weeks in period 1 followed by the same treatment for 12 weeks in period 2 (total treatment period of 24 weeks).<br>|
| Experimental: Part I - BI 50 mg (fasted)<br>Part I - 50 milligram (mg) BI 730357 taken orally once daily as a film-coated tablet in the morning while fasted for 12 weeks in period 1 followed by the same treatment for 12 weeks in period 2 (total treatment period of 24 weeks). Participants who failed to achieve a Psoriasis Area Severity Index score (PASI) 50 response at Week 12 were switched to a 100 mg dose, participants switching dose were imputed as failure for records after week 12, under original randomized treatment arm. | Drug: BI 50 mg (fasted)<br>* 50 milligram (mg) BI 730357 taken orally once daily as a film-coated tablet in the morning while fasted for 12 weeks in period 1 followed by the same treatment for 12 weeks in period 2 (total treatment period of 24 weeks).<br>|
| Experimental: Part I - BI 100 mg (fasted)<br>Part I - 100 milligram (mg) BI 730357 taken orally once daily as a film-coated tablet in the morning while fasted for 12 weeks in period 1 followed by the same treatment for 12 weeks in period 2 (total treatment period of 24 weeks). Participants who failed to achieve a Psoriasis Area Severity Index score (PASI) 50 response at Week 12 were switched to a 200 mg dose, participants switching dose were imputed as failure for records after week 12, under original randomized treatment arm. | Drug: BI 100 mg (fasted)<br>* 100 milligram (mg) BI 730357 taken orally once daily as a film-coated tablet in the morning while fasted for 12 weeks in period 1 followed by the same treatment for 12 weeks in period 2 (total treatment period of 24 weeks).<br>|
| Experimental: Part I - BI 200 mg (fasted)<br>Part I - 200 milligram (mg) BI 730357 taken orally once daily as a film-coated tablet in the morning while fasted for 12 weeks in period 1 followed by the same treatment for 12 weeks in period 2 (total treatment period of 24 weeks). | Drug: BI 200 mg (fasted)<br>* 200 milligram (mg) BI 730357 taken orally once daily as a film-coated tablet in the morning while fasted for 12 weeks in period 1 followed by the same treatment for 12 weeks in period 2 (total treatment period of 24 weeks).<br>|
| Placebo Comparator: Part II - Placebo (fed)<br>Part II - 4 film-coated tablets of matching Placebo were taken orally in the morning with a meal and 2 film-coated tablets of matching Placebo were taken orally in the evening with a meal for 12 weeks. | Drug: Placebo (fed)<br>* 4 film-coated tablets of matching Placebo were taken orally in the morning with a meal and 2 film-coated tablets of matching Placebo were taken orally in the evening with a meal for 12 weeks.<br>|
| Experimental: Part II - BI 400 mg once daily (fed)<br>Part II - 4 film-coated tablets of 100 milligram (mg) BI 730357 (400 mg in total) were taken orally in the morning with a meal and 2 film-coated tablets of matching Placebo were taken orally in the evening with a meal for 12 weeks. | Drug: BI 400 mg once daily (fed)<br>* 4 film-coated tablets of 100 milligram (mg) BI 730357 (400 mg in total) were taken orally in the morning with a meal and 2 film-coated tablets of matching Placebo were taken orally in the evening with a meal for 12 weeks.<br>|
| Experimental: Part II - BI 200 mg twice daily, 400 mg total (fed)<br>Part II - 2 film-coated tablets of 100 milligram (mg) BI 730357 were taken orally with a meal in the morning and evening (twice daily; total daily dosage: 400 mg) for 12 weeks. | Drug: BI 200 mg twice daily, 400 mg total (fed)<br>* 2 film-coated tablets of 100 milligram (mg) BI 730357 were taken orally with a meal in the morning and evening (twice daily; total daily dosage: 400 mg) for 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Who Achieved Psoriasis Area Severity Index Score (PASI) 75 at Week 12 | Number of patients who achieved Psoriasis Area Severity Index score (PASI) 75 at week 12. The PASI is a tool which provides a numeric scoring for patients overall psoriasis disease state, ranging from 0 to 72. It is a linear combination of percent of surface area of skin that is affected and the severity of erythema, infiltration, and desquamation over four body regions. Higher scores indicating higher severity, while a score of 0 indicates no disease. PASI 75 is based on the percent reduction from baseline, generally summarized as a dichotomous outcome based on achieving over an 75% reduction. No statistical comparisons were planned or carried out for Part 2 of the trial. | Assesment at week 12 of treatment | 
| Number of Patients Who Achieved a Static Physician's Global Assessment Score of 'Clear' or 'Almost Clear' (sPGA 0/1) at Week 12. | Number of patients who achieved a static Physician's Global Assessment score of 'clear' or 'almost clear' (sPGA 0/1) at Week 12. The sPGA used in this trial is a 5 point score ranging from 0 to 4, based on the physician's assessment of the average thickness, erythema, and scaling of all psoriatic lesions. The assessment is considered static which refers to the patients disease state at the time of the assessments, without comparison to any of the subject's previous disease states, whether at Baseline or at a previous visit. A lower score indicates less body coverage, with 0 being clear and 1 being almost clear. No statistical comparisons were planned or carried out for Part 2 of the trial. | Assesment at week 12 of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Who Achieved Psoriasis Area Severity Index Score (PASI) 50 at Week 12 | Number of patients who achieved Psoriasis Area Severity Index score (PASI) 50 at week 12. The PASI is a tool which provides a numeric scoring for patients overall psoriasis disease state, ranging from 0 to 72. It is a linear combination of percent of surface area of skin that is affected and the severity of erythema, infiltration, and desquamation over four body regions. Higher scores indicating higher severity, while a score of 0 indicates no disease. PASI 50 is based on the percent reduction from baseline, generally summarized as a dichotomous outcome based on achieving over an 50% reduction. No hypothesis testing was planned or carried out for Part II. | Assesment at week 12 of treatment | 
| Number of Patients Who Achieved Psoriasis Area Severity Index Score (PASI) 90 at Week 12 | Number of patients who achieved Psoriasis Area Severity Index score (PASI) 90 at week 12. The PASI is a tool which provides a numeric scoring for patients overall psoriasis disease state, ranging from 0 to 72. It is a linear combination of percent of surface area of skin that is affected and the severity of erythema, infiltration, and desquamation over four body regions. Higher scores indicating higher severity, while a score of 0 indicates no disease. PASI 90 is based on the percent reduction from baseline, generally summarized as a dichotomous outcome based on achieving over an 90% reduction. No statistical comparisons were planned or carried out for Part 2 of the trial. Statistical analysis could not be performed for arms with 0 participants reaching PASI 90. | Assesment at week 12 of treatment | 
| Number of Patients Who Achieved Psoriasis Area Severity Index Score (PASI) 100 at Week 12 | Number of patients who achieved Psoriasis Area Severity Index score (PASI) 100 at week 12. The PASI is a tool which provides a numeric scoring for patients overall psoriasis disease state, ranging from 0 to 72. It is a linear combination of percent of surface area of skin that is affected and the severity of erythema, infiltration, and desquamation over four body regions. Higher scores indicating higher severity, while a score of 0 indicates no disease. PASI 100 is based on the percent reduction from baseline, generally summarized as a dichotomous outcome based on achieving over an 100% reduction. No statistical comparisons were planned or carried out for Part 2 of the trial. Statistical analysis could not be performed for arms with 0 participants reaching PASI 100. | Assesment at week 12 of treatment | 
| Number of Patients Who Achieved Psoriasis Area Severity Index Score (PASI) 75 at Weeks 16, 20, and 24 | Number of patients who achieved Psoriasis Area Severity Index score (PASI) 75 at weeks 16, 20 and 24. The PASI is a tool which provides a numeric scoring for patients overall psoriasis disease state, ranging from 0 to 72. It is a linear combination of percent of surface area of skin that is affected and the severity of erythema, infiltration, and desquamation over four body regions. Higher scores indicating higher severity, while a score of 0 indicates no disease. PASI 75 is based on the percent reduction from baseline, generally summarized as a dichotomous outcome based on achieving over an 75% reduction. | Assesment at week 16, 20 and 24 of treatment | 
| Number of Patients Who Achieved a Static Physician's Global Assessment Score of 'Clear' (sPGA 0) at Week 12 | Number of patients who achieved a static Physician's Global Assessment score of 'clear' (sPGA 0) at Week 12. The sPGA used in this trial is a 5 point score ranging from 0 to 4, based on the physician's assessment of the average thickness, erythema, and scaling of all psoriatic lesions. The assessment is considered static which refers to the patients disease state at the time of the assessments, without comparison to any of the subject's previous disease states, whether at Baseline or at a previous visit. A lower score indicates less body coverage, with 0 being clear and 1 being almost clear. No statistical comparisons were planned or carried out for Part 2 of the trial. | Assesment at week 12 of treatment | 
| Number of Patients Who Achieved a Static Physician's Global Assessment Score of 'Clear' or 'Almost Clear' (sPGA 0/1) at Weeks 16, 20, and 24 | Number of patients who achieved a static Physician's Global Assessment score of 'clear' or 'almost clear' (sPGA 0/1) at Week 16, 20 and 24. The sPGA used in this trial is a 5 point score ranging from 0 to 4, based on the physician's assessment of the average thickness, erythema, and scaling of all psoriatic lesions. The assessment is considered static which refers to the patients disease state at the time of the assessments, without comparison to any of the subject's previous disease states, whether at Baseline or at a previous visit. A lower score indicates less body coverage, with 0 being clear and 1 being almost clear. | Assesment at week 16, 20 and 24 of treatment | 
| Overall Change From Baseline in Psoriasis Symptoms Evaluated Using the Total Score of the Psoriasis Symptoms Scale (PSS) at Week 12 | Overall change from baseline in psoriasis symptoms evaluated using the total score of the Psoriasis Symptoms Scale (PSS) at Week 12. The PSS is a four-item patient-reported outcome (PRO) instrument that assesses the severity of psoriasis symptoms in patients with moderate to severe psoriasis. The symptoms included are: pain, redness, itching and burning from psoriasis. Current symptom severity is assessed for a 24 hour recall period using a 5-point verbal rating scale, the PSS score ranges from 0 (none) to 4 (very severe). The symptom scores are added to an unweighted total score (range: 0 to 16). Presented 'Mean' values are actually 'Adjusted Mean'. No hypothesis testing was planned or carried out for Part II. | Assesment at week 12 of treatment | 
| Number of Patients Who Achieved a Dermatology Life Quality Index Score of 'no Effect on Patient's Life' (DLQI 0/1) at Week 12 | Number of patients who achieved a Dermatology Life Quality Index score of 'no effect on patient's life' (DLQI 0/1) at Week 12. The DLQI is a subject-administered, ten-question, quality of life questionnaire covering 6 domains including symptoms and feelings, daily activities, leisure, work and school, personal relationships and treatment. Item scores range from 0 (not relevant/not at all) to 3 (very much). Question 7 is a yes/ no question where yes is scored as 3. DLQI total score is calculated by summing the scores of each question resulting in a range of 0 to 30 where 0-1 = no effect on subject's life, 2-5 = small effect, 6-10 = moderate effect, 11-20 = very large effect, and 21-30 = extremely large effect on subject's life. The higher the score, the more the quality of life is impaired. A 4-point change from baseline is considered a clinically important difference. No hypothesis testing was planned or carried out for Part II. | Assesment at week 12 of treatment |