A Study to Test How Well Patients With Plaque Psoriasis Tolerate BI 730357 Over a Longer Period and How Effective it is

Study Overview
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Brief Summary
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To assess long-term safety, tolerability, and efficacy of BI 730357 in patients with moderate to severe chronic plaque psoriasis.

Official Title
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Phase II Long-term Extension Study to Assess the 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: BI 730357
* Drug: Placebo to match BI 730357


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Woman Of Child Bearing 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. Patients with moderate-to-severe plaque Psoriasis (PsO) who have completed treatment in the preceding trial without early discontinuation, agree to continue treatment in 1407-0005, and for patients entering from Part 1 of trial 1407-0030 --- achieve a ≥PASI50 response upon completing the trial 1407-0030 Week 24 end-of-treatment visit for patients entering from Part 2 of trial 1407-0030 --- achieve a ≥PASI50 response upon completing the trial 1407-0030 Week 12 end-of-treatment visit or perceived patient improvement, at the discretion of the Investigator 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. Currently enrolled in another investigational device or drug trial or is receiving other investigational treatment(s) (with the exception of 1407-0030). Intake of any restricted medication or any drug considered likely to interfere with the safe conduct of the trial. Any plan to receive a live vaccination during the 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. Women who are pregnant, nursing, or who plan to become pregnant while in the trial. Any documented active or suspected malignancy, 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 and tuberculosis. Evidence of a disease (including known or suspected IBD, 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 (C-SSRS) in the past 12 months (i.e., active suicidal thought with intent but without specific plan), or active suicidal thought with plan and intent in the past. Unwillingness to adhere to the rules of UV-light protection Ongoing AEs consistent with intolerance of trial medication (including gastric intolerance) from 1407-0030, that in the opinion of the investigator would compromise the safety of the patient.
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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 25 mg BI 730357<br>25 mg BI 730357 + placebo under fasted conditions. | Drug: BI 730357<br>* Film-coated tablet<br>Drug: Placebo to match BI 730357<br>* Film-coated tablet<br>|
| Experimental: 50 mg BI 730357<br>50 mg BI 730357 + placebo under fasted conditions. | Drug: BI 730357<br>* Film-coated tablet<br>Drug: Placebo to match BI 730357<br>* Film-coated tablet<br>|
| Experimental: 100 mg BI 730357<br>100 mg BI 730357 + placebo under fasted conditions. | Drug: BI 730357<br>* Film-coated tablet<br>Drug: Placebo to match BI 730357<br>* Film-coated tablet<br>|
| Experimental: 200 mg BI 730357<br>200 mg BI 730357 + placebo under fasted conditions | Drug: BI 730357<br>* Film-coated tablet<br>Drug: Placebo to match BI 730357<br>* Film-coated tablet<br>|
| Experimental: 400 mg BI 730357<br>400 mg BI 730357 + placebo under fasted conditions. | Drug: BI 730357<br>* Film-coated tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Number of participants with treatment emergent adverse events (TEAEs). For dose groups 25 mg - 200 mg BI, TEAEs are reported separately for period 1 and period 2. Period 1: All patients who started in period 1 are reported by starting dose (25, 50, 100 and 200 mg). Period 2: Only patients who participated in period 2 are reported by dose sequence group. For dose group 400 mg BI, TEAEs are reported overall (period 1 + period 2). Number of participants with TEAEs is reported. | For part 1 patients in period 1: Up to 117 days. For part 1 patients in period 2: From week 13 onwards, up to 692 days. For part 2 patients (period 1 + 2): Up to 802 days. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Psoriasis Area and Severity Index (PASI)50/PASI75/PASI90/PASI100 Response at Week 24 | Number of participants with PASI50/75/90/100 response, where PASI50/75/90/100 is 50%/75%/90%/100% reduction in PASI score. The PASI score is an established measure of clinical efficacy for psoriasis medications, which provides a numeric scoring for patients overall psoriasis disease state, ranging from 0 to 72, with a lower score indicating a better outcome. 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. The endpoint is based on the percent reduction from baseline, summarized as a dichotomous outcome based on achieving over an X% reduction (or PASI X), where X is 50, 75, 90 and 100. The percent reduction from baseline is calculated by % PASI reduction from baseline = ((PASI at baseline - PASI at Visit X) / PASI at baseline) *100, at all visits with PASI collected. | At baseline and at week 24. | 
| Number of Participants With Static Physician Global Assessment (sPGA) Clear or Almost Clear Response at Week 24 | Number of participants with sPGA clear or almost clear response at week 24. The sPGA is a 5 point score based on the physician's assessment of the average thickness, erythema, and scaling of all psoriatic lesions. The score ranges from 0 - 4, with a lower score indicating a better outcome. 0= clear (no signs of psoriasis), almost clear; mild; moderate; 4 = severe (e.g. deep dark red coloration). | At week 24. | 
| Number of Participants With Static Physician Global Assessment (sPGA) Clear Response at Week 24 | Number of participants with sPGA clear response at week 24. The sPGA is a 5 point score based on the physician's assessment of the average thickness, erythema, and scaling of all psoriatic lesions. The score ranges from 0 - 4, with a lower score indicating a better outcome. 0= clear (No signs of psoriasis), almost clear; mild; moderate; 4 = severe (e.g. deep dark red coloration). | At week 24. | 
| Number of Participants With Psoriasis Area and Severity Index (PASI)50/PASI75/PASI90 or PASI100 Response at Any Time and Loss of PASI Response | The time-to-loss analysis of PASI response was not performed because the analysis would not provide any statistically valid estimates of the parameter due to the premature ending of the trial. Instead, the number of participants with PASI50/75/90/100 response at any time and loss of response at the last efficacy assessment is reported. PASI50/75/90/100 is 50%/75%/90%/100% reduction in PASI score. PASI score is a measure of clinical efficacy for psoriasis medications, which ranges from 0 to 72, with a lower score indicating a better outcome. A patient was a PASI responder if he or she achieved a response at any time from enrollment to 7 days (Residual effect period (REP)) after last dosing date. A patient with the event of loss of response was a responder that lost their PASI response at the last efficacy assessment regardless if it was done within 7 days (REP) after the last dosing date or not. | Up to 802 days. | 
| Number of Participants With Static Physician's Global Assessment (sPGA) Clear or Almost Clear Response at Any Time and Loss of sPGA Clear or Almost Clear Response | The time-to-loss analysis of PASI response was not performed because the analysis would not provide any statistically valid estimates of the parameter due to the premature ending of the trial. Instead, the number of participants with sPGA clear or almost clear response at any time, and loss of response at the last efficacy assessment is reported. The sPGA is based on the physician's assessment of average thickness, erythema and scaling of all psoriatic lesions. It ranges from 0 to 4, with 0=clear (best outcome), 1=almost clear, 2=mild, 3=moderate and 4=severe (worst outcome). A patient was an sPGA responder if he or she achieved a response at any time from enrolment to 7 days (residual effect period (REP)) after last dosing date. A patient with the event of loss of response was a responder that lost their sPGA response at the last efficacy assessment regardless if it was done within 7 days (REP) after the last dosing date or not. | Up to 802 days. | 
| Number of Participants With Static Physician's Global Assessment (sPGA) Clear Response at Any Time and Loss of sPGA Clear Response | The time-to-loss analysis of PASI response was not performed because the analysis would not provide any statistically valid estimates of the parameter due to the premature ending of the trial. Instead, the number of participants with sPGA clear response at any time, and loss of response at the last efficacy assessment is reported. The sPGA is based on the physician's assessment of the average thickness, erythema, and scaling of all psoriatic lesions. It ranges from 0 to 4, with 0=clear (best outcome), 1=almost clear, 2=mild, 3=moderate and 4=severe (worst outcome). A patient was a sPGA responder if he or she achieved a response at any time from enrolment to 7 days (residual effect period (REP)) after last dosing date. A patient with the event of loss of response was a responder that lost their sPGA response at the last efficacy assessment regardless if it was done within 7 days (REP) after the last dosing date or not. | Up to 802 days. |