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

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

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

Study Overview

• Status: Completed
• Conditions: Psoriasis
• Intervention / Treatment: 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)

• Study Type: Interventional
• Enrollment (Actual): 274
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Surrey, British Columbia, Canada, V3V 0C6
      • Enverus Medical Research
    • Surrey, British Columbia, Canada, V3R 6A7
      • Dr Chih-ho Hong Medical Inc
  • New Brunswick
    • Fredericton, New Brunswick, Canada, E3B 1G9
      • Dr. Irina Turchin PC Inc.
  • Ontario
    • London, Ontario, Canada, N6A 3H7
      • The Guenther Dermatology Research Centre
    • Mississauga, Ontario, Canada, L5H 1G9
      • DermEdge Research Inc.
    • North Bay, Ontario, Canada, P1B 3Z7
      • North Bay Dermatology Centre
    • Oakville, Ontario, Canada, L6J 7W5
      • The Centre for Clinical Trials
    • Peterborough, Ontario, Canada, K9J 5K2
      • Skin Centre For Dermatology
    • Richmond Hill, Ontario, Canada, L4B 1A5
      • The Centre for Dermatology
    • Waterloo, Ontario, Canada, N2J 1C4
      • K. Papp Clinical Research Inc.
    • Windsor, Ontario, Canada, N8W 1E6
      • XLR8 Medical Research Inc.
• Germany
  • Berlin, Germany, 10117
    • Charité - Universitätsmedizin Berlin
  • Bochum, Germany, 44793
    • Studienzentrum im Jahrhunderthaus
  • Frankfurt am Main, Germany, 60596
    • Universitatsklinikum Frankfurt
  • Hamburg, Germany, 20537
    • TFS Trial Form Support GmbH
  • Heidelberg, Germany, 69120
    • Universitätsklinikum Heidelberg
  • Lübeck, Germany, 23538
    • Universitätsklinikum Schleswig-Holstein, Campus Lübeck
  • Münster, Germany, 48149
    • Universitatsklinikum Munster
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Total Skin and Beauty Dermatology Center, PC
  • California
    • Los Angeles, California, United States, 90045
      • Dermatology Research Associates
    • Santa Ana, California, United States, 92701
      • Southern California Dermatology Inc.
  • Georgia
    • Alpharetta, Georgia, United States, 30022
      • Hamilton Research
    • Sandy Springs, Georgia, United States, 30328
      • Advanced Medical Research Pc
  • Indiana
    • Indianapolis, Indiana, United States, 46250
      • Dawes Fretzin Clinical Research Group, LLC
  • New Jersey
    • East Windsor, New Jersey, United States, 08520
      • The Psoriasis Treatment Center of Central New Jersey
  • New York
    • New York, New York, United States, 10003
      • Icahn School of Medicine at Mount Sinai
  • Ohio
    • Cincinnati, Ohio, United States, 45236
      • Synexus
  • Rhode Island
    • Johnston, Rhode Island, United States, 02919
      • Clinical Partners, LLC
  • South Carolina
    • Charleston, South Carolina, United States, 29407
      • Clinical Research Center of the Carolinas
  • South Dakota
    • Rapid City, South Dakota, United States, 57702
      • Health Concepts
  • Texas
    • Dallas, Texas, United States, 75246
      • Menter Dermatology Research Institute
    • Houston, Texas, United States, 77004
      • Center For Clinical Studies
    • Webster, Texas, United States, 77598
      • Center For Clinical Studies
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Virginia Clinical Research, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Part I - Placebo (fasted); 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); 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).
Experimental: Part I - BI 25 mg (fasted); 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); 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).
Experimental: Part I - BI 50 mg (fasted); 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); 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).
Experimental: Part I - BI 100 mg (fasted); 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); 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).
Experimental: Part I - BI 200 mg (fasted); 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); 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).
Placebo Comparator: Part II - Placebo (fed); 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); 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.
Experimental: Part II - BI 400 mg once daily (fed); 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); 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.
Experimental: Part II - BI 200 mg twice daily, 400 mg total (fed); 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); 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2018
• Primary Completion (Actual): May 6, 2021
• Study Completion (Actual): May 26, 2021

Study Registration Dates

• First Submitted: August 15, 2018
• First Submitted That Met QC Criteria: August 15, 2018
• First Posted (Actual): August 17, 2018

Study Record Updates

• Last Update Posted (Actual): August 3, 2022
• Last Update Submitted That Met QC Criteria: July 8, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis
• Other Study ID Numbers: 1407-0030; 2017-004659-21 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

After the study is completed and the primary manuscript is accepted for publishing, researchers can use this following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement".

Also, Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to find information in order to request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.

The data shared are the raw clinical study data sets.

• IPD Sharing Time Frame: After all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
• IPD Sharing Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by both the independent review panel and the sponsor, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a 'Data Sharing Agreement'.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No