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

Boehringer Ingelheim

Status and phase: Completed; Phase 2

Conditions: Psoriasis

Treatments: Drug: BI 25 mg (fasted); Drug: BI 400 mg once daily (fed); Drug: BI 50 mg (fasted); Drug: BI 200 mg (fasted); Drug: Placebo (fed); Drug: BI 100 mg (fasted); Drug: Placebo (fasted); Drug: BI 200 mg twice daily, 400 mg total (fed)

Study type: Interventional

Funder types: Industry

Identifiers

NCT03635099

1407-0030

2017-004659-21 (EudraCT Number)

Details and patient eligibility

About

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

Enrollment: 274 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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274 participants in 8 patient groups, including a placebo group

Part I - Placebo (fasted)

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo (fasted)

Part I - BI 25 mg (fasted)

Experimental group

Description:

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.

Treatment:

Drug: BI 25 mg (fasted)

Part I - BI 50 mg (fasted)

Experimental group

Description:

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.

Treatment:

Drug: BI 50 mg (fasted)

Part I - BI 100 mg (fasted)

Experimental group

Description:

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.

Treatment:

Drug: BI 100 mg (fasted)

Part I - BI 200 mg (fasted)

Experimental group

Description:

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).

Treatment:

Drug: BI 200 mg (fasted)

Part II - Placebo (fed)

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo (fed)

Part II - BI 400 mg once daily (fed)

Experimental group

Description:

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.

Treatment:

Drug: BI 400 mg once daily (fed)

Part II - BI 200 mg twice daily, 400 mg total (fed)

Experimental group

Description:

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.

Treatment:

Drug: BI 200 mg twice daily, 400 mg total (fed)