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Clinical Trial Results:
Phase II long-term extension study to assess the safety, tolerability, and efficacy of BI 730357 in patients with moderate-to-severe plaque psoriasis

Summary
EudraCT number	2018-003487-31
Trial protocol	DE
Global end of trial date	27 Jul 2021

Results information
Results version number	v1(current)
This version publication date	09 Aug 2022
First version publication date	09 Aug 2022
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

1407-0005

ISRCTN number

US NCT number

NCT03835481

WHO universal trial number (UTN)

Sponsor organisation name

Boehringer Ingelheim

Sponsor organisation address

Binger Straße 173, Ingelheim am Rhein, Germany, 55216

Public contact

Boehringer Ingelheim, Call Centre, Boehringer Ingelheim, 001 18002430127, clintriage.rdg@boehringer-ingelheim.com

Scientific contact

Boehringer Ingelheim, Call Centre, Boehringer Ingelheim, 001 18002430127, clintriage.rdg@boehringer-ingelheim.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

08 Oct 2021

Is this the analysis of the primary completion data?

Yes

Primary completion date

22 Jun 2021

Global end of trial reached?

Yes

Global end of trial date

27 Jul 2021

Was the trial ended prematurely?

Yes

Main objective of the trial

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

Protection of trial subjects

Only subjects that met all the study inclusion and none of the exclusion criteria were to be entered in the study. All subjects were free to withdraw from the clinical trial at any time for any reason given. Close monitoring of all subjects was adhered to throughout the trial conduct.

Background therapy

Evidence for comparator

Actual start date of recruitment

29 Mar 2019

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Canada: 40

Country: Number of subjects enrolled

Germany: 25

Country: Number of subjects enrolled

United States: 100

Worldwide total number of subjects

165

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

137

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Long-term extension trial in patients with psoriasis who completed the preceding trial 1407-0030. Patients rolling over from part 1 remained on their blinded treatment until the open label period started at week 13 (dose group 25-200 mg). Patients rolling over from part 2 were assigned at visit 1 to receive open label treatment with 400 mg BI.

Screening details

All subjects were screened for eligibility prior to participation in the trial. Only subjects which met all inclusion and none of the exclusion criteria were included in the trial. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.

Period 1 title

Period 1

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Blinding implementation details

Patients entering the extension trial will remain on their blinded BI 730357 dose treatment from the preceding trial until the open label period of 1407-0005 begins at Visit 2.

Are arms mutually exclusive

Yes

25 mg BI 730357

Arm description

Patients entering from part 1 of 1407-0030 were administered 1 film-coated tablet of 25 milligram (mg) BI 730357 and 3 film-coated tablets of placebo orally once daily (q.d.) under fasted conditions for the initial 12 week double-blind treatment period (period 1). At day 1 of week 13 (visit 2) patients were reassigned to the 100 mg BI 730357 open label dose, receiving 1 film-coated tablet of 100 mg BI 730357 orally administered once daily until end of study (period 2) or received an optional up-titration to 200 mg BI 730357.

Arm type

Experimental

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Investigational medicinal product name

BI 730357

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

50 mg BI 730357

Arm description

Patients entering from part 1 of 1407-0030 were administered 1 film-coated tablet of 50 milligram (mg) BI 730357 and 3 film-coated tablets of placebo orally once daily (q.d.) under fasted conditions for the initial 12 week double-blind treatment period (period 1). At day 1 of week 13 (visit 2) patients were reassigned to the 100 mg BI 730357 open-label dose, receiving 1 film-coated tablet of 100 mg BI 730357 orally administered once daily until end of study (period 2) or received an optional up-titration to 200 mg BI 730357.

Arm type

Experimental

Investigational medicinal product name

BI 730357

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

100 mg BI 730357

Arm description

Patients entering from part 1 of 1407-0030 were administered 1 film-coated tablet of 100 milligram (mg) BI 730357 and 3 film-coated tablet of placebo orally once daily (q.d.) under fasted conditions for the initial 12 week double-blind treatment period (period 1). At day 1 of week 13 (visit 2) patients were assigned to 100 mg BI 730357 open label dose, receiving 1 film-coated tablet of 100 mg BI 730357 orally administered once daily until end of study (period 2) or received an optional up-titration to 200 mg BI 730357.

Arm type

Experimental

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Investigational medicinal product name

BI 730357

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

200 mg BI 730357

Arm description

Patients entering from part 1 of 1407-0030 were administered 2 film-coated tablets of 100 milligram (mg) BI 730357 and 2 film-coated tablets of placebo orally once daily (q.d.) under fasted conditions for the initial 12 week double-blind treatment period (period 1). At day 1 of week 13 (visit 2) patients were assigned to 200 mg BI 730357 open label dose, receiving 2 film-coated tablets of 100 mg BI 730357 orally administered once daily until end of study (period 2).

Arm type

Experimental

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Investigational medicinal product name

BI 730357

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

400 mg BI 730357

Arm description

Arm type

Experimental

Investigational medicinal product name

BI 730357

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Number of subjects in period 1	25 mg BI 730357	50 mg BI 730357	100 mg BI 730357	200 mg BI 730357	400 mg BI 730357
Started	2	20	16	49	78
Completed	2	18	15	46	37
Not completed	0	2	1	3	41
Consent withdrawn by subject	-	-	1	-	5
Other not stated below	-	-	-	1	1
Lost to follow-up	-	-	-	1	-
Termination of treatment by sponsor	-	-	-	-	35
Protocol deviation	-	2	-	1	-

Period 2 title

Period 2

Is this the baseline period?

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Blinding implementation details

Open label period.

Are arms mutually exclusive

Yes

100 mg BI 730357

Arm description

Arm type

Experimental

Investigational medicinal product name

BI 730357

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

At day 1 of week 13 (visit 2) patients were assigned to 100 mg BI 730357 open label dose, receiving 1 film-coated tablet of 100 mg BI 730357 orally administered once daily until end of study (period 2) or received an optional up-titration to 200 mg BI 730357.

200 mg BI 730357

Arm description

Arm type

Experimental

Investigational medicinal product name

BI 730357

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

At day 1 of week 13 (visit 2) patients were assigned to 200 mg BI 730357 open label dose, receiving 2 film-coated tablets of 100 mg BI 730357 orally administered once daily until end of study (period 2).

400 mg BI 730357

Arm description

Arm type

Experimental

Investigational medicinal product name

BI 730357

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Number of subjects in period 2	100 mg BI 730357	200 mg BI 730357	400 mg BI 730357
Started	35	46	37
Completed	0	0	0
Not completed	35	46	37
Consent withdrawn by subject	7	9	1
Adverse event, non-fatal	1	1	-
Termination of treatment by sponsor	23	31	35
Lost to follow-up	4	3	-
Other not stated above	-	1	1
Covid-19 related, not due to Adverse event	-	1	-

Baseline characteristics

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Reporting group title

25 mg BI 730357

Reporting group description

Reporting group title

50 mg BI 730357

Reporting group description

Reporting group title

100 mg BI 730357

Reporting group description

Reporting group title

200 mg BI 730357

Reporting group description

Reporting group title

400 mg BI 730357

Reporting group description

Reporting group values	25 mg BI 730357	50 mg BI 730357	100 mg BI 730357	200 mg BI 730357	400 mg BI 730357	Total
Number of subjects	2	20	16	49	78	165
Age categorical
Units: Subjects
In utero	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0
Adults (18-64 years)	2	15	9	42	69	137
From 65-84 years	0	5	7	7	9	28
85 years and over	0	0	0	0	0	0
Age Continuous
Units: Years
arithmetic mean (standard deviation)	41.0 ± 2.8	47.2 ± 18.3	58.1 ± 13.5	49.9 ± 13.3	44.5 ± 13.3	-
Sex: Female, Male
Units: Participants
Female	0	8	7	12	22	49
Male	2	12	9	37	56	116
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0	0	0	0	0	0
Asian	0	0	2	6	7	15
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0
Black or African American	1	3	1	1	6	12
White	1	17	13	42	64	137
More than one race	0	0	0	0	0	0
Unknown or Not Reported	0	0	0	0	1	1
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	1	6	2	12	23	44
Not Hispanic or Latino	1	14	14	37	55	121
Unknown or Not Reported	0	0	0	0	0	0

Subject analysis set title

25 mg BI - 100 mg BI

Subject analysis set type

Per protocol

Subject analysis set description

Patients entering from part 1 of 1407-0030 were administered 1 film-coated tablet of 25 mg BI 730357 and 3 film-coated tablets of placebo orally once daily (q.d.) under fasted conditions for the initial 12 week double-blind treatment period (period 1). At day 1 of week 13 (visit 2) patients were reassigned to the 100 mg BI 730357 open label dose, receiving 1 film-coated tablet of 100 mg BI 730357 orally administered once daily until end of study (period 2).

Subject analysis set title

25 mg BI - 100 mg BI - 200 mg BI

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

50 mg BI - 100 mg BI

Subject analysis set type

Per protocol

Subject analysis set description

Patients entering from part 1 of 1407-0030 were administered 1 film-coated tablet of 50 mg BI 730357 and 3 film-coated tablets of placebo orally once daily (q.d.) under fasted conditions for the initial 12 week double-blind treatment period (period 1). At day 1 of week 13 (visit 2) patients were reassigned to the 100 mg BI 730357 open label dose, receiving 1 film-coated tablet of 100 mg BI 730357 orally administered once daily until end of study (period 2).

Subject analysis set title

50 mg BI - 100 mg BI - 200 mg BI

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

100 mg BI - 100 mg BI

Subject analysis set type

Per protocol

Subject analysis set description

Patients entering from part 1 of 1407-0030 were administered 1 film-coated tablet of 100 mg BI 730357 and 3 film-coated tablets of placebo orally once daily (q.d.) under fasted conditions for the initial 12 week double-blind treatment period (period 1). At day 1 of week 13 (visit 2) patients were reassigned to the 100 mg BI 730357 open label dose, receiving 1 film-coated tablet of 100 mg BI 730357 orally administered once daily until end of study (period 2).

Subject analysis set title

100 mg BI - 100 mg BI - 200 mg BI

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

200 mg BI - 200 mg BI

Subject analysis set type

Per protocol

Subject analysis set description

Patients entering from part 1 of 1407-0030 were administered 2 film-coated tablets of 100 milligram (mg) BI 730357 and 2 film-coated tablets of placebo orally once daily (q.d.) under fasted conditions for the initial 12 week double-blind treatment period (period 1). At day 1 of week 13 (visit 2) patients were assigned to the 200 mg BI 730357 open label dose, receiving 2 film-coated tablets of 100 mg BI 730357 orally administered once daily until end of study (period 2).

Subject analysis set title

400 mg BI - 400 mg BI

Subject analysis set type

Per protocol

Subject analysis set description

Patients entering from part 2 of 1407-0030 were administered open label treatment of 4 film-coated tablets of 100 milligram (mg) BI730357 orally once daily (QD) under fed conditions throughout the trial. Patients in this group are those part 2 patients who have received treatment for more than 12 weeks.

Subject analysis sets values	25 mg BI - 100 mg BI	25 mg BI - 100 mg BI - 200 mg BI	50 mg BI - 100 mg BI	50 mg BI - 100 mg BI - 200 mg BI	100 mg BI - 100 mg BI	100 mg BI - 100 mg BI - 200 mg BI	200 mg BI - 200 mg BI	400 mg BI - 400 mg BI
Number of subjects	1	1	5	13	6	9	46	37
Age categorical
Units: Subjects
In utero
Preterm newborn infants (gestational age < 37 wks)
Newborns (0-27 days)
Infants and toddlers (28 days-23 months)
Children (2-11 years)
Adolescents (12-17 years)
Adults (18-64 years)
From 65-84 years
85 years and over
Age Continuous
Units: Years
arithmetic mean (standard deviation)	1 ±	0 ±	3 ±	8 ±	3 ±	6 ±	28 ±	±
Sex: Female, Male
Units: Participants
Female
Male
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native
Asian
Native Hawaiian or Other Pacific Islander
Black or African American
White
More than one race
Unknown or Not Reported
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino
Not Hispanic or Latino
Unknown or Not Reported

End points

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Reporting group title

25 mg BI 730357

Reporting group description

Reporting group title

50 mg BI 730357

Reporting group description

Reporting group title

100 mg BI 730357

Reporting group description

Reporting group title

200 mg BI 730357

Reporting group description

Reporting group title

400 mg BI 730357

Reporting group description

Reporting group title

100 mg BI 730357

Reporting group description

Reporting group title

200 mg BI 730357

Reporting group description

Reporting group title

400 mg BI 730357

Reporting group description

Subject analysis set title

25 mg BI - 100 mg BI

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

25 mg BI - 100 mg BI - 200 mg BI

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

50 mg BI - 100 mg BI

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

50 mg BI - 100 mg BI - 200 mg BI

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

100 mg BI - 100 mg BI

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

100 mg BI - 100 mg BI - 200 mg BI

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

200 mg BI - 200 mg BI

Subject analysis set type

Per protocol

Subject analysis set description

Patients entering from part 1 of 1407-0030 were administered 2 film-coated tablets of 100 milligram (mg) BI 730357 and 2 film-coated tablets of placebo orally once daily (q.d.) under fasted conditions for the initial 12 week double-blind treatment period (period 1). At day 1 of week 13 (visit 2) patients were assigned to the 200 mg BI 730357 open label dose, receiving 2 film-coated tablets of 100 mg BI 730357 orally administered once daily until end of study (period 2).

Subject analysis set title

400 mg BI - 400 mg BI

Subject analysis set type

Per protocol

Subject analysis set description

Primary: Number of participants with treatment emergent adverse events (TEAEs)

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End point title

Number of participants with treatment emergent adverse events (TEAEs) ^[1]

End point description

Number of participants with treatment emergent adverse events (TEAEs). For dose groups 25 mg - 200 mg BI, TEAEs are reported seperately 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. Treated Set: All patients who received at least one dose in the extension trial.

End point type

Primary

End point timeframe

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.

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis have been conducted for the primary endpoint

End point values	25 mg BI 730357	50 mg BI 730357	100 mg BI 730357	200 mg BI 730357	400 mg BI 730357	25 mg BI - 100 mg BI	25 mg BI - 100 mg BI - 200 mg BI	50 mg BI - 100 mg BI	50 mg BI - 100 mg BI - 200 mg BI	100 mg BI - 100 mg BI	100 mg BI - 100 mg BI - 200 mg BI	200 mg BI - 200 mg BI
Number of subjects analysed	2	20	16	49	78	1	1	5	13	6	9	46
Units: Participants	0	6	6	10	14	1	0	3	8	3	6	28

No statistical analyses for this end point

Secondary: Number of participants with Psoriasis Area and Severity Index (PASI)50/PASI75/PASI90/PASI100 response at week 24

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End point title

Number of participants with Psoriasis Area and Severity Index (PASI)50/PASI75/PASI90/PASI100 response at week 24

End point description

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. Treated Set. Results are reported by dose-sequence group.

End point type

Secondary

End point timeframe

At baseline and at week 24.

End point values	25 mg BI - 100 mg BI	25 mg BI - 100 mg BI - 200 mg BI	50 mg BI - 100 mg BI	50 mg BI - 100 mg BI - 200 mg BI	100 mg BI - 100 mg BI	100 mg BI - 100 mg BI - 200 mg BI	200 mg BI - 200 mg BI	400 mg BI - 400 mg BI
Number of subjects analysed	1	1	4	13	6	9	45	16
Units: Participants
PASI50	0	1	4	12	2	8	33	9
PASI75	0	1	3	9	2	3	23	6
PASI90	0	1	1	4	0	2	10	5
PASI100	9	1	1	2	0	0	3	2

No statistical analyses for this end point

Secondary: Number of participants with Static Physician Global Assessment (sPGA) clear or almost clear response at week 24

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End point title

Number of participants with Static Physician Global Assessment (sPGA) clear or almost clear response at week 24

End point description

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), 1= almost clear; 2= mild; 3= moderate; 4 = severe (e.g. deep dark red coloration). Treated Set. Results are reported by dose-sequence group. Only participants with non-missing results are reported.

End point type

Secondary

End point timeframe

At week 24.

End point values	25 mg BI - 100 mg BI	25 mg BI - 100 mg BI - 200 mg BI	50 mg BI - 100 mg BI	50 mg BI - 100 mg BI - 200 mg BI	100 mg BI - 100 mg BI	100 mg BI - 100 mg BI - 200 mg BI	200 mg BI - 200 mg BI	400 mg BI - 400 mg BI
Number of subjects analysed	1	1	4	13	6	9	45	16
Units: Participants	0	1	2	5	1	3	18	7

No statistical analyses for this end point

Secondary: Number of participants with Static Physician Global Assessment (sPGA) clear response at week 24

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End point title

Number of participants with Static Physician Global Assessment (sPGA) clear response at week 24

End point description

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), 1= almost clear; 2= mild; 3= moderate; 4 = severe (e.g. deep dark red coloration). Treated Set. Results are reported by dose sequence group. Only participants with non-missing results are reported.

End point type

Secondary

End point timeframe

At week 24.

End point values	25 mg BI - 100 mg BI	25 mg BI - 100 mg BI - 200 mg BI	50 mg BI - 100 mg BI	50 mg BI - 100 mg BI - 200 mg BI	100 mg BI - 100 mg BI	100 mg BI - 100 mg BI - 200 mg BI	200 mg BI - 200 mg BI	400 mg BI - 400 mg BI
Number of subjects analysed	1	1	4	13	6	9	45	16
Units: Participants	0	1	1	2	0	0	3	2

No statistical analyses for this end point

Secondary: Number of participants with Psoriasis Area and Severity Index (PASI)50/PASI75/PASI90 or PASI100 response at any time and loss of PASI response

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End point title

Number of participants with Psoriasis Area and Severity Index (PASI)50/PASI75/PASI90 or PASI100 response at any time and loss of PASI response ^[2]

End point description

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. Treated Set.

End point type

Secondary

End point timeframe

Up to 802 days.

Notes
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Results are reported per starting dose (50, 100, 200 and 400 mg) for patients who participated only in period 1, and per dose-sequence group for patients who participated in period 1 and period 2.

End point values	50 mg BI 730357	100 mg BI 730357	200 mg BI 730357	400 mg BI 730357	25 mg BI - 100 mg BI	25 mg BI - 100 mg BI - 200 mg BI	50 mg BI - 100 mg BI	50 mg BI - 100 mg BI - 200 mg BI	100 mg BI - 100 mg BI	100 mg BI - 100 mg BI - 200 mg BI	200 mg BI - 200 mg BI	400 mg BI - 400 mg BI
Number of subjects analysed	2	1	3	41	1	1	5	13	6	9	46	37
Units: Participants
PASI50 Responders	0	1	2	23	1	1	5	13	6	9	46	30
PASI50 Loss of Response	0	0	1	1	0	0	0	1	5	3	11	4
PASI75 Responders	0	1	0	12	1	1	4	12	3	6	32	21
PASI75 Loss of Response	0	0	0	1	1	0	1	2	2	1	12	5
PASI90 Responders	0	1	0	2	0	1	2	5	0	3	21	10
PASI90 Loss of Response	0	0	0	0	0	0	0	2	0	1	12	2
PASI100 Responders	0	1	0	1	0	1	2	4	0	1	12	4
PASI100 Loss of Response	0	0	0	0	0	0	1	3	0	0	7	1

No statistical analyses for this end point

Secondary: 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

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End point title

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 ^[3]

End point description

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. Treated Set.

End point type

Secondary

End point timeframe

Up to 802 days.

Notes
[3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Results are reported per starting dose (50, 100, 200 and 400 mg) for patients who participated only in period 1, and per dose-sequence group for patients who participated in period 1 and period 2.

End point values	50 mg BI 730357	100 mg BI 730357	200 mg BI 730357	400 mg BI 730357	25 mg BI - 100 mg BI	25 mg BI - 100 mg BI - 200 mg BI	50 mg BI - 100 mg BI	50 mg BI - 100 mg BI - 200 mg BI	100 mg BI - 100 mg BI	100 mg BI - 100 mg BI - 200 mg BI	200 mg BI - 200 mg BI	400 mg BI - 400 mg BI
Number of subjects analysed	2	1	3	41	1	1	5	13	6	9	46	37
Units: Participants
Resonders	0	1	0	13	0	1	3	9	3	6	32	17
Loss of response	0	0	0	2	0	0	1	4	3	2	18	3

No statistical analyses for this end point

Secondary: Number of participants with Static Physician’s Global Assessment (sPGA) clear response at any time and loss of sPGA clear response

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End point title

Number of participants with Static Physician’s Global Assessment (sPGA) clear response at any time and loss of sPGA clear response ^[4]

End point description

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. Treated Set.

End point type

Secondary

End point timeframe

Up to 802 days.

Notes
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Results are reported per starting dose (50, 100, 200 and 400 mg) for patients who participated only in period 1, and per dose-sequence group for patients who participated in period 1 and period 2.

End point values	50 mg BI 730357	100 mg BI 730357	200 mg BI 730357	400 mg BI 730357	25 mg BI - 100 mg BI	25 mg BI - 100 mg BI - 200 mg BI	50 mg BI - 100 mg BI	50 mg BI - 100 mg BI - 200 mg BI	100 mg BI - 100 mg BI	100 mg BI - 100 mg BI - 200 mg BI	200 mg BI - 200 mg BI	400 mg BI - 400 mg BI
Number of subjects analysed	2	1	3	41	1	1	5	13	6	9	46	37
Units: Participants
Resonders	0	1	0	1	0	1	2	4	0	1	12	4
Loss of response	0	0	0	0	0	0	1	3	0	0	7	1

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Period 1: From start of treatment until end of period 1 plus 7 days of residual effect period, up to 117 days. Period 1 and Period 2: From start of treatment until end of period 2, plus 7 days of residual effect period, up to 802 days.

Adverse event reporting additional description

Treated Set (TS): All patients who received at least one dose of treatment in the extension trial. Adverse events are reported per starting dose (50, 100, 200 and 400 mg) for patients who participated only in period 1, and per dose-sequence group for patients who participated in period 1 and period 2.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

24.0

Reporting group title

50 mg BI 730357

Reporting group description

Reporting group title

50 mg BI - 100 mg BI

Reporting group description

Reporting group title

100 mg BI 730357

Reporting group description

Reporting group title

25 mg BI - 100 mg BI - 200 mg BI

Reporting group description

Reporting group title

25 mg BI - 100 mg BI

Reporting group description

Reporting group title

400 mg BI 730357

Reporting group description

Reporting group title

200 mg BI 730357

Reporting group description

Reporting group title

200 mg BI - 200 mg BI

Reporting group description

Patients entering from part 1 of 1407-0030 were administered 2 film-coated tablets of 100 milligram (mg) BI 730357 and 2 film-coated tablets of placebo orally once daily (q.d.) under fasted conditions for the initial 12 week double-blind treatment period (period 1). At day 1 of week 13 (visit 2) patients were assigned to the 200 mg BI 730357 open label dose, receiving 2 film-coated tablets of 100 mg BI 730357 orally administered once daily until end of study (period 2).

Reporting group title

400 mg BI - 400 mg BI

Reporting group description

Reporting group title

50 mg BI - 100 mg BI - 200 mg BI

Reporting group description

Reporting group title

100 mg BI - 100 mg BI - 200 mg BI

Reporting group description

Reporting group title

100 mg BI - 100 mg BI

Reporting group description

50 mg BI 730357

50 mg BI - 100 mg BI

100 mg BI 730357

25 mg BI - 100 mg BI - 200 mg BI

25 mg BI - 100 mg BI

400 mg BI 730357

200 mg BI 730357

200 mg BI - 200 mg BI

400 mg BI - 400 mg BI

50 mg BI - 100 mg BI - 200 mg BI

100 mg BI - 100 mg BI - 200 mg BI

100 mg BI - 100 mg BI

Total subjects affected by serious adverse events

subjects affected / exposed

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 41 (0.00%)

0 / 3 (0.00%)

2 / 46 (4.35%)

0 / 37 (0.00%)

1 / 13 (7.69%)

2 / 9 (22.22%)

2 / 6 (33.33%)

number of deaths (all causes)

number of deaths resulting from adverse events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Basal cell carcinoma

subjects affected / exposed

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 41 (0.00%)

0 / 3 (0.00%)

0 / 46 (0.00%)

0 / 37 (0.00%)

1 / 13 (7.69%)

0 / 9 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Squamous cell carcinoma of skin

subjects affected / exposed

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 41 (0.00%)

0 / 3 (0.00%)

0 / 46 (0.00%)

0 / 37 (0.00%)

0 / 13 (0.00%)

2 / 9 (22.22%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

Tendon rupture

subjects affected / exposed

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 41 (0.00%)

0 / 3 (0.00%)

0 / 46 (0.00%)

0 / 37 (0.00%)

0 / 13 (0.00%)

0 / 9 (0.00%)

1 / 6 (16.67%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Cardiac disorders

Pericarditis

subjects affected / exposed

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 41 (0.00%)

0 / 3 (0.00%)

1 / 46 (2.17%)

0 / 37 (0.00%)

0 / 13 (0.00%)

0 / 9 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal and urinary disorders

Nephrolithiasis

subjects affected / exposed

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 41 (0.00%)

0 / 3 (0.00%)

1 / 46 (2.17%)

0 / 37 (0.00%)

0 / 13 (0.00%)

0 / 9 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infections and infestations

Erysipelas

subjects affected / exposed

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 41 (0.00%)

0 / 3 (0.00%)

0 / 46 (0.00%)

0 / 37 (0.00%)

0 / 13 (0.00%)

0 / 9 (0.00%)

1 / 6 (16.67%)

occurrences causally related to treatment / all

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Pyelonephritis

subjects affected / exposed

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 41 (0.00%)

0 / 3 (0.00%)

1 / 46 (2.17%)

0 / 37 (0.00%)

0 / 13 (0.00%)

0 / 9 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Urosepsis

subjects affected / exposed

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 41 (0.00%)

0 / 3 (0.00%)

1 / 46 (2.17%)

0 / 37 (0.00%)

0 / 13 (0.00%)

0 / 9 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	50 mg BI 730357	50 mg BI - 100 mg BI	100 mg BI 730357	25 mg BI - 100 mg BI - 200 mg BI	25 mg BI - 100 mg BI	400 mg BI 730357	200 mg BI 730357	200 mg BI - 200 mg BI	400 mg BI - 400 mg BI	50 mg BI - 100 mg BI - 200 mg BI	100 mg BI - 100 mg BI - 200 mg BI	100 mg BI - 100 mg BI
Total subjects affected by non serious adverse events
subjects affected / exposed	0 / 2 (0.00%)	3 / 5 (60.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)	1 / 1 (100.00%)	2 / 41 (4.88%)	1 / 3 (33.33%)	24 / 46 (52.17%)	5 / 37 (13.51%)	9 / 13 (69.23%)	7 / 9 (77.78%)	3 / 6 (50.00%)
Investigations
Aspartate aminotransferase increased
subjects affected / exposed	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	1 / 46 (2.17%)	1 / 37 (2.70%)	0 / 13 (0.00%)	0 / 9 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	0	0	1	1	0	0	1
Alanine aminotransferase increased
subjects affected / exposed	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 3 (33.33%)	1 / 46 (2.17%)	1 / 37 (2.70%)	0 / 13 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	1	1	1	0	0	0
Blood potassium increased
subjects affected / exposed	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	0 / 46 (0.00%)	0 / 37 (0.00%)	1 / 13 (7.69%)	0 / 9 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0
C-reactive protein increased
subjects affected / exposed	0 / 2 (0.00%)	1 / 5 (20.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	1 / 46 (2.17%)	0 / 37 (0.00%)	0 / 13 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0	0	0	1	0	0	0	0
Liver function test increased
subjects affected / exposed	0 / 2 (0.00%)	1 / 5 (20.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	1 / 46 (2.17%)	0 / 37 (0.00%)	0 / 13 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0	0	0	2	0	0	0	0
Gamma-glutamyltransferase increased
subjects affected / exposed	0 / 2 (0.00%)	1 / 5 (20.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	1 / 46 (2.17%)	0 / 37 (0.00%)	0 / 13 (0.00%)	0 / 9 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	1	0	0	0	0	0	2	0	0	0	1
Injury, poisoning and procedural complications
Skin laceration
subjects affected / exposed	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	0 / 46 (0.00%)	1 / 37 (2.70%)	1 / 13 (7.69%)	0 / 9 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	0	0
Cardiac disorders
Palpitations
subjects affected / exposed	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	0 / 46 (0.00%)	0 / 37 (0.00%)	0 / 13 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0
Nervous system disorders
Carpal tunnel syndrome
subjects affected / exposed	0 / 2 (0.00%)	1 / 5 (20.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	0 / 46 (0.00%)	0 / 37 (0.00%)	0 / 13 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0
Cervical radiculopathy
subjects affected / exposed	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	0 / 46 (0.00%)	0 / 37 (0.00%)	1 / 13 (7.69%)	0 / 9 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0
Headache
subjects affected / exposed	0 / 2 (0.00%)	0 / 5 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	3 / 46 (6.52%)	1 / 37 (2.70%)	0 / 13 (0.00%)	1 / 9 (11.11%)	1 / 6 (16.67%)
occurrences all number	0	0	1	0	0	0	0	3	1	0	1	2
Hypoaesthesia
subjects affected / exposed	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	0 / 46 (0.00%)	0 / 37 (0.00%)	0 / 13 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0
General disorders and administration site conditions
Fatigue
subjects affected / exposed	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 3 (0.00%)	0 / 46 (0.00%)	2 / 37 (5.41%)	0 / 13 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	2	0	0	0
Pyrexia
subjects affected / exposed	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	0 / 46 (0.00%)	0 / 37 (0.00%)	0 / 13 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0
Malaise
subjects affected / exposed	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	0 / 46 (0.00%)	0 / 37 (0.00%)	1 / 13 (7.69%)	0 / 9 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0
Gastrointestinal disorders
Constipation
subjects affected / exposed	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	0 / 46 (0.00%)	0 / 37 (0.00%)	0 / 13 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0
Diarrhoea
subjects affected / exposed	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	3 / 46 (6.52%)	0 / 37 (0.00%)	1 / 13 (7.69%)	0 / 9 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	4	0	1	0	0
Gastritis
subjects affected / exposed	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	0 / 46 (0.00%)	0 / 37 (0.00%)	1 / 13 (7.69%)	0 / 9 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0
Reproductive system and breast disorders
Benign prostatic hyperplasia
subjects affected / exposed	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	0 / 46 (0.00%)	0 / 37 (0.00%)	0 / 13 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	3 / 46 (6.52%)	0 / 37 (0.00%)	1 / 13 (7.69%)	0 / 9 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	3	0	1	0	0
Epistaxis
subjects affected / exposed	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	0 / 46 (0.00%)	0 / 37 (0.00%)	0 / 13 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0
Oropharyngeal pain
subjects affected / exposed	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	0 / 46 (0.00%)	2 / 37 (5.41%)	0 / 13 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	2	0	0	0
Rhinitis allergic
subjects affected / exposed	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	0 / 46 (0.00%)	0 / 37 (0.00%)	0 / 13 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0
Skin and subcutaneous tissue disorders
Dermatitis contact
subjects affected / exposed	0 / 2 (0.00%)	1 / 5 (20.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	0 / 46 (0.00%)	0 / 37 (0.00%)	0 / 13 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0
Eczema
subjects affected / exposed	0 / 2 (0.00%)	1 / 5 (20.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	0 / 46 (0.00%)	0 / 37 (0.00%)	1 / 13 (7.69%)	0 / 9 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	1	0	0
Pruritus
subjects affected / exposed	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	1 / 46 (2.17%)	0 / 37 (0.00%)	1 / 13 (7.69%)	0 / 9 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0
Seborrhoeic dermatitis
subjects affected / exposed	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	0 / 46 (0.00%)	0 / 37 (0.00%)	1 / 13 (7.69%)	0 / 9 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0
Psoriasis
subjects affected / exposed	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	2 / 46 (4.35%)	0 / 37 (0.00%)	0 / 13 (0.00%)	1 / 9 (11.11%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	1	1
Urticaria
subjects affected / exposed	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	0 / 46 (0.00%)	0 / 37 (0.00%)	0 / 13 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	2 / 46 (4.35%)	0 / 37 (0.00%)	0 / 13 (0.00%)	2 / 9 (22.22%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	0	0	3	0	0	2	1
Back pain
subjects affected / exposed	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	1 / 46 (2.17%)	0 / 37 (0.00%)	0 / 13 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	1	0
Rotator cuff syndrome
subjects affected / exposed	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	3 / 46 (6.52%)	0 / 37 (0.00%)	0 / 13 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	3	0	0	1	0
Infections and infestations
Gastroenteritis viral
subjects affected / exposed	0 / 2 (0.00%)	1 / 5 (20.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	0 / 46 (0.00%)	0 / 37 (0.00%)	0 / 13 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0
Gastroenteritis
subjects affected / exposed	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	3 / 46 (6.52%)	0 / 37 (0.00%)	0 / 13 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	3	0	0	0	0
Hepatitis E
subjects affected / exposed	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	0 / 46 (0.00%)	0 / 37 (0.00%)	1 / 13 (7.69%)	0 / 9 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0
Laryngitis
subjects affected / exposed	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	0 / 46 (0.00%)	0 / 37 (0.00%)	0 / 13 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0
Nasopharyngitis
subjects affected / exposed	0 / 2 (0.00%)	1 / 5 (20.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	3 / 46 (6.52%)	0 / 37 (0.00%)	1 / 13 (7.69%)	0 / 9 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	1	1	0	0	0	0	3	0	1	0	1
Tinea cruris
subjects affected / exposed	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	0 / 46 (0.00%)	0 / 37 (0.00%)	0 / 13 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0
Sinusitis
subjects affected / exposed	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 3 (0.00%)	1 / 46 (2.17%)	0 / 37 (0.00%)	0 / 13 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0	1	0	0	1	0
Upper respiratory tract infection
subjects affected / exposed	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	2 / 46 (4.35%)	0 / 37 (0.00%)	1 / 13 (7.69%)	2 / 9 (22.22%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	0	0	2	0	1	2	1
Tinea pedis
subjects affected / exposed	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	1 / 46 (2.17%)	0 / 37 (0.00%)	0 / 13 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	1	0
Vulvovaginal candidiasis
subjects affected / exposed	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	0 / 46 (0.00%)	0 / 37 (0.00%)	1 / 13 (7.69%)	0 / 9 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0
Urinary tract infection
subjects affected / exposed	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	1 / 46 (2.17%)	0 / 37 (0.00%)	1 / 13 (7.69%)	0 / 9 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0
Wound infection
subjects affected / exposed	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	0 / 46 (0.00%)	0 / 37 (0.00%)	1 / 13 (7.69%)	0 / 9 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0
Metabolism and nutrition disorders
Glucose tolerance impaired
subjects affected / exposed	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	0 / 46 (0.00%)	0 / 37 (0.00%)	0 / 13 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0
Hypercholesterolaemia
subjects affected / exposed	0 / 2 (0.00%)	1 / 5 (20.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	0 / 46 (0.00%)	0 / 37 (0.00%)	0 / 13 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0
Type 2 diabetes mellitus
subjects affected / exposed	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 3 (0.00%)	3 / 46 (6.52%)	0 / 37 (0.00%)	0 / 13 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	3	0	0	0	0

More information

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Were there any global substantial amendments to the protocol? Yes

21 May 2019

The requirement for contraception in male study participants and use of a barrier method was removed following new nonclinical data, which showed no genotoxicity or suspected human teratogenicity/fetotoxicity at therapeutic systemic exposure levels. The benefit-risk assessment was updated to include the information that no drug-drug interactions of CYP3A4 substrates and BI 730357 as a perpetrator were to be expected. The adverse event of special interest (AESI) “Mycobacterium tuberculosis” was replaced by “all mycobacterial infections” to include and cover a more complete picture of opportunistic infections in the definition. The residual effect period was reduced from 28 days to 7 days.

04 Jun 2019

No changes were made to the content of the CTP. The amendment was a technical update due to errors in the signature process of Version 2.0.

06 Oct 2020

Part 2 was added to align with the addition of Part 2 to trial 1407-0030 and to allow those patients to roll over to this trial. Additional safety information was included to ensure the safety of patients who had been in the placebo arm of 1407-0030. The original patient population was described as Part 1. Patients in Part 1 on the 100 mg dose were permitted to up-titrate to a 200 mg dose because data from 1407-0030 indicated that 100 mg was sub-optimal. Guidance was provided to investigators to manage visit disruptions due to Covid-19. Remote source data verification (SDV) was permitted in certain circumstances, and patient status could be monitored flexibly during the Covid-19 pandemic if in-person visits were not possible. AEs consistent with gastric intolerance or gastritis were designated as AESIs to reflect the latest results from drug-drug interaction and toxicology trials. Candidiasis was removed as an exclusion criterion and was no longer considered a safety concern. Urinalysis variables were updated to correspond to current central laboratory standard tests and reporting. The wording of the primary endpoint was revised because the definition of ‘an endpoint’ should be at individual level at one particular time point, and to make the wording consistent across the project.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

The trial was ended prematurely by the sponsor as a precautionary measure following nonclinical findings. As a consequence, primary and secondary endpoints were limited to descriptive outcome measures. The recruitment was completed as planned.

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Clinical trials

Clinical Trial Results:
Phase II long-term extension study to assess the safety, tolerability, and efficacy of BI 730357 in patients with moderate-to-severe plaque psoriasis

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of participants with treatment emergent adverse events (TEAEs)

Primary: Number of participants with treatment emergent adverse events (TEAEs)

Secondary: Number of participants with Psoriasis Area and Severity Index (PASI)50/PASI75/PASI90/PASI100 response at week 24

Secondary: Number of participants with Psoriasis Area and Severity Index (PASI)50/PASI75/PASI90/PASI100 response at week 24

Secondary: Number of participants with Static Physician Global Assessment (sPGA) clear or almost clear response at week 24

Secondary: Number of participants with Static Physician Global Assessment (sPGA) clear or almost clear response at week 24

Secondary: Number of participants with Static Physician Global Assessment (sPGA) clear response at week 24

Secondary: Number of participants with Static Physician Global Assessment (sPGA) clear response at week 24

Secondary: Number of participants with Psoriasis Area and Severity Index (PASI)50/PASI75/PASI90 or PASI100 response at any time and loss of PASI response

Secondary: Number of participants with Psoriasis Area and Severity Index (PASI)50/PASI75/PASI90 or PASI100 response at any time and loss of PASI response

Secondary: 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

Secondary: 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

Secondary: Number of participants with Static Physician’s Global Assessment (sPGA) clear response at any time and loss of sPGA clear response

Secondary: Number of participants with Static Physician’s Global Assessment (sPGA) clear response at any time and loss of sPGA clear response

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical trials

Clinical Trial Results: Phase II long-term extension study to assess the safety, tolerability, and efficacy of BI 730357 in patients with moderate-to-severe plaque psoriasis

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of participants with treatment emergent adverse events (TEAEs)

Primary: Number of participants with treatment emergent adverse events (TEAEs)

Secondary: Number of participants with Psoriasis Area and Severity Index (PASI)50/PASI75/PASI90/PASI100 response at week 24

Secondary: Number of participants with Psoriasis Area and Severity Index (PASI)50/PASI75/PASI90/PASI100 response at week 24

Secondary: Number of participants with Static Physician Global Assessment (sPGA) clear or almost clear response at week 24

Secondary: Number of participants with Static Physician Global Assessment (sPGA) clear or almost clear response at week 24

Secondary: Number of participants with Static Physician Global Assessment (sPGA) clear response at week 24

Secondary: Number of participants with Static Physician Global Assessment (sPGA) clear response at week 24

Secondary: Number of participants with Psoriasis Area and Severity Index (PASI)50/PASI75/PASI90 or PASI100 response at any time and loss of PASI response

Secondary: Number of participants with Psoriasis Area and Severity Index (PASI)50/PASI75/PASI90 or PASI100 response at any time and loss of PASI response

Secondary: 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

Secondary: 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

Secondary: Number of participants with Static Physician’s Global Assessment (sPGA) clear response at any time and loss of sPGA clear response

Secondary: Number of participants with Static Physician’s Global Assessment (sPGA) clear response at any time and loss of sPGA clear response

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
Phase II long-term extension study to assess the safety, tolerability, and efficacy of BI 730357 in patients with moderate-to-severe plaque psoriasis