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Clinical Trial Results:
A Phase 3, Multicenter, Randomized, Double-Blind Study With an Active-Controlled Initial Treatment Period Followed by a Dose-Blind Maintenance Treatment Period to Evaluate the Efficacy and Safety of Bimekizumab in Adult Subjects With Moderate to Severe Chronic Plaque Psoriasis

Summary
EudraCT number	2016-003392-22
Trial protocol	DE HU
Global end of trial date	26 Feb 2020

Results information
Results version number	v1
This version publication date	06 Mar 2021
First version publication date	06 Mar 2021
Other versions	v2

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

PS0008

ISRCTN number

US NCT number

NCT03412747

WHO universal trial number (UTN)

Sponsor organisation name

UCB Biopharma SRL

Sponsor organisation address

Allée de la Recherche 60, Brussels, Belgium, 1070

Public contact

Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.com

Scientific contact

Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.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

09 Apr 2020

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

26 Feb 2020

Was the trial ended prematurely?

Main objective of the trial

Compare the efficacy of bimekizumab administered subcutaneously (sc) for 16 weeks versus adalimumab in the treatment of subjects with moderate to severe plaque psoriasis (PSO)

Protection of trial subjects

During the conduct of the study all participants were closely monitored.

Background therapy

Background therapy as permitted in the protocol

Evidence for comparator

Adalimumab is a widely used treatment option for patients with moderate to severe plaque PSO who are candidates for systemic therapy or phototherapy. Adalimumab is a human immunoglobulin (Ig) G1 monoclonal antibody that binds specifically to tumor-necrosis factor (TNF). The efficacy of TNFα inhibitors in treating psoriasis is attributed to their inhibition of Th17-Tcells.

Actual start date of recruitment

26 Jan 2018

Long term follow-up planned

Yes

Long term follow-up rationale

Safety

Long term follow-up duration

3 Years

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 21

Country: Number of subjects enrolled

Canada: 77

Country: Number of subjects enrolled

Germany: 50

Country: Number of subjects enrolled

Hungary: 38

Country: Number of subjects enrolled

Poland: 126

Country: Number of subjects enrolled

Russian Federation: 14

Country: Number of subjects enrolled

Korea, Republic of: 5

Country: Number of subjects enrolled

Taiwan: 6

Country: Number of subjects enrolled

United States: 141

Worldwide total number of subjects

478

EEA total number of subjects

214

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)

434

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

The study started to enroll patients in January 2018 and concluded in February 2020.

Screening details

This study included 4 periods: a Screening Period (2 to 5 weeks), an Initial Treatment Period (16 weeks), a Maintenance Treatment Period (40 weeks), and a Safety Follow-Up (SFU) Visit (20 weeks after the final dose of study drug). Participant Flow refers to the Randomized Set.

Period 1 title

Initial Treatment Period: Wk0-Wk16

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Carer, Investigator, Subject, Assessor

Are arms mutually exclusive

Yes

Bimekizumab Arm 2

Arm description

Study participants received bimekizumab dose regimen 1 for 16 weeks and proceeded with bimekizumab dose regimen 2 until Week 56. Study participants received placebo at pre-specified time-points to maintain the blinding.

Arm type

Experimental

Investigational medicinal product name

Bimekizumab

Investigational medicinal product code

UCB4940

Other name

BKZ

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Study participants received bimekizumab at pre-defined timepoints in dose regimen 1 and/or dose regimen 2.

Bimekizumab Arm 1

Arm description

Study participants received bimekizumab dose regimen 1 for 56 weeks. Study participants received placebo at pre-specified time-points to maintain the blinding.

Arm type

Experimental

Investigational medicinal product name

Bimekizumab

Investigational medicinal product code

UCB4940

Other name

BKZ

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Study participants received bimekizumab at pre-defined timepoints in dose regimen 1 and/or dose regimen 2.

Adalimumab Arm

Arm description

Study participants received adalimumab for 24 weeks and then received bimekizumab dose regimen 1 until Week 56. Study participants received placebo at pre-specified time-points to maintain the blinding.

Arm type

Active comparator

Investigational medicinal product name

Adalimumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Adalimumab (ADA) was administered according to the labeling recommendations.

Number of subjects in period 1	Bimekizumab Arm 2	Bimekizumab Arm 1	Adalimumab Arm
Started	161	158	159
Completed	154	153	150
Not completed	7	5	9
Adverse event, serious fatal	-	-	1
Consent withdrawn by subject	4	1	1
Adverse event, non-fatal	2	2	3
Participant moved out of state	1	-	-
Lost to follow-up	-	2	1
Lack of efficacy	-	-	1
Protocol deviation	-	-	2

Period 2 title

Maintenance Treatment Period: Wk16-Wk24

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Assessor, Carer, Investigator, Subject

Are arms mutually exclusive

Yes

Bimekizumab Arm 2

Arm description

Arm type

Experimental

Investigational medicinal product name

Bimekizumab

Investigational medicinal product code

UCB4940

Other name

BKZ

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Study participants received bimekizumab at pre-defined timepoints in dose regimen 1 and/or dose regimen 2.

Bimekizumab Arm 1

Arm description

Study participants received bimekizumab dose regimen 1 for 56 weeks. Study participants received placebo at pre-specified time-points to maintain the blinding.

Arm type

Experimental

Investigational medicinal product name

Bimekizumab

Investigational medicinal product code

UCB4940

Other name

BKZ

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Study participants received bimekizumab at pre-defined timepoints in dose regimen 1 and/or dose regimen 2.

Adalimumab Arm

Arm description

Arm type

Active comparator

Investigational medicinal product name

Adalimumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Adalimumab (ADA) was administered according to the labeling recommendations.

Number of subjects in period 2	Bimekizumab Arm 2	Bimekizumab Arm 1	Adalimumab Arm
Started	154	153	150
Completed	149	152	149
Not completed	5	1	1
Consent withdrawn by subject	1	-	-
Adverse event, non-fatal	3	1	-
Lost to follow-up	-	-	1
Lack of efficacy	1	-	-

Period 3 title

Maintenance Treatment Period: Wk24-Wk56

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Assessor, Carer, Investigator, Subject

Are arms mutually exclusive

Yes

Bimekizumab Arm 2

Arm description

Arm type

Experimental

Investigational medicinal product name

Bimekizumab

Investigational medicinal product code

UCB4940

Other name

BKZ

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Study participants received bimekizumab at pre-defined timepoints in dose regimen 1 and/or dose regimen 2.

Bimekizumab Arm 1

Arm description

Study participants received bimekizumab dose regimen 1 for 56 weeks. Study participants received placebo at pre-specified time-points to maintain the blinding.

Arm type

Experimental

Investigational medicinal product name

Bimekizumab

Investigational medicinal product code

UCB4940

Other name

BKZ

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Study participants received bimekizumab at pre-defined timepoints in dose regimen 1 and/or dose regimen 2.

Adalimumab Arm

Arm description

Arm type

Active comparator

Investigational medicinal product name

Adalimumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Adalimumab (ADA) was administered according to the labeling recommendations.

Number of subjects in period 3	Bimekizumab Arm 2	Bimekizumab Arm 1	Adalimumab Arm
Started	149	152	149
Completed	143	143	133
Not completed	6	9	16
Consent withdrawn by subject	3	1	4
Adverse event, non-fatal	3	4	6
Moving out of town	-	1	-
Lost to follow-up	-	2	5
Lack of efficacy	-	1	1

Baseline characteristics

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Reporting group title

Bimekizumab Arm 2

Reporting group description

Reporting group title

Bimekizumab Arm 1

Reporting group description

Study participants received bimekizumab dose regimen 1 for 56 weeks. Study participants received placebo at pre-specified time-points to maintain the blinding.

Reporting group title

Adalimumab Arm

Reporting group description

Reporting group values	Bimekizumab Arm 2	Bimekizumab Arm 1	Adalimumab Arm	Total
Number of subjects	161	158	159	478
Age categorical
Units: Subjects
<=18 years	3	0	2	5
Between 18 and 65 years	145	147	137	429
>=65 years	13	11	20	44
Age continuous
Units: years
arithmetic mean (standard deviation)	44.0 ( 13.5 )	45.3 ( 13.2 )	45.5 ( 14.3 )	-
Gender categorical
Units: Subjects
Female	49	56	45	150
Male	112	102	114	328

End points

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Reporting group title

Bimekizumab Arm 2

Reporting group description

Reporting group title

Bimekizumab Arm 1

Reporting group description

Study participants received bimekizumab dose regimen 1 for 56 weeks. Study participants received placebo at pre-specified time-points to maintain the blinding.

Reporting group title

Adalimumab Arm

Reporting group description

Reporting group title

Bimekizumab Arm 2

Reporting group description

Reporting group title

Bimekizumab Arm 1

Reporting group description

Study participants received bimekizumab dose regimen 1 for 56 weeks. Study participants received placebo at pre-specified time-points to maintain the blinding.

Reporting group title

Adalimumab Arm

Reporting group description

Reporting group title

Bimekizumab Arm 2

Reporting group description

Reporting group title

Bimekizumab Arm 1

Reporting group description

Study participants received bimekizumab dose regimen 1 for 56 weeks. Study participants received placebo at pre-specified time-points to maintain the blinding.

Reporting group title

Adalimumab Arm

Reporting group description

Subject analysis set title

Bimekizumab Arm 1 + Arm 2 (RS)

Subject analysis set type

Full analysis

Subject analysis set description

This group consisted of participants from both Arm 1 and Arm 2 who received bimekizumab dose regimen 1 for 16 weeks. Participants formed the Randomized Set (RS).

Subject analysis set title

Adalimumab Arm (RS)

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

Bimekizumab Arm 2 (RS)

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

Bimekizumab Arm 1 (RS)

Subject analysis set type

Full analysis

Subject analysis set description

Study participants received bimekizumab dose regimen 1 for 56 weeks. Study participants received placebo at pre-specified time-points to maintain the blinding. Participants formed the Randomized Set (RS).

Subject analysis set title

Bimekizumab Arm 2 through Week 24 (SS)

Subject analysis set type

Safety analysis

Subject analysis set description

Participants received bimekizumab dose regimen 1 for 16 weeks and proceeded with bimekizumab dose regimen 2 until Week 24. Participants received placebo at pre-specified time-points to maintain the blinding. Participants formed the Safety Set (SS).

Subject analysis set title

Bimekizumab Arm 1 through Week 24 (SS)

Subject analysis set type

Safety analysis

Subject analysis set description

Participants received bimekizumab dose regimen 1 for 24 weeks. Participants received placebo at pre-specified time-points to maintain the blinding. Participants formed the SS.

Subject analysis set title

Adalimumab Arm through Week 24 (SS)

Subject analysis set type

Safety analysis

Subject analysis set description

Participants received adalimumab for 24 weeks. Participants received placebo at pre-specified time-points to maintain the blinding. Participants formed the SS.

Subject analysis set title

Any bimekizumab dose regimen 2 (BKZ Set)

Subject analysis set type

Safety analysis

Subject analysis set description

This arm consisted of all participants who received bimekizumab dose regimen 2 at any time in the study (up to 56 weeks). Participants formed the Bimekizumab Set (BKZ Set).

Subject analysis set title

Any bimekizumab dose regimen 1 (BKZ Set)

Subject analysis set type

Safety analysis

Subject analysis set description

This arm consisted of all participants who received bimekizumab dose regimen 1 at any time in the study (up to 56 weeks). Participants formed the BKZ Set (BKZ Set).

Primary: Percentage of Participants with a Psoriasis Area and Severity Index 90 (PASI90) response at Week 16

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End point title

Percentage of Participants with a Psoriasis Area and Severity Index 90 (PASI90) response at Week 16

End point description

The PASI90 response assessments are based on at least 90% improvement in the PASI score from Baseline. Body divided into 4 areas: head, arms, trunk to groin, and legs to top of buttocks. Assignment of an average score for the redness, thickness, and scaling for each of the 4 body areas with a score of 0 (clear) to 4 (very marked). Determining the percentage of skin covered with PSO for each of the body areas and converting to a 0 to 6 scale. Final PASI= average redness, thickness, and scaliness of the psoriatic skin lesions, multiplied by the involved psoriasis area score of the respective section, and weighted by the percentage of the person’s affected skin for the respective section. The minimum possible PASI score is 0= no disease, the maximum score is 72= maximal disease. The Randomized Set (RS) consisted of all randomized study participants. Both BKZ Arm 1 and BKZ Arm 2 are identical in terms of treatment received until Week 16 and therefore they are combined for analyses.

End point type

Primary

End point timeframe

Week 16

End point values	Bimekizumab Arm 1 + Arm 2 (RS)	Adalimumab Arm (RS)
Number of subjects analysed	319	159
Units: percentage of participants
number (not applicable)	86.2	47.2

Statistical analysis 1

Statistical analysis description

Risk Difference: BKZ-ADA calculated using stratified CMH.

Comparison groups

Bimekizumab Arm 1 + Arm 2 (RS) v Adalimumab Arm (RS)

Number of subjects included in analysis

478

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[1]

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

39.3

Confidence interval

level

95%

sides

2-sided

lower limit

30.9

upper limit

47.7

Notes
[1] - The evaluation of non-inferiority is tested at a 1-sided alpha level of 0.025 and based on a 1-sided 97.5% CI and a non-inferiority margin of 10%.

Statistical Analysis 2

Statistical analysis description

Odds ratio: BKZ/ADA calculated using stratified Cochran-Mantel-Haenszel (CMH) test with region and prior biologic exposure as stratification variables.

Comparison groups

Bimekizumab Arm 1 + Arm 2 (RS) v Adalimumab Arm (RS)

Number of subjects included in analysis

478

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[2]

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

7.459

Confidence interval

level

95%

sides

2-sided

lower limit

4.709

upper limit

11.816

Notes
[2] - P-values for the comparison of treatment groups were based on the CMH test from the general association.

Primary: Percentage of Participants With an Investigator's Global Assessment (IGA) Response (Clear or Almost Clear With at Least 2-Category Improvement Relative to Baseline) at Week 16

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End point title

Percentage of Participants With an Investigator's Global Assessment (IGA) Response (Clear or Almost Clear With at Least 2-Category Improvement Relative to Baseline) at Week 16

End point description

The IGA measures the overall psoriasis severity following a 5-point scale (0-4), where scale 0= clear, no signs of psoriasis; presence of post-inflammatory hyperpigmentation, scale 1= almost clear, no thickening; normal to pink coloration; no to minimal focal scaling, scale 2= mild thickening, pink to light red coloration and predominately fine scaling, 3= moderate, clearly distinguishable to moderate thickening; dull to bright red, clearly distinguishable to moderate thickening; moderate scaling and 4= severe thickening with hard edges; bright to deep dark red coloration; severe/coarse scaling covering almost all or all lesions. IGA response was defined as clear [0] or almost clear [1] with at least a two-category improvement from Baseline at Week 16. The Randomized Set (RS) consisted of all randomized study participants. Both BKZ Arm 1 and BKZ Arm 2 are identical in terms of treatment received until Week 16 and therefore they are combined for analyses.

End point type

Primary

End point timeframe

Week 16

End point values	Bimekizumab Arm 1 + Arm 2 (RS)	Adalimumab Arm (RS)
Number of subjects analysed	319	159
Units: percentage of participants
number (not applicable)	85.3	57.2

Statistical analysis 1

Statistical analysis description

Risk Difference: BKZ-ADA calculated using stratified CMH.

Comparison groups

Bimekizumab Arm 1 + Arm 2 (RS) v Adalimumab Arm (RS)

Number of subjects included in analysis

478

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[3]

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

28.2

Confidence interval

level

95%

sides

2-sided

lower limit

19.7

upper limit

36.7

Notes
[3] - The evaluation of non-inferiority is tested at a 1-sided alpha level of 0.025 and based on a 1-sided 97.5% CI and a non-inferiority margin of 10%.

Statistical analysis 2

Statistical analysis description

Odds ratio: BKZ/ADA calculated using stratified Cochran-Mantel-Haenszel (CMH) test with region and prior biologic exposure as stratification variables.

Comparison groups

Bimekizumab Arm 1 + Arm 2 (RS) v Adalimumab Arm (RS)

Number of subjects included in analysis

478

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[4]

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

4.341

Confidence interval

level

95%

sides

2-sided

lower limit

2.785

upper limit

6.765

Notes
[4] - P-values for the comparison of treatment groups were based on the CMH test from the general association.

Secondary: Percentage of Participants With a PASI90 Response at Week 24

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End point title

Percentage of Participants With a PASI90 Response at Week 24

End point description

The PASI90 response assessments are based on at least 90% improvement in the PASI score from Baseline. Body divided into 4 areas: head, arms, trunk to groin, and legs to top of buttocks. Assignment of an average score for the redness, thickness, and scaling for each of the 4 body areas with a score of 0 (clear) to 4 (very marked). Determining the percentage of skin covered with PSO for each of the body areas and converting to a 0 to 6 scale. Final PASI= average redness, thickness, and scaliness of the psoriatic skin lesions, multiplied by the involved psoriasis area score of the respective section, and weighted by the percentage of the person’s affected skin for the respective section. The minimum possible PASI score is 0= no disease, the maximum score is 72= maximal disease. The Randomized Set (RS) consisted of all randomized study participants. BKZ Arm 1 and BKZ Arm 2 were also combined for analyses purposes at Week 24 since they differ only one dose (Week 20).

End point type

Secondary

End point timeframe

Week 24

End point values	Bimekizumab Arm 1 + Arm 2 (RS)	Adalimumab Arm (RS)	Bimekizumab Arm 2 (RS)	Bimekizumab Arm 1 (RS)
Number of subjects analysed	319	159	161	158
Units: percentage of participants
number (not applicable)	85.6	51.6	85.1	86.1

Statistical analysis 1

Statistical analysis description

Odds ratio: BKZ/ADA calculated using stratified Cochran-Mantel-Haenszel (CMH) test with region and prior biologic exposure as stratification variables.

Comparison groups

Bimekizumab Arm 1 (RS) v Adalimumab Arm (RS)

Number of subjects included in analysis

317

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[5]

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

6.231

Confidence interval

level

95%

sides

2-sided

lower limit

3.515

upper limit

11.046

Notes
[5] - P-values for the comparison of treatment groups were based on the CMH test from the general association.

Statistical Analysis 2

Statistical analysis description

Odds ratio: BKZ/ADA calculated using stratified CMH test with region and prior biologic exposure as stratification variables.

Comparison groups

Bimekizumab Arm 1 + Arm 2 (RS) v Adalimumab Arm (RS)

Number of subjects included in analysis

478

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[6]

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

5.75

Confidence interval

level

95%

sides

2-sided

lower limit

3.657

upper limit

9.041

Notes
[6] - P-values for the comparison of treatment groups were based on the CMH test from the general association.

Secondary: Percentage of Participants With an IGA Response (Clear or Almost Clear with at least 2-category improvement relative to Baseline) at Week 24

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End point title

Percentage of Participants With an IGA Response (Clear or Almost Clear with at least 2-category improvement relative to Baseline) at Week 24

End point description

The IGA measures the overall psoriasis severity following a 5-point scale (0-4), where scale 0= clear, no signs of psoriasis; presence of post-inflammatory hyperpigmentation, scale 1= almost clear, no thickening; normal to pink coloration; no to minimal focal scaling, scale 2= mild thickening, pink to light red coloration and predominately fine scaling, 3= moderate, clearly distinguishable to moderate thickening; dull to bright red, clearly distinguishable to moderate thickening; moderate scaling and 4= severe thickening with hard edges; bright to deep dark red coloration; severe/coarse scaling covering almost all or all lesions. IGA response was defined as clear [0] with at least a two-category improvement from Baseline at Week 24. The Randomized Set (RS) consisted of all randomized study participants. BKZ Arm 1 and BKZ Arm 2 were also combined for analyses purposes at Week 24 since they differ only one dose (Week 20).

End point type

Secondary

End point timeframe

Week 24

End point values	Bimekizumab Arm 1 + Arm 2 (RS)	Adalimumab Arm (RS)	Bimekizumab Arm 2 (RS)	Bimekizumab Arm 1 (RS)
Number of subjects analysed	319	159	161	158
Units: percentage of participants
number (not applicable)	86.5	57.9	87.0	86.1

Statistical analysis 1

Statistical analysis description

Odds ratio: BKZ/ADA calculated using stratified Cochran-Mantel-Haenszel (CMH) test with region and prior biologic exposure as stratification variables.

Comparison groups

Bimekizumab Arm 1 (RS) v Adalimumab Arm (RS)

Number of subjects included in analysis

317

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[7]

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

4.724

Confidence interval

level

95%

sides

2-sided

lower limit

2.683

upper limit

8.318

Notes
[7] - P-values for the comparison of treatment groups were based on the CMH test from the general association.

Statistical analysis 2

Statistical analysis description

Odds ratio: BKZ/ADA calculated using stratified CMH test with region and prior biologic exposure as stratification variables.

Comparison groups

Bimekizumab Arm 1 + Arm 2 (RS) v Adalimumab Arm (RS)

Number of subjects included in analysis

478

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[8]

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

4.762

Confidence interval

level

95%

sides

2-sided

lower limit

3.014

upper limit

7.523

Notes
[8] - P-values for the comparison of treatment groups were based on the CMH test from the general association.

Secondary: Percentage of Participants With a PASI75 Response at Week 4

Top of page

End point title

Percentage of Participants With a PASI75 Response at Week 4

End point description

The PASI75 response assessments are based on at least 75% improvement in the PASI score from Baseline. Body divided into 4 areas: head, arms, trunk to groin, and legs to top of buttocks. Assignment of an average score for the redness, thickness, and scaling for each of the 4 body areas with a score of 0 (clear) to 4 (very marked). Determining the percentage of skin covered with PSO for each of the body areas and converting to a 0 to 6 scale. Final PASI= average redness, thickness, and scaliness of the psoriatic skin lesions, multiplied by the involved psoriasis area score of the respective section, and weighted by the percentage of the person’s affected skin for the respective section. The minimum possible PASI score is 0= no disease, the maximum score is 72= maximal disease. The Randomized Set (RS) consisted of all randomized study participants. Both BKZ Arm 1 and BKZ Arm 2 are identical in terms of treatment received until Week 16 and therefore they are combined for analyses.

End point type

Secondary

End point timeframe

Week 4

End point values	Bimekizumab Arm 1 + Arm 2 (RS)	Adalimumab Arm (RS)
Number of subjects analysed	319	159
Units: percentage of participants
number (not applicable)	76.5	31.4

Statistical analysis 1

Statistical analysis description

Odds ratio: BKZ/ADA calculated using stratified Cochran-Mantel-Haenszel (CMH) test with region and prior biologic exposure as stratification variables.

Comparison groups

Bimekizumab Arm 1 + Arm 2 (RS) v Adalimumab Arm (RS)

Number of subjects included in analysis

478

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[9]

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

7.103

Confidence interval

level

95%

sides

2-sided

lower limit

4.637

upper limit

10.88

Notes
[9] - P-values for the comparison of treatment groups were based on the CMH test from the general association.

Secondary: Percentage of Participants With a PASI100 Response at Week 16

Top of page

End point title

Percentage of Participants With a PASI100 Response at Week 16

End point description

The PASI100 response assessments are based on a 100% improvement in the PASI score from Baseline. Body divided into 4 areas: head, arms, trunk to groin, and legs to top of buttocks. Assignment of an average score for the redness, thickness, and scaling for each of the 4 body areas with a score of 0 (clear) to 4 (very marked). Determining the percentage of skin covered with PSO for each of the body areas and converting to a 0 to 6 scale. Final PASI= average redness, thickness, and scaliness of the psoriatic skin lesions, multiplied by the involved psoriasis area score of the respective section, and weighted by the percentage of the person’s affected skin for the respective section. The minimum possible PASI score is 0= no disease, the maximum score is 72= maximal disease. The Randomized Set (RS) consisted of all randomized study participants. Both BKZ Arm 1 and BKZ Arm 2 are identical in terms of treatment received until Week 16 and therefore they are combined for analyses.

End point type

Secondary

End point timeframe

Week 16

End point values	Bimekizumab Arm 1 + Arm 2 (RS)	Adalimumab Arm (RS)
Number of subjects analysed	319	159
Units: percentage of participants
number (not applicable)	60.8	23.9

Statistical analysis 1

Statistical analysis description

Odds ratio: BKZ/ADA calculated using stratified Cochran-Mantel-Haenszel (CMH) test with region and prior biologic exposure as stratification variables.

Comparison groups

Bimekizumab Arm 1 + Arm 2 (RS) v Adalimumab Arm (RS)

Number of subjects included in analysis

478

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[10]

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

4.974

Confidence interval

level

95%

sides

2-sided

lower limit

3.23

upper limit

7.661

Notes
[10] - P-values for the comparison of treatment groups were based on the CMH test from the general association.

Secondary: Percentage of Participants With a PASI100 Response at Week 24

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End point title

Percentage of Participants With a PASI100 Response at Week 24

End point description

The PASI100 response assessments are based on a 100% improvement in the PASI score from Baseline. Body divided into 4 areas: head, arms, trunk to groin, and legs to top of buttocks. Assignment of an average score for the redness, thickness, and scaling for each of the 4 body areas with a score of 0 (clear) to 4 (very marked). Determining the percentage of skin covered with PSO for each of the body areas and converting to a 0 to 6 scale. Final PASI= average redness, thickness, and scaliness of the psoriatic skin lesions, multiplied by the involved psoriasis area score of the respective section, and weighted by the percentage of the person’s affected skin for the respective section. The minimum possible PASI score is 0= no disease, the maximum score is 72= maximal disease. The Randomized Set (RS) consisted of all randomized study participants. BKZ Arm 1 and BKZ Arm 2 were also combined for analyses purposes at Week 24 since they differ only one dose (Week 20)

End point type

Secondary

End point timeframe

Week 24

End point values	Bimekizumab Arm 1 + Arm 2 (RS)	Adalimumab Arm (RS)	Bimekizumab Arm 2 (RS)	Bimekizumab Arm 1 (RS)
Number of subjects analysed	319	159	161	158
Units: percentage of participants
number (not applicable)	66.8	29.6	65.8	67.7

Statistical analysis 1

Statistical analysis description

Odds ratio: BKZ/ADA calculated using stratified Cochran-Mantel-Haenszel (CMH) test with region and prior biologic exposure as stratification variables.

Comparison groups

Bimekizumab Arm 1 (RS) v Adalimumab Arm (RS)

Number of subjects included in analysis

317

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[11]

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

5.249

Confidence interval

level

95%

sides

2-sided

lower limit

3.207

upper limit

8.593

Notes
[11] - P-values for the comparison of treatment groups were based on the CMH test from the general association.

Statistical analysis 2

Statistical analysis description

Odds ratio: BKZ/ADA calculated using stratified CMH test with region and prior biologic exposure as stratification variables.

Comparison groups

Bimekizumab Arm 1 + Arm 2 (RS) v Adalimumab Arm (RS)

Number of subjects included in analysis

478

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[12]

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

4.974

Confidence interval

level

95%

sides

2-sided

lower limit

3.257

upper limit

7.594

Notes
[12] - P-values for the comparison of treatment groups were based on the CMH test from the general association.

Secondary: Percentage of Participants With a PASI90 Response at Week 56

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End point title

Percentage of Participants With a PASI90 Response at Week 56

End point description

PASI90 response assessments are based on at least 90% improvement in the PASI score from Baseline. Body divided into 4 areas: head/arms/trunk to groin/and legs to top of buttocks. Assignment of an average score for the redness/thickness/scaling for each of the 4 body areas with a score of 0 (clear)-4 (very marked). Determining the percentage of skin covered with PSO for each of the body areas and converting to a 0-6 scale. Final PASI=average redness/thickness/scaliness of the psoriatic skin lesions multiplied by the involved psoriasis area score of the respective section and weighted by the percentage of the person’s affected skin for the respective section. The min possible PASI score is 0=no disease, max score is 72=maximal disease. The RS consisted of all randomized study participants. ADA participants were not included as they did not start BKZ treatment at Baseline, thus did not have a year of BKZ treatment. The purpose of this table is to look at response after one year of BKZ.

End point type

Secondary

End point timeframe

Week 56

End point values	Bimekizumab Arm 2 (RS)	Bimekizumab Arm 1 (RS)
Number of subjects analysed	161	158
Units: percentage of participants
number (not applicable)	82.6	84.8

No statistical analyses for this end point

Secondary: Percentage of Participants With an IGA Response (Clear or Almost Clear with at least 2-category improvement relative to Baseline) at Week 56

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End point title

Percentage of Participants With an IGA Response (Clear or Almost Clear with at least 2-category improvement relative to Baseline) at Week 56

End point description

IGA measures the overall psoriasis severity following a 5-point scale (0-4), where scale 0=clear, no signs of psoriasis; presence of post-inflammatory hyperpigmentation, scale 1=almost clear, no thickening; normal to pink coloration; no to minimal focal scaling, scale 2=mild thickening, pink to light red coloration and predominately fine scaling, 3=moderate, clearly distinguishable to moderate thickening; dull to bright red, clearly distinguishable to moderate thickening; moderate scaling and 4=severe thickening with hard edges; bright to deep dark red coloration; severe/coarse scaling covering almost all or all lesions. IGA response was defined as clear [0]/almost clear [1] with at least a 2-category improvement from Baseline at Wk56. The RS consisted of all randomized study participants. ADA participants were not included as they did not start BKZ treatment at Baseline, thus did not have a year of BKZ treatment. The purpose of this table is to look at response after one year of BKZ.

End point type

Secondary

End point timeframe

Week 56

End point values	Bimekizumab Arm 2 (RS)	Bimekizumab Arm 1 (RS)
Number of subjects analysed	161	158
Units: percentage of participants
number (not applicable)	83.2	82.3

No statistical analyses for this end point

Secondary: Number of Treatment-emergent Adverse Events (TEAEs) Adjusted by Duration of Participant Exposure to Study Treatment from Baseline to Week 24

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End point title

Number of Treatment-emergent Adverse Events (TEAEs) Adjusted by Duration of Participant Exposure to Study Treatment from Baseline to Week 24

End point description

The number of TEAEs adjusted by duration of exposure to study treatment was scaled such that provided an incidence rate per 100 patient-years. If a participant had multiple events, the time of exposure was calculated to the first occurrence of the AE being considered. If a participant had no events, the total time at risk was used. The Safety Set (SS) consisted of all study participants who received at least 1 dose of IMP.

End point type

Secondary

End point timeframe

From Baseline to Week 24

End point values	Bimekizumab Arm 2 through Week 24 (SS)	Bimekizumab Arm 1 through Week 24 (SS)	Adalimumab Arm through Week 24 (SS)
Number of subjects analysed	161	158	159
Units: no. of new events per 100 subject-years
number (confidence interval 95%)	310.44 (256.52 to 372.34)	300.71 (247.60 to 361.83)	297.54 (244.77 to 358.31)

No statistical analyses for this end point

Secondary: Number of Serious Adverse Events (SAEs) Adjusted by Duration of Participant Exposure to Study Treatment from Baseline to Week 24

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End point title

Number of Serious Adverse Events (SAEs) Adjusted by Duration of Participant Exposure to Study Treatment from Baseline to Week 24

End point description

The number of SAEs adjusted by duration of exposure to study treatment was scaled such that it provided an incidence rate per 100 patient-years. If a participant had multiple events, the time of exposure was calculated to the first occurrence of the AE being considered. If a participant had no events, the total time at risk was used. The Safety Set (SS) consisted of all study participants that received at least 1 dose of IMP.

End point type

Secondary

End point timeframe

From Baseline to Week 24

End point values	Bimekizumab Arm 2 through Week 24 (SS)	Bimekizumab Arm 1 through Week 24 (SS)	Adalimumab Arm through Week 24 (SS)
Number of subjects analysed	161	158	159
Units: no. of new events per 100 subject-years
number (confidence interval 95%)	1.37 (0.03 to 7.66)	5.61 (1.53 to 14.38)	6.98 (2.27 to 16.30)

No statistical analyses for this end point

Secondary: Number of Treatment-emergent Adverse Events (TEAEs) Leading to Withdrawal Adjusted by Duration of Participant Exposure to Study Treatment from Baseline to Week 24

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End point title

Number of Treatment-emergent Adverse Events (TEAEs) Leading to Withdrawal Adjusted by Duration of Participant Exposure to Study Treatment from Baseline to Week 24

End point description

The number of TEAEs leading to discontinuation adjusted by duration of exposure to study treatment was scaled such that it provided an incidence rate per 100 patient-years. If a participant had multiple events, the time of exposure was calculated to the first occurrence of the AE being considered. If a participant had no events, the total time at risk was used. The Safety Set (SS) consisted of all study participants that received at least 1 dose of IMP.

End point type

Secondary

End point timeframe

From Baseline to Week 24

End point values	Bimekizumab Arm 2 through Week 24 (SS)	Bimekizumab Arm 1 through Week 24 (SS)	Adalimumab Arm through Week 24 (SS)
Number of subjects analysed	161	158	159
Units: no. of new events per 100 subject-years
number (confidence interval 95%)	8.30 (3.05 to 18.07)	4.16 (0.86 to 12.17)	6.98 (2.27 to 16.29)

No statistical analyses for this end point

Secondary: Number of Treatment-emergent Adverse Events (TEAEs) Adjusted by Duration of Participant Exposure to Study Treatment from Baseline to Safety Follow-Up Visit (up to Week 72)

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End point title

Number of Treatment-emergent Adverse Events (TEAEs) Adjusted by Duration of Participant Exposure to Study Treatment from Baseline to Safety Follow-Up Visit (up to Week 72)

End point description

The number of TEAEs adjusted by duration of exposure to study treatment was scaled such that it provided an incidence rate per 100 patient-years. If a participant had multiple events, the time of exposure was calculated to the first occurrence of the AE being considered. If a participant had no events, the total time at risk was used. The Bimekizumab Set (BKZ Set) consisted of all study participants who received at least 1 dose of bimekizumab in this study.

End point type

Secondary

End point timeframe

From Baseline to Safety Follow-Up Visit (up to Week 72)

End point values	Any bimekizumab dose regimen 2 (BKZ Set)	Any bimekizumab dose regimen 1 (BKZ Set)
Number of subjects analysed	154	468
Units: no. of new events per 100 subject-years
number (confidence interval 95%)	231.38 (191.68 to 276.88)	262.41 (235.37 to 291.71)

No statistical analyses for this end point

Secondary: Number of Serious Adverse Events (SAEs) Adjusted by Duration of Participant Exposure to Study Treatment from Baseline to Safety Follow-Up Visit (up to Week 72)

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End point title

Number of Serious Adverse Events (SAEs) Adjusted by Duration of Participant Exposure to Study Treatment from Baseline to Safety Follow-Up Visit (up to Week 72)

End point description

The number of SAEs adjusted by duration of exposure to study treatment was scaled such that it provided an incidence rate per 100 patient-years. If a participant had multiple events, the time of exposure was calculated to the first occurrence of the AE being considered. If a participant had no events, the total time at risk was used. The Bimekizumab Set (BKZ Set) consisted of all study participants who received at least 1 dose of bimekizumab in this study.

End point type

Secondary

End point timeframe

From Baseline to Safety Follow-Up Visit (up to Week 72)

End point values	Any bimekizumab dose regimen 2 (BKZ Set)	Any bimekizumab dose regimen 1 (BKZ Set)
Number of subjects analysed	154	468
Units: no. of new events per 100 subject-years
number (confidence interval 95%)	7.03 (3.04 to 13.86)	5.34 (3.05 to 8.67)

No statistical analyses for this end point

Secondary: Number of Treatment-emergent Adverse Events (TEAEs) Leading to Withdrawal Adjusted by Duration of Participant Exposure to Study Treatment from Baseline to Safety Follow-Up Visit (up to Week 72)

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End point title

Number of Treatment-emergent Adverse Events (TEAEs) Leading to Withdrawal Adjusted by Duration of Participant Exposure to Study Treatment from Baseline to Safety Follow-Up Visit (up to Week 72)

End point description

The number of TEAEs leading to discontinuation adjusted by duration of exposure to study treatment was scaled such that it provided an incidence rate per 100 patient-years. If a participant had multiple events, the time of exposure was calculated to the first occurrence of the AE being considered. If a participant had no events, the total time at risk was used. The Bimekizumab Set (BKZ Set) consisted of all study participants who received at least 1 dose of bimekizumab in this study.

End point type

Secondary

End point timeframe

From Baseline to Safety Follow-Up Visit (up to Week 72)

End point values	Any bimekizumab dose regimen 2 (BKZ Set)	Any bimekizumab dose regimen 1 (BKZ Set)
Number of subjects analysed	154	468
Units: no. of new events per 100 subject-years
number (confidence interval 95%)	4.37 (1.42 to 10.19)	4.62 (2.53 to 7.75)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Treatment-emergent AEs were collected from Baseline to Safety Follow-Up Visit (up to Week 72)

Adverse event reporting additional description

Treatment-emergent AEs were defined as those AEs that had a start date on or following the first dose of study treatment through the final dose of study treatment + 140 days (covering up to Safety Follow-Up Visit for study participants not enrolling in Open-label Extension (OLE) study).

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

19.0

Reporting group title

Bimekizumab Arm 2 through Week 24 (SS)

Reporting group description

Reporting group title

Bimekizumab Arm 1 through Week 24 (SS)

Reporting group description

Participants received bimekizumab dose regimen 1 for 24 weeks. Participants received placebo at pre-specified time-points to maintain the blinding. Participants formed the SS.

Reporting group title

Adalimumab Arm through Week 24 (SS)

Reporting group description

Participants received adalimumab for 24 weeks. Participants received placebo at pre-specified time-points to maintain the blinding. Participants formed the SS.

Reporting group title

Any bimekizumab dose regimen 2 (BKZ Set)

Reporting group description

This arm consisted of all participants who received bimekizumab dose regimen 2 at any time in the study (up to 56 weeks). Participants formed the Bimekizumab Set (BKZ Set).

Reporting group title

Any bimekizumab dose regimen 1 (BKZ Set)

Reporting group description

This arm consisted of all participants who received bimekizumab dose regimen 1 at any time in the study (up to 56 weeks). Participants formed the BKZ Set (BKZ Set).

Serious adverse events	Bimekizumab Arm 2 through Week 24 (SS)	Bimekizumab Arm 1 through Week 24 (SS)	Adalimumab Arm through Week 24 (SS)	Any bimekizumab dose regimen 2 (BKZ Set)	Any bimekizumab dose regimen 1 (BKZ Set)
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 161 (0.62%)	4 / 158 (2.53%)	5 / 159 (3.14%)	8 / 154 (5.19%)	16 / 468 (3.42%)
number of deaths (all causes)	0	0	1	0	0
number of deaths resulting from adverse events	0	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of the tongue
subjects affected / exposed	0 / 161 (0.00%)	0 / 158 (0.00%)	1 / 159 (0.63%)	0 / 154 (0.00%)	0 / 468 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
Colon cancer
subjects affected / exposed	0 / 161 (0.00%)	0 / 158 (0.00%)	0 / 159 (0.00%)	1 / 154 (0.65%)	0 / 468 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Hypertension
subjects affected / exposed	0 / 161 (0.00%)	0 / 158 (0.00%)	0 / 159 (0.00%)	1 / 154 (0.65%)	0 / 468 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
subjects affected / exposed	0 / 161 (0.00%)	1 / 158 (0.63%)	0 / 159 (0.00%)	0 / 154 (0.00%)	1 / 468 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Non-cardiac chest pain
subjects affected / exposed	0 / 161 (0.00%)	0 / 158 (0.00%)	0 / 159 (0.00%)	1 / 154 (0.65%)	0 / 468 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
Sarcoidosis
subjects affected / exposed	0 / 161 (0.00%)	0 / 158 (0.00%)	0 / 159 (0.00%)	0 / 154 (0.00%)	1 / 468 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Ovarian cyst ruptured
subjects affected / exposed	0 / 161 (0.00%)	1 / 158 (0.63%)	0 / 159 (0.00%)	0 / 154 (0.00%)	1 / 468 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Hepatic enzyme increased
subjects affected / exposed	0 / 161 (0.00%)	0 / 158 (0.00%)	0 / 159 (0.00%)	1 / 154 (0.65%)	0 / 468 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Subdural haematoma
subjects affected / exposed	0 / 161 (0.00%)	0 / 158 (0.00%)	0 / 159 (0.00%)	0 / 154 (0.00%)	1 / 468 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Coronary artery stenosis
subjects affected / exposed	0 / 161 (0.00%)	0 / 158 (0.00%)	0 / 159 (0.00%)	0 / 154 (0.00%)	1 / 468 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Carotid artery stenosis
subjects affected / exposed	0 / 161 (0.00%)	0 / 158 (0.00%)	1 / 159 (0.63%)	0 / 154 (0.00%)	0 / 468 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Haemorrhagic anaemia
subjects affected / exposed	0 / 161 (0.00%)	0 / 158 (0.00%)	0 / 159 (0.00%)	1 / 154 (0.65%)	0 / 468 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Retinal detachment
subjects affected / exposed	0 / 161 (0.00%)	1 / 158 (0.63%)	0 / 159 (0.00%)	0 / 154 (0.00%)	1 / 468 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Irritable bowel syndrome
subjects affected / exposed	0 / 161 (0.00%)	1 / 158 (0.63%)	0 / 159 (0.00%)	0 / 154 (0.00%)	1 / 468 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haemorrhoidal haemorrhage
subjects affected / exposed	0 / 161 (0.00%)	0 / 158 (0.00%)	1 / 159 (0.63%)	0 / 154 (0.00%)	0 / 468 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatitis
subjects affected / exposed	0 / 161 (0.00%)	0 / 158 (0.00%)	0 / 159 (0.00%)	0 / 154 (0.00%)	1 / 468 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastric polyps
subjects affected / exposed	0 / 161 (0.00%)	0 / 158 (0.00%)	0 / 159 (0.00%)	0 / 154 (0.00%)	1 / 468 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Duodenal ulcer haemorrhage
subjects affected / exposed	0 / 161 (0.00%)	0 / 158 (0.00%)	0 / 159 (0.00%)	1 / 154 (0.65%)	0 / 468 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Umbilical hernia
subjects affected / exposed	0 / 161 (0.00%)	0 / 158 (0.00%)	0 / 159 (0.00%)	1 / 154 (0.65%)	0 / 468 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis
subjects affected / exposed	0 / 161 (0.00%)	0 / 158 (0.00%)	0 / 159 (0.00%)	0 / 154 (0.00%)	1 / 468 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Subcutaneous abscess
subjects affected / exposed	0 / 161 (0.00%)	0 / 158 (0.00%)	0 / 159 (0.00%)	0 / 154 (0.00%)	1 / 468 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Erysipelas
subjects affected / exposed	0 / 161 (0.00%)	0 / 158 (0.00%)	0 / 159 (0.00%)	1 / 154 (0.65%)	0 / 468 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Calculus urinary
subjects affected / exposed	0 / 161 (0.00%)	0 / 158 (0.00%)	1 / 159 (0.63%)	0 / 154 (0.00%)	0 / 468 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
subjects affected / exposed	0 / 161 (0.00%)	0 / 158 (0.00%)	1 / 159 (0.63%)	0 / 154 (0.00%)	1 / 468 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Cellulitis
subjects affected / exposed	1 / 161 (0.62%)	0 / 158 (0.00%)	0 / 159 (0.00%)	0 / 154 (0.00%)	3 / 468 (0.64%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infected dermal cyst
subjects affected / exposed	0 / 161 (0.00%)	0 / 158 (0.00%)	1 / 159 (0.63%)	0 / 154 (0.00%)	0 / 468 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Anal abscess
subjects affected / exposed	0 / 161 (0.00%)	0 / 158 (0.00%)	0 / 159 (0.00%)	0 / 154 (0.00%)	1 / 468 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Appendicitis
subjects affected / exposed	0 / 161 (0.00%)	0 / 158 (0.00%)	0 / 159 (0.00%)	1 / 154 (0.65%)	0 / 468 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Helicobacter infection
subjects affected / exposed	0 / 161 (0.00%)	0 / 158 (0.00%)	0 / 159 (0.00%)	0 / 154 (0.00%)	1 / 468 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Diabetes mellitus inadequate control
subjects affected / exposed	0 / 161 (0.00%)	0 / 158 (0.00%)	0 / 159 (0.00%)	0 / 154 (0.00%)	1 / 468 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Type 2 diabetes mellitus
subjects affected / exposed	0 / 161 (0.00%)	0 / 158 (0.00%)	0 / 159 (0.00%)	0 / 154 (0.00%)	1 / 468 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Bimekizumab Arm 2 through Week 24 (SS)	Bimekizumab Arm 1 through Week 24 (SS)	Adalimumab Arm through Week 24 (SS)	Any bimekizumab dose regimen 2 (BKZ Set)	Any bimekizumab dose regimen 1 (BKZ Set)
Total subjects affected by non serious adverse events
subjects affected / exposed	65 / 161 (40.37%)	61 / 158 (38.61%)	62 / 159 (38.99%)	60 / 154 (38.96%)	182 / 468 (38.89%)
Vascular disorders
Hypertension
subjects affected / exposed	9 / 161 (5.59%)	6 / 158 (3.80%)	13 / 159 (8.18%)	4 / 154 (2.60%)	19 / 468 (4.06%)
occurrences all number	10	6	13	4	20
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	5 / 161 (3.11%)	8 / 158 (5.06%)	4 / 159 (2.52%)	5 / 154 (3.25%)	14 / 468 (2.99%)
occurrences all number	5	9	6	5	16
Infections and infestations
Nasopharyngitis
subjects affected / exposed	27 / 161 (16.77%)	32 / 158 (20.25%)	38 / 159 (23.90%)	28 / 154 (18.18%)	79 / 468 (16.88%)
occurrences all number	40	46	50	35	113
Oral candidiasis
subjects affected / exposed	19 / 161 (11.80%)	15 / 158 (9.49%)	0 / 159 (0.00%)	17 / 154 (11.04%)	66 / 468 (14.10%)
occurrences all number	26	20	0	26	104
Upper respiratory tract infection
subjects affected / exposed	12 / 161 (7.45%)	7 / 158 (4.43%)	15 / 159 (9.43%)	13 / 154 (8.44%)	30 / 468 (6.41%)
occurrences all number	14	8	21	16	40
Pharyngitis
subjects affected / exposed	5 / 161 (3.11%)	4 / 158 (2.53%)	1 / 159 (0.63%)	11 / 154 (7.14%)	13 / 468 (2.78%)
occurrences all number	7	4	1	11	14

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Were there any global substantial amendments to the protocol? Yes

06 Apr 2018

Protocol Amendment 2 (06 Apr 2018) included the following modifications: • Extended the duration of the Screening Period, and therefore the overall study duration, by 1 week • Updated list of current treatment for Psoriasis (PSO) to reflect changes in labeling and approved countries • Updated list of completed and ongoing bimekizumab studies to reflect completion of study UP0042 • Clarified calculation of PASI response rates • Removed references to pharmacodynamic (PD) assessments as they were not conducted in this study • Updated the schedule of study assessments to include a hematology and biochemistry sample at Week 28, and to modify the visits at which the Tuberculosis (TB) questionnaire, body weight, physical examination, and Electrocardiogram (ECG) were assessed • Clarified that all visits from first dose to Week 24 would have a ±3 day visit window, while all visits from Week 28 to end of study would have a ±7 day window • Clarified the dosing window • Modified exclusion criterion to clarify exclusion of study participants who participated in other studies of bimekizumab, other medications (systemic or topical), or devices • Modified exclusion criteria to exclude use of prohibited PSO medications • Modified exclusion criteria pertaining to history of malignancy, systemic disease, and major depression • Added new withdrawal criteria for nonresponders and for study participants with newly diagnosed inflammatory bowel disease (IBD) • Clarified withdrawal criteria for study participants with depression or suicidal ideation or behavior • Corrected information pertaining to how adalimumab was supplied • Updated prohibited concomitant medications to include tildrakizumab and risankizumab • Corrected discrepancies between Study procedures by visit and Schedule of study assessments • Revised Psoriatic Arthritis Screening and Evaluation (PASE) questionnaire scoring • Clarified definition of abortion • Updated laboratory measurements to be performed

06 Apr 2018

Continuation of Protocol Amendment 2: • Provided additional details for requirements for investigational medicinal product (IMP) rechallenge in the event of potential drug-induced liver injury (PDILI) • Defined a bimekizumab Set as an analysis population • Clarified regions for analyses • Updated the sequence testing and analysis of secondary efficacy variables In addition, minor spelling, editorial, and formatting changes were made, and the List of abbreviations was updated.

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.

None reported

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Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Participants with a Psoriasis Area and Severity Index 90 (PASI90) response at Week 16

Primary: Percentage of Participants with a Psoriasis Area and Severity Index 90 (PASI90) response at Week 16

Primary: Percentage of Participants With an Investigator's Global Assessment (IGA) Response (Clear or Almost Clear With at Least 2-Category Improvement Relative to Baseline) at Week 16

Primary: Percentage of Participants With an Investigator's Global Assessment (IGA) Response (Clear or Almost Clear With at Least 2-Category Improvement Relative to Baseline) at Week 16

Secondary: Percentage of Participants With a PASI90 Response at Week 24

Secondary: Percentage of Participants With a PASI90 Response at Week 24

Secondary: Percentage of Participants With an IGA Response (Clear or Almost Clear with at least 2-category improvement relative to Baseline) at Week 24

Secondary: Percentage of Participants With an IGA Response (Clear or Almost Clear with at least 2-category improvement relative to Baseline) at Week 24

Secondary: Percentage of Participants With a PASI75 Response at Week 4

Secondary: Percentage of Participants With a PASI75 Response at Week 4

Secondary: Percentage of Participants With a PASI100 Response at Week 16

Secondary: Percentage of Participants With a PASI100 Response at Week 16

Secondary: Percentage of Participants With a PASI100 Response at Week 24

Secondary: Percentage of Participants With a PASI100 Response at Week 24

Secondary: Percentage of Participants With a PASI90 Response at Week 56

Secondary: Percentage of Participants With a PASI90 Response at Week 56

Secondary: Percentage of Participants With an IGA Response (Clear or Almost Clear with at least 2-category improvement relative to Baseline) at Week 56

Secondary: Percentage of Participants With an IGA Response (Clear or Almost Clear with at least 2-category improvement relative to Baseline) at Week 56

Secondary: Number of Treatment-emergent Adverse Events (TEAEs) Adjusted by Duration of Participant Exposure to Study Treatment from Baseline to Week 24

Secondary: Number of Treatment-emergent Adverse Events (TEAEs) Adjusted by Duration of Participant Exposure to Study Treatment from Baseline to Week 24

Secondary: Number of Serious Adverse Events (SAEs) Adjusted by Duration of Participant Exposure to Study Treatment from Baseline to Week 24

Secondary: Number of Serious Adverse Events (SAEs) Adjusted by Duration of Participant Exposure to Study Treatment from Baseline to Week 24

Secondary: Number of Treatment-emergent Adverse Events (TEAEs) Leading to Withdrawal Adjusted by Duration of Participant Exposure to Study Treatment from Baseline to Week 24

Secondary: Number of Treatment-emergent Adverse Events (TEAEs) Leading to Withdrawal Adjusted by Duration of Participant Exposure to Study Treatment from Baseline to Week 24

Secondary: Number of Treatment-emergent Adverse Events (TEAEs) Adjusted by Duration of Participant Exposure to Study Treatment from Baseline to Safety Follow-Up Visit (up to Week 72)

Secondary: Number of Treatment-emergent Adverse Events (TEAEs) Adjusted by Duration of Participant Exposure to Study Treatment from Baseline to Safety Follow-Up Visit (up to Week 72)

Secondary: Number of Serious Adverse Events (SAEs) Adjusted by Duration of Participant Exposure to Study Treatment from Baseline to Safety Follow-Up Visit (up to Week 72)

Secondary: Number of Serious Adverse Events (SAEs) Adjusted by Duration of Participant Exposure to Study Treatment from Baseline to Safety Follow-Up Visit (up to Week 72)

Secondary: Number of Treatment-emergent Adverse Events (TEAEs) Leading to Withdrawal Adjusted by Duration of Participant Exposure to Study Treatment from Baseline to Safety Follow-Up Visit (up to Week 72)

Secondary: Number of Treatment-emergent Adverse Events (TEAEs) Leading to Withdrawal Adjusted by Duration of Participant Exposure to Study Treatment from Baseline to Safety Follow-Up Visit (up to Week 72)

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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