PA0008

UCB Biopharma SPRL

Allée de la Recherche 60, Brussels, Belgium, 1070

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

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

No

No

No

Final

06 Dec 2018

No

Yes

16 Jul 2018

No

Assess the dose-response based on the efficacy of bimekizumab.

During this study all study participants were closely monitored.

27 Oct 2016

Yes

Yes

Czech Republic: 26

Germany: 16

Hungary: 3

Poland: 108

Russian Federation: 13

United States: 40

206

153

0

0

0

0

0

0

185

21

0

Double-Blind Period

Randomised - controlled

Yes

Placebo

PBO

Solution for injection

Subcutaneous use

Subjects were administered Placebo, as 2 subcutaneous injections, in the lateral abdominal wall, or upper outer thigh.

Bimekizumab

UCB4940

Solution for injection

Subcutaneous use

Subjects were administered different BKZ doses, as 2 subcutaneous injections, in the lateral abdominal wall, or upper outer thigh.

Bimekizumab

UCB4940

Solution for injection

Subcutaneous use

Subjects were administered different BKZ doses, as 2 subcutaneous injections, in the lateral abdominal wall, or upper outer thigh.

Bimekizumab

UCB4940

Solution for injection

Subcutaneous use

Subjects were administered different BKZ doses, as 2 subcutaneous injections, in the lateral abdominal wall, or upper outer thigh.

Bimekizumab

UCB4940

Solution for injection

Subcutaneous use

Subjects were administered different BKZ doses, as 2 subcutaneous injections, in the lateral abdominal wall, or upper outer thigh.

Dose-Blind Period

Randomised - controlled

Yes

Bimekizumab

UCB4940

Solution for injection

Subcutaneous use

Subjects were administered different BKZ doses, as 2 subcutaneous injections, in the lateral abdominal wall, or upper outer thigh.

Bimekizumab

UCB4940

Solution for injection

Subcutaneous use

Subjects were administered different BKZ doses, as 2 subcutaneous injections, in the lateral abdominal wall, or upper outer thigh.

Bimekizumab

UCB4940

Solution for injection

Subcutaneous use

Subjects were administered different BKZ doses, as 2 subcutaneous injections, in the lateral abdominal wall, or upper outer thigh.

Bimekizumab

UCB4940

Solution for injection

Subcutaneous use

Subjects were administered different BKZ doses, as 2 subcutaneous injections, in the lateral abdominal wall, or upper outer thigh.

Bimekizumab

UCB4940

Solution for injection

Subcutaneous use

Subjects were administered different BKZ doses, as 2 subcutaneous injections, in the lateral abdominal wall, or upper outer thigh.

Bimekizumab

UCB4940

Solution for injection

Subcutaneous use

Subjects were administered different BKZ doses, as 2 subcutaneous injections, in the lateral abdominal wall, or upper outer thigh.

Bimekizumab

UCB4940

Solution for injection

Subcutaneous use

Subjects were administered different BKZ doses, as 2 subcutaneous injections, in the lateral abdominal wall, or upper outer thigh.

Placebo

BKZ 16 mg

BKZ 160 mg

BKZ 160 mg LD

BKZ 320 mg

Placebo (FAS)

Participants received Placebo during the 12 Weeks Double-Blind Period, forming the Full Analysis Set (FAS).

BKZ 16 mg (FAS)

Participants received Bimekizumab (BKZ) 16 milligrams (mg) every 4 weeks (Q4W) during the 12 Weeks Double-Blind Period, forming the Full Analysis Set (FAS).

BKZ 160 mg (FAS)

Participants received Bimekizumab (BKZ) 160 mg every 4 weeks (Q4W) during the 12 Weeks Double-Blind Period followed by the same dose during the 36 Weeks Dose-Blind Period, forming the Full Analysis Set (FAS).

BKZ 160 mg LD (FAS)

Participants received Bimekizumab (BKZ) 320 mg at Baseline followed by 160 mg every 4 weeks (Q4W) during the 12 Weeks Double-Blind Period, forming the Full Analysis Set (FAS).

BKZ 320 mg (FAS)

Participants received Bimekizumab (BKZ) 320 mg every 4 weeks (Q4W) during the 12 Weeks Double-Blind Period followed by the same dose during the 36 Weeks Dose-Blind Period, forming the Full Analysis Set (FAS).

BKZ 160 mg + BKZ 160 mg LD (SS)

Participants received Bimekizumab (BKZ) 160 mg every 4 weeks (Q4W) and Bimekizumab (BKZ) 320 mg at Baseline followed by 160 mg Q4W during the 12 Weeks Double-Blind Period followed by Bimekizumab (BKZ) 160 mg Q4W during the 36 Weeks Dose-Blind Period, forming the Safety Set (SS).

BKZ 320 mg (SS)

Participants received Bimekizumab (BKZ) 320 mg every 4 weeks (Q4W) during the 12 Weeks Double-Blind Period followed by the same dose during the 36 Weeks Dose-Blind Period, forming the Safety Set (SS).

Placebo (PK-PPS)

Participants received Placebo during the 12 Weeks Double-Blind Period, forming the Pharmacokinetic Per-Protocol Set (PK-PPS).

BKZ 16 mg (PK-PPS)

Participants received Bimekizumab (BKZ) 16 milligrams (mg) every 4 weeks (Q4W) during the 12 Weeks Double-Blind Period, forming the Pharmacokinetic Per-Protocol Set (PK-PPS).

BKZ 160 mg (PK-PPS)

Participants received Bimekizumab (BKZ) 160 mg every 4 weeks (Q4W) during the 12 Weeks Double-Blind Period followed by the same dose during the 36 Weeks Dose-Blind Period, forming the Pharmacokinetic Per-Protocol Set (PK-PPS).

BKZ 160 mg LD (PK-PPS)

Participants received Bimekizumab (BKZ) 320 mg at Baseline followed by 160 mg every 4 weeks (Q4W) during the 12 Weeks Double-Blind Period, forming the Pharmacokinetic Per-Protocol Set (PK-PPS).

BKZ 320 mg (PK-PPS)

Participants received Bimekizumab (BKZ) 320 mg every 4 weeks (Q4W) during the 12 Weeks Double-Blind Period followed by the same dose during the 36 Weeks Dose-Blind Period, forming the Pharmacokinetic Per-Protocol Set (PK-PPS).

Placebo - BKZ 160 mg (DBS)

After the 12 Weeks Double-Blind Period participants randomized to Placebo were re-randomized to receive Bimekizumab (BKZ) 160 mg every 4 weeks (Q4W) for 36 weeks in the Dose-Blind Period. Participants are a subgroup from the Dose-Blind Set (DBS). The subgroup contained participants who were part of the PK-PPS and DBS.

Placebo - BZK 320 mg (DBS)

After the 12 Weeks Double-Blind Period participants randomized to Placebo were re-randomized to receive Bimekizumab (BKZ) 320 mg every 4 weeks (Q4W) for 36 weeks in the Dose-Blind Period. Participants are a subgroup from the Dose-Blind Set (DBS). The subgroup contained participants who were part of the PK-PPS and DBS.

BKZ 16 mg - BKZ 160 mg (DBS)

After the 12 Weeks Double-Blind Period participants randomized to Bimekizumab (BKZ) 16 mg every 4 weeks (Q4W) were re-randomized to receive BKZ 160 mg Q4W for 36 weeks in the Dose-Blind Period. Participants are a subgroup from the Dose-Blind Set (DBS). The subgroup contained participants who were part of the PK-PPS and DBS.

BZK 16 mg - BZK 320 mg (DBS)

After the 12 Weeks Double-Blind Period participants randomized to Bimekizumab (BKZ) 16 mg every 4 weeks (Q4W) were re-randomized to receive BKZ 320 mg Q4W for 36 weeks in the Dose-Blind Period. Participants are a subgroup from the Dose-Blind Set (DBS). The subgroup contained participants who were part of the PK-PPS and DBS.

BZK 160 mg LD - BZK 160 mg (DBS)

After the 12 Weeks Double-Blind Period participants randomized to Bimekizumab (BKZ) 320 mg at Baseline followed by 160 mg every 4 weeks (Q4W) were re-randomized to receive BKZ 160 mg Q4W for 36 weeks in the Dose-Blind Period. Participants are a subgroup from the Dose-Blind Set (DBS). The subgroup contained participants who were part of the PK-PPS and DBS.

BZK 160 mg - BKZ 160 mg (DBS)

After the 12 Weeks Double-Blind Period participants randomized to Bimekizumab (BKZ) 160 mg every 4 weeks (Q4W) were re-randomized to receive BKZ 160 mg Q4W for 36 weeks in the Dose-Blind Period. Participants are a subgroup from the Dose-Blind Set (DBS). The subgroup contained participants who were part of the PK-PPS and DBS.

BKZ 320 mg - BKZ 320 mg (DBS)

After the 12 Weeks Double-Blind Period participants randomized to Bimekizumab (BKZ) 320 mg every 4 weeks (Q4W) were re-randomized to receive BKZ 320 mg Q4W for 36 weeks in the Dose-Blind Period. Participants are a subgroup from the Dose-Blind Set (DBS). The subgroup contained participants who were part of the PK-PPS and DBS.

Placebo

BKZ 16 mg

BKZ 160 mg

BKZ 160 mg LD

BKZ 320 mg

Placebo - BKZ 160 mg

Placebo - BZK 320 mg

BKZ 16 mg - BKZ 160 mg

BZK 16 mg - BZK 320 mg

BZK 160 mg LD - BZK 160 mg

BZK 160 mg - BKZ dose 160 mg

BKZ 320 mg - BKZ 320 mg

Placebo (FAS)

Participants received Placebo during the 12 Weeks Double-Blind Period, forming the Full Analysis Set (FAS).

BKZ 16 mg (FAS)

Participants received Bimekizumab (BKZ) 16 milligrams (mg) every 4 weeks (Q4W) during the 12 Weeks Double-Blind Period, forming the Full Analysis Set (FAS).

BKZ 160 mg (FAS)

Participants received Bimekizumab (BKZ) 160 mg every 4 weeks (Q4W) during the 12 Weeks Double-Blind Period followed by the same dose during the 36 Weeks Dose-Blind Period, forming the Full Analysis Set (FAS).

BKZ 160 mg LD (FAS)

Participants received Bimekizumab (BKZ) 320 mg at Baseline followed by 160 mg every 4 weeks (Q4W) during the 12 Weeks Double-Blind Period, forming the Full Analysis Set (FAS).

BKZ 320 mg (FAS)

Participants received Bimekizumab (BKZ) 320 mg every 4 weeks (Q4W) during the 12 Weeks Double-Blind Period followed by the same dose during the 36 Weeks Dose-Blind Period, forming the Full Analysis Set (FAS).

BKZ 160 mg + BKZ 160 mg LD (SS)

Participants received Bimekizumab (BKZ) 160 mg every 4 weeks (Q4W) and Bimekizumab (BKZ) 320 mg at Baseline followed by 160 mg Q4W during the 12 Weeks Double-Blind Period followed by Bimekizumab (BKZ) 160 mg Q4W during the 36 Weeks Dose-Blind Period, forming the Safety Set (SS).

BKZ 320 mg (SS)

Participants received Bimekizumab (BKZ) 320 mg every 4 weeks (Q4W) during the 12 Weeks Double-Blind Period followed by the same dose during the 36 Weeks Dose-Blind Period, forming the Safety Set (SS).

Placebo (PK-PPS)

Participants received Placebo during the 12 Weeks Double-Blind Period, forming the Pharmacokinetic Per-Protocol Set (PK-PPS).

BKZ 16 mg (PK-PPS)

Participants received Bimekizumab (BKZ) 16 milligrams (mg) every 4 weeks (Q4W) during the 12 Weeks Double-Blind Period, forming the Pharmacokinetic Per-Protocol Set (PK-PPS).

BKZ 160 mg (PK-PPS)

Participants received Bimekizumab (BKZ) 160 mg every 4 weeks (Q4W) during the 12 Weeks Double-Blind Period followed by the same dose during the 36 Weeks Dose-Blind Period, forming the Pharmacokinetic Per-Protocol Set (PK-PPS).

BKZ 160 mg LD (PK-PPS)

Participants received Bimekizumab (BKZ) 320 mg at Baseline followed by 160 mg every 4 weeks (Q4W) during the 12 Weeks Double-Blind Period, forming the Pharmacokinetic Per-Protocol Set (PK-PPS).

BKZ 320 mg (PK-PPS)

Participants received Bimekizumab (BKZ) 320 mg every 4 weeks (Q4W) during the 12 Weeks Double-Blind Period followed by the same dose during the 36 Weeks Dose-Blind Period, forming the Pharmacokinetic Per-Protocol Set (PK-PPS).

Placebo - BKZ 160 mg (DBS)

After the 12 Weeks Double-Blind Period participants randomized to Placebo were re-randomized to receive Bimekizumab (BKZ) 160 mg every 4 weeks (Q4W) for 36 weeks in the Dose-Blind Period. Participants are a subgroup from the Dose-Blind Set (DBS). The subgroup contained participants who were part of the PK-PPS and DBS.

Placebo - BZK 320 mg (DBS)

After the 12 Weeks Double-Blind Period participants randomized to Placebo were re-randomized to receive Bimekizumab (BKZ) 320 mg every 4 weeks (Q4W) for 36 weeks in the Dose-Blind Period. Participants are a subgroup from the Dose-Blind Set (DBS). The subgroup contained participants who were part of the PK-PPS and DBS.

BKZ 16 mg - BKZ 160 mg (DBS)

After the 12 Weeks Double-Blind Period participants randomized to Bimekizumab (BKZ) 16 mg every 4 weeks (Q4W) were re-randomized to receive BKZ 160 mg Q4W for 36 weeks in the Dose-Blind Period. Participants are a subgroup from the Dose-Blind Set (DBS). The subgroup contained participants who were part of the PK-PPS and DBS.

BZK 16 mg - BZK 320 mg (DBS)

After the 12 Weeks Double-Blind Period participants randomized to Bimekizumab (BKZ) 16 mg every 4 weeks (Q4W) were re-randomized to receive BKZ 320 mg Q4W for 36 weeks in the Dose-Blind Period. Participants are a subgroup from the Dose-Blind Set (DBS). The subgroup contained participants who were part of the PK-PPS and DBS.

BZK 160 mg LD - BZK 160 mg (DBS)

After the 12 Weeks Double-Blind Period participants randomized to Bimekizumab (BKZ) 320 mg at Baseline followed by 160 mg every 4 weeks (Q4W) were re-randomized to receive BKZ 160 mg Q4W for 36 weeks in the Dose-Blind Period. Participants are a subgroup from the Dose-Blind Set (DBS). The subgroup contained participants who were part of the PK-PPS and DBS.

BZK 160 mg - BKZ 160 mg (DBS)

After the 12 Weeks Double-Blind Period participants randomized to Bimekizumab (BKZ) 160 mg every 4 weeks (Q4W) were re-randomized to receive BKZ 160 mg Q4W for 36 weeks in the Dose-Blind Period. Participants are a subgroup from the Dose-Blind Set (DBS). The subgroup contained participants who were part of the PK-PPS and DBS.

BKZ 320 mg - BKZ 320 mg (DBS)

After the 12 Weeks Double-Blind Period participants randomized to Bimekizumab (BKZ) 320 mg every 4 weeks (Q4W) were re-randomized to receive BKZ 320 mg Q4W for 36 weeks in the Dose-Blind Period. Participants are a subgroup from the Dose-Blind Set (DBS). The subgroup contained participants who were part of the PK-PPS and DBS.

The ACR50 response rate was based on 50% improvement relative to Baseline in the following measures: •Tender Joint Count (TJC) based on 78 joints •Swollen Joint Count (SJC) based on 76 joints •3 of the 5 remaining core set measures: -Disease activity as assessed by Patient’s Global Assessment of Disease Activity (PGADA) -Disease activity as assessed by Physician’s Global Assessment of Disease Activity (PhGADA) -Pain as assessed by Patient’s Assessment of Arthritis Pain (PtAAP) -Physical function as assessed by Health Assessment Questionnaire – Disability Index (HAQ-DI) -Acute phase response as assessed by high sensitivity C-reactive protein (hs CRP).

Primary

Week 12

Statistic and p-value were calculated using a Cochran-Mantel-Haenszel test (test for non-zero correlation statistic) based on modified ridit scores and including geographic region and prior Tumor Necrosis Factor (TNF) inhibitor exposure as stratification factors. The 160 loading dose arm was not considered in the dose-response because this is a mixed dose and the test is examining linear dose response.

Placebo (FAS) v BKZ 16 mg (FAS) v BKZ 160 mg (FAS) v BKZ 160 mg LD (FAS) v BKZ 320 mg (FAS)

206

Pre-specified

999

2-sided

For differences in relation to placebo: Odds Ratio, confidence interval, and p-value were derived from a logistic regression model including fixed effects for treatment, geographic region and prior Tumor Factor Necrosis (TNF) inhibitor exposure.

Placebo (FAS) v BKZ 16 mg (FAS)

83

Pre-specified

4.2

2-sided

For differences in relation to placebo: Odds Ratio, confidence interval, and p-value were derived from a logistic regression model including fixed effects for treatment, geographic region and prior Tumor Factor Necrosis (TNF) inhibitor exposure.

Placebo (FAS) v BKZ 160 mg (FAS)

83

Pre-specified

8.1

2-sided

For differences in relation to placebo: Odds Ratio, confidence interval, and p-value were derived from a logistic regression model including fixed effects for treatment, geographic region and prior Tumor Factor Necrosis (TNF) inhibitor exposure.

Placebo (FAS) v BKZ 160 mg LD (FAS)

83

Pre-specified

9.7

2-sided

For differences in relation to placebo: Odds Ratio, confidence interval, and p-value were derived from a logistic regression model including fixed effects for treatment, geographic region and prior Tumor Factor Necrosis (TNF) inhibitor exposure.

Placebo (FAS) v BKZ 320 mg (FAS)

83

Pre-specified

3.7

2-sided

The ACR20 response rate was based on 20% improvement relative to Baseline in the following measures: •TJC based on 78 joints •SJC based on 76 joints •3 of the 5 remaining core set measures: -Disease activity as assessed by PGADA -Disease activity as assessed by PhGADA -Pain as assessed by PtAAP -Physical function as assessed by HAQ-DI -Acute phase response as assessed by hs CRP Note: Nonresponder imputation was used to account for missing data in the primary analysis, the study participants with a missing ACR score at Week 12 or who discontinued IMP prior to the Week 12 Visit were considered nonresponders for the primary analysis.

Secondary

Week 12

For differences in relation to Placebo: Odds Ratio, confidence interval, and p-value were derived from a logistic regression model including fixed effects for treatment, geographic region and prior Tumor Necrosis Factor (TNF) inhibitor exposure.

Placebo (FAS) v BKZ 16 mg (FAS)

83

Pre-specified

4.6

2-sided

For differences in relation to Placebo: Odds Ratio, confidence interval, and p-value were derived from a logistic regression model including fixed effects for treatment, geographic region and prior Tumor Necrosis Factor (TNF) inhibitor exposure.

Placebo (FAS) v BKZ 160 mg (FAS)

83

Pre-specified

11

2-sided

For differences in relation to Placebo: Odds Ratio, confidence interval, and p-value were derived from a logistic regression model including fixed effects for treatment, geographic region and prior Tumor Necrosis Factor (TNF) inhibitor exposure.

Placebo (FAS) v BKZ 160 mg LD (FAS)

83

Pre-specified

6.2

2-sided

For differences in relation to Placebo: Odds Ratio, confidence interval, and p-value were derived from a logistic regression model including fixed effects for treatment, geographic region and prior Tumor Necrosis Factor (TNF) inhibitor exposure.

Placebo (FAS) v BKZ 320 mg (FAS)

83

Pre-specified

4.2

2-sided

The ACR70 response rate was based on 70% improvement relative to Baseline in the following measures: •TJC based on 78 joints •SJC based on 76 joints •3 of the 5 remaining core set measures: -Disease activity as assessed by PGADA -Disease activity as assessed by PhGADA -Pain as assessed by PtAAP -Physical function as assessed by HAQ-DI -Acute phase response as assessed by hs CRP Note: Nonresponder imputation was used to account for missing data in the primary analysis, the study participants with a missing ACR score at Week 12 or who discontinued IMP prior to the Week 12 Visit were considered nonresponders for the primary analysis.

Secondary

Week 12

For differences in relation to Placebo: Odds Ratio, confidence interval, and p-value were derived from a logistic regression model including fixed effects for treatment, geographic region and prior Tumor Necrosis Factor (TNF) inhibitor exposure.

Placebo (FAS) v BKZ 16 mg (FAS)

83

Pre-specified

2.4

2-sided

For differences in relation to Placebo: Odds Ratio, confidence interval, and p-value were derived from a logistic regression model including fixed effects for treatment, geographic region and prior Tumor Necrosis Factor (TNF) inhibitor exposure.

Placebo (FAS) v BKZ 160 mg (FAS)

83

Pre-specified

4.1

2-sided

For differences in relation to Placebo: Odds Ratio, confidence interval, and p-value were derived from a logistic regression model including fixed effects for treatment, geographic region and prior Tumor Necrosis Factor (TNF) inhibitor exposure.

Placebo (FAS) v BKZ 160 mg LD (FAS)

83

Pre-specified

7.5

2-sided

For differences in relation to Placebo: Odds Ratio, confidence interval, and p-value were derived from a logistic regression model including fixed effects for treatment, geographic region and prior Tumor Necrosis Factor (TNF) inhibitor exposure.

Placebo (FAS) v BKZ 320 mg (FAS)

83

Pre-specified

2.9

2-sided

The PASI90 response assessments are based on at least 90% improvement in the PASI score from Baseline. This is a scoring system that averages the redness, thickness, and scaliness of the psoriatic lesions (on a 0-4 scale), and weights the resulting score by the area of skin involved. 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.

Secondary

Week 12

The PASI75 response assessments are based on at least 75% improvement in the PASI score from Baseline. This is a scoring system that averages the redness, thickness, and scaliness of the psoriatic lesions (on a 0-4 scale), and weights the resulting score by the area of skin involved. 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.

Secondary

Week 12

From Week 1 and up to the end of safety follow-up visit, 20 weeks after the final dose

At Week 12, Placebo and BKZ 16 mg subjects were re-randomized to either BKZ 160 mg or BKZ 320 mg. Subjects randomized to BKZ 160 mg with 160 mg loading dose at Baseline remained on BKZ 160 mg treatment. Subjects randomized to BKZ 160 mg and BKZ 320 mg at Baseline were not re-randomized at Week 12 and remained on their original treatment.

19.0

BKZ 320 mg (SS)

BKZ 160 mg + BKZ 160 mg LD (SS)