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Clinical Trial Results:
A Phase 3, Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo- and Active-Controlled Study Followed by a Placebo-Controlled Maintenance Period and Open-Label Follow-Up to Evaluate the Efficacy and Safety of Certolizumab Pegol in Subjects With Moderate to Severe Chronic Plaque Psoriasis

Summary
EudraCT number	2014-003492-36
Trial protocol	GB DE HU CZ NL PL BG FR
Global end of trial date	17 Dec 2018

Results information
Results version number	v1
This version publication date	01 Jan 2020
First version publication date	01 Jan 2020
Other versions	v2

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

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Trial information

Top of page

Sponsor protocol code

PS0003

ISRCTN number

US NCT number

NCT02346240

WHO universal trial number (UTN)

Sponsor organisation name

UCB Biopharma SPRL

Sponsor organisation address

Allée de la Recherche 60, Brussels, Belgium, B-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

11 Feb 2019

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

17 Dec 2018

Was the trial ended prematurely?

Main objective of the trial

To compare the efficacy of certolizumab pegol (CZP) administered subcutaneously (sc) at the doses of CZP 400 mg every 2 weeks (Q2W) and CZP 200 mg Q2W after a loading dose of CZP 400 mg Q2W at Weeks 0, 2, and 4 to placebo in the treatment of moderate to severe chronic plaque psoriasis (PSO).

Protection of trial subjects

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

Background therapy

Background therapy/concomitant medication was permitted as defined in the study protocol.

Evidence for comparator

Etanercept (ETN) is a fusion protein consisting of the fragment crystallizable (Fc) fragment of Immunoglobulin G1 (IgG1) with the Type 2 soluble Tumor Necrosis Factor (TNF) alpha receptor. ETN is specific for TNF alpha and lymphotoxin alpha. ETN was the first TNF alpha inhibitor approved for the treatment of psoriasis and is part of the standard armamentarium. The approved initial dose is 50 milligrams (mg) twice weekly. The safety and efficacy profile of ETN is well established. The first approval worldwide for ETN was in the United States in 1998 for the treatment of rheumatoid arthritis and in 2004 for psoriasis. All of these factors make ETN an ideal active comparator in this study.

Actual start date of recruitment

11 Feb 2015

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Bulgaria: 25

Country: Number of subjects enrolled

Czech Republic: 80

Country: Number of subjects enrolled

France: 14

Country: Number of subjects enrolled

Germany: 63

Country: Number of subjects enrolled

Hungary: 25

Country: Number of subjects enrolled

Netherlands: 3

Country: Number of subjects enrolled

Poland: 233

Country: Number of subjects enrolled

United Kingdom: 24

Country: Number of subjects enrolled

United States: 92

Worldwide total number of subjects

559

EEA total number of subjects

467

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)

519

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

This study started to enroll participants in February 2015, from multiple sites in Europe and United States and concluded in December 2018. 559 participants are included in the Randomized Set (RS) shown in the Participant Flow.

Screening details

The study included a Screening Period, an Initial Treatment Period up to Week 16, a Maintenance Treatment Period up to Week 48, an Open-Label Extension Treatment Period up to Week 144 and a Safety Follow-up Period up to Week 157. The Participants Flow refers to the Randomized Set, the Maintenance Set and the Open Label Set.

Period 1 title

Initial Period (Baseline to Week 16)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Blinding implementation details

CZP and placebo treatments were administered in a double-blind fashion (the sponsor, subject, and blinded site staff remained blinded to treatment assignment during the first 16 weeks of the study). Etanercept treatments were administered in a single-blind fashion (the sponsor and the blinded site staff remained blinded, but the subject and unblinded study staff knew the treatment assignment during the first 16 weeks of the study).

Are arms mutually exclusive

Yes

Placebo Q2W

Arm description

Placebo subcutaneous (sc) injections every 2 weeks (Q2W) through Week 14. Treatment received from Week 16-48 is based on initial treatment and response to treatment: •PASI75 responders at Week 16 continued to receive blinded Placebo. PASI75 non-responders at Week 16 were removed from blinded study medication and escaped to Certolizumab pegol (CZP) 400 mg Q2W. Participants who received unblinded CZP 400 mg Q2W for 16 weeks and did not achieve a PASI50 response were withdrawn from the study. Participants could enter a 96-week open-label extension period after completing the Maintenance Period (Weeks 16-48) and receive CZP under certain conditions.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

PBO

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subcutaneous injections every 2 weeks (Q2W)

Etanercept

Arm description

Etanercept (ETN) 50 mg subcutaneous (sc) injections twice per week throughout Week 11.5. •PASI75 responders at Week 16 were re-randomized to either CZP (loading dose of 400 mg at Weeks 16, 18, and 20 followed by 200 mg Q2W) or Placebo Q2W. Participants who did not achieve a PASI75 response at Week 16 escaped to CZP 400 mg Q2W. Participants who received unblinded CZP 400 mg Q2W for 16 weeks and did not achieve a PASI50 response were withdrawn from the study. Participants could enter a 96-week open-label extension period after completing the Maintenance Period and receive CZP under certain conditions.

Arm type

Active comparator

Investigational medicinal product name

Etanercept

Investigational medicinal product code

ETN

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subcutaneous injections: 50 mg twice weekly

CZP 200 mg Q2W

Arm description

CZP 400 mg injections at Weeks 0, 2, 4, followed by CZP 200 mg every 2 weeks (Q2W) from Week 6 to Week 14. Treatment received from Week 16-48 is based on initial treatment and response to treatment: •PASI75 responders at Week 16 were re-randomized to receive either CZP 200 mg Q2W or CZP 400 mg every 4 weeks (Q4W); with Placebo administered on alternate dosing weeks to maintain the blind) Or Placebo Q2W. Participants who did not achieve a PASI75 response at Week 16 were removed from blinded study medication and escaped to CZP 400 mg Q2W. Participants who received unblinded CZP 400 mg Q2W for 16 weeks and did not achieve a PASI50 response were withdrawn from the study. Participants could enter a 96-week open-label extension period after completing the Maintenance Period and receive CZP under certain conditions.

Arm type

Experimental

Investigational medicinal product name

Certolizumab pegol

Investigational medicinal product code

CZP

Other name

Cimzia

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subcutaneous injections: 200 mg every 2 weeks (Q2W) or 400 mg Q2W

CZP 400 mg Q2W

Arm description

CZP 400 mg injections every 2 weeks (Q2W) through Week 14. Treatment received from Week 16-48 is based on initial treatment and response to treatment: •PASI75 responders at Week 16 were re-randomized to CZP 200 mg Q2W or CZP 400 mg Q2W or Placebo Q2W. Participants who did not achieve a PASI75 response at Week 16 were removed from blinded study medication and escaped to CZP 400 mg Q2W. Participants who received unblinded CZP 400 mg Q2W for 16 weeks and did not achieve a PASI50 response were withdrawn from the study. Participants could enter a 96-week open-label extension period after completing the Maintenance Period and receive CZP under certain conditions.

Arm type

Experimental

Investigational medicinal product name

Certolizumab pegol

Investigational medicinal product code

CZP

Other name

Cimzia

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subcutaneous injections: 200 mg every 2 weeks (Q2W) or 400 mg Q2W

Number of subjects in period 1	Placebo Q2W	Etanercept	CZP 200 mg Q2W	CZP 400 mg Q2W
Started	57	170	165	167
Completed Week 16	55	159	159	162
Finished Wk16 started Maintenance Period	55	159	159	160
Completed	55	159	159	160
Not completed	2	11	6	7
Consent withdrawn by subject	1	2	3	2
Subject missed 3 visits	-	-	1	-
Adverse event, non-fatal	-	4	1	1
Non-compliance	-	1	-	1
Lost to follow-up	1	2	1	3
Lack of efficacy	-	1	-	-
Protocol deviation	-	1	-	-

Period 2 title

Maintenance Period (Week 16 to Week 48)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Blinding implementation details

Participants who entered the escape arms of the study received open-label CZP 400 mg every 2 weeks. Participants who relapsed were removed from the placebo-controlled Maintenance Period and entered the OLE Period.

Are arms mutually exclusive

Yes

Placebo/Placebo Q2W

Arm description

This arm consisted of participants initially randomized in the Placebo arm, who achieved a PASI75 response at Week 16 and continued to receive blinded Placebo in the Maintenance Period (Week 16 to Week 48).

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

PBO

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subcutaneous injections every 2 weeks (Q2W)

Etanercept/Placebo Q2W

Arm description

This arm consisted of participants initially randomized in the Etanercept arm, who achieved a PASI75 response at Week 16 and were re-randomized to receive blinded Placebo in the Maintenance Period (Week 16 to Week 48).

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

PBO

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subcutaneous injections every 2 weeks (Q2W)

Investigational medicinal product name

Etanercept

Investigational medicinal product code

ETN

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subcutaneous injections: 50 mg twice weekly

Etanercept/CZP 200 mg Q2W

Arm description

This arm consisted of participants initially randomized in the Etanercept arm, who achieved a PASI75 response at Week 16 and were re-randomized to receive blinded CZP 200 mg Q2W in the Maintenance Period (Week 16 to Week 48).

Arm type

Experimental

Investigational medicinal product name

Certolizumab pegol

Investigational medicinal product code

CZP

Other name

Cimzia

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subcutaneous injections: 200 mg every 2 weeks (Q2W) or 400 mg Q2W

Investigational medicinal product name

Etanercept

Investigational medicinal product code

ETN

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subcutaneous injections: 50 mg twice weekly

CZP 200 mg Q2W/Placebo Q2W

Arm description

This arm consisted of participants initially randomized in the CZP 200 mg arm, who achieved a PASI75 response at Week 16 and were re-randomized to receive blinded Placebo in the Maintenance Period (Week 16 to Week 48).

Arm type

Placebo

Investigational medicinal product name

Certolizumab pegol

Investigational medicinal product code

CZP

Other name

Cimzia

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subcutaneous injections: 200 mg every 2 weeks (Q2W) or 400 mg Q2W

Investigational medicinal product name

Placebo

Investigational medicinal product code

PBO

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subcutaneous injections every 2 weeks (Q2W)

CZP 200 mg Q2W/CZP 200 mg Q2W

Arm description

This arm consisted of participants initially randomized in the CZP 200 mg arm, who achieved a PASI75 response at Week 16 and were re-randomized to receive blinded CZP 200 mg Q2W in the Maintenance Period (Week 16 to Week 48).

Arm type

Experimental

Investigational medicinal product name

Certolizumab pegol

Investigational medicinal product code

CZP

Other name

Cimzia

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subcutaneous injections: 200 mg every 2 weeks (Q2W) or 400 mg Q2W

CZP 200 mg Q2W/CZP 400 mg Q4W

Arm description

This arm consisted of participants initially randomized in the CZP 200 mg arm, who achieved a PASI75 response at Week 16 and were re-randomized to receive blinded CZP 400 mg Q4W in the Maintenance Period (Week 16 to Week 48).

Arm type

Experimental

Investigational medicinal product name

Certolizumab pegol

Investigational medicinal product code

CZP

Other name

Cimzia

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subcutaneous injections: 200 mg every 2 weeks (Q2W) or 400 mg Q2W

CZP 400 mg Q2W/Placebo Q2W

Arm description

This arm consisted of participants initially randomized in the CZP 400 mg arm, who achieved a PASI75 response at Week 16 and were re-randomized to receive blinded Placebo in the Maintenance Period (Week 16 to Week 48).

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

PBO

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subcutaneous injections every 2 weeks (Q2W)

Investigational medicinal product name

Certolizumab pegol

Investigational medicinal product code

CZP

Other name

Cimzia

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subcutaneous injections: 200 mg every 2 weeks (Q2W) or 400 mg Q2W

CZP 400 mg Q2W/CZP 200 mg Q2W

Arm description

This arm consisted of participants initially randomized in the CZP 400 mg arm, who achieved a PASI75 response at Week 16 and were re-randomized to receive blinded CZP 200 mg Q2W in the Maintenance Period (Week 16 to Week 48).

Arm type

Experimental

Investigational medicinal product name

Certolizumab pegol

Investigational medicinal product code

CZP

Other name

Cimzia

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subcutaneous injections: 200 mg every 2 weeks (Q2W) or 400 mg Q2W

CZP 400 mg Q2W/CZP 400 mg Q2W

Arm description

This arm consisted of participants initially randomized in the CZP 400 mg arm, who achieved a PASI75 response at Week 16 and were re-randomized to receive blinded CZP 400 mg Q2W in the Maintenance Period (Week 16 to Week 48).

Arm type

Experimental

Investigational medicinal product name

Certolizumab pegol

Investigational medicinal product code

CZP

Other name

Cimzia

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subcutaneous injections: 200 mg every 2 weeks (Q2W) or 400 mg Q2W

Placebo Q2W/Escape CZP 400 mg Q2W

Arm description

This arm consisted of participants initially randomized in the Placebo arm, who did not achieve a PASI75 response at Week 16 escaped from the blinded treatment and received CZP 400 mg every two weeks. Participants who did not achieve PASI50 after 16 weeks of unblinded treatment were withdrawn from the study.

Arm type

Experimental

Investigational medicinal product name

Certolizumab pegol

Investigational medicinal product code

CZP

Other name

Cimzia

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subcutaneous injections: 200 mg every 2 weeks (Q2W) or 400 mg Q2W

Investigational medicinal product name

Placebo

Investigational medicinal product code

PBO

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subcutaneous injections every 2 weeks (Q2W)

Etanercept/Escape CZP 400 mg Q2W

Arm description

This arm consisted of participants initially randomized in the Etanercept arm, who did not achieve a PASI75 response at Week 16 escaped from the treatment and received CZP 400 mg every two weeks. Participants who did not achieve PASI50 after 16 weeks of unblinded treatment were withdrawn from the study.

Arm type

Experimental

Investigational medicinal product name

Etanercept

Investigational medicinal product code

ETN

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subcutaneous injections: 50 mg twice weekly

Investigational medicinal product name

Certolizumab pegol

Investigational medicinal product code

CZP

Other name

Cimzia

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subcutaneous injections: 200 mg every 2 weeks (Q2W) or 400 mg Q2W

CZP 200 mg Q2W/Escape CZP 400 mg Q2W

Arm description

This arm consisted of participants initially randomized in the CZP 200 mg arm, who did not achieve a PASI75 response at Week 16 escaped from the blinded treatment and received CZP 400 mg every two weeks. Participants who did not achieve PASI50 after 16 weeks of unblinded treatment were withdrawn from the study.

Arm type

Experimental

Investigational medicinal product name

Certolizumab pegol

Investigational medicinal product code

CZP

Other name

Cimzia

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subcutaneous injections: 200 mg every 2 weeks (Q2W) or 400 mg Q2W

CZP 400 mg Q2W/Escape CZP 400 mg Q2W

Arm description

This arm consisted of participants initially randomized in the CZP 400 mg arm, who did not achieve a PASI75 response at Week 16 escaped from the blinded treatment and received CZP 400 mg every two weeks. Participants who did not achieve PASI50 after 16 weeks of unblinded treatment were withdrawn from the study.

Arm type

Experimental

Investigational medicinal product name

Certolizumab pegol

Investigational medicinal product code

CZP

Other name

Cimzia

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subcutaneous injections: 200 mg every 2 weeks (Q2W) or 400 mg Q2W

Number of subjects in period 2	Placebo/Placebo Q2W	Etanercept/Placebo Q2W	Etanercept/CZP 200 mg Q2W	CZP 200 mg Q2W/Placebo Q2W	CZP 200 mg Q2W/CZP 200 mg Q2W	CZP 200 mg Q2W/CZP 400 mg Q4W	CZP 400 mg Q2W/Placebo Q2W	CZP 400 mg Q2W/CZP 200 mg Q2W	CZP 400 mg Q2W/CZP 400 mg Q2W	Placebo Q2W/Escape CZP 400 mg Q2W	Etanercept/Escape CZP 400 mg Q2W	CZP 200 mg Q2W/Escape CZP 400 mg Q2W	CZP 400 mg Q2W/Escape CZP 400 mg Q2W
Started	2	24	50	22	44	44	25	50	49	53	85	49	36
Completed Maintenance Period	2	23	48	20	40	43	23	47	49	46	71	36	30
Finished Wk48 entered Open-label Period	2	23	48	20	40	43	23	47	49	45	68	35	29
Completed	2	23	48	20	40	43	23	47	49	45	68	35	29
Not completed	0	1	2	2	4	1	2	3	0	8	17	14	7
Moved out of state	-	-	1	-	-	-	-	-	-	-	-	-	-
Consent withdrawn by subject	-	1	1	1	1	-	1	2	-	2	5	2	1
Adverse events and alcohol problem	-	-	-	-	-	1	-	-	-	-	-	-	-
Withdrawn by Sponsor	-	-	-	-	-	-	-	-	-	-	1	-	-
Adverse event, non-fatal	-	-	-	1	2	-	-	-	-	1	4	1	2
Patient’s decisions	-	-	-	-	-	-	1	-	-	-	-	-	-
Sponsor decision due to non-compliance	-	-	-	-	1	-	-	1	-	1	1	-	-
Unavailability due to business trip	-	-	-	-	-	-	-	-	-	-	1	-	-
Lost to follow-up	-	-	-	-	-	-	-	-	-	-	1	-	-
Patient request due to non-compliance	-	-	-	-	-	-	-	-	-	-	1	-	-
Lack of efficacy	-	-	-	-	-	-	-	-	-	1	-	3	-
Did not achieve PASI50	-	-	-	-	-	-	-	-	-	3	3	8	4

Period 3 title

Open-Label Period (Week 48 to Week 144)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Placebo/CZP 200 mg Q2W OLE

Arm description

This arm consisted of participants from the Placebo-controlled Maintenance Period, who achieved PASI50 response (had no relapse) at Week 48 and entered the 96-Weeks OLE Period receiving CZP 200 mg Q2W.

Arm type

Experimental

Investigational medicinal product name

Placebo

Investigational medicinal product code

PBO

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subcutaneous injections every 2 weeks (Q2W)

Investigational medicinal product name

Certolizumab pegol

Investigational medicinal product code

CZP

Other name

Cimzia

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subcutaneous injections: 200 mg every 2 weeks (Q2W) or 400 mg Q2W

CZP 200 mg Q2W/CZP 200 mg Q2W OLE

Arm description

This arm consisted of participants who received CZP 200 mg Q2W in the Maintenance Period, who achieved a PASI50 response (had no relapse) at Week 48 and entered OLE.

Arm type

Experimental

Investigational medicinal product name

Certolizumab pegol

Investigational medicinal product code

CZP

Other name

Cimzia

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subcutaneous injections: 200 mg every 2 weeks (Q2W) or 400 mg Q2W

CZP 400 mg Q4W/CZP 200 mg Q2W OLE

Arm description

This arm consisted of participants who received CZP 400 mg Q4W in the Maintenance Period, who achieved a PASI50 response (had no relapse) at Week 48 and entered OLE on the CZP 200mg Q2W dose.

Arm type

Experimental

Investigational medicinal product name

Certolizumab pegol

Investigational medicinal product code

CZP

Other name

Cimzia

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subcutaneous injections: 200 mg every 2 weeks (Q2W) or 400 mg Q2W

CZP 400 mg Q2W/CZP 200 mg Q2W OLE

Arm description

This arm consisted of participants who received CZP 400 mg Q2W in the Maintenance Period, who achieved a PASI50 response (had no relapse) at Week 48 and entered OLE on the CZP 200mg Q2W dose.

Arm type

Experimental

Investigational medicinal product name

Certolizumab pegol

Investigational medicinal product code

CZP

Other name

Cimzia

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subcutaneous injections: 200 mg every 2 weeks (Q2W) or 400 mg Q2W

Esc CZP 400 mg Q2W/CZP 400 mg Q2W OLE

Arm description

This arm consisted of participants who received open-label CZP 400mg Q2W in the Maintenance Period and entered OLE.

Arm type

Experimental

Investigational medicinal product name

Certolizumab pegol

Investigational medicinal product code

CZP

Other name

Cimzia

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subcutaneous injections: 200 mg every 2 weeks (Q2W) or 400 mg Q2W

Placebo/CZP 400 mg Q2W OLE

Arm description

This arm consisted of participants from the Placebo-controlled Maintenance Period, who did not achieve PASI50 response (had relapse) and entered the 96-weeks OLE Period receiving CZP 400 mg Q2W.

Arm type

Experimental

Investigational medicinal product name

Placebo

Investigational medicinal product code

PBO

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subcutaneous injections every 2 weeks (Q2W)

Investigational medicinal product name

Certolizumab pegol

Investigational medicinal product code

CZP

Other name

Cimzia

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subcutaneous injections: 200 mg every 2 weeks (Q2W) or 400 mg Q2W

Any CZP/CZP 400 mg Q2W OLE

Arm description

This arm consisted of participants who relapsed on CZP 200 mg Q2W, CZP 400 mg Q4W and 400 mg Q2W.

Arm type

Experimental

Investigational medicinal product name

Certolizumab pegol

Investigational medicinal product code

CZP

Other name

Cimzia

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subcutaneous injections: 200 mg every 2 weeks (Q2W) or 400 mg Q2W

Number of subjects in period 3	Placebo/CZP 200 mg Q2W OLE	CZP 200 mg Q2W/CZP 200 mg Q2W OLE	CZP 400 mg Q4W/CZP 200 mg Q2W OLE	CZP 400 mg Q2W/CZP 200 mg Q2W OLE	Esc CZP 400 mg Q2W/CZP 400 mg Q2W OLE	Placebo/CZP 400 mg Q2W OLE	Any CZP/CZP 400 mg Q2W OLE
Started	34	122	41	48	177	34	16
Completed	31	105	34	45	146	27	8
Not completed	3	17	7	3	31	7	8
Adverse event, serious fatal	-	1	1	-	1	-	-
Consent withdrawn by subject	-	4	1	-	10	1	1
Adverse event, non-fatal	1	6	2	3	13	3	3
Lost to follow-up	2	2	3	-	1	1	1
No PASI50 response	-	2	-	-	4	2	3
No efficacy of study medication	-	1	-	-	-	-	-
Lack of efficacy	-	1	-	-	1	-	-
Protocol deviation	-	-	-	-	1	-	-

Baseline characteristics

Top of page

Reporting group title

Placebo Q2W

Reporting group description

Reporting group title

Etanercept

Reporting group description

Reporting group title

CZP 200 mg Q2W

Reporting group description

Reporting group title

CZP 400 mg Q2W

Reporting group description

Reporting group values	Placebo Q2W	Etanercept	CZP 200 mg Q2W	CZP 400 mg Q2W	Total
Number of subjects	57	170	165	167	559
Age categorical
Units: Subjects
<=18 years	0	1	0	2	3
Between 18 and 65 years	53	156	153	154	516
>=65 years	4	13	12	11	40
Age continuous
Units: years
arithmetic mean (standard deviation)	46.5 ± 12.5	44.6 ± 14.1	46.7 ± 13.5	45.4 ± 12.4	-
Gender categorical
Units: Subjects
Female	23	43	52	60	178
Male	34	127	113	107	381

Subject analysis set title

Placebo Q2W (RS)

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

Etanercept (RS)

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

CZP 200 mg Q2W (RS)

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

CZP 400 mg Q2W (RS)

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

Placebo/Placebo Q2W (WK16RS)

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

Etanercept/Placebo Q2W (WK16RS)

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

Etanercept/CZP 200 mg Q2W (WK16RS)

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

CZP 200 mg Q2W/Placebo Q2W (WK16RS)

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

CZP 200 mg Q2W/CZP 200 mg Q2W (WK16RS)

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

CZP 200 mg Q2W/CZP 400 mg Q4W (WK16RS)

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

CZP 400 mg Q2W/Placebo Q2W (WK16RS)

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

CZP 400 mg Q2W/CZP 200 mg Q2W (WK16RS)

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

CZP 400 mg Q2W/CZP 400 mg Q2W (WK16RS)

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

CZP 200 mg Q2W (TCS)

Subject analysis set type

Safety analysis

Subject analysis set description

This arm consisted of all participants who received CZP 200 mg at any time during the study.

Subject analysis set title

CZP 400 mg Q2W (TCS)

Subject analysis set type

Safety analysis

Subject analysis set description

This arm consisted of all participants who received CZP 400 mg at any time during the study.

Subject analysis sets values	Placebo Q2W (RS)	Etanercept (RS)	CZP 200 mg Q2W (RS)	CZP 400 mg Q2W (RS)	Placebo/Placebo Q2W (WK16RS)	Etanercept/Placebo Q2W (WK16RS)	Etanercept/CZP 200 mg Q2W (WK16RS)	CZP 200 mg Q2W/Placebo Q2W (WK16RS)	CZP 200 mg Q2W/CZP 200 mg Q2W (WK16RS)	CZP 200 mg Q2W/CZP 400 mg Q4W (WK16RS)	CZP 400 mg Q2W/Placebo Q2W (WK16RS)	CZP 400 mg Q2W/CZP 200 mg Q2W (WK16RS)	CZP 400 mg Q2W/CZP 400 mg Q2W (WK16RS)	CZP 200 mg Q2W (TCS)	CZP 400 mg Q2W (TCS)
Number of subjects	57	170	165	167	2	24	50	22	44	44	25	50	49	373	412
Age categorical
Units: Subjects
<=18 years	0	1	0	2	0	0	0	0	0	0	1	1	0	2	3
Between 18 and 65 years	53	156	153	154	2	24	47	21	43	38	24	45	45	346	377
>=65 years	4	13	12	11	0	0	3	1	1	6	0	4	4	25	32
Age continuous
Units: years
arithmetic mean (standard deviation)	46.5 ± 12.5	44.6 ± 14.1	46.7 ± 13.5	45.4 ± 12.4	41.5 ± 26.2	47.2 ± 13.5	43.3 ± 12.9	47.3 ± 14.9	43.2 ± 12.4	49.4 ± 15.1	42.9 ± 9.7	43.3 ± 11.9	44.6 ± 13.0	45.3 ± 13.0	45.8 ± 13.2
Gender categorical
Units: Subjects
Female	23	43	52	60	2	6	13	7	14	14	11	18	17	115	131
Male	34	127	113	107	0	18	37	15	30	30	14	32	32	258	281

End points

Top of page

Reporting group title

Placebo Q2W

Reporting group description

Reporting group title

Etanercept

Reporting group description

Reporting group title

CZP 200 mg Q2W

Reporting group description

Reporting group title

CZP 400 mg Q2W

Reporting group description

Reporting group title

Placebo/Placebo Q2W

Reporting group description

Reporting group title

Etanercept/Placebo Q2W

Reporting group description

Reporting group title

Etanercept/CZP 200 mg Q2W

Reporting group description

Reporting group title

CZP 200 mg Q2W/Placebo Q2W

Reporting group description

Reporting group title

CZP 200 mg Q2W/CZP 200 mg Q2W

Reporting group description

Reporting group title

CZP 200 mg Q2W/CZP 400 mg Q4W

Reporting group description

Reporting group title

CZP 400 mg Q2W/Placebo Q2W

Reporting group description

Reporting group title

CZP 400 mg Q2W/CZP 200 mg Q2W

Reporting group description

Reporting group title

CZP 400 mg Q2W/CZP 400 mg Q2W

Reporting group description

Reporting group title

Placebo Q2W/Escape CZP 400 mg Q2W

Reporting group description

Reporting group title

Etanercept/Escape CZP 400 mg Q2W

Reporting group description

Reporting group title

CZP 200 mg Q2W/Escape CZP 400 mg Q2W

Reporting group description

Reporting group title

CZP 400 mg Q2W/Escape CZP 400 mg Q2W

Reporting group description

Reporting group title

Placebo/CZP 200 mg Q2W OLE

Reporting group description

Reporting group title

CZP 200 mg Q2W/CZP 200 mg Q2W OLE

Reporting group description

This arm consisted of participants who received CZP 200 mg Q2W in the Maintenance Period, who achieved a PASI50 response (had no relapse) at Week 48 and entered OLE.

Reporting group title

CZP 400 mg Q4W/CZP 200 mg Q2W OLE

Reporting group description

This arm consisted of participants who received CZP 400 mg Q4W in the Maintenance Period, who achieved a PASI50 response (had no relapse) at Week 48 and entered OLE on the CZP 200mg Q2W dose.

Reporting group title

CZP 400 mg Q2W/CZP 200 mg Q2W OLE

Reporting group description

This arm consisted of participants who received CZP 400 mg Q2W in the Maintenance Period, who achieved a PASI50 response (had no relapse) at Week 48 and entered OLE on the CZP 200mg Q2W dose.

Reporting group title

Esc CZP 400 mg Q2W/CZP 400 mg Q2W OLE

Reporting group description

This arm consisted of participants who received open-label CZP 400mg Q2W in the Maintenance Period and entered OLE.

Reporting group title

Placebo/CZP 400 mg Q2W OLE

Reporting group description

This arm consisted of participants from the Placebo-controlled Maintenance Period, who did not achieve PASI50 response (had relapse) and entered the 96-weeks OLE Period receiving CZP 400 mg Q2W.

Reporting group title

Any CZP/CZP 400 mg Q2W OLE

Reporting group description

This arm consisted of participants who relapsed on CZP 200 mg Q2W, CZP 400 mg Q4W and 400 mg Q2W.

Subject analysis set title

Placebo Q2W (RS)

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

Etanercept (RS)

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

CZP 200 mg Q2W (RS)

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

CZP 400 mg Q2W (RS)

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

Placebo/Placebo Q2W (WK16RS)

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

Etanercept/Placebo Q2W (WK16RS)

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

Etanercept/CZP 200 mg Q2W (WK16RS)

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

CZP 200 mg Q2W/Placebo Q2W (WK16RS)

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

CZP 200 mg Q2W/CZP 200 mg Q2W (WK16RS)

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

CZP 200 mg Q2W/CZP 400 mg Q4W (WK16RS)

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

CZP 400 mg Q2W/Placebo Q2W (WK16RS)

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

CZP 400 mg Q2W/CZP 200 mg Q2W (WK16RS)

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

CZP 400 mg Q2W/CZP 400 mg Q2W (WK16RS)

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

CZP 200 mg Q2W (TCS)

Subject analysis set type

Safety analysis

Subject analysis set description

This arm consisted of all participants who received CZP 200 mg at any time during the study.

Subject analysis set title

CZP 400 mg Q2W (TCS)

Subject analysis set type

Safety analysis

Subject analysis set description

This arm consisted of all participants who received CZP 400 mg at any time during the study.

Primary: Proportion of subjects who achieve a Psoriasis Activity and Severity Index (PASI75) response at Week 12

Top of page

End point title

Proportion of subjects who achieve a Psoriasis Activity and Severity Index (PASI75) response at Week 12

End point description

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.

End point type

Primary

End point timeframe

Week 12

End point values	Placebo Q2W (RS)	Etanercept (RS)	CZP 200 mg Q2W (RS)	CZP 400 mg Q2W (RS)
Number of subjects analysed	57	170	165	167
Units: percentage of participants
number (not applicable)	5.0	53.3	61.3	66.7

Statistical Analysis 1

Statistical analysis description

The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.

Comparison groups

Placebo Q2W (RS) v CZP 400 mg Q2W (RS)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

superiority

Method

Regression, Logistic

Parameter type

Estimated difference in responder rate

Point estimate

61.6

Confidence interval

level

95%

sides

2-sided

lower limit

52.1

upper limit

71.2

Statistical Analysis 2

Statistical analysis description

The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.

Comparison groups

Placebo Q2W (RS) v CZP 200 mg Q2W (RS)

Number of subjects included in analysis

222

Analysis specification

Pre-specified

Analysis type

superiority

Method

Regression, Logistic

Parameter type

Estimated difference in responder rate

Point estimate

56.2

Confidence interval

level

95%

sides

2-sided

lower limit

46.4

upper limit

Statistical Analysis 3

Statistical analysis description

The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.

Comparison groups

Placebo Q2W (RS) v CZP 400 mg Q2W (RS)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[1]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

37.988

Confidence interval

level

95%

sides

2-sided

lower limit

11.312

upper limit

127.576

Notes
[1] - The p-value is evaluated at a 2-sided significance level for CZP 400 mg vs. PBO.

Statistical Analysis 4

Statistical analysis description

The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.

Comparison groups

Placebo Q2W (RS) v CZP 200 mg Q2W (RS)

Number of subjects included in analysis

222

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[2]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

30.023

Confidence interval

level

95%

sides

2-sided

lower limit

8.971

upper limit

100.481

Notes
[2] - The p-value is evaluated at a 2-sided significance level for CZP 200 mg vs. PBO.

Statistical Analysis 5

Statistical analysis description

The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.

Comparison groups

Etanercept (RS) v CZP 400 mg Q2W (RS)

Number of subjects included in analysis

337

Analysis specification

Pre-specified

Analysis type

superiority

Method

Regression, Logistic

Parameter type

Estimated difference in responder rate

Point estimate

13.4

Confidence interval

level

95%

sides

2-sided

lower limit

2.7

upper limit

24.1

Statistical Analysis 6

Statistical analysis description

The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.

Comparison groups

Etanercept (RS) v CZP 200 mg Q2W (RS)

Number of subjects included in analysis

335

Analysis specification

Pre-specified

Analysis type

superiority

Method

Regression, Logistic

Parameter type

Estimated difference in responder rate

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.9

upper limit

18.9

Statistical Analysis 7

Statistical analysis description

The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.

Comparison groups

Etanercept (RS) v CZP 400 mg Q2W (RS)

Number of subjects included in analysis

337

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0152 ^[3]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.756

Confidence interval

level

95%

sides

2-sided

lower limit

1.114

upper limit

2.768

Notes
[3] - The p-value is evaluated at a 2-sided significance level for CZP 400 mg vs. ETN.

Statistical Analysis 8

Statistical analysis description

The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.

Comparison groups

Etanercept (RS) v CZP 200 mg Q2W (RS)

Number of subjects included in analysis

335

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1523 ^[4]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.388

Confidence interval

level

95%

sides

2-sided

lower limit

0.886

upper limit

2.175

Notes
[4] - The p-value is evaluated at a 2-sided significance level for CZP 200 mg vs. ETN

Secondary: Proportion of subjects who achieve a Physician’s Global Assessment (PGA) Clear or Almost Clear response (with at least 2 category improvement) at Week 12

Top of page

End point title

Proportion of subjects who achieve a Physician’s Global Assessment (PGA) Clear or Almost Clear response (with at least 2 category improvement) at Week 12

End point description

The Investigator assessed the overall severity of Psoriasis (PSO) using the following 5-point scale: 0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe.

End point type

Secondary

End point timeframe

Week 12

End point values	Placebo Q2W (RS)	Etanercept (RS)	CZP 200 mg Q2W (RS)	CZP 400 mg Q2W (RS)
Number of subjects analysed	57	170	165	167
Units: percentage of participants
number (not applicable)	1.9	39.2	39.8	50.3

Statistical Analysis 1

Statistical analysis description

The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.

Comparison groups

Placebo Q2W (RS) v CZP 400 mg Q2W (RS)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

superiority

Method

Regression, Logistic

Parameter type

Estimated difference in responder rate

Point estimate

48.5

Confidence interval

level

95%

sides

2-sided

lower limit

39.33

upper limit

57.63

Statistical Analysis 2

Statistical analysis description

The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.

Comparison groups

Placebo Q2W (RS) v CZP 200 mg Q2W (RS)

Number of subjects included in analysis

222

Analysis specification

Pre-specified

Analysis type

superiority

Method

Regression, Logistic

Parameter type

Estimated difference in responder rate

Point estimate

37.9

Confidence interval

level

95%

sides

2-sided

lower limit

28.88

upper limit

46.96

Statistical Analysis 3

Statistical analysis description

The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.

Comparison groups

Placebo Q2W (RS) v CZP 400 mg Q2W (RS)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[5]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

56.129

Confidence interval

level

95%

sides

2-sided

lower limit

7.787

upper limit

404.555

Notes
[5] - The p-value is evaluated at a 2-sided significance level for CZP 400 mg vs. PBO

Statistical Analysis 4

Statistical analysis description

The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.

Comparison groups

Placebo Q2W (RS) v CZP 200 mg Q2W (RS)

Number of subjects included in analysis

222

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0004 ^[6]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

36.566

Confidence interval

level

95%

sides

2-sided

lower limit

5.061

upper limit

264.196

Notes
[6] - The p-value is evaluated at a 2-sided significance level for CZP 200 mg vs. PBO

Secondary: Proportion of subjects who achieve a Psoriasis Activity and Severity Index (PASI90) response at Week 12

Top of page

End point title

Proportion of subjects who achieve a Psoriasis Activity and Severity Index (PASI90) response at Week 12

End point description

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.

End point type

Secondary

End point timeframe

Week 12

End point values	Placebo Q2W (RS)	Etanercept (RS)	CZP 200 mg Q2W (RS)	CZP 400 mg Q2W (RS)
Number of subjects analysed	57	170	165	167
Units: percentage of participants
number (not applicable)	0.2	27.1	31.2	34.0

Statistical Analysis 1

Statistical analysis description

The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.

Comparison groups

Placebo Q2W (RS) v CZP 400 mg Q2W (RS)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

superiority

Method

Regression, Logistic

Parameter type

Estimated difference in responder rate

Point estimate

33.8

Confidence interval

level

95%

sides

2-sided

lower limit

20.68

upper limit

46.98

Statistical Analysis 2

Statistical analysis description

The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.

Comparison groups

Placebo Q2W (RS) v CZP 200 mg Q2W (RS)

Number of subjects included in analysis

222

Analysis specification

Pre-specified

Analysis type

superiority

Method

Regression, Logistic

Parameter type

Estimated difference in responder rate

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

18.18

upper limit

43.8

Statistical Analysis 3

Statistical analysis description

The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.

Comparison groups

Placebo Q2W (RS) v CZP 400 mg Q2W (RS)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[7]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

39.949

Confidence interval

level

95%

sides

2-sided

lower limit

8.407

upper limit

189.828

Notes
[7] - The p-value is evaluated at a 2-sided significance level for CZP 400 mg vs. PBO

Statistical Analysis 4

Statistical analysis description

The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.

Comparison groups

Placebo Q2W (RS) v CZP 200 mg Q2W (RS)

Number of subjects included in analysis

222

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[8]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

35.084

Confidence interval

level

95%

sides

2-sided

lower limit

7.363

upper limit

167.179

Notes
[8] - The p-value is evaluated at a 2-sided significance level for CZP 200 mg vs. PBO

Secondary: Proportion of subjects who achieve a Psoriasis Activity and Severity Index (PASI75) response at Week 16

Top of page

End point title

Proportion of subjects who achieve a Psoriasis Activity and Severity Index (PASI75) response at Week 16

End point description

End point type

Secondary

End point timeframe

Week 16

End point values	Placebo Q2W (RS)	CZP 200 mg Q2W (RS)	CZP 400 mg Q2W (RS)
Number of subjects analysed	57	165	167
Units: percentage of participants
number (not applicable)	3.8	68.2	74.7

Statistical Analysis 1

Statistical analysis description

The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.

Comparison groups

Placebo Q2W (RS) v CZP 400 mg Q2W (RS)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

superiority

Method

Regression, Logistic

Parameter type

Estimated difference in responder rate

Point estimate

70.9

Confidence interval

level

95%

sides

2-sided

lower limit

62.15

upper limit

79.59

Statistical Analysis 2

Statistical analysis description

The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.

Comparison groups

Placebo Q2W (RS) v CZP 200 mg Q2W (RS)

Number of subjects included in analysis

222

Analysis specification

Pre-specified

Analysis type

superiority

Method

Regression, Logistic

Parameter type

Estimated difference in responder rate

Point estimate

64.4

Confidence interval

level

95%

sides

2-sided

lower limit

55.12

upper limit

73.63

Statistical Analysis 3

Statistical analysis description

The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.

Comparison groups

Placebo Q2W (RS) v CZP 400 mg Q2W (RS)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[9]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

76.277

Confidence interval

level

95%

sides

2-sided

lower limit

17.952

upper limit

324.094

Notes
[9] - The p-value is evaluated at a 2-sided significance level for CZP 400 mg vs. PBO

Statistical Analysis 4

Statistical analysis description

The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.

Comparison groups

Placebo Q2W (RS) v CZP 200 mg Q2W (RS)

Number of subjects included in analysis

222

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[10]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

55.413

Confidence interval

level

95%

sides

2-sided

lower limit

13.135

upper limit

233.782

Notes
[10] - The p-value is evaluated at a 2-sided significance level for CZP 200 mg vs. PBO

Secondary: Proportion of subjects who achieve a Physician’s Global Assessment (PGA) Clear or Almost Clear response (with at least 2 category improvement) at Week 16

Top of page

End point title

Proportion of subjects who achieve a Physician’s Global Assessment (PGA) Clear or Almost Clear response (with at least 2 category improvement) at Week 16

End point description

The Investigator assessed the overall severity of Psoriasis (PSO) using the following 5-point scale: 0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe.

End point type

Secondary

End point timeframe

Week 16

End point values	Placebo Q2W (RS)	CZP 200 mg Q2W (RS)	CZP 400 mg Q2W (RS)
Number of subjects analysed	57	165	167
Units: percentage of participants
number (not applicable)	3.4	48.3	58.4

Statistical Analysis 1

Statistical analysis description

The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.

Comparison groups

Placebo Q2W (RS) v CZP 400 mg Q2W (RS)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

superiority

Method

Regression, Logistic

Parameter type

Estimated difference in responder rate

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

45.59

upper limit

64.35

Statistical Analysis 2

Statistical analysis description

The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.

Comparison groups

Placebo Q2W (RS) v CZP 200 mg Q2W (RS)

Number of subjects included in analysis

222

Analysis specification

Pre-specified

Analysis type

superiority

Method

Regression, Logistic

Parameter type

Estimated difference in responder rate

Point estimate

44.9

Confidence interval

level

95%

sides

2-sided

lower limit

35.39

upper limit

54.49

Statistical Analysis 3

Statistical analysis description

The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.

Comparison groups

Placebo Q2W (RS) v CZP 400 mg Q2W (RS)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[11]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

40.717

Confidence interval

level

95%

sides

2-sided

lower limit

9.741

upper limit

170.198

Notes
[11] - The p-value is evaluated at a 2-sided significance level for CZP 400 mg vs. PBO

Statistical Analysis 4

Statistical analysis description

The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.

Comparison groups

Placebo Q2W (RS) v CZP 200 mg Q2W (RS)

Number of subjects included in analysis

222

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[12]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

27.165

Confidence interval

level

95%

sides

2-sided

lower limit

6.504

upper limit

113.453

Notes
[12] - The p-value is evaluated at a 2-sided significance level for CZP 200 mg vs. PBO

Secondary: Proportion of subjects who achieve a Psoriasis Activity and Severity Index (PASI90) response at Week 16

Top of page

End point title

Proportion of subjects who achieve a Psoriasis Activity and Severity Index (PASI90) response at Week 16

End point description

End point type

Secondary

End point timeframe

Week 16

End point values	Placebo Q2W (RS)	CZP 200 mg Q2W (RS)	CZP 400 mg Q2W (RS)
Number of subjects analysed	57	165	167
Units: percentage of participants
number (not applicable)	0.3	39.8	49.1

Statistical Analysis 1

Statistical analysis description

The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.

Comparison groups

Placebo Q2W (RS) v CZP 400 mg Q2W (RS)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

superiority

Method

Regression, Logistic

Parameter type

Estimated difference in responder rate

Point estimate

48.8

Confidence interval

level

95%

sides

2-sided

lower limit

34.22

upper limit

63.41

Statistical Analysis 2

Statistical analysis description

The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.

Comparison groups

Placebo Q2W (RS) v CZP 200 mg Q2W (RS)

Number of subjects included in analysis

222

Analysis specification

Pre-specified

Analysis type

superiority

Method

Regression, Logistic

Parameter type

Estimated difference in responder rate

Point estimate

39.5

Confidence interval

level

95%

sides

2-sided

lower limit

25.58

upper limit

53.38

Statistical Analysis 3

Statistical analysis description

The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.

Comparison groups

Placebo Q2W (RS) v CZP 400 mg Q2W (RS)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[13]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

72.278

Confidence interval

level

95%

sides

2-sided

lower limit

14.65

upper limit

356.602

Notes
[13] - The p-value is evaluated at a 2-sided significance level for CZP 400 mg vs. PBO

Statistical Analysis 4

Statistical analysis description

The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.

Comparison groups

Placebo Q2W (RS) v CZP 200 mg Q2W (RS)

Number of subjects included in analysis

222

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[14]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

49.527

Confidence interval

level

95%

sides

2-sided

lower limit

10.002

upper limit

245.256

Notes
[14] - The p-value is evaluated at a 2-sided significance level for CZP 200 mg vs. PBO

Secondary: Proportion of subjects who achieve a Psoriasis Activity and Severity Index (PASI75) response at Week 48 for those achieving PASI75 at Week 16

Top of page

End point title

Proportion of subjects who achieve a Psoriasis Activity and Severity Index (PASI75) response at Week 48 for those achieving PASI75 at Week 16

End point description

End point type

Secondary

End point timeframe

Week 48

End point values	Placebo/Placebo Q2W (WK16RS)	Etanercept/Placebo Q2W (WK16RS)	Etanercept/CZP 200 mg Q2W (WK16RS)	CZP 200 mg Q2W/Placebo Q2W (WK16RS)	CZP 200 mg Q2W/CZP 200 mg Q2W (WK16RS)	CZP 200 mg Q2W/CZP 400 mg Q4W (WK16RS)	CZP 400 mg Q2W/Placebo Q2W (WK16RS)	CZP 400 mg Q2W/CZP 200 mg Q2W (WK16RS)	CZP 400 mg Q2W/CZP 400 mg Q2W (WK16RS)
Number of subjects analysed	2	24	50	22	44	44	25	50	49
Units: percentage of participants
number (not applicable)	100	8.3	82.0	45.5	79.5	88.6	36.0	80.0	98.0

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Adverse Events (AEs) were collected from Baseline (Week 0) until Week 144.

Adverse event reporting additional description

At Week 16, most PBO-randomized participants escaped to CZP 400 mg Q2W and all ETN-randomized participants switched to PBO or CZP, leading to a significantly lower exposure in PBO/ETN arms than in CZP arms. Considering the limitations of such comparison, AEs reported while the participants were on PBO or ETN are not included in this summary.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

18.1

Reporting group title

CZP 200 mg Q2W (TCS)

Reporting group description

This arm consisted of all participants who received CZP 200 mg at any time during the study.

Reporting group title

CZP 400 mg Q2W (TCS)

Reporting group description

This arm consisted of all participants who received CZP 400 mg at any time during the study.

Serious adverse events	CZP 200 mg Q2W (TCS)	CZP 400 mg Q2W (TCS)
Total subjects affected by serious adverse events
subjects affected / exposed	37 / 373 (9.92%)	51 / 412 (12.38%)
number of deaths (all causes)	2	1
number of deaths resulting from adverse events	1	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anaplastic oligodendroglioma
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Glioblastoma
subjects affected / exposed	1 / 373 (0.27%)	0 / 412 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hodgkin's disease
subjects affected / exposed	1 / 373 (0.27%)	0 / 412 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Laryngeal cancer
subjects affected / exposed	1 / 373 (0.27%)	0 / 412 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Clear cell renal cell carcinoma
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Benign neoplasm of bladder
subjects affected / exposed	1 / 373 (0.27%)	0 / 412 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular disorders
Hypertensive crisis
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Peripheral arterial occlusive disease
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Abortion
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Abortion missed
subjects affected / exposed	1 / 373 (0.27%)	0 / 412 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pregnancy with contraceptive
subjects affected / exposed	1 / 373 (0.27%)	0 / 412 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
General disorders and administration site conditions
Inflammation
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Systemic inflammatory response syndrome
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Nodule
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular stent thrombosis
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Immune system disorders
Sarcoidosis
subjects affected / exposed	1 / 373 (0.27%)	0 / 412 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
House dust allergy
subjects affected / exposed	1 / 373 (0.27%)	0 / 412 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Reproductive system and breast disorders
Cervical polyp
subjects affected / exposed	1 / 373 (0.27%)	0 / 412 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ovarian cyst
subjects affected / exposed	1 / 373 (0.27%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Uterine cyst
subjects affected / exposed	1 / 373 (0.27%)	0 / 412 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Endometrial hyperplasia
subjects affected / exposed	1 / 373 (0.27%)	0 / 412 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Uterine polyp
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Dyspnoea
subjects affected / exposed	1 / 373 (0.27%)	0 / 412 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Chronic obstructive pulmonary disease
subjects affected / exposed	2 / 373 (0.54%)	0 / 412 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Nasal septum deviation
subjects affected / exposed	1 / 373 (0.27%)	0 / 412 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Psychiatric disorders
Bipolar I disorder
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Depression
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Investigations
Mycobacterium tuberculosis complex test negative
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Blood creatine phosphokinase increased
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Injury, poisoning and procedural complications
Meniscus injury
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Concussion
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Craniocerebral injury
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Extradural haematoma
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Wrist fracture
subjects affected / exposed	0 / 373 (0.00%)	2 / 412 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Foot fracture
subjects affected / exposed	1 / 373 (0.27%)	0 / 412 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Forearm fracture
subjects affected / exposed	1 / 373 (0.27%)	0 / 412 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Lower limb fracture
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Radius fracture
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ulna fracture
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ligament rupture
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Laceration
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Facial bones fracture
subjects affected / exposed	1 / 373 (0.27%)	0 / 412 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Rib fracture
subjects affected / exposed	1 / 373 (0.27%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac disorders
Intracardiac mass
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Coronary artery disease
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac failure
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Acute coronary syndrome
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Acute myocardial infarction
subjects affected / exposed	1 / 373 (0.27%)	0 / 412 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	1 / 1	0 / 0
Angina pectoris
subjects affected / exposed	1 / 373 (0.27%)	0 / 412 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nervous system disorders
Migraine
subjects affected / exposed	0 / 373 (0.00%)	2 / 412 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Primary progressive multiple sclerosis
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ear and labyrinth disorders
Vestibular disorder
subjects affected / exposed	1 / 373 (0.27%)	0 / 412 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Tympanic membrane perforation
subjects affected / exposed	1 / 373 (0.27%)	0 / 412 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Eye disorders
Cataract
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Retinal detachment
subjects affected / exposed	1 / 373 (0.27%)	0 / 412 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Large intestine polyp
subjects affected / exposed	1 / 373 (0.27%)	0 / 412 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Crohn's disease
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Abdominal pain
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Haemorrhoids
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Inguinal hernia
subjects affected / exposed	1 / 373 (0.27%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Upper gastrointestinal haemorrhage
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Peptic ulcer
subjects affected / exposed	1 / 373 (0.27%)	0 / 412 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Umbilical hernia
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Liver disorder
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Acute hepatic failure
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatitis
subjects affected / exposed	1 / 373 (0.27%)	0 / 412 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Erythrodermic psoriasis
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Guttate psoriasis
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Psoriasis
subjects affected / exposed	1 / 373 (0.27%)	0 / 412 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pustular psoriasis
subjects affected / exposed	1 / 373 (0.27%)	0 / 412 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Purpura
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Skin ulcer
subjects affected / exposed	1 / 373 (0.27%)	0 / 412 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Renal and urinary disorders
Urinary bladder haemorrhage
subjects affected / exposed	1 / 373 (0.27%)	0 / 412 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Acute kidney injury
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Nephrolithiasis
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Renal cyst
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Sacroiliitis
subjects affected / exposed	1 / 373 (0.27%)	0 / 412 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Spinal pain
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Chondropathy
subjects affected / exposed	1 / 373 (0.27%)	0 / 412 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Polymyalgia rheumatica
subjects affected / exposed	1 / 373 (0.27%)	0 / 412 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Mobility decreased
subjects affected / exposed	1 / 373 (0.27%)	0 / 412 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Compartment syndrome
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	3 / 373 (0.80%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 4	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Psoriatic arthropathy
subjects affected / exposed	1 / 373 (0.27%)	0 / 412 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Appendiceal abscess
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Appendicitis perforated
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	1 / 373 (0.27%)	0 / 412 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pancreas infection
subjects affected / exposed	1 / 373 (0.27%)	0 / 412 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Rectal abscess
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	1 / 373 (0.27%)	0 / 412 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Osteomyelitis
subjects affected / exposed	1 / 373 (0.27%)	0 / 412 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Escherichia sepsis
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Endophthalmitis
subjects affected / exposed	1 / 373 (0.27%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia klebsiella
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	1 / 373 (0.27%)	2 / 412 (0.49%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	1 / 373 (0.27%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Bacteraemia
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Sepsis
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pyoderma
subjects affected / exposed	1 / 373 (0.27%)	0 / 412 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Subcutaneous abscess
subjects affected / exposed	1 / 373 (0.27%)	0 / 412 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Erysipelas
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Tuberculosis
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pyelonephritis
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Metabolism and nutrition disorders
Obesity
subjects affected / exposed	0 / 373 (0.00%)	1 / 412 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0

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

Non-serious adverse events	CZP 200 mg Q2W (TCS)	CZP 400 mg Q2W (TCS)
Total subjects affected by non serious adverse events
subjects affected / exposed	150 / 373 (40.21%)	159 / 412 (38.59%)
Vascular disorders
Hypertension
subjects affected / exposed	20 / 373 (5.36%)	24 / 412 (5.83%)
occurrences all number	21	24
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	17 / 373 (4.56%)	18 / 412 (4.37%)
occurrences all number	20	20
Infections and infestations
Bronchitis
subjects affected / exposed	18 / 373 (4.83%)	18 / 412 (4.37%)
occurrences all number	21	19
Nasopharyngitis
subjects affected / exposed	57 / 373 (15.28%)	66 / 412 (16.02%)
occurrences all number	84	83
Upper respiratory tract infection
subjects affected / exposed	39 / 373 (10.46%)	45 / 412 (10.92%)
occurrences all number	58	64
Viral upper respiratory tract infection
subjects affected / exposed	23 / 373 (6.17%)	11 / 412 (2.67%)
occurrences all number	38	13

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Were there any global substantial amendments to the protocol? Yes

20 Apr 2015

Global Protocol Amendment 1 incorporated the country-specific amendments in the UK (Amendments 0.1 and 0.5), the Czech Republic (Amendment 0.2), Germany (Amendment 0.3), and France (Amendment 0.4). In addition, the following changes were made: •Updated study contact information. •The treatment received in Period 3 was based on initial treatment and response to treatment at Week 16. All CZP and Placebo (PBO) treatments were to be administered by dedicated unblinded site personnel at site visits. -Subjects initially randomized to CZP 200 mg Q2W were rerandomized (2:2:1) to receive either CZP 200 mg Q2W or CZP 400 mg Q4W (with PBO administered on alternate dosing weeks to maintain the blind) or PBO •Etanercept (ETN) treatments were allowed to be administered by trained study staff on site or outside of the study center (to allow flexibility around self-administration). If ETN was self-administered, compliance was to be recorded on a drug administration log by the subject and data were to be entered into the electronic Case Report form (eCRF) by study personnel. The percentage of doses missed (2 or more doses changed to 25% or more of the doses) was updated; ETN was administered more frequently than CZP or placebo during the Initial Treatment Period. •The number of planned sites was increased (from 50 to 67) and Australia and Canada were removed. •Exclusion Criterion #6 was clarified to include latex hypersensitivity. •Changes were made to drug accountability to allow for on-site destruction with prior Sponsor approval. •Secukinumab was added as a prohibited concomitant treatment. •Stratification across sites based on prior biologic use was eliminated. •Text describing the modified Nail Psoriasis Severity Index (mNAPSI) was updated. •Elispot testing for tuberculosis was removed. The chest x-ray required at screening was not needed if an x-ray had already been performed within 3 months of screening. •A center-by-treatment interaction analysis was added and described.

23 Dec 2015

Global Protocol Amendment 2 included the following changes: •CIMPACT (name of the PS0003 protocol) was added. •Updated study contact information. •Having at least a 90% reduction from Baseline in Psoriasis Area and Severity Index (PASI90) at Weeks 12 and 16 were added as secondary efficacy variables and PASI90 at Week 12 was included in the sequential testing procedure for the efficacy analysis. •Added time to onset of PASI90 as an efficacy variable. Deleted time to loss of PASI75 response at Week 16. Added EQ-5D-Visual Analog Scale (VAS) (inadvertently omitted in previous protocol). •Clarified the dosing period during the Initial Treatment Period, assessments performed, and use of unblinded study staff for drug administration. •Clarified study medication administration in Open-label Extension (OLE) Treatment Period. •Added secukinumab 24 weeks prior to the Baseline Visit as an exclusion for prior treatment. •Clarified the withdrawal criteria and addition of a withdrawal criterion to be consistent with the study population. See Exclusion Criterion #6. •Text was added to clarify that the unblinded team at the site was to transition their activities once the Week 48 visits (blinded Maintenance Treatment Period) were completed. •Clarified prohibited concomitant medications and therapies. •Added a window for the Safety Follow-Up (SFU) Visit (10 weeks after final dose); the visit should have occurred no more than 3 days prior to the scheduled visit date and within 14 days after the scheduled visit date (-3 days/+14 days). •Addition of a “Treated with CZP Set” (TCS) to further assess the safety of CZP in subjects with PSO. Addition of a Maintenance Set (MS) to further assess the efficacy and safety of CZP in long-term treatment of PSO.

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

http://www.ncbi.nlm.nih.gov/pubmed/29660425

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Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Proportion of subjects who achieve a Psoriasis Activity and Severity Index (PASI75) response at Week 12

Primary: Proportion of subjects who achieve a Psoriasis Activity and Severity Index (PASI75) response at Week 12

Secondary: Proportion of subjects who achieve a Physician’s Global Assessment (PGA) Clear or Almost Clear response (with at least 2 category improvement) at Week 12

Secondary: Proportion of subjects who achieve a Physician’s Global Assessment (PGA) Clear or Almost Clear response (with at least 2 category improvement) at Week 12

Secondary: Proportion of subjects who achieve a Psoriasis Activity and Severity Index (PASI90) response at Week 12

Secondary: Proportion of subjects who achieve a Psoriasis Activity and Severity Index (PASI90) response at Week 12

Secondary: Proportion of subjects who achieve a Psoriasis Activity and Severity Index (PASI75) response at Week 16

Secondary: Proportion of subjects who achieve a Psoriasis Activity and Severity Index (PASI75) response at Week 16

Secondary: Proportion of subjects who achieve a Physician’s Global Assessment (PGA) Clear or Almost Clear response (with at least 2 category improvement) at Week 16

Secondary: Proportion of subjects who achieve a Physician’s Global Assessment (PGA) Clear or Almost Clear response (with at least 2 category improvement) at Week 16

Secondary: Proportion of subjects who achieve a Psoriasis Activity and Severity Index (PASI90) response at Week 16

Secondary: Proportion of subjects who achieve a Psoriasis Activity and Severity Index (PASI90) response at Week 16

Secondary: Proportion of subjects who achieve a Psoriasis Activity and Severity Index (PASI75) response at Week 48 for those achieving PASI75 at Week 16

Secondary: Proportion of subjects who achieve a Psoriasis Activity and Severity Index (PASI75) response at Week 48 for those achieving PASI75 at Week 16

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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