Efficacy and Safety Study of Certolizumab Pegol (CZP) Versus Active Comparator and Placebo in Subjects With Plaque Psoriasis (PSO)

Phase 3

Completed

Conditions: Plaque Psoriasis
Psoriasis

Interventions: Biological: Certolizumab Pegol
Other: Placebo
Biological: Etanercept

Registration Number: NCT02346240

Lead Sponsor: UCB Biopharma S.P.R.L.

Brief Summary: The purpose of this study is to investigate the efficacy and safety of two dose levels of certolizumab pegol compared to active comparator and placebo in adults with moderate to severe chronic plaque psoriasis.

Detailed Description: This study consists of the following Periods:

* Initial Treatment Period from Week 0 to Week 16

* Maintenance Treatment Period from Week 16 to Week 48

* Open-label Extension Treatment Period (96 weeks)

* Safety Follow-Up (10 weeks)

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 559

Inclusion Criteria

Provided informed consent
Adult men or women >= 18 years
Chronic plaque psoriasis for at least 6 months
Baseline psoriasis activity and severity index >= 12 and body surface area >= 10 % and Physician's Global Assessments score >= 3
Candidate for systemic psoriasis therapy and/or phototherapy and/or chemophototherapy
Other protocol-defined inclusion criteria may apply

Exclusion Criteria

Erythrodermic, guttate, generalized pustular form of psoriasis
History of current, chronic, or recurrent infections of viral, bacterial, or fungal origin as described in the protocol
Congestive heart failure
History of a lymphoproliferative disorder including lymphoma or current signs and symptoms suggestive of lymphoproliferative disease
Concurrent malignancy or a history of malignancy as described in the protocol
History of, or suspected, demyelinating disease of the central nervous system (e.g., multiple sclerosis or optic neuritis)
Female subjects who are breastfeeding, pregnant, or plan to become pregnant during the study or within 5 months following last dose of study drug in the UK, Czech Republic, Germany, and France, and within 3 months for all other countries. Male subjects who are planning a partner pregnancy during the study or within 5 months following the last dose in France and within 10 weeks in all other countries
Any other condition which, in the Investigator's judgment, would make the subject unsuitable for participation in the study
Other protocol-defined exclusion criteria may apply

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CZP 200 mg	Certolizumab Pegol	Certolizumab Pegol (CZP) subcutaneous (sc) injection 400 mg at Weeks 0, 2, 4, followed by CZP 200 mg every two weeks (Q2W) from Week 6 to Week 14. The treatment received from Week 16 to Week 48 is based on initial treatment and response to treatment at Week 16: * Subjects with a PASI75 response at Week 16 will be 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. * Subjects who do not achieve a PASI75 response at Week 16 will be removed from blinded study medication and escape to CZP 400 mg Q2W. Subjects who receive unblinded CZP 400 mg Q2W for 16 weeks and do not achieve a PASI50 response will be withdrawn from the study. Subjects can enter a 96-week open-label extension period after completing the Maintenance Period and receive CZP under certain conditions.
CZP 400 mg	Certolizumab Pegol	Certolizumab Pegol subcutaneous (sc) injection 400 mg every two weeks (Q2W) through Week 14. The treatment received from Week 16 to Week 48 is based on initial treatment and response to treatment at Week 16: * Subjects with a PASI75 response at Week 16 will be re-randomized to CZP 200 mg Q2W or CZP 400 mg Q2W or Placebo Q2W. * Subjects who do not achieve a PASI75 response at Week 16 will be removed from blinded study medication and escape to CZP 400 mg Q2W. Subjects who receive unblinded CZP 400 mg Q2W for 16 weeks and do not achieve a PASI50 response will be withdrawn from the study. Subjects can enter a 96-week open-label extension period after completing the Maintenance Period and receive CZP under certain conditions.
Placebo	Placebo	Placebo subcutaneous (sc) injection every two weeks (Q2W). The treatment received from Week 16 to Week 48 is based on initial treatment and response to treatment at Week 16: * Subjects with a PASI75 response at Week 16 continue to receive blinded Placebo. * Subjects who do not achieve a PASI75 response at Week 16 will be removed from blinded study medication and escape to CZP 400 mg Q2W. Subjects who receive unblinded CZP 400 mg Q2W for 16 weeks and do not achieve a PASI50 response will be withdrawn from the study. Subjects can enter a 96-week open-label extension period after completing the Maintenance Period and receive CZP under certain conditions.
Etanercept	Etanercept	Etanercept (ETN) subcutaneous (sc) injection 50 mg twice weekly through Week 12. The treatment received from Week 16 to Week 48 is based on initial treatment and response to treatment at Week 16: * Subjects with a PASI75 response at Week 16 will be re-randomized to either Certolizumab Pegol (loading dose of 400 mg at Weeks 16, 18, and 20 followed by 200 mg Q2W) or Placebo Q2W. * Subjects who do not achieve a PASI75 response at Week 16 will be removed from blinded study medication and escape to CZP 400 mg Q2W. Subjects who receive unblinded CZP 400 mg Q2W for 16 weeks and do not achieve a PASI50 response will be withdrawn from the study. Subjects can enter a 96-week open-label extension period after completing the Maintenance Period and receive CZP under certain conditions.

Primary Outcome Measures

Name	Time	Method
Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI75) Response at Week 12	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 Outcome Measures

Name	Time	Method
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	Week 12	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.
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	Week 16	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.
Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI90) Response at Week 16	Week 16	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.
Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI90) Response at Week 12	Week 12	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.
Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI75) Response at Week 16	Week 16	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.
Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI75) Response at Week 48 for Those Achieving PASI75 at Week 16	Week 48	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.

Trial Locations

Locations (70): Ps0003 400
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Henderson, Nevada, United States
Ps0003 403
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Houston, Texas, United States
Ps0003 365
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Kiel, Schleswig-Holstein, Germany
Ps0003 369
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Dresden, Germany
Ps0003 378
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Bochum, Nordrhein-Westfalen, Germany
Ps0003 342
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Varna, Bulgaria
Ps0003 382
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Budapest, Hungary
Ps0003 375
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Berlin, Germany
Ps0003 367
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Berlin, Germany
Ps0003 368
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Frankfurt am Main, Hessen, Germany
Ps0003 363
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Erfurt, Thueringen, Germany
Ps0003 422
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Wrocław, Dolnoslaskie, Poland
Ps0003 424
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Poznań, Wielkopolskie, Poland
Ps0003 344
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Plovdiv, Bulgaria
Ps0003 373
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Muenchen, Bayern, Germany
Ps0003 338
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Warszawa, Mazowieckie, Poland
Ps0003 423
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Gdynia, Poland
Ps0003 384
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Budapest, Hungary
Ps0003 345
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Dupnitsa, Kyustendil, Bulgaria
Ps0003 380
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Debrecen, Hajdú-Bihar, Hungary
Ps0003 330
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Torun, Kujawsko-pomorskie, Poland
Ps0003 427
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Gdańsk, Poland
Ps0003 391
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Hexham, Northumberland, United Kingdom
Ps0003 336
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Warszawa, Poland
Ps0003 390
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Dundee, Angus, United Kingdom
Ps0003 383
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Budapest, Hungary
Ps0003 320
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Nice cedex 3, France
Ps0003 405
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San Diego, California, United States
Ps0003 406
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San Antonio, Texas, United States
Ps0003 317
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Mobile, Alabama, United States
Ps0003 304
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West Palm Beach, Florida, United States
Ps0003 316
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Washington, District of Columbia, United States
Ps0003 306
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Little Rock, Arkansas, United States
Ps0003 301
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Beverly Hills, California, United States
Ps0003 307
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Los Angeles, California, United States
Ps0003 407
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Portland, Oregon, United States
Ps0003 310
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Indianapolis, Indiana, United States
Ps0003 343
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Sofia, Sofia-Grad, Bulgaria
Ps0003 404
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Buffalo, New York, United States
Ps0003 319
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Verona, New Jersey, United States
Ps0003 401
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Dallas, Texas, United States
Ps0003 352
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Praha, Czechia
Ps0003 311
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Webster, Texas, United States
Ps0003 353
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Pardubice, District Of Columbia, Czechia
Ps0003 351
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Pardubice, Czechia
Ps0003 325
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Toulouse Cedex 9, France
Ps0003 371
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Wuppertal, Nordrhein-Westfalen, Germany
Ps0003 350
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Ústí nad Labem, Czechia
Ps0003 370
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Mainz, Rheinland-Pfalz, Germany
Ps0003 374
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Friedrichshafen, Baden-Wuerttemberg, Germany
Ps0003 372
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Berlin, Germany
Ps0003 361
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Giessen, Germany
Ps0003 340
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Breda, Netherlands
Ps0003 362
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Hamburg, Germany
Ps0003 366
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Hannover, Germany
Ps0003 381
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Orosháza, Bekes, Hungary
Ps0003 421
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Warszawa, Mazowieckie, Poland
Ps0003 425
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Białystok, Poland
Ps0003 393
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Edgbaston, United Kingdom
Ps0003 335
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Lublin, Lubelskie, Poland
Ps0003 333
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Bialystok, Podlaskie, Poland
Ps0003 332
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Szczecin, Poland
Ps0003 339
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Wrocław, Poland
Ps0003 394
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Liverpool, United Kingdom
Ps0003 392
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Manchester, United Kingdom
Ps0003 302
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Springfield, Illinois, United States
Ps0003 313
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West Dundee, Illinois, United States
Ps0003 309
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Johnston, Rhode Island, United States
Ps0003 395
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Cardiff, Wales, United Kingdom
Ps0003 334
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Katowice, Slaskie, Poland