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

Study Overview
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Brief Summary
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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
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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)

Official Title
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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

Conditions
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Psoriasis, Plaque Psoriasis

Intervention / Treatment
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* Biological: Certolizumab Pegol
* Biological: Etanercept
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CZP 200 mg<br>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. | Biological: Certolizumab Pegol<br>* Active Substance: Certolizumab Pegol Pharmaceutical Form: Solution for injection in pre-filled syringe Concentration: 200 mg/ mL Route of Administration: Subcutaneous use<br>* Other names: CZP;|
| Experimental: CZP 400 mg<br>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. | Biological: Certolizumab Pegol<br>* Active Substance: Certolizumab Pegol Pharmaceutical Form: Solution for injection in pre-filled syringe Concentration: 200 mg/ mL Route of Administration: Subcutaneous use<br>* Other names: CZP;|
| Active Comparator: Etanercept<br>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. | Biological: Etanercept<br>* Active Substance: Etanercept Pharmaceutical Form: Solution for injection in pre-filled syringe Concentration: 50 mg / mL Route of Administration: Subcutaneous use<br>* Other names: ETN;|
| Placebo Comparator: Placebo<br>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. | Other: Placebo<br>* Active Substance: Placebo Pharmaceutical Form: Solution for injection in pre-filled syringe Concentration: 0.9 % saline Route of Administration: Subcutaneous use<br>* Other names: PBO;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI75) Response at 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. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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. | Week 12 | 
| Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI90) Response at 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. | Week 12 | 
| Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI75) Response at 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. | Week 16 | 
| 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 | 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. | Week 16 | 
| Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI90) Response at 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. | Week 16 | 
| Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI75) Response at Week 48 for Those Achieving PASI75 at 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. | Week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Certolizumab Pegol, Cimzia, Psoriasis