An Efficacy and Safety Study of Two Dose Levels of Certolizumab Pegol (CZP) 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 in adults with moderate to severe chronic plaque psoriasis when administered every 2 weeks.

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 Treatment Period from Week 48 to Week 144 Safety Follow-Up Period from Week 144 to Week 152

Official Title
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A Phase 3, Multicenter, Randomized, Double-Blind, Parallel-Group, Study Followed by a Dose-Blind 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
* 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 Czech Republic and Germany) and within 3 months for all other countries. Male subjects who are planning a partner pregnancy during the study or within 10 weeks following the last dose of study drug 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>CZP 400 mg at Weeks 0, 2, 4, followed by CZP 200 mg every two weeks (Q2W) from Week 6 to Week 14. Treatment received from Week 16-48 is based on initial treatment and response to treatment: PASI50 responders at Week 16 continue to receive CZP 200 mg Q2W. PASI50 non-responders at Week 16 will be removed from blinded study medication and escape to unblinded 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. PASI50 non-responders at Week 32 or a later time point will be withdrawn from the study. Subjects who complete the Maintenance Period (with PASI50 response at Week 48) enter the Open-label Extension Period on CZP 200 mg Q2W. Week 48 completers in the escape arm continue to receive CZP 400 mg Q2W or may switch to CZP 200 mg Q2W. Depending on PASI50 or PASI75 responses at Week 60 or a later time point, subjects may switch to CZP 400 mg Q2W or withdraw from the study. | 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>CZP 400 mg every two weeks (Q2W) through Week 14. Treatment received from Week 16 - 48 is based on initial treatment and response to treatment: PASI50 responders at Week 16 continue to receive CZP 400 mg Q2W. PASI50 non-responders 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. PASI50 non-responders at Week 32 or a later time point will be withdrawn from the study. Subjects who complete the Maintenance Period (with PASI50 response at Week 48) enter the Open-label Extension (OLE) Period on CZP 200 mg Q2W. Week 48 completers in the escape arm continue to receive CZP 400 mg Q2W or may switch to CZP 200 mg Q2W. Subjects who achieve a PASI75 response during the OLE Phase may switch to CZP 200 mg Q2W. | 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;|
| Placebo Comparator: Placebo<br>Placebo subcutaneous (sc) injection every two weeks (Q2W). Treatment received from Week 16 - 48 is based on initial treatment and response to treatment: PASI50 responders at Week 16, who do not achieve a PASI75 response at Week 16 receive CZP 400 mg at Weeks 16, 18 and 20 (loading doses) followed by CZP 200 mg Q2W starting at Week 22. PASI75 responders at Week 16 continue to receive Placebo. PASI50 non-responders 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. PASI50 non-responders at Week 32 or a later time point will be withdrawn from the study. Subjects who complete the Maintenance Period (with PASI50 response at Week 48) enter the Open-label Extension Period on CZP 200 mg Q2W. Week 48 completers in the escape arm continue to receive CZP 400 mg Q2W or may switch to CZP 200 mg Q2W. | 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 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. | At Week 16 | 
| Proportion of Subjects Who Achieve a Physician's Global Assessment (PGA) Clear or Almost Clear (With at Least 2-category Improvement) Response 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. | At Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | At Week 16 | 
| Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16 | The DLQI is a subject-reported questionnaire designed for use in adult participants with PSO. The DLQI is a skin disease-specific questionnaire aimed at the evaluation of how symptoms and treatment affect patients' health related quality of life (HRQoL). This instrument asks participants about symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. It has been shown to be valid and reproducible in PSO patients. The DLQI score ranges from 0 to 30 with higher scores indicating lower HRQoL. A higher than of equal to (>=) 4-point change in the DLQI score (DLQI response) has been reported to be meaningful for the patient (within-patient minimal important difference Basra et al, 2015) a DLQI absolute score of lower than or equal to (=<) 1 indicates DLQI remission (i.e., no or small impact of the disease on HRQoL). | At Week 16 | 
| Proportion of Subjects Who Achieve a Physician's Global Assessment (PGA) Clear or Almost Clear (With at Least 2-category Improvement) Response at Week 48 | 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. | At Week 48 | 
| Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI75) Response at 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. | At 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