A Study to Test the Efficacy and Safety of Certolizumab Pegol in Japanese Subjects With Moderate to Severe Chronic Psoriasis

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate the efficacy and safety of Certolizumab Pegol (CZP) in the treatment of moderate to severe chronic plaque Psoriasis (PSO) in Japanese subjects.

Official Title
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Phase 2/3, Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study To Evaluate the Efficacy and Safety of Certolizumab Pegol in Japanese Subjects With Moderate to Severe Chronic Psoriasis

Conditions
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Moderate to Severe Psoriasis, Generalized Pustular Psoriasis and Erythrodermic Psoriasis

Intervention / Treatment
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* Other: Placebo
* Drug: Certolizumab Pegol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is male or female, >= 20 years of age. Institutional Review Board-approved written informed consent form is signed and dated by the subject. Other protocol-defined inclusion criteria may apply. For subjects with moderate to severe chronic plaque psoriasis (PSO) Chronic plaque psoriasis for at least 6 months. Baseline Psoriasis Activity and Severity Index (PASI) >=12 and Body Surface Area (BSA) affected by PSO >=10% and Physician's Global Assessment (PGA) score of 3 or higher. Candidates for systemic PSO therapy and/or phototherapy and/or chemophototherapy. For subjects with generalized pustular PSO or erythrodermic PSO Diagnosis of generalized pustular PSO or erythrodermic PSO at Screening. History of plaque-type PSO if subjects have a diagnosis of erythrodermic PSO. Baseline BSA affected by PSO >=80% if subjects have a diagnosis of erythrodermic PSO. Exclusion Criteria: Female subject who is breastfeeding, pregnant, or plans to become pregnant during the study or within 5 months following last dose of study drug. Male subject who is planning a partner pregnancy during the study or within 5 months following the last dose of study drug. Subject has guttate psoriasis or drug-induced psoriasis. For subjects with moderate to severe plaque psoriasis, erythrodermic or pustular forms of psoriasis also are excluded. History of current, chronic, or recurrent infections of viral, bacterial, or fungal origin as described in the protocol. Also, subjects with a high risk of infection in the Investigator's opinion. History of a lymphoproliferative disorder including lymphoma or current signs and symptoms suggestive of lymphoproliferative disease. History of other malignancy or concurrent malignancy as described in the protocol. Class III or IV congestive heart failure History of, or suspected, demyelinating disease of the central nervous system (e.g., multiple sclerosis or optic neuritis). Subject has any other condition which, in the Investigator's judgment, would make the subject unsuitable for inclusion in the study. Concurrent medication restrictions as described in the protocol. Subject with known tuberculosis (TB) infection, at high risk of acquiring TB infection, or with untreated latent tuberculosis infection (LTBI) or current or history of nontuberculous mycobacterial (NTMB) infection. Subject has any protocol defined clinically significant laboratory abnormalities at the screening Other protocol-defined exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 20 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 |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo subcutaneous (sc) injection every two weeks (Q2W) | Other: Placebo<br>* Pharmaceutical Form: Solution for injection in pre-filled syringe Concentration: 0.9 % saline Route of Administration: Subcutaneous use Q2W<br>* Other names: PBO;|
| Experimental: CZP 200 mg<br>Certolizumab Pegol subcutaneous (sc) injection 400 mg at Weeks 0, 2, 4, followed by Certolizumab Pegol subcutaneous (sc) injection 200 mg every two weeks (Q2W) with PBO administered to maintain the blind, starting at Week 6 | Other: Placebo<br>* Pharmaceutical Form: Solution for injection in pre-filled syringe Concentration: 0.9 % saline Route of Administration: Subcutaneous use Q2W<br>* Other names: PBO;Drug: Certolizumab Pegol<br>* 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). | Drug: Certolizumab Pegol<br>* Pharmaceutical Form: Solution for injection in pre-filled syringe Concentration: 200 mg/mL Route of Administration: Subcutaneous use<br>* Other names: CZP;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Achieving a 75 % or Higher Improvement in Psoriasis Area and Severity Index (PASI) Score at Week 16 | The PASI75 response assessments were 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Who Achieve a Physician's Global Assessment (PGA) Clear or Almost Clear Response (With at Least 2-category Improvement) at Week 16 | This Outcome Measure applied to participants with moderate to severe chronic plaque Psoriasis (PSO). 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 | 
| Percentage of Subjects Achieving a 90 % or Higher Improvement in Psoriasis Area and Severity Index (PASI) Score at Week 16 | The PASI90 response assessments were 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 | 
| Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16 | This Outcome Measure applied to participants with moderate to severe chronic plaque Psoriasis (PSO). 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 asked 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 or 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). | Baseline and Week 16 | 
| Change From Baseline in Itch Numeric Rating Scale at Week 16 | This Outcome Measure applied to participants with moderate to severe chronic plaque Psoriasis (PSO). The Itch Numeric Rating Scale (NRS) has been developed as a simple, single item instrument to assess the patient-reported severity of itch at its most intense during the past 24h period. Participants indicate itch severity by circling the integer that best describes the worst level of itching due to PSO in the past 24h period on an 11-point scale anchored at 0, representing no itching and 10, representing worst itch imaginable (Kimball et al, 2016). | Baseline and Week 16 | 
| Plasma Concentration of Certolizumab Pegol (CZP) | Plasma concentration was expressed in micrograms per milliliter (μg/mL). Values below Lower Limit of Quantification (LLOQ) were set to half the LLOQ to present summaries. The geometric mean and geometric coefficient of variation were only displayed if at least 2/3 of the data were above the LLOQ. | Blood samples were collected at Baseline (Week 0) and at Weeks 2, 4, 6, 8, 12, 16, 24, 32, 40, 52, 60 | 
| Percentage of Participants With Positive Anti-Certolizumab Pegol-antibody Levels in Plasma | A pre-anti-drug (CZP) antibody (ADA) positive subject was defined as having a confirmed positive sample at Baseline. A pre-ADA negative subject was defined as having a Screening below the cut point (BCP) sample, or a screening above the cut point (ACP) sample, but not confirmed positive at Baseline. A treatment-emergent ADA positive subject was defined as either 1) pre-ADA negative subjects having at least 1 ADA confirmed positive sample or 2) pre-ADA positive subjects with at least 1 sample with greater then or equal to (>=) 1.67-fold increase from Baseline on CZP treatment. | Blood samples will be collected at Baseline (Week 0) and at Weeks 2, 4, 6, 8, 12, 16, 24, 32, 40, 52, 60 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Psoriasis, PSO, Chronic plaque psoriasis, Certolizumb Pegol, Cimzia, Generalized pustular psoriasis and erythrodermic psoriasis