A Study to Evaluate the Efficacy, Safety, and Drug Concentration of Certolizumab Pegol (CZP) in Children and Adolescent Study Participants With Moderate to Severe Chronic Plaque Psoriasis (PSO)

Study Overview
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Brief Summary
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The purpose of the study is to demonstrate the efficacy and safety of certolizumab pegol in the treatment of moderate to severe chronic plaque psoriasis in study participants aged 6 to 11 and 12 to 17 years.

Official Title
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Multicenter, Randomized, Parallel-Group, Double-Blind, Placebo-Controlled (12-17 Years) Including a Single Open-Label Arm (6-11 Years) Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Certolizumab Pegol (CZP) in Pediatric Study Participants With Moderate to Severe Chronic Plaque Psoriasis (PSO)

Conditions
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Moderate Chronic Plaque Psoriasis, Severe Chronic Plaque Psoriasis, Mixed Guttate/Plaque Psoriasis

Intervention / Treatment
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* Drug: Certolizumab pegol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Study participant must have a diagnosis of moderate to severe plaque psoriasis (PSO) for ≥3 months and: Body Surface Area (BSA) affected by psoriasis ≥10 % Physician's Global Assessment (PGA) score ≥3 (on a scale from 0 to 4) Psoriasis Area and Severity Index (PASI) score is ≥12 or PASI score is ≥10 and <12 with at least one of the following: Clinically relevant facial or scalp involvement Clinically relevant genital involvement Clinically relevant palm and sole involvement Clinically relevant axillary involvement Study participants aged ≥12 years may alternatively have a diagnosis of moderate to severe mixed guttate/plaque PSO with >50 % to <80 % guttate lesions for ≥3 months, and must meet the same criteria listed above Study participant must be a candidate for systemic psoriasis therapy and/or phototherapy and/or photochemotherapy Exclusion Criteria: Study participant previously participated in this study or has previously been treated with certolizumab pegol (CZP) Study participant has generalized pustular or erythrodermic psoriasis (PSO) Study participant has guttate PSO without plaque PSO Study participant has had a primary failure to an anti-tumor necrosis factor agent Study participant has had prior exposure to >2 biologic therapies Study participant has a history of severe major depression or suicide attempt (including an actual attempt, interrupted attempt, or aborted attempt), or has had suicidal ideation in the past 6 months as indicated by a positive response (Yes) to either Question 4 or Question 5 of the Screening/Baseline version of the Columbia Suicide Severity Rating Scale (CSSRS) at Screening

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 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: Cohort A - certolizumab pegol<br>Enrolling study participants aged 12 to 17 years (inclusive). Study participants in this arm will receive weight-based subcutaneous doses of certolizumab pegol from Week 1 to Week 52 and through the subsequent Open-Label Extension Period. | Drug: Certolizumab pegol<br>* Certolizumab Pegol Pharmaceutical Form: Solution for injection in pre-filled syringe Route of Administration: Subcutaneous use Other Names: Cimzia CDP870 CZP<br>|
| Placebo Comparator: Cohort A - placebo<br>Enrolling study participants aged 12 to 17 years (inclusive). Study participants in this arm will receive weight-based subcutaneous doses of placebo from Week 1 to 16 and certolizumab pegol to Week 52 and through the subsequent Open-Label Extension Period. | Drug: Certolizumab pegol<br>* Certolizumab Pegol Pharmaceutical Form: Solution for injection in pre-filled syringe Route of Administration: Subcutaneous use Other Names: Cimzia CDP870 CZP<br>Drug: Placebo<br>* Placebo Pharmaceutical Form: Solution for injection in pre-filled syringe Route of Administration: Subcutaneous use Other Names: -PBO<br>|
| Experimental: Cohort B - certolizumab pegol<br>Enrolling study participants aged 6 to 11 years (inclusive). Study participants in this arm will receive weight-based subcutaneous doses of certolizumab pegol from Week 1 to Week 52 and through the subsequent Open-Label Extension Period. | Drug: Certolizumab pegol<br>* Certolizumab Pegol Pharmaceutical Form: Solution for injection in pre-filled syringe Route of Administration: Subcutaneous use Other Names: Cimzia CDP870 CZP<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants achieving a 75% or higher improvement in Psoriasis Area and Severity Index (PASI) score 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 | 
| Percentage of participants who achieve a Physician's Global Assessment (PGA) Clear or Almost Clear response (with at least a 2-category improvement) at Week 16 | The Investigator assess 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants achieving a 90% or higher improvement in Psoriasis Area and Severity Index (PASI) score 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 | 
| Percentage of participants achieving CDLQI score of 0 or 1 at Week 16 | The Children's Dermatology Life Quality Index (CDLQI) is a dermatology-specific quality of life instrument designed to assess the impact of the disease on a child's quality of life (Lewis-Jones and Finlay, 1995). The CDLQI is a 10-item questionnaire with 4 response options (Not at all/Not relevant=0, A little=1, Quite a lot=2, and Very much=3) and a recall period of 1 week. In addition to evaluating overall quality of life, the CDLQI can be used to assess 6 different aspects that may affect quality of life: symptoms and feelings, leisure, school or holidays, personal relationships, sleep, and treatment. The CDLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0; the higher the score, the greater impairment in quality of life. | Week 16 | 
| Percentage of participants achieving a 100% improvement in Psoriasis Area and Severity Index (PASI) score at Week 16 | The PASI100 response assessments are based on 100% 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 | 
| Percentage of participants achieving a 75% or higher improvement in Psoriasis Area and Severity Index (PASI) score at Week 52 | 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 52 | 
| Percentage of participants who achieve a Physician's Global Assessment (PGA) Clear or Almost Clear response (with at least a 2-category improvement) at Week 52 | The Investigator assess the overall severity of Psoriasis (PSO) using the following 5-point scale: 0= clear, 1= almost clear, 2= mild, 3= moderate, 4= severe. | Week 52 | 
| Percentage of participants achieving a 90% or higher improvement in Psoriasis Area and Severity Index (PASI) score at Week 52 | 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 52 | 
| Percentage of participants achieving a 100% improvement in Psoriasis Area and Severity Index (PASI) score at Week 52 | The PASI100 response assessments are based on 100% 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 52 | 
| Percentage of participants achieving CDLQI score of 0 or 1 at Week 52 | The Children's Dermatology Life Quality Index (CDLQI) is a dermatology-specific quality of life instrument designed to assess the impact of the disease on a child's quality of life (Lewis-Jones and Finlay, 1995). The CDLQI is a 10-item questionnaire with 4 response options (Not at all/Not relevant=0, A little=1, Quite a lot=2, and Very much=3) and a recall period of 1 week. In addition to evaluating overall quality of life, the CDLQI can be used to assess 6 different aspects that may affect quality of life: symptoms and feelings, leisure, school or holidays, personal relationships, sleep, and treatment. The CDLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0; the higher the score, the greater impairment in quality of life. | Week 52 | 
| Incidence of serious treatment emergent adverse events | A serious treatment emergent adverse event (serious TEAE) is any untoward medical occurrence that at any dose: Results in death Is life-threatening Requires in patient hospitalization or prolongation of existing hospitalization Is a congenital anomaly or birth defect Is an infection that requires treatment parenteral antibiotics Other important medical events which based on medical or scientific judgement may jeopardize the patients, or may require medical or surgical intervention to prevent any of the above | From Baseline until participant reaches 18 years of age or Cimzia becomes commercially available for pediatric PSO in participant's region (up to 12 years) | 
| Incidence of treatment emergent adverse events leading to withdrawal | A treatment emergent adverse event (TEAE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. | From Baseline until participant reaches 18 years of age or Cimzia becomes commercially available for pediatric PSO in participant's region (up to 12 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic plaque psoriasis, Certolizumab pegol, Cimzia, Pediatric study, Phase 3