Pediatric Arthritis Study of Certolizumab Pegol

Study Overview
=================
Brief Summary
-----------------
A Multicenter, Open-label Study to Assess the Pharmacokinetics, Safety and Efficacy of Certolizumab Pegol in Children and Adolescents With Moderately to Severely Active Polyarticular-course Juvenile Idiopathic Arthritis (JIA).

Detailed Description
-----------------
The overall study consists of a Screening Period of up to 4 weeks and an Open-Label Treatment Period which will continue until the approval of the marketing application for the Polyarticular-course Juvenile Idiopathic Arthritis (JIA) indication in the study participant's country or region or until further notice from UCB (approximately 4-6 years duration; depending on region). A Final Visit will be conducted 12 weeks after last dose of study medication. Overall, study visits will occur monthly during the first 6 months and every 2 months afterwards. All patients will receive active treatment with Certolizumab Pegol. The dose will depend on actual weight. Home dosing will be allowed between study visits. If less than 50 % of the study population achieves an adequate response to the treatment (American College of Rheumatology Pediatric 30 % (PedACR30) response) at Week 16, the study will be entirely discontinued.

Official Title
-----------------
A Multicenter, Open-label Study to Assess the Pharmacokinetics, Safety and Efficacy of Certolizumab Pegol in Children and Adolescents With Moderately to Severely Active Polyarticular-course Juvenile Idiopathic Arthritis (JIA)

Conditions
-----------------
Polyarticular-course Juvenile Idiopathic Arthritis (JIA)

Intervention / Treatment
-----------------
* Drug: Certolizumab Pegol (CZP)
* Drug: Certolizumab Pegol (CZP)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Study participant is 2 to 17 years of age (inclusive) at Baseline (Visit 2) Study participants must weigh ≥10 kg (22lb) at Baseline (Visit 2) Study participants must have had onset of signs and symptoms consistent with a diagnosis of Juvenile Idiopathic Arthritis (JIA) (according to the International League of Associations for Rheumatology Classification of Juvenile Idiopathic Arthritis, 2001) and initiation of JIA treatment for at least 6 months prior to Baseline (Visit 2). Eligible JIA categories include: polyarthritis rheumatoid factor-positive, polyarthritis rheumatoid factor-negative, extended oligoarthritis, juvenile psoriatic arthritis, and enthesitis-related arthritis (ERA) Study participants must have active polyarticular-course disease, defined as ≥5 joints with active arthritis at Screening and at Baseline Study participants must have had an inadequate response to, or intolerance to, at least 1 disease-modifying antirheumatic drug (DMARD) (nonbiologic or biologic). For example, study participant had prior inadequate response to methotrexate (MTX) (based on the Investigator's clinical judgment) If the study participant is using MTX, then the study participant must have been on MTX for a minimum of 3 months at Screening. In addition, the dose must have been stable for at least 1 month before Screening at ≥10 to ≤15 mg/m^2 per week. If the study participant is not using MTX, then the treatment must have been previously withdrawn for documented reasons of intolerability or inadequate response If the study participant is using oral corticosteroid therapy, the dose must have been stable for at least 7 days prior to the Baseline arthritis assessment at a maximum dose of 10 mg or 0.2 mg/kg prednisone (or equivalent) per day, whichever is the smaller dose Exclusion Criteria: Study participant has previously been exposed to more than 2 biologic agents Study participant previously failed to respond to treatment with more than one tumor necrosis factor alpha (TNFα) antagonist drug Study participant is currently receiving or has received any experimental (biological or nonbiological) therapy (within or outside a clinical study) in the 3 months or 5 half-lives prior to Baseline (Visit 2), whichever is longer Study participant had previous treatment with a biological therapy for juvenile idiopathic arthritis (JIA) that resulted in a severe hypersensitivity reaction or an anaphylactic reaction Study participant previously participated in this study or has previously been treated with CZP (whether in a study or not) Study participant has a history of systemic JIA, with or without systemic features Study participant has a secondary, noninflammatory type of rheumatic disease or of joint pains (eg, fibromyalgia) that in the Investigator's opinion is symptomatic enough to interfere with evaluation of the effect of study medication Study participant has other inflammatory arthritis (eg, systemic lupus erythematosus, inflammatory bowel disease-related) Study participant has active uveitis or a history of active uveitis within the preceding 6 months Study participant has current, chronic or recurrent clinically significant infections Study participant has a current sign or symptom which may indicate infection (eg, fever, cough), a history of chronic or recurrent infections within the same organ system (more than 3 episodes requiring antibiotics/antivirals during the 12 months prior to Screening [Visit 1]), had a recent (within the 6 months prior to Screening [Visit 1]) serious or life-threatening infection (including herpes zoster), or is at a high risk of infection in the Investigator's opinion (eg, study participants with leg ulcers, indwelling urinary catheter, and persistent or recurrent chest infections or permanently bed-ridden or wheelchair bound)

Ages Eligible for Study
-----------------
Minimum Age: 2 Years
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Certolizumab Pegol<br>Active treatment with Certolizumab Pegol; dose adjustment is based on weight. | Drug: Certolizumab Pegol (CZP)<br>* CZP will be administered subcutaneously as a fixed dose based on weight every 2 weeks (Q2W) or every 4 weeks (Q4W) throughout the study. CZP will be provided by UCB as a CZP 200 mg/ml solution for single subcutaneous (sc) injection, in a single use prefilled syringe (PFS). Each PFS contains an extractable volume of 0.25 mL, 0.5 mL or 1 mL of CZP solution. Eligible subjects will begin with 3 loading doses of CZP followed by a treatment dose for the duration of the study based on the weight range. Reduced CZP regimen (after implementation of protocol amendments 4 and 5): 10 to < 20 kg: Loading dose = 50 mg Q2W (1 x 0.25 mL sc); treatment dose = 50 mg Q4W (1 x 0.25 mL sc); 20 to < 40 kg: Loading dose = 100 mg Q2W (1 x 0.5 mL sc,); treatment dose = 50 mg Q2W (1 x 0.25 mL sc); ≥ 40 kg: Loading dose = 200 mg Q2W (1 x 1.0 mL sc); treatment dose = 100 mg Q2W (1 x 0.5 mL sc);<br>* Other names: Cimzia;Drug: Certolizumab Pegol (CZP)<br>* CZP will be administered subcutaneously as a fixed dose based on weight every 2 weeks (Q2W) or every 4 weeks (Q4W) throughout the study. CZP will be provided by UCB as a CZP 200 mg/ml solution for single subcutaneous (sc) injection, in a single use prefilled syringe (PFS). Each PFS contains an extractable volume of 0.25 mL, 0.5 mL or 1 mL of CZP solution. Eligible subjects will begin with 3 loading doses of CZP followed by a treatment dose for the duration of the study based on the weight range. Original CZP regimen (prior to implementation of protocol amendments 4 and 5 and after implementation of protocol amendment 9): 10 to < 20 kg: Loading dose = 100 mg Q2W (1 x 0.5 mL sc); treatment dose = 50 mg Q2W (1 x 0.25 mL sc); 20 to < 40 kg: Loading dose = 200 mg Q2W (1 x 1.0 mL sc,); treatment dose = 100 mg Q2W (1 x 0.5 mL sc); ≥ 40 kg: Loading dose = 400 mg Q2W (2 x 1.0 mL sc); treatment dose = 200 mg Q2W (1 x 1.0 mL sc);<br>* Other names: Cimzia;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Certolizumab Pegol (CZP) Plasma Concentration level at Week 16 | Certolizumab Pegol (CZP) Plasma Concentration level is measured in μg/mL. | Week 16 | 
| Certolizumab Pegol (CZP) Plasma Concentration level at Week 48 | Certolizumab Pegol (CZP) Plasma Concentration level is measured in μg/mL. | Week 48 | 
| Anti-Certolizumab Pegol (anti-CZP) Antibody level at Week 16 |  | Week 16 | 
| Anti-Certolizumab Pegol (anti-CZP) Antibody level at Week 48 |  | Week 48 | 
| Incidence of serious treatment-emergent adverse events (TEAEs) during the study | A Serious Adverse Event (SAE) 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 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 (Week 0) up to the Final Visit (12 weeks after final dose of CZP) | 
| Incidence of treatment-emergent adverse events (TEAEs) leading to permanent withdrawal of the Investigational Medicinal Product (IMP) during the study | An Adverse Event (AE) is any untoward medical occurrence in a subject or trial subject that is administered a drug or biologic (medicinal product) or that is using a medical device. The event does not necessarily have a causal relationship with that treatment or usage. | From Baseline (Week 0) up to the Final Visit (12 weeks after final dose of CZP) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| American College of Rheumatology Pediatric 30 % (PedACR30) Response at Week 16 | The assessment of the PedACR30 at Week 16 compared to Baseline is based on a 30 % or greater improvement in at least 3 of the 6 core set measures with no more than 1 of the remaining worsened by >30 %. The 6 core set measures are: Number of joints with active arthritis (joints with swelling not due to deformity or inactive synovitis, or joints with limitation of motion with pain, tenderness, or both) Number of joints with limitation of range of motion Physician's Global Assessment of Disease Activity (VAS) CHAQ completed by parent or caregiver Parent's Global Assessment of Overall Well-Being (VAS) Acute phase reactant (CRP) | Week 16 | 
| American College of Rheumatology Pediatric 50 % (PedACR50) Response at Week 16 | The assessment of the PedACR50 at Week 16 compared to Baseline is based on a 50 % or greater improvement in at least 3 of the 6 core set measures with no more than 1 of the remaining worsened by >30 %. The 6 core set measures are: Number of joints with active arthritis (joints with swelling not due to deformity or inactive synovitis, or joints with limitation of motion with pain, tenderness, or both) Number of joints with limitation of range of motion Physician's Global Assessment of Disease Activity (VAS) CHAQ completed by parent or caregiver Parent's Global Assessment of Overall Well-Being (VAS) Acute phase reactant (CRP) | Week 16 | 
| American College of Rheumatology Pediatric 70 % (PedACR70) Response at Week 16 | The assessment of the PedACR70 at Week 16 compared to Baseline is based on a 70 % or greater improvement in at least 3 of the 6 core set measures with no more than 1 of the remaining worsened by >30 %. The 6 core set measures are: Number of joints with active arthritis (joints with swelling not due to deformity or inactive synovitis, or joints with limitation of motion with pain, tenderness, or both) Number of joints with limitation of range of motion Physician's Global Assessment of Disease Activity (VAS) CHAQ completed by parent or caregiver Parent's Global Assessment of Overall Well-Being (VAS) Acute phase reactant (CRP) | Week 16 | 
| American College of Rheumatology Pediatric 90 % (PedACR90) Response at Week 16 | The assessment of the PedACR90 at Week 16 compared to Baseline is based on a 90 % or greater improvement in at least 3 of the 6 core set measures with no more than 1 of the remaining worsened by >30 %. The 6 core set measures are: Number of joints with active arthritis (joints with swelling not due to deformity or inactive synovitis, or joints with limitation of motion with pain, tenderness, or both) Number of joints with limitation of range of motion Physician's Global Assessment of Disease Activity (VAS) CHAQ completed by parent or caregiver Parent's Global Assessment of Overall Well-Being (VAS) Acute phase reactant (CRP) | Week 16 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cimzia, JIA, Polyarticular, Oligoarticular, Enthesitis-related-Arthritis, Juvenile Idiopathic Arthritis, Juvenile Psoriatic Arthritis, Certolizumab Pegol, PASCAL, CDP870