Pediatric Arthritis Study of Certolizumab Pegol (PASCAL)

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)

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).

Study Overview

• Status: Completed
• Conditions: Polyarticular-course Juvenile Idiopathic Arthritis (JIA)
• Intervention / Treatment: Drug: Certolizumab Pegol (CZP); Drug: Certolizumab Pegol (CZP)

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.

• Study Type: Interventional
• Enrollment (Actual): 193
• Phase: Phase 3

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • RA0043 2
• Brazil
  • Curitiba, Brazil
    • Ra0043 15
  • Porto Alegre, Brazil
    • Ra0043 14
  • Sao Paulo, Brazil
    • Ra0043 12
• Canada
  • Calgary, Canada
    • Ra0043 21
  • Montreal, Canada
    • Ra0043 22
  • Toronto, Canada
    • Ra0043 20
• Chile
  • Santiago, Chile
    • Ra0043 60
• Mexico
  • Mexico, Mexico
    • Ra0043 31
  • Mexico D.F., Mexico
    • Ra0043 32
  • Monterrey, Mexico
    • Ra0043 30
  • San Luis Potosi, Mexico
    • Ra0043 33
• Russian Federation
  • Moscow, Russian Federation
    • Ra0043 41
  • Moscow, Russian Federation
    • Ra0043 43
  • St. Petersburg, Russian Federation
    • Ra0043 40
  • Tolyatti, Russian Federation
    • Ra0043 42
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Ra0043 71
  • California
    • Los Angeles, California, United States, 90027-6062
      • Ra0043 79
    • San Francisco, California, United States, 94143
      • Ra0043 84
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Ra0043 83
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Ra0043 81
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ra0043 82
    • Chicago, Illinois, United States, 60637
      • Ra0043 90
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Ra0043 75
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Ra0043 80
    • Livingston, New Jersey, United States, 07039
      • Ra0043 77
  • New York
    • New Hyde Park, New York, United States, 11042
      • Ra0043 85
    • New York, New York, United States, 10032
      • Ra0043 87
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Ra0043 74
    • Durham, North Carolina, United States, 27710
      • Ra0043 76
  • Ohio
    • Avon, Ohio, United States, 44011
      • Ra0043 70
    • Cincinnati, Ohio, United States, 45229
      • Ra0043 73
    • Cleveland, Ohio, United States, 44109
      • Ra0043 78
    • Cleveland, Ohio, United States, 44195
      • Ra0043 95
    • Columbus, Ohio, United States, 43205-2694
      • Ra0043 86
  • Oregon
    • Portland, Oregon, United States, 97227
      • Ra0043 89

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Certolizumab Pegol; Active treatment with Certolizumab Pegol; dose adjustment is based on weight.

Drug: Certolizumab Pegol (CZP); 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); Other Names: Cimzia; Drug: Certolizumab Pegol (CZP); 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); 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 was measured in micrograms per milliliter (ug/ml).	Week 16
Certolizumab Pegol (CZP) Plasma Concentration Level at Week 48	Certolizumab Pegol (CZP) plasma concentration level was measured in ug/mL.	Week 48
Number of Participants With Anti-Certolizumab Pegol (Anti-CZP) Antibody Level at Week 16	Number of participants with anti-CZP antibodies were reported.	Week 16
Number of Participants With Anti-Certolizumab Pegol (Anti-CZP) Antibody Level at Week 48	Number of participants with anti-CZP antibodies were reported.	Week 48
Number of Participants With 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 deaths, is life-threatening, requires in patient hospitalization or prolongation of existing hospitalization, is a congenital anomaly or birth defect and 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. TEAEs are defined as AEs starting on or after first administration of CZP and up to 70 days after last dose of study medication.	From Baseline (Week 0) up to the Final Visit (70 days after final dose of CZP) (maximum up to 12 years)
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Leading to Permanent Withdrawal of the Investigational Medicinal Product (IMP) During the Study	An AE is any untoward medical occurrence in a patient or clinical investigation study participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not related to the IMP. TEAEs are defined as AEs starting on or after first administration of CZP and up to 70 days after last dose of study medication. TEAEs leading to permanent withdrawal of the IMP during the study were reported in this outcome measure.	From Baseline (Week 0) up to the Final Visit (70 days after final dose of CZP) (maximum up to 12 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Meeting American College of Rheumatology Pediatric 30 % (PedACR30) Response Criteria at Week 16	PedACR30-at least 30% improvement from baseline in 3 of any 6 core set measures, with no more than 1 of remaining variables worsening by >30%: Number of joints with active arthritis; Number of joints with limitation of range of motion; Physician's Global Assessment of Disease Activity (using visual analog scale (VAS): 100mm; 0= very good, and 100= very poor); CHAQ (30 questions, 8 domains, scores for each domain are averaged to calculate total score [ 0= no disability to 3= very severe disability]); Parent's Global Assessment of Overall Well-Being (using VAS: 100mm; 0= Very well to 100= Very poor); C-reactive protein (CRP)	Week 16
Percentage of Participants Meeting American College of Rheumatology Pediatric 50 % (PedACR50) Response Criteria at Week 16	PedACR50- at least 50% improvement from baseline in 3 of any 6 core set measures, with no more than 1 of remaining variables worsening by >30%: Number of joints with active arthritis; Number of joints with limitation of range of motion; Physician's Global Assessment (PGA) of Disease Activity (using VAS: 100mm; 0= very good, and 100= very poor); Childhood Health Assessment Questionnaire (CHAQ) (30 questions, 8 domains, scores for each domain are averaged to calculate total score [ 0= no disability to 3= very severe disability]); Parent's Global Assessment of Overall Well-Being (using VAS: 100mm; 0= Very well to 100= Very poor); CRP	Week 16
Percentage of Participants Meeting American College of Rheumatology Pediatric 70 % (PedACR70) Response Criteria at Week 16	PedACR70- at least 70% improvement from baseline in 3 of any 6 following core set measures, with no more than 1 of remaining variables worsening by >30%: Number of joints with active arthritis; Number of joints with limitation of range of motion; Physician's Global Assessment of Disease Activity (using VAS: 100mm; 0= very good, and 100= very poor); CHAQ (30 questions, 8 domains, scores for each domain are averaged to calculate total score [ 0= no disability to 3= very severe disability]); Parent's Global Assessment of Overall Well-Being (using VAS: 100mm; 0= Very well to 100= Very poor); CRP	Week 16
Percentage of Participants Meeting American College of Rheumatology Pediatric 90 % (PedACR90) Response Criteria at Week 16	PedACR90- at least 90% improvement from baseline in 3 of any 6 following core set measures, with no more than 1 of remaining variables worsening by >30%: Number of joints with active arthritis; Number of joints with limitation of range of motion; Physician's Global Assessment of Disease Activity (using VAS: 100mm; 0= very good, and 100= very poor); CHAQ (30 questions, 8 domains, scores for each domain are averaged to calculate total score [ 0= no disability to 3= very severe disability]); Parent's Global Assessment of Overall Well-Being (using VAS: 100mm; 0= Very well to 100= Very poor); CRP	Week 16

Collaborators and Investigators

• Sponsor: UCB BIOSCIENCES GmbH
• Collaborators: PRA Health Sciences
• Investigators: Study Director: UCB Cares, 001 844 599 2273 (UCB)

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2012
• Primary Completion (Actual): April 8, 2024
• Study Completion (Actual): April 8, 2024

Study Registration Dates

• First Submitted: March 7, 2012
• First Submitted That Met QC Criteria: March 7, 2012
• First Posted (Estimated): March 9, 2012

Study Record Updates

• Last Update Posted (Actual): October 23, 2024
• Last Update Submitted That Met QC Criteria: September 26, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: JIA; Cimzia; Certolizumab Pegol; Juvenile Idiopathic Arthritis; CDP870; Polyarticular; Oligoarticular; Enthesitis-related-Arthritis; Juvenile Psoriatic Arthritis; PASCAL
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Arthritis; Arthritis, Juvenile; Tumor Necrosis Factor Inhibitors; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Certolizumab Pegol
• Other Study ID Numbers: RA0043

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe, or global development is discontinued, and 18 months after trial completion. Investigators may request access to anonymized individual patient-level data and redacted trial documents which may include: analysis-ready datasets, study protocol, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal. This plan may change if the risk of re-identifying trial participants is determined to be too high after the trial is completed; in this case and to protect participants, individual patient-level data would not be made available.
• IPD Sharing Time Frame: Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe or global development is discontinued, and 18 months after trial completion.
• IPD Sharing Access Criteria: Qualified researchers may request access to anonymized IPD and redacted study documents which may include: raw datasets, analysis-ready datasets, study protocol, blank case report form, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR