Pediatric Arthritis Study of Certolizumab Pegol

Polyarticular-course Juvenile Idiopathic Arthritis (JIA) Clinical Trial

— PASCAL  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01550003
• Other study ID #: RA0043
• Status: Completed
• Phase: Phase 3
• Start date: March 8, 2012
• Est. completion date: April 8, 2024

Study information

• Verified date: April 2024
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 193
• Est. completion date: April 8, 2024
• Est. primary completion date: April 8, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 17 Years

Eligibility

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 (TNFa) 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)

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Juvenile
• Polyarticular-course Juvenile Idiopathic Arthritis (JIA)

Intervention

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);
• 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);

Locations

Country	Name	City	State
Argentina	RA0043 2	Buenos Aires
Brazil	Ra0043 15	Curitiba
Brazil	Ra0043 14	Porto Alegre
Brazil	Ra0043 12	Sao Paulo
Canada	Ra0043 21	Calgary
Canada	Ra0043 22	Montreal
Canada	Ra0043 20	Toronto
Chile	Ra0043 60	Santiago
Mexico	Ra0043 31	Mexico
Mexico	Ra0043 32	Mexico D.F.
Mexico	Ra0043 30	Monterrey
Mexico	Ra0043 33	San Luis Potosi
Russian Federation	Ra0043 41	Moscow
Russian Federation	Ra0043 43	Moscow
Russian Federation	Ra0043 40	St. Petersburg
Russian Federation	Ra0043 42	Tolyatti
United States	Ra0043 70	Avon	Ohio
United States	Ra0043 74	Charlotte	North Carolina
United States	Ra0043 82	Chicago	Illinois
United States	Ra0043 90	Chicago	Illinois
United States	Ra0043 73	Cincinnati	Ohio
United States	Ra0043 78	Cleveland	Ohio
United States	Ra0043 95	Cleveland	Ohio
United States	Ra0043 86	Columbus	Ohio
United States	Ra0043 76	Durham	North Carolina
United States	Ra0043 80	Hackensack	New Jersey
United States	Ra0043 83	Hartford	Connecticut
United States	Ra0043 75	Indianapolis	Indiana
United States	Ra0043 71	Little Rock	Arkansas
United States	Ra0043 77	Livingston	New Jersey
United States	Ra0043 79	Los Angeles	California
United States	Ra0043 85	New Hyde Park	New York
United States	Ra0043 87	New York	New York
United States	Ra0043 89	Portland	Oregon
United States	Ra0043 84	San Francisco	California
United States	Ra0043 81	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
UCB BIOSCIENCES GmbH	PRA Health Sciences

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Canada,  Chile,  Mexico,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Certolizumab Pegol (CZP) Plasma Concentration level at Week 16	Certolizumab Pegol (CZP) Plasma Concentration level is measured in µg/mL.	Week 16
Primary	Certolizumab Pegol (CZP) Plasma Concentration level at Week 48	Certolizumab Pegol (CZP) Plasma Concentration level is measured in µg/mL.	Week 48
Primary	Anti-Certolizumab Pegol (anti-CZP) Antibody level at Week 16		Week 16
Primary	Anti-Certolizumab Pegol (anti-CZP) Antibody level at Week 48		Week 48
Primary	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)
Primary	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	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
Secondary	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
Secondary	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
Secondary	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