PASCAL: Pediatric Arthritis Study of Certolizumab Pegol

Sponsor

UCB BIOSCIENCES GmbH (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT01550003

Collaborator

PRA Health Sciences (Industry)

193

Enrollment

Locations

Arm

145.7

Anticipated Duration (Months)

5.4

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Polyarticular-course Juvenile Idiopathic Arthritis (JIA)	Drug: Certolizumab Pegol (CZP) Drug: Certolizumab Pegol (CZP)	Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

193 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Actual Study Start Date :

Mar 8, 2012

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Apr 30, 2024

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Certolizumab Pegol (CZP) Plasma Concentration level at Week 16 [Week 16]
Certolizumab Pegol (CZP) Plasma Concentration level is measured in μg/mL.
Certolizumab Pegol (CZP) Plasma Concentration level at Week 48 [Week 48]
Certolizumab Pegol (CZP) Plasma Concentration level is measured in μg/mL.
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 [From Baseline (Week 0) up to the Final Visit (12 weeks after final dose of CZP)]
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
Incidence of treatment-emergent adverse events (TEAEs) leading to permanent withdrawal of the Investigational Medicinal Product (IMP) during the study [From Baseline (Week 0) up to the Final Visit (12 weeks after final dose of CZP)]
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.

Secondary Outcome Measures

American College of Rheumatology Pediatric 30 % (PedACR30) Response at Week 16 [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)
American College of Rheumatology Pediatric 50 % (PedACR50) Response at Week 16 [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)
American College of Rheumatology Pediatric 70 % (PedACR70) Response at Week 16 [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)
American College of Rheumatology Pediatric 90 % (PedACR90) Response at Week 16 [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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ra0043 71	Little Rock	Arkansas	United States	72202
2	Ra0043 79	Los Angeles	California	United States	90027-6062
3	Ra0043 84	San Francisco	California	United States	94143
4	Ra0043 83	Hartford	Connecticut	United States	06106
5	Ra0043 81	Washington	District of Columbia	United States	20010
6	Ra0043 82	Chicago	Illinois	United States	60611
7	Ra0043 90	Chicago	Illinois	United States	60637
8	Ra0043 75	Indianapolis	Indiana	United States	46202
9	Ra0043 80	Hackensack	New Jersey	United States	07601
10	Ra0043 77	Livingston	New Jersey	United States	07039
11	Ra0043 85	New Hyde Park	New York	United States	11042
12	Ra0043 87	New York	New York	United States	10032
13	Ra0043 74	Charlotte	North Carolina	United States	28203
14	Ra0043 76	Durham	North Carolina	United States	27710
15	Ra0043 70	Avon	Ohio	United States	44011
16	Ra0043 73	Cincinnati	Ohio	United States	45229
17	Ra0043 78	Cleveland	Ohio	United States	44109
18	Ra0043 95	Cleveland	Ohio	United States	44195
19	Ra0043 86	Columbus	Ohio	United States	43205-2694
20	Ra0043 89	Portland	Oregon	United States	97227
21	RA0043 2	Buenos Aires		Argentina
22	Ra0043 15	Curitiba		Brazil
23	Ra0043 14	Porto Alegre		Brazil
24	Ra0043 12	Sao Paulo		Brazil
25	Ra0043 21	Calgary		Canada
26	Ra0043 22	Montreal		Canada
27	Ra0043 20	Toronto		Canada
28	Ra0043 60	Santiago		Chile
29	Ra0043 32	Mexico D.F.		Mexico
30	Ra0043 31	Mexico		Mexico
31	Ra0043 30	Monterrey		Mexico
32	Ra0043 33	San Luis Potosi		Mexico
33	Ra0043 41	Moscow		Russian Federation
34	Ra0043 43	Moscow		Russian Federation
35	Ra0043 40	St. Petersburg		Russian Federation
36	Ra0043 42	Tolyatti		Russian Federation