The Use of Certolizumab Pegol for Treatment of Active Crohn's Disease in Children and Adolescents

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, efficacy, pharmacokinetics, and immunogenicity of certolizumab pegol treatment in pediatric subjects, aged 6 to 17, with moderately to severely active Crohn's disease. The target enrollment is 160 subjects.

Official Title
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A Phase 2, Open-label, Multicenter Study to Assess the Safety and Efficacy of Certolizumab Pegol in Children and Adolescents With Active Crohn's Disease (NURTURE Study)

Conditions
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Crohn's Disease

Intervention / Treatment
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* Drug: Certolizumab Pegol
* Drug: Certolizumab Pegol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with active Crohn's Disease (CD) confirmed 3 months prior to Screening Subjects with a Pediatric Crohn's Disease Activity Index (PCDAI) score of > 30 at Week 0 Subjects between the ages of 6 and 17, inclusive, prior to baseline dosing Subjects must weigh > 20 kg (44 lbs) Subjects must have normal Electrocardiogram (ECG) or no medically relevant abnormalities as assessed by the investigator Subjects must meet Tuberculosis (TB) screening criteria Subjects taking corticosteroids, antibiotics and analgesics must have stable dosing, as defined, for one week Exclusion Criteria: Subjects who score > 5 on the perirectal disease item of the PCDAI at Baseline Subjects who have had an active enterocutaneous fistulae within 3 months prior to Baseline Subjects with non-enterocutaneous fistulae, signs or symptoms of bowel obstruction or short bowel syndrome Subjects with a functional colostomy or ileostomy Subjects who have had surgical bowel resection within 6 months prior to Baseline or who may be planning any resection while enrolled in the study Subjects with clinical suspicion of intraabdominal abscesses Subjects with a positive stool result for enteric pathogens and/or parasites Subject has received any investigational biological therapies (within or outside a clinical trial) within 12 weeks prior to Screening or has been dosed in any clinical trial using non biological therapies within 4 weeks prior to Screening Subjects who have lost response to another Tumor Necrosis Factor (TNF) agent Subjects may not use another TNF agent within 12 weeks of Screening Visit Subjects with any prior exposure to natalizumab Subjects who have received mycophenolate or thalidomide within 4 weeks prior to Screening Subjects who have received cyclosporin or tacrolimus within 6 months prior to Screening Subjects who have received parenteral corticosteroids within 2 weeks prior to Screening Subjects who have received corticosteroids or corticotrophins for indications other than CD within 2 weeks of Screening Subject has a current or recent history (within 6 months prior to Screening) of significant and severe renal, hepatic, hematological, gastrointestinal (other than CD), endocrine, pulmonary, cardiac, neurological, or cerebral disease including blood dyscrasia (eg, pancytopenia, aplastic anemia), demyelinating disease (eg, multiple sclerosis, myelitis, optic neuritis), or ischemic heart disease Subjects with a current sign or symptom indicating recent or chronic infections (including herpes zoster) Subject has negative test for Immunoglobulin G (IgG) against Varicella zoster (chicken pox) Subjects who have not completed their primary vaccination series, or are planning to have a live vaccine administered during the study period or up to 3 months after last dose of study drug Subject has a history of TB or a positive chest x-ray suggestive of TB Subjects with known concurrent viral hepatitis or Acquired Immune Deficiency Syndrome (AIDS) or known Human Immunodeficiency Virus (HIV) infection Subjects with concurrent malignancy or history of malignancy, excluding treated squamous cell carcinoma of the skin Subject has concurrent bowel dysplasia or a history of bowel dysplasia in the 5 years prior to Screening Subjects with a history lymphoproliferative disorder including lymphoma or signs and symptoms suggestive of lymphoma at any time

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Maintenance High-Dose<br>Maintenance High-Dose group: 400 mg Certolizumab Pegol for subjects ≥ 40 kg or 200 mg Certolizumab Pegol for subjects 20 to < 40 kg | Drug: Certolizumab Pegol<br>* 400 mg administered subcutaneously at once every 4 weeks for subjects ≥ 40 kg or 200 mg for subjects 20 to < 40 kg *prior to this dosing regimen, subjects will undergo an induction of Certolizumab Pegol administered subcutaneously every 2 weeks (total 3 injections) at of either 400 mg for subjects ≥ 40 kg or 200 mg for subjects 20 to < 40 kg<br>* Other names: CDP870;|
| Active Comparator: Maintenance Low-Dose<br>Maintenance Low-Dose group: 200 mg Certolizumab Pegol for subjects ≥ 40 kg or 100 mg Certolizumab Pegol for subjects 20 to < 40 kg | Drug: Certolizumab Pegol<br>* 200 mg administered subcutaneously at once every 4 weeks for subjects ≥ 40 kg or 200 mg for subjects 20 to < 40 kg *prior to this dosing regimen, subjects will undergo an induction of Certolizumab Pegol administered subcutaneously every 2 weeks (total 3 injections) at of either 400 mg for subjects ≥ 40 kg or 200 mg for subjects 20 to < 40 kg<br>* Other names: CDP870;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects in Clinical Remission at Week 62 | Clinical remission is defined as a Pediatric Crohn's Disease Activity Index (PCDAI) score ≤ 10. The Pediatric Crohn's Disease Activity Index (PCDAI) consists of 4 domains (laboratory, height/weight, examination, and history) with several assessments that are converted into a PCDAI score which can range from 0 to 100 points, with a higher score indicating more severe disease activity. | Week 62 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Pediatric Crohn's Disease Activity Index (PCDAI) Scores at Week 62 | The Pediatric Crohn's Disease Activity Index (PCDAI) consists of 4 domains (laboratory, height/weight, examination, and history) with several assessments that are converted into a PCDAI score which can range from 0 to 100 points, with a higher score indicating more severe disease activity. | Week 62 | 
| Change in Pediatric Crohn's Disease Activity Index (PCDAI) Scores From Week 0 to the End of the Study (Week 62) | The Pediatric Crohn's Disease Activity Index (PCDAI) consists of 4 domains (laboratory, height/weight, examination, and history) with several assessments that are converted into a PCDAI score which can range from 0 to 100 points, with a higher score indicating more severe disease activity. A negative value in change from Baseline indicates an improvement from Baseline to Week 62. | From Week 0 to Week 62 | 
| Percentage of Subjects Achieving Clinical Response From Week 0 to the End of the Study (Week 62) | Clinical response is defined as a decrease from Week 0 in Pediatric Crohn's Disease Activity Index (PCDAI) score of ≥ 15 points and a total PCDAI score ≤ 30 points. The Pediatric Crohn's Disease Activity Index (PCDAI) consists of 4 domains (laboratory, height/weight, examination, and history) with several assessments that are converted into a PCDAI score which can range from 0 to 100 points, with a higher score indicating more severe disease activity. | From Week 0 to Week 62 | 
| C-Reactive Protein (CRP) Levels at Week 62 | The C-Reactive Protein (CRP) is a considered marker of inflammation in subjects with Crohn's Disease (CD) | Week 62 | 
| Change in C-Reactive Protein (CRP) Levels From Week 0 to the End of the Study (Week 62) | The C-Reactive Protein (CRP) is a considered marker of inflammation in subjects with Crohn's Disease (CD). Changes from Baseline in CRP levels are expressed as a ratio with the value measured at Baseline as the denominator. | From Week 0 to Week 62 | 
| Erythrocyte Sedimentation Rate (ESR) at Week 62 | The Erythrocyte Sedimentation Rate (ESR) is a considered biomarker of inflammation in subjects with Crohn's Disease (CD). | Week 62 | 
| Change in Erythrocyte Sedimentation Rate (ESR) From Week 0 to the End of the Study (Week 62) | The Erythrocyte Sedimentation Rate (ESR) is a considered biomarker of inflammation in subjects with Crohn's Disease (CD). Changes from Baseline in CRP levels are expressed as a ratio with the value measured at baseline as the denominator. | From Week 0 to Week 62 | 
| Change in Growth Scores (Tanner Stage [Assessing Puberty]) From Week 0 to the End of the Study (Week 62) | The Tanner stage is an assessment of developmental stage on external genitalia and pubic hair (boys), and on breast and pubic hair (girls). Values range from 1 to 5 where a higher number indicates more development. | From Week 0 to Week 62 | 
| Percentage of Subjects Who Initiated Steroid Tapering | Subjects receiving corticosteroids at Screening may start a defined tapering schedule between Weeks 2 and 8. Corticosteroid tapering must start at the latest by Week 8. Corticosteroid doses are tapered at different rates depending on the subject's dose. | From Week 2 up to Week 8 | 
| Percentage of Subjects in Corticosteroid-free Remission at the End of the Study | Corticosteroid use at end of study is defined as 84 days past the last dose of study medication. Remission is assessed at the last visit where Pediatric Crohn's Disease Activity index (PCDAI) data is available. | Last/Withdrawal Visit (up to Week 62) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Certolizumab Pegol, Cimzia ®, Crohn's Disease