A Study to Test Efficacy, Safety, and Pharmacokinetics of Certolizumab Pegol in Children and Adolescents With Moderately to Severely Active Crohn's Disease

Study Overview
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Brief Summary
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The purpose of the study is to assess efficacy, safety and tolerability of 2 dose regimens of certolizumab pegol

Official Title
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A Phase 3, Randomized, Double-Blind, Multicenter Study Including an Active Reference Arm to Evaluate Efficacy, Safety, and Pharmacokinetics of Certolizumab Pegol in Children and Adolescents (6 to 17 Years of Age) With Moderately to Severely Active Crohn's Disease

Conditions
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Crohn's Disease

Intervention / Treatment
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* Drug: Certolizumab pegol
* Drug: Adalimumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant must be 6 to 17 years, inclusive, at the time of signing informed consent/assent Participant has been diagnosed with active Crohn's disease (CD) as confirmed by endoscopic examination with/without histological confirmation ≤12 weeks before the Screening Visit Participant has moderately to severely active disease despite current treatment Participant has an inadequate response or intolerance to conventional therapy Participants are certolizumab pegol (CZP) and adalimumab (ADA) naïve Exclusion Criteria: Participant has had an extensive colonic resection, subtotal or total colectomy, diagnosis of short bowel syndrome or a history of >3 small bowel resections Participant has had a primary failure (ie, lack of response within the first 12 weeks of treatment) to any anti-Tumor necrosis factor-α agent for treatment of Crohn's disease

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
Interventional Model Description: The study will be conducted in 3 parts: Part A will investigate 2 certolizumab pegol (CZP) dosing regimens with the objective of selecting a regimen that provides the highest rate of clinical remission. A cohort of participants will receive adalimumab (ADA) as a reference arm in Part A to assess clinical remission rates at Week 26 in this population. Endoscopic remission at Week 26 will also be evaluated Part B will assess maintenance of clinical remission from Week 26 through Week 52 Part C is an optional open-label extension (OLE) of CZP after Part B, and will evaluate the long-term safety of CZP through Week 156
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Certolizumab pegol low dose arm<br>Participants randomized to certolizumab pegol (CZP) who weigh ≥17 kg to <40 kg will receive placebo at Week 0 and a loading dose of 200 mg at Weeks 0, 2, and 4, followed by a maintenance dose of 100 mg CZP subcutaneously (sc) every 2 weeks (Q2W). Participants randomized to CZP who weigh ≥40 kg will receive placebo at Week 0 and a loading dose of 400 mg at Weeks 0, 2, and 4, followed by placebo and a maintenance dose of 200 mg CZP sc Q2W. | Drug: Certolizumab pegol<br>* Pharmaceutical form: Solution for injection Route of administration: Subcutaneous Subjects will receive certolizumab pegol in a pre-specified sequence during the Treatment Periods.<br>Drug: Placebo<br>* Pharmaceutical form: Solution for injection Route of administration: Subcutaneous Subjects will receive placebo in a pre-specified sequence during the Treatment Periods.<br>|
| Experimental: Certolizumab pegol high dose arm<br>Participants randomized to CZP who weigh ≥17 kg to <40 kg will receive placebo at Week 0 and a loading dose of 200 mg at Weeks 0, 2, and 4, followed by a maintenance dose of 200 mg CZP sc Q2W. Participants randomized to CZP who weigh ≥40 kg will receive placebo at Week 0 and a loading dose of 400 mg at Weeks 0, 2, and 4, followed by a maintenance dose of 300 mg CZP sc Q2W. | Drug: Certolizumab pegol<br>* Pharmaceutical form: Solution for injection Route of administration: Subcutaneous Subjects will receive certolizumab pegol in a pre-specified sequence during the Treatment Periods.<br>Drug: Placebo<br>* Pharmaceutical form: Solution for injection Route of administration: Subcutaneous Subjects will receive placebo in a pre-specified sequence during the Treatment Periods.<br>|
| Active Comparator: Adalimumab reference arm<br>Participants randomized to adalimumab who weigh ≥17 kg to <40 kg will receive a loading dose of 80 mg at Week 0 and 40 mg at Week 2, followed by a maintenance dose of 20 mg sc Q2W. Participants randomized to Adalimumab who weigh ≥40 kg will receive a loading dose of 160 mg at Week 0 and 80 mg at Week 2, 40 mg and placebo at week 4 followed by a maintenance dose of 40 mg sc and placebo Q2W. | Drug: Adalimumab<br>* Pharmaceutical form: Solution for injection Route of administration: Subcutaneous Subjects will receive adalimumab in a pre-specified sequence during the Treatment Periods.<br>Drug: Placebo<br>* Pharmaceutical form: Solution for injection Route of administration: Subcutaneous Subjects will receive placebo in a pre-specified sequence during the Treatment Periods.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical remission based on total Pediatric Crohn's Disease Activity Index (PCDAI) score ≤10.0 points at Week 26 | 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 total PCDAI score which can range from 0 to 100 points, with a higher score indicating more severe disease activity. | Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical remission (modified) at Week 26 | Clinical remission (modified) is defined as a Pediatric Crohn's Disease Activity Index (PCDAI) score ≤ 10 and the abdominal pain and stool frequency items in the PCDAI having scores of 0. 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 26 | 
| Corticosteroid-free clinical remission at Week 26 | Corticosteroid free clinical remission is defined as not taking corticosteroids after tapering, within 4 weeks prior to Week 26, and total PCDAI score ≤10.0 points and the abdominal pain and stool frequency items in the PCDAI having scores of 0 at Week 26. | Week 26 | 
| Clinical response at Week 26 and Week 52 | 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. | Week 26; Week 52 | 
| Endoscopic remission at Week 26 | Endoscopic remission is defined as Simple Endoscopic Score for Crohn's Disease [SES-CD] from 0 to 2, with a higher score indicating more disease activity. SES-CD is based on four endoscopic variables (presence and size of ulcers, proportion of surface covered by ulcers, proportion of surface affected by disease, and presence and severity of stenosis). Each of the four SES-CD variables is scored from 0 to 3, with the sum of the scores for each variable ranging from 0 to 15, except for the presence and extent of stenosis, which ranges from 0 to 11, yielding a total SES-CD score of 0-56. | Week 26 | 
| Clinical remission based on total PCDAI score ≤10.0 points at Week 52 | 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 total PCDAI score which can range from 0 to 100 points, with a higher score indicating more severe disease activity. | Week 52 | 
| Clinical remission (modified) at Week 52 | Clinical remission (modified) is defined as a Pediatric Crohn's Disease Activity Index (PCDAI) score ≤ 10 and the abdominal pain and stool frequency items in the PCDAI having scores of 0. 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 52 | 
| Incidence of serious Treatment Emergent Adverse Event (TEAEs) | A Serious Treatment Emergent Adverse Event is any untoward medical occurrence that at any dose: Results in death Is life-threatening Requires inpatient hospitalization or prolongation of existing hospitalization Results in persistent disability/incapacity Is a congenital anomaly/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 to the Safety Follow-Up visit (Week 166) | 
| Incidence of TEAEs leading to permanent withdrawal of investigational medicinal product | An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. | From Baseline to the Safety Follow-Up visit (Week 166) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CD, Certolizumab pegol, Cimzia, Phase 3, Crohn's disease, Pediatric, Kids, OHANA