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

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

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

Study Overview

• Status: Withdrawn
• Conditions: Crohn's Disease
• Intervention / Treatment: Drug: Certolizumab pegol; Drug: Placebo; Drug: Adalimumab

• Study Type: Interventional
• Phase: Phase 3

Expanded Access

Available outside the clinical trial. See expanded access record.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Certolizumab pegol low dose arm; 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; Pharmaceutical form: Solution for injection; Route of administration: Subcutaneous Subjects will receive certolizumab pegol in a pre-specified sequence during the Treatment Periods.; Drug: Placebo; Pharmaceutical form: Solution for injection; Route of administration: Subcutaneous Subjects will receive placebo in a pre-specified sequence during the Treatment Periods.
Experimental: Certolizumab pegol high dose arm; 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; Pharmaceutical form: Solution for injection; Route of administration: Subcutaneous Subjects will receive certolizumab pegol in a pre-specified sequence during the Treatment Periods.; Drug: Placebo; Pharmaceutical form: Solution for injection; Route of administration: Subcutaneous Subjects will receive placebo in a pre-specified sequence during the Treatment Periods.
Active Comparator: Adalimumab reference arm; 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: Placebo; Pharmaceutical form: Solution for injection; Route of administration: Subcutaneous Subjects will receive placebo in a pre-specified sequence during the Treatment Periods.; Drug: Adalimumab; Pharmaceutical form: Solution for injection; Route of administration: Subcutaneous Subjects will receive adalimumab in a pre-specified sequence during the Treatment Periods.

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: UCB Biopharma SRL

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2021
• Primary Completion (Anticipated): September 1, 2023
• Study Completion (Anticipated): April 1, 2026

Study Registration Dates

• First Submitted: November 19, 2020
• First Submitted That Met QC Criteria: November 19, 2020
• First Posted (Actual): November 25, 2020

Study Record Updates

• Last Update Posted (Actual): June 23, 2021
• Last Update Submitted That Met QC Criteria: June 17, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Pediatric; Cimzia; Crohn's disease; CD; Phase 3; Kids; Certolizumab pegol; OHANA
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Adalimumab; Certolizumab Pegol
• Other Study ID Numbers: CD0003

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 prespecified 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 study 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; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes