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

• ClinicalTrials.gov Identifier: NCT00899678
• Recruitment Status: Terminated
• First Posted: May 12, 2009
• Results First Posted: November 21, 2013
• Last Update Posted: August 7, 2018
• Sponsor: UCB Celltech
• Information provided by (Responsible Party): UCB Pharma ( UCB Celltech )

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Crohn's Disease
• Intervention: Drug: Certolizumab Pegol
• Enrollment: 99

Participant Flow

Recruitment Details	The Participant Flow refers to the Safety Set (SS) population. The Safety Population includes all subjects enrolled who received at least 1 injection of study treatment.
Pre-assignment Details	During an Induction Period (Weeks 0 to 6), subjects were administered Certolizumab Pegol (CZP) subcutaneously every 2 weeks (Q2W). Subjects who showed a clinical response at Week 6 were randomized in a 1:1 ratio to one of 2 dose groups. Subjects who did not respond at Week 6 were withdrawn from the study.

Arm/Group Title	Induction Only	Maintenance Low-Dose	Maintenance High-Dose
Arm/Group Description	Induction Only is the period between the Week 0 dose and prior to first maintenance dose (Week 8). Induction Only includes all subjects who received a dose during the Induction Period but did not receive any treatment during the Maintenance Period. During the Induction Period (Weeks 0 to 6), subjects were administered Certolizumab Pegol (CZP) subcutaneously every 2 weeks (Q2W) (for a total of 3 administrations of drug) at a dose of either: 400 mg for subjects ≥ 40 kg; 200 mg for subjects 20 to < 40 kg	Maintenance Low-Dose group*: 200 mg Certolizumab Pegol once every 4 weeks for subjects ≥ 40 kg or 100 mg Certolizumab Pegol once every 4 weeks for subjects 20 to < 40 kg *prior to this dosing regimen, subjects underwent 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	Maintenance High-Dose group*: 400 mg Certolizumab Pegol once every 4 weeks for subjects ≥ 40 kg or 200 mg Certolizumab Pegol once every 4 weeks for subjects 20 to < 40 kg *prior to this dosing regimen, subjects underwent 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
Period Title: Induction Period (Weeks 0 to 6)
Started	27 [1]	37	35
Completed	2 [2]	37	35
Not Completed	25	0	0
Reason Not Completed
Adverse Event	6	0	0
Lack of Efficacy	17	0	0
Protocol Violation	1	0	0
Other reason	1	0	0
[1] Induction only includes subjects that discontinued before Maintenance Period.; [2] 2 subjects completed the Induction Phase, but discontinued prior to receiving any Maintenance doses.
Period Title: Maintenance Period (Weeks 8 to 62)
Started	0 [1]	37	35
Completed	0	12	7
Not Completed	0	25	28
Reason Not Completed
Adverse Event	0	10	5
Lack of Efficacy	0	11	18
Protocol Violation	0	1	1
Withdrawal by Subject	0	1	2
Other reason	0	2	2
[1] Induction only includes subjects that discontinued before Maintenance Period.

Baseline Characteristics

Arm/Group Title		Induction Only	Maintenance Low-Dose	Maintenance High-Dose	Total
Arm/Group Description		Induction Only is the period between the Week 0 dose and prior to first maintenance dose (Week 8). Induction Only includes all subjects who received a dose during the Induction Period but did not receive any treatment during the Maintenance Period. During the Induction Period (Weeks 0 to 6), subjects were administered Certolizumab Pegol (CZP) subcutaneously every 2 weeks (Q2W) (for a total of 3 administrations of drug) at a dose of either: 400 mg for subjects ≥ 40 kg; 200 mg for subjects 20 to < 40 kg	Maintenance Low-Dose group*: 200 mg Certolizumab Pegol once every 4 weeks for subjects ≥ 40 kg or 100 mg Certolizumab Pegol once every 4 weeks for subjects 20 to < 40 kg *prior to this dosing regimen, subjects underwent 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	Maintenance High-Dose group*: 400 mg Certolizumab Pegol once every 4 weeks for subjects ≥ 40 kg or 200 mg Certolizumab Pegol once every 4 weeks for subjects 20 to < 40 kg *prior to this dosing regimen, subjects underwent 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	Total of all reporting groups
Overall Number of Baseline Participants		27	37	35	99
Baseline Analysis Population Description		The Baseline characteristics refer to the Safety Set (SS) population. The Safety Population includes all subjects enrolled who received at least 1 injection of study treatment.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	27 participants	37 participants	35 participants	99 participants
		13.8 (2.67)	13.2 (2.41)	13.4 (2.46)	13.4 (2.48)
Age, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	27 participants	37 participants	35 participants	99 participants
6-11 years		6	9	8	23
12-17 years		21	28	27	76
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	27 participants	37 participants	35 participants	99 participants
	Female	10 37.0%	10 27.0%	21 60.0%	41 41.4%
	Male	17 63.0%	27 73.0%	14 40.0%	58 58.6%
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	27 participants	37 participants	35 participants	99 participants
American Indian / Alaskan Native		0	0	0	0
Asian		1	0	0	1
Black		3	3	8	14
Native Hawaiian or other Pacific islander		0	0	0	0
White		22	32	27	81
Other / Mixed		1	2	0	3
Weight; Mean (Standard Deviation); Unit of measure: Kilogram
	Number Analyzed	27 participants	37 participants	35 participants	99 participants
		46.50 (12.565)	45.67 (14.638)	50.35 (18.569)	47.55 (15.642)
Height; Mean (Standard Deviation); Unit of measure: Centimeter
	Number Analyzed	27 participants	37 participants	35 participants	99 participants
		157.46 (13.841)	155.32 (13.589)	157.22 (13.320)	156.57 (13.460)
Body Mass Index (BMI); Mean (Standard Deviation); Unit of measure: Kilogram per square meter
	Number Analyzed	27 participants	37 participants	35 participants	99 participants
		18.39 (2.504)	18.51 (3.531)	19.79 (4.897)	18.93 (3.869)
Body Surface Area (BSA); Mean (Standard Deviation); Unit of measure: Square meter
	Number Analyzed	27 participants	37 participants	35 participants	99 participants
		1.42 (0.250)	1.39 (0.272)	1.47 (0.319)	1.43 (0.283)

Outcome Measures

1. Primary Outcome

Title	Percentage of Subjects in Clinical Remission at Week 62
Description	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.
Time Frame	Week 62

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) population

Arm/Group Title	Maintenance Low-Dose	Maintenance High-Dose
Arm/Group Description:	Maintenance Low-Dose group*: 200 mg Certolizumab Pegol once every 4 weeks for subjects ≥ 40 kg or 100 mg Certolizumab Pegol once every 4 weeks for subjects 20 to < 40 kg *prior to this dosing regimen, subjects underwent 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	Maintenance High-Dose group*: 400 mg Certolizumab Pegol once every 4 weeks for subjects ≥ 40 kg or 200 mg Certolizumab Pegol once every 4 weeks for subjects 20 to < 40 kg *prior to this dosing regimen, subjects underwent 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
Overall Number of Participants Analyzed	37	35
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	24.3; (10.5 to 38.1)	17.1; (4.7 to 29.6)

2. Secondary Outcome

Title	Absolute Pediatric Crohn's Disease Activity Index (PCDAI) Scores at Week 62
Description	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.
Time Frame	Week 62

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) population. At the start of the Maintenance Period, the FAS had 37 subjects in the Low-Dose group and 35 subjects in the High-Dose group. However, at Week 62, there were only 11 subjects in the Low-Dose group and 7 subjects in the High-Dose group with valid Pediatric Crohn's Disease Activity Index (PCDAI) scores.

Arm/Group Title	Maintenance Low-Dose	Maintenance High-Dose
Arm/Group Description:	Maintenance Low-Dose group*: 200 mg Certolizumab Pegol once every 4 weeks for subjects ≥ 40 kg or 100 mg Certolizumab Pegol once every 4 weeks for subjects 20 to < 40 kg *prior to this dosing regimen, subjects underwent 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	Maintenance High-Dose group*: 400 mg Certolizumab Pegol once every 4 weeks for subjects ≥ 40 kg or 200 mg Certolizumab Pegol once every 4 weeks for subjects 20 to < 40 kg *prior to this dosing regimen, subjects underwent 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
Overall Number of Participants Analyzed	11	7
Mean (Standard Deviation); Unit of Measure: Score on a scale
	8.18 (6.900)	7.14 (7.830)

3. Secondary Outcome

Title	Change in Pediatric Crohn's Disease Activity Index (PCDAI) Scores From Week 0 to the End of the Study (Week 62)
Description	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.
Time Frame	From Week 0 to Week 62

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) population. At the start of the Maintenance Period, the FAS had 37 subjects in the Low-Dose group and 35 subjects in the High- Dose group. However, at Week 62, there were only 11 subjects in the Low-Dose group and 7 subjects in the High-Dose group with valid Pediatric Crohn's Disease Activity Index (PCDAI) scores.

Arm/Group Title	Maintenance Low-Dose	Maintenance High-Dose
Arm/Group Description:	Maintenance Low-Dose group*: 200 mg Certolizumab Pegol once every 4 weeks for subjects ≥ 40 kg or 100 mg Certolizumab Pegol once every 4 weeks for subjects 20 to < 40 kg *prior to this dosing regimen, subjects underwent 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	Maintenance High-Dose group*: 400 mg Certolizumab Pegol once every 4 weeks for subjects ≥ 40 kg or 200 mg Certolizumab Pegol once every 4 weeks for subjects 20 to < 40 kg *prior to this dosing regimen, subjects underwent 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
Overall Number of Participants Analyzed	11	7
Mean (Standard Deviation); Unit of Measure: units on a scale
	-29.77 (8.097)	-27.14 (5.669)

4. Secondary Outcome

Title	Percentage of Subjects Achieving Clinical Response From Week 0 to the End of the Study (Week 62)
Description	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.
Time Frame	From Week 0 to Week 62

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) population

Arm/Group Title	Maintenance Low-Dose	Maintenance High-Dose
Arm/Group Description:	Maintenance Low-Dose group*: 200 mg Certolizumab Pegol once every 4 weeks for subjects ≥ 40 kg or 100 mg Certolizumab Pegol once every 4 weeks for subjects 20 to < 40 kg *prior to this dosing regimen, subjects underwent 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	Maintenance High-Dose group*: 400 mg Certolizumab Pegol once every 4 weeks for subjects ≥ 40 kg or 200 mg Certolizumab Pegol once every 4 weeks for subjects 20 to < 40 kg *prior to this dosing regimen, subjects underwent 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
Overall Number of Participants Analyzed	37	35
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	29.7; (15.0 to 44.5)	20.0; (6.7 to 33.3)

5. Secondary Outcome

Title	C-Reactive Protein (CRP) Levels at Week 62
Description	The C-Reactive Protein (CRP) is a considered marker of inflammation in subjects with Crohn's Disease (CD)
Time Frame	Week 62

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) population. At the start of the Maintenance Period, the FAS had 37 subjects in the Low-Dose group and 35 subjects in the High- Dose group. However, at Week 62, there were only 11 subjects in the Low-Dose group and 7 subjects in the High-Dose group with valid C-Reactive Protein (CRP) levels.

Arm/Group Title	Maintenance Low-Dose	Maintenance High-Dose
Arm/Group Description:	Maintenance Low-Dose group*: 200 mg Certolizumab Pegol once every 4 weeks for subjects ≥ 40 kg or 100 mg Certolizumab Pegol once every 4 weeks for subjects 20 to < 40 kg *prior to this dosing regimen, subjects underwent 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	Maintenance High-Dose group*: 400 mg Certolizumab Pegol once every 4 weeks for subjects ≥ 40 kg or 200 mg Certolizumab Pegol once every 4 weeks for subjects 20 to < 40 kg *prior to this dosing regimen, subjects underwent 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
Overall Number of Participants Analyzed	11	7
Geometric Mean (95% Confidence Interval); Unit of Measure: mg/L
	7.2; (2.5 to 20.7)	5.8; (2.1 to 15.7)

6. Secondary Outcome

Title	Change in C-Reactive Protein (CRP) Levels From Week 0 to the End of the Study (Week 62)
Description	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.
Time Frame	From Week 0 to Week 62

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) population. At the start of the Maintenance Period, the FAS had 37 subjects in the Low-Dose group and 35 subjects in the High- Dose group. However, at Week 62, there were only 11 subjects in the Low-Dose group and 7 subjects in the High-Dose group with valid C-Reactive Protein (CRP) levels.

Arm/Group Title	Maintenance Low-Dose	Maintenance High-Dose
Arm/Group Description:	Maintenance Low-Dose group*: 200 mg Certolizumab Pegol once every 4 weeks for subjects ≥ 40 kg or 100 mg Certolizumab Pegol once every 4 weeks for subjects 20 to < 40 kg *prior to this dosing regimen, subjects underwent 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	Maintenance High-Dose group*: 400 mg Certolizumab Pegol once every 4 weeks for subjects ≥ 40 kg or 200 mg Certolizumab Pegol once every 4 weeks for subjects 20 to < 40 kg *prior to this dosing regimen, subjects underwent 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
Overall Number of Participants Analyzed	11	7
Geometric Mean (95% Confidence Interval); Unit of Measure: ratio
	0.49; (0.17 to 1.41)	1.84; (0.27 to 12.71)

7. Secondary Outcome

Title	Erythrocyte Sedimentation Rate (ESR) at Week 62
Description	The Erythrocyte Sedimentation Rate (ESR) is a considered biomarker of inflammation in subjects with Crohn's Disease (CD).
Time Frame	Week 62

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) population. At the start of the Maintenance Period, the FAS had 37 subjects in the Low-Dose group and 35 subjects in the High- Dose group. However, at Week 62, there were only 12 subjects in the Low-Dose group and 7 subjects in the High-Dose group with a valid Erythrocyte Sedimentation Rate (ESR).

Arm/Group Title	Maintenance Low-Dose	Maintenance High-Dose
Arm/Group Description:	Maintenance Low-Dose group*: 200 mg Certolizumab Pegol once every 4 weeks for subjects ≥ 40 kg or 100 mg Certolizumab Pegol once every 4 weeks for subjects 20 to < 40 kg *prior to this dosing regimen, subjects underwent 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	Maintenance High-Dose group*: 400 mg Certolizumab Pegol once every 4 weeks for subjects ≥ 40 kg or 200 mg Certolizumab Pegol once every 4 weeks for subjects 20 to < 40 kg *prior to this dosing regimen, subjects underwent 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
Overall Number of Participants Analyzed	12	7
Geometric Mean (95% Confidence Interval); Unit of Measure: mm/h
	20.9; (11.8 to 37.2)	25.2; (12.3 to 51.7)

8. Secondary Outcome

Title	Change in Erythrocyte Sedimentation Rate (ESR) From Week 0 to the End of the Study (Week 62)
Description	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.
Time Frame	From Week 0 to Week 62

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) population. At the start of the Maintenance Period, the FAS had 37 subjects in the Low-Dose group and 35 subjects in the High- Dose group. However, at Week 62, there were only 12 subjects in the Low-Dose group and 7 subjects in the High-Dose group with a valid Erythrocyte Sedimentation Rate (ESR).

Arm/Group Title	Maintenance Low-Dose	Maintenance High-Dose
Arm/Group Description:	Maintenance Low-Dose group*: 200 mg Certolizumab Pegol once every 4 weeks for subjects ≥ 40 kg or 100 mg Certolizumab Pegol once every 4 weeks for subjects 20 to < 40 kg *prior to this dosing regimen, subjects underwent 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	Maintenance High-Dose group*: 400 mg Certolizumab Pegol once every 4 weeks for subjects ≥ 40 kg or 200 mg Certolizumab Pegol once every 4 weeks for subjects 20 to < 40 kg *prior to this dosing regimen, subjects underwent 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
Overall Number of Participants Analyzed	12	7
Geometric Mean (95% Confidence Interval); Unit of Measure: ratio
	0.57; (0.31 to 1.04)	1.08; (0.39 to 3.02)

9. Secondary Outcome

Title	Change in Growth Scores (Tanner Stage [Assessing Puberty]) From Week 0 to the End of the Study (Week 62)
Description	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.
Time Frame	From Week 0 to Week 62

Outcome Measure Data

Analysis Population Description

Full Analysis Analysis (FAS) population. At the start of the Maintenance Period, the FAS had 37 subjects in the Low-Dose group and 35 subjects in the High- Dose group. However, at Week 62, there were only 10 subjects in the Low-Dose group and 7 subjects in the High-Dose group with valid Growth scores.

Arm/Group Title	Maintenance Low-Dose	Maintenance High-Dose
Arm/Group Description:	Maintenance Low-Dose group*: 200 mg Certolizumab Pegol once every 4 weeks for subjects ≥ 40 kg or 100 mg Certolizumab Pegol once every 4 weeks for subjects 20 to < 40 kg *prior to this dosing regimen, subjects underwent 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	Maintenance High-Dose group*: 400 mg Certolizumab Pegol once every 4 weeks for subjects ≥ 40 kg or 200 mg Certolizumab Pegol once every 4 weeks for subjects 20 to < 40 kg *prior to this dosing regimen, subjects underwent 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
Overall Number of Participants Analyzed	10	7
Measure Type: Number; Unit of Measure: participants
Increase from Stage I to Stage II	2	0
Increase from Stage I to Stage III	1	1
Increase from Stage II to Stage III	0	1
Increase from Stage III to Stage IV	2	0
Increase from Stage IV to Stage V	0	1
Decrease from Stage IV to Stage III	1	1
Subjects remained in Stage I	0	1
Subjects remained in Stage III	0	2
Subjects remained in Stage IV	1	0
Subjects remained in Stage V	3	0

10. Secondary Outcome

Title	Percentage of Subjects Who Initiated Steroid Tapering
Description	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.
Time Frame	From Week 2 up to Week 8

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) population. There were only 21 subjects in the Low-Dose group and 20 subjects in the High-Dose group who took steroids during the Maintenance Period.

Arm/Group Title	Maintenance Low-Dose	Maintenance High-Dose
Arm/Group Description:	Maintenance Low-Dose group*: 200 mg Certolizumab Pegol once every 4 weeks for subjects ≥ 40 kg or 100 mg Certolizumab Pegol once every 4 weeks for subjects 20 to < 40 kg *prior to this dosing regimen, subjects underwent 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	Maintenance High-Dose group*: 400 mg Certolizumab Pegol once every 4 weeks for subjects ≥ 40 kg or 200 mg Certolizumab Pegol once every 4 weeks for subjects 20 to < 40 kg *prior to this dosing regimen, subjects underwent 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
Overall Number of Participants Analyzed	21	20
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of subjects
	71.4; (52.1 to 90.8)	65.0; (44.1 to 85.9)

11. Secondary Outcome

Title	Percentage of Subjects in Corticosteroid-free Remission at the End of the Study
Description	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.
Time Frame	Last/Withdrawal Visit (up to Week 62)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) population. There were only 21 subjects in the Low-Dose group and 20 subjects in the High-Dose group who took steroids during the Maintenance Period.

Arm/Group Title	Maintenance Low-Dose	Maintenance High-Dose
Arm/Group Description:	Maintenance Low-Dose group*: 200 mg Certolizumab Pegol once every 4 weeks for subjects ≥ 40 kg or 100 mg Certolizumab Pegol once every 4 weeks for subjects 20 to < 40 kg *prior to this dosing regimen, subjects underwent 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	Maintenance High-Dose group*: 400 mg Certolizumab Pegol once every 4 weeks for subjects ≥ 40 kg or 200 mg Certolizumab Pegol once every 4 weeks for subjects 20 to < 40 kg *prior to this dosing regimen, subjects underwent 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
Overall Number of Participants Analyzed	21	20
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of paticipants
	23.8; (5.6 to 42.0)	15.0; (0.0 to 30.6)

Adverse Events

Time Frame	Adverse Events (AEs) were collected over 68 weeks (from Week -6 to Week 62).
Adverse Event Reporting Description	Adverse Events (AEs) refer to the Safety Set (SS) population. All subjects in the Safety Population (n=99) participated in the Induction Period. There were 27 subjects who did not continue into the Maintenance Period.
Arm/Group Title	Induction Period		Maintenance Low-Dose		Maintenance High-Dose		Overall Study
Arm/Group Description	Induction Only is the period between the Week 0 dose and prior to first maintenance dose (Week 8). Induction Only includes all subjects who received a dose during the Induction Period but did not receive any treatment during the Maintenance Period. During the Induction Period (Weeks 0 to 6), subjects were administered Certolizumab Pegol (CZP) subcutaneously every 2 weeks (Q2W) (for a total of 3 administrations of drug) at a dose of either: 400 mg for subjects ≥ 40 kg; 200 mg for subjects 20 to < 40 kg		Maintenance Low-Dose group*: 200 mg Certolizumab Pegol once every 4 weeks for subjects ≥ 40 kg or 100 mg Certolizumab Pegol once every 4 weeks for subjects 20 to < 40 kg *prior to this dosing regimen, subjects underwent 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		Maintenance High-Dose group*: 400 mg Certolizumab Pegol once every 4 weeks for subjects ≥ 40 kg or 200 mg Certolizumab Pegol once every 4 weeks for subjects 20 to < 40 kg *prior to this dosing regimen, subjects underwent 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		Overall Study comprises Induction Period and Maintenance Period (Week -6 to Week 62).
All-Cause Mortality
	Induction Period		Maintenance Low-Dose		Maintenance High-Dose		Overall Study
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--		--/--		--/--
Serious Adverse Events
	Induction Period		Maintenance Low-Dose		Maintenance High-Dose		Overall Study
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/99 (6.06%)		4/37 (10.81%)		4/35 (11.43%)		14/99 (14.14%)
Blood and lymphatic system disorders
Anaemia * 1	1/99 (1.01%)	1	0/37 (0.00%)	0	0/35 (0.00%)	0	1/99 (1.01%)	1
Gastrointestinal disorders
Abdominal Pain * 1	0/99 (0.00%)	0	0/37 (0.00%)	0	1/35 (2.86%)	1	1/99 (1.01%)	1
Anal fistula * 1	0/99 (0.00%)	0	1/37 (2.70%)	1	0/35 (0.00%)	0	1/99 (1.01%)	1
Crohn's disease * 1	1/99 (1.01%)	1	0/37 (0.00%)	0	0/35 (0.00%)	0	1/99 (1.01%)	1
Diarrhoea * 1	0/99 (0.00%)	0	1/37 (2.70%)	1	0/35 (0.00%)	0	1/99 (1.01%)	1
Haematochezia * 1	1/99 (1.01%)	1	0/37 (0.00%)	0	1/35 (2.86%)	1	2/99 (2.02%)	2
Vomiting * 1	1/99 (1.01%)	1	0/37 (0.00%)	0	0/35 (0.00%)	0	1/99 (1.01%)	1
General disorders
Pyrexia * 1	0/99 (0.00%)	0	1/37 (2.70%)	1	0/35 (0.00%)	0	1/99 (1.01%)	1
Infections and infestations
Candidiasis * 1	0/99 (0.00%)	0	1/37 (2.70%)	1	0/35 (0.00%)	0	1/99 (1.01%)	1
Gastroenteritis * 1	0/99 (0.00%)	0	0/37 (0.00%)	0	1/35 (2.86%)	1	1/99 (1.01%)	1
Gastroenteritis viral * 1	2/99 (2.02%)	2	0/37 (0.00%)	0	0/35 (0.00%)	0	2/99 (2.02%)	2
Oral herpes * 1	0/99 (0.00%)	0	1/37 (2.70%)	1	0/35 (0.00%)	0	1/99 (1.01%)	1
Salmonellosis * 1	1/99 (1.01%)	1	0/37 (0.00%)	0	0/35 (0.00%)	0	1/99 (1.01%)	1
Viral infection * 1	0/99 (0.00%)	0	0/37 (0.00%)	0	1/35 (2.86%)	1	1/99 (1.01%)	1
Perineal abscess * 1	0/99 (0.00%)	0	1/37 (2.70%)	1	0/35 (0.00%)	0	1/99 (1.01%)	1
Investigations
Weight decreased * 1	0/99 (0.00%)	0	0/37 (0.00%)	0	1/35 (2.86%)	1	1/99 (1.01%)	1
Metabolism and nutrition disorders
Dehydration * 1	1/99 (1.01%)	1	0/37 (0.00%)	0	0/35 (0.00%)	0	1/99 (1.01%)	1
Psychiatric disorders
Depression * 1	0/99 (0.00%)	0	1/37 (2.70%)	1	0/35 (0.00%)	0	1/99 (1.01%)	1
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 15.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Induction Period		Maintenance Low-Dose		Maintenance High-Dose		Overall Study
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	59/99 (59.60%)		28/37 (75.68%)		27/35 (77.14%)		78/99 (78.79%)
Gastrointestinal disorders
Abdominal pain * 1	4/99 (4.04%)	4	3/37 (8.11%)	4	4/35 (11.43%)	4	10/99 (10.10%)	12
Abdominal pain upper * 1	4/99 (4.04%)	4	5/37 (13.51%)	5	2/35 (5.71%)	3	9/99 (9.09%)	12
Anal inflammation * 1	0/99 (0.00%)	0	0/37 (0.00%)	0	2/35 (5.71%)	2	2/99 (2.02%)	2
Constipation * 1	3/99 (3.03%)	3	3/37 (8.11%)	3	1/35 (2.86%)	1	7/99 (7.07%)	7
Crohn's disease * 1	0/99 (0.00%)	0	5/37 (13.51%)	7	7/35 (20.00%)	8	12/99 (12.12%)	15
Diarrhoea * 1	7/99 (7.07%)	7	3/37 (8.11%)	5	3/35 (8.57%)	7	12/99 (12.12%)	19
Gastrooesophageal reflux disease * 1	2/99 (2.02%)	2	2/37 (5.41%)	2	2/35 (5.71%)	2	5/99 (5.05%)	6
Mouth ulceration * 1	2/99 (2.02%)	2	3/37 (8.11%)	3	3/35 (8.57%)	3	8/99 (8.08%)	8
Nausea * 1	6/99 (6.06%)	8	3/37 (8.11%)	3	2/35 (5.71%)	2	10/99 (10.10%)	13
Stomatitis * 1	2/99 (2.02%)	3	1/37 (2.70%)	1	2/35 (5.71%)	2	5/99 (5.05%)	6
Toothache * 1	1/99 (1.01%)	1	3/37 (8.11%)	3	0/35 (0.00%)	0	3/99 (3.03%)	4
Vomiting * 1	6/99 (6.06%)	7	3/37 (8.11%)	3	6/35 (17.14%)	10	13/99 (13.13%)	20
General disorders
Fatigue * 1	3/99 (3.03%)	3	3/37 (8.11%)	4	0/35 (0.00%)	0	6/99 (6.06%)	7
Injection site pain * 1	22/99 (22.22%)	55	4/37 (10.81%)	17	6/35 (17.14%)	36	22/99 (22.22%)	108
Pyrexia * 1	9/99 (9.09%)	15	6/37 (16.22%)	7	9/35 (25.71%)	9	20/99 (20.20%)	31
Infections and infestations
Ear infection * 1	1/99 (1.01%)	1	2/37 (5.41%)	2	1/35 (2.86%)	1	4/99 (4.04%)	4
Influenza * 1	1/99 (1.01%)	1	3/37 (8.11%)	3	2/35 (5.71%)	3	6/99 (6.06%)	7
Nasopharyngitis * 1	5/99 (5.05%)	5	1/37 (2.70%)	1	2/35 (5.71%)	2	8/99 (8.08%)	8
Pharyngitis * 1	1/99 (1.01%)	1	2/37 (5.41%)	2	0/35 (0.00%)	0	3/99 (3.03%)	3
Sinusitis * 1	2/99 (2.02%)	2	3/37 (8.11%)	3	1/35 (2.86%)	1	5/99 (5.05%)	6
Upper respiratory tract infection * 1	0/99 (0.00%)	0	8/37 (21.62%)	9	2/35 (5.71%)	2	10/99 (10.10%)	11
Urinary tract infection * 1	0/99 (0.00%)	0	0/37 (0.00%)	0	2/35 (5.71%)	2	2/99 (2.02%)	2
Viral infection * 1	2/99 (2.02%)	3	4/37 (10.81%)	4	3/35 (8.57%)	5	9/99 (9.09%)	12
Injury, poisoning and procedural complications
Contusion * 1	0/99 (0.00%)	0	2/37 (5.41%)	2	0/35 (0.00%)	0	2/99 (2.02%)	2
Ligament sprain * 1	0/99 (0.00%)	0	2/37 (5.41%)	2	0/35 (0.00%)	0	2/99 (2.02%)	2
Investigations
C-reactive protein increased * 1	0/99 (0.00%)	0	0/37 (0.00%)	0	2/35 (5.71%)	2	2/99 (2.02%)	2
Weight decreased * 1	2/99 (2.02%)	2	2/37 (5.41%)	2	1/35 (2.86%)	3	4/99 (4.04%)	7
Metabolism and nutrition disorders
Decreased appetite * 1	4/99 (4.04%)	4	3/37 (8.11%)	3	1/35 (2.86%)	1	8/99 (8.08%)	8
Musculoskeletal and connective tissue disorders
Arthralgia * 1	6/99 (6.06%)	7	4/37 (10.81%)	4	2/35 (5.71%)	2	12/99 (12.12%)	13
Myalgia * 1	0/99 (0.00%)	0	2/37 (5.41%)	2	0/35 (0.00%)	0	2/99 (2.02%)	2
Nervous system disorders
Headache * 1	9/99 (9.09%)	12	4/37 (10.81%)	10	3/35 (8.57%)	4	12/99 (12.12%)	26
Respiratory, thoracic and mediastinal disorders
Cough * 1	5/99 (5.05%)	5	3/37 (8.11%)	3	2/35 (5.71%)	5	8/99 (8.08%)	13
Oropharyngeal pain * 1	5/99 (5.05%)	5	2/37 (5.41%)	2	2/35 (5.71%)	2	8/99 (8.08%)	9
Rhinorrhoea * 1	0/99 (0.00%)	0	1/37 (2.70%)	1	2/35 (5.71%)	2	3/99 (3.03%)	3
Skin and subcutaneous tissue disorders
Acne * 1	3/99 (3.03%)	3	1/37 (2.70%)	1	1/35 (2.86%)	1	5/99 (5.05%)	5
Rash * 1	2/99 (2.02%)	2	3/37 (8.11%)	6	0/35 (0.00%)	0	5/99 (5.05%)	8
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 15.0

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: UCB Clinical Trial Call Center
• Organization: UCB
• Phone: +1 877 822 9493

• Responsible Party: UCB Pharma ( UCB Celltech )
• ClinicalTrials.gov Identifier: NCT00899678
• Other Study ID Numbers: C87035; 2014-004381-24 ( EudraCT Number )
• First Submitted: April 29, 2009
• First Posted: May 12, 2009
• Results First Submitted: June 28, 2013
• Results First Posted: November 21, 2013
• Last Update Posted: August 7, 2018