Clinical Study of CDP870/Certolizumab Pegol in Patients With Active Crohn's Disease

A Phase II, Multi-center, Double-blind, Placebo-controlled, Parallel-group, Dose-response Study to Assess the Safety and Efficacy of CDP870/Certolizumab Pegol, Dosed Subcutaneously in Patients With Active Crohn's Disease

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00291668

Enrollment

Registered

2006-02-14

Start date

2006-03-02

Completion date

2007-11-08

Last updated

2020-08-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Crohn's Disease

Keywords

Crohn's Disease, CDP870, Certolizumab pegol

Brief summary

This is a multi-centre, randomized, double-blind, dose response clinical study of CDP870 in patients with Crohn's disease.

Interventions

BIOLOGICALCertolizumab Pegol

* Active Substance: Certolizumab Pegol * Pharmaceutical Form: Solution for injection in pre-filled syringe * Concentration: 200 mg/mL * Route of Administration: Subcutaneous use

OTHERPlacebo

* Active Substance: isotonic sodium chloride solution * Pharmaceutical Form: Solution for injection * Concentration: 1 mL * Route of Administration: Subcutaneous use

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

16 Years to 65 Years

Healthy volunteers

Inclusion criteria

Inclusion Criteria: * Patients who are diagnosed with Crohn's disease (according to the Crohn's disease diagnostic criteria developed by the research group on intractable inflammatory bowel disorders \[Shimoyama group, January 25, 2002\]) at least 24 weeks before the starting date of the observation period * Patients with Crohn's Disease Activity Index (CDAI) score ranging from 220 to 450 inclusive during the observation period * C-reactive protein (CRP) of 1 mg/dL or higher in the laboratory test performed at the start of the observation period

Exclusion criteria

* Stoma patient * Patients with a history of severe hypersensitivity or anphylactic reaction to anti-TNF alpha antibody * Patients who participated in a clinical study with CDP870 * Pregnant or lactating patients, patients of childbearing potential, or patients who will attempt pregnancy during the study period * Patients who are judged inappropriate for enrollment by the principal investigator or subinvestigators

Design outcomes

Primary

Measure	Time frame	Description
Crohn's Disease Activity Index (CDAI) Response (Clinical Response or Remission) at Week 6	Baseline, Week 6	CDAI Response is presented as the percentage of subjects with clinical response at Week 6 or remission at Week 6. Clinical response is defined as at least a 100-point decrease from the Week 0 CDAI score, where change = (CDAI score at Week 6) - (CDAI score at Week 0). Remission is defined as a CDAI of \<= 150 at Week 6.

Secondary

Measure	Time frame	Description
Concentration of C-reactive Protein (CRP) Value at Week 6	Week 6	CRP data for subjects receiving rescue medication were excluded.
C-reactive Protein (CRP) Ratio to Baseline at Week 2	Baseline, Week 2	CRP data for subjects receiving rescue medication were excluded.
Crohn's Disease Activity Index (CDAI) Score at Week 2	Week 2	The Crohn's Disease Activity Index (CDAI) is used to quantify the symptoms of subjects with Crohn's Disease. The CDAI score can range from 0-600 (600 indicating the worst disease). It is the sum of 8 subscores, only the summary score is used here. A CDAI score of 150 or less is considered as remission and a score above 450 indicates extremely severe disease. A decrease in CDAI over time indicates improvement in disease activity.
C-reactive Protein (CRP) Ratio to Baseline at Week 4	Baseline, Week 4	CRP data for subjects receiving rescue medication were excluded.
Crohn's Disease Activity Index (CDAI) Score at Week 6	Week 6	The Crohn's Disease Activity Index (CDAI) is used to quantify the symptoms of subjects with Crohn's Disease. The CDAI score can range from 0-600 (600 indicating the worst disease). It is the sum of 8 subscores, only the summary score is used here. A CDAI score of 150 or less is considered as remission and a score above 450 indicates extremely severe disease. A decrease in CDAI over time indicates improvement in disease activity.
Percentage of Subjects Who Achieve CDAI Response at Week 2	Baseline, Week 2	CDAI Response at Week 2 is defined as clinical response at Week 2 or remission at Week 2. Clinical response is defined as at least a 100-point decrease from the Week 0 CDAI score, where change = (CDAI score at Week 2) - (CDAI score at Week 0). Remission is defined as a CDAI score of \<= 150 points.
Percentage of Subjects Who Achieve CDAI Response at Week 4	Baseline, Week 4	CDAI Response at Week 4 is defined as clinical response at Week 4 or remission at Week 4. Clinical response is defined as at least a 100-point decrease from the Week 0 CDAI score, where change = (CDAI score at Week 4) - (CDAI score at Week 0). Remission is defined as a CDAI score of \<= 150 points.
Percentage of Subjects Who Achieve a Reduction in CDAI Scores of at Least 70 Points at Week 2	Baseline, Week 2	The Crohn's Disease Activity Index (CDAI) is used to quantify the symptoms of subjects with Crohn's Disease. A score of 150 or below indicates disease remission and a score above 450 indicates extremely severe disease. A decrease in CDAI over time indicates improvement in disease activity.
Percentage of Subjects Who Achieve a Reduction in CDAI Scores of at Least 70 Points at Week 4	Baseline, Week 4	The Crohn's Disease Activity Index (CDAI) is used to quantify the symptoms of subjects with Crohn's Disease. A score of 150 or below indicates disease remission and a score above 450 indicates extremely severe disease. A decrease in CDAI over time indicates improvement in disease activity.
Percentage of Subjects Who Achieve a Reduction in CDAI Scores of at Least 70 Points at Week 6	Baseline, Week 6	The Crohn's Disease Activity Index (CDAI) is used to quantify the symptoms of subjects with Crohn's Disease. A score of 150 or below indicates disease remission and a score above 450 indicates extremely severe disease. A decrease in CDAI over time indicates improvement in disease activity.
Percentage of Subjects Who Achieve Remission (CDAI <= 150) at Week 2	Week 2	Remission at Week 2 is defined as a CDAI score \<= 150 points at Week 2.
C-reactive Protein (CRP) Ratio to Baseline at Week 6	Baseline, Week 6	CRP data for subjects receiving rescue medication were excluded.
Crohn's Disease Activity Index (CDAI) Score at Week 4	Week 4	The Crohn's Disease Activity Index (CDAI) is used to quantify the symptoms of subjects with Crohn's Disease. The CDAI score can range from 0-600 (600 indicating the worst disease). It is the sum of 8 subscores, only the summary score is used here. A CDAI score of 150 or less is considered as remission and a score above 450 indicates extremely severe disease. A decrease in CDAI over time indicates improvement in disease activity.
Percentage of Subjects Who Achieve Remission (CDAI <= 150) at Week 6	Week 6	Remission at Week 6 is defined as a CDAI score \<= 150 points at Week 6.
Percentage of Subjects Who Achieve Clinical Response (Reduction in CDAI Scores of at Least 100 Points) at Week 2	Baseline, Week 2	Clinical response is defined as at least a 100-point decrease from the Week 0 CDAI score, where change = (CDAI score at Week 2) - (CDAI score at Week 0).
Percentage of Subjects Who Achieve Clinical Response (Reduction in CDAI Scores of at Least 100 Points) at Week 4	Baseline, Week 4	Clinical response is defined as at least a 100-point decrease from the Week 0 CDAI score, where change = (CDAI score at Week 4) - (CDAI score at Week 0).
Percentage of Subjects Who Achieve Clinical Response (Reduction in CDAI Scores of at Least 100 Points) at Week 6	Baseline, Week 6	Clinical response is defined as at least a 100-point decrease from the Week 0 CDAI score, where change = (CDAI score at Week 6) - (CDAI score at Week 0).
Inflammatory Bowel Disease Questionnaire (IBDQ) Global Score at Week 2	Week 2	The IBDQ global score is calculated as the sum of the responses (each ranging from 1 to 7) to all 32 questions on the IBDQ and can therefore range from 32 to 224. A higher score indicates a better quality of life.
Inflammatory Bowel Disease Questionnaire (IBDQ) Global Score at Week 4	Week 4	The IBDQ global score is calculated as the sum of the responses (each ranging from 1 to 7) to all 32 questions on the IBDQ and can therefore range from 32 to 224. A higher score indicates a better quality of life.
Inflammatory Bowel Disease Questionnaire (IBDQ) Global Score at Week 6	Week 6	The IBDQ global score is calculated as the sum of the responses (each ranging from 1 to 7) to all 32 questions on the IBDQ and can therefore range from 32 to 224. A higher score indicates a better quality of life.
Inflammatory Bowel Disease Questionnaire (IBDQ) Domain Scores at Week 2	Week 2	The total IBDQ score consists of 32 questions, each ranging from 1 to 7, with higher scores indicating a better quality of life. There are 4 IBDQ Domain Scores: * Bowel Symptoms Domain Score, ranging from 10 to 70 (10 questions ranging from 1 to 7) * Systemic Symptoms Domain Score, ranging from 5 to 35 (5 questions ranging from 1 to 7 ) * Emotional Function Domain Score, ranging from 12 to 84 (12 questions ranging from 1 to 7) * Social Function Domain Score, ranging from 5 to 35 (5 questions ranging from 1 to 7 )
Inflammatory Bowel Disease Questionnaire (IBDQ) Domain Scores at Week 4	Week 4	The total IBDQ score consists of 32 questions, each ranging from 1 to 7, with higher scores indicating a better quality of life. There are 4 IBDQ Domain Scores: * Bowel Symptoms Domain Score, ranging from 10 to 70 (10 questions ranging from 1 to 7) * Systemic Symptoms Domain Score, ranging from 5 to 35 (5 questions ranging from 1 to 7 ) * Emotional Function Domain Score, ranging from 12 to 84 (12 questions ranging from 1 to 7) * Social Function Domain Score, ranging from 5 to 35 (5 questions ranging from 1 to 7 )
Inflammatory Bowel Disease Questionnaire (IBDQ) Domain Scores at Week 6	Week 6	The total IBDQ score consists of 32 questions, each ranging from 1 to 7, with higher scores indicating a better quality of life. There are 4 IBDQ Domain Scores: * Bowel Symptoms Domain Score, ranging from 10 to 70 (10 questions ranging from 1 to 7) * Systemic Symptoms Domain Score, ranging from 5 to 35 (5 questions ranging from 1 to 7 ) * Emotional Function Domain Score, ranging from 12 to 84 (12 questions ranging from 1 to 7) * Social Function Domain Score, ranging from 5 to 35 (5 questions ranging from 1 to 7 )
Concentration of C-reactive Protein (CRP) Value at Week 2	Week 2	CRP data for subjects receiving rescue medication were excluded.
Concentration of C-reactive Protein (CRP) Value at Week 4	Week 4	CRP data for subjects receiving rescue medication were excluded.
Percentage of Subjects Who Achieve Remission (CDAI <= 150) at Week 4	Week 4	Remission at Week 4 is defined as a CDAI score \<= 150 points at Week 4.

Countries

Japan

Participant flow

Recruitment details

This study started to enroll subjects in March 2006 and conluded in November 2007.

Pre-assignment details

Participant Flow refers to the Safety Set, including all randomized subjects who received at least one dose of study medication (Placebo or Certolizumab Pegol).

Participants by arm

Arm	Count
Placebo Subjects received two subcutaneous (sc) injections of Placebo on Weeks 0 (first dose), 2 and 4.	32
Certolizumab Pegol 200 mg Subjects received one subcutaneous (sc) injection of 200 mg CZP and one injection of Placebo to maintain the study blind on Weeks 0 (first dose), 2 and 4.	30
Certolizumab Pegol 400 mg Subjects received two subcutaneous (sc) injections of 200 mg CZP on Weeks 0 (first dose), 2 and 4.	32
Total Title	94
Total	188

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	AE, non-serious non-fatal	1	0	0
Overall Study	Lack of Efficacy	1	0	0
Overall Study	SAE, non-fatal	1	1	1
Overall Study	SAE, non-fatal+AE, non-serious non-fatal	1	0	0

Baseline characteristics

Characteristic	Placebo	Certolizumab Pegol 200 mg	Certolizumab Pegol 400 mg	Total Title
Age, Categorical <=18 years	2 Participants	2 Participants	2 Participants	6 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	30 Participants	28 Participants	30 Participants	88 Participants
Age, Continuous	30.6 years STANDARD_DEVIATION 8.16	32.7 years STANDARD_DEVIATION 9.34	31.4 years STANDARD_DEVIATION 8.27	31.5 years STANDARD_DEVIATION 8.54
Sex: Female, Male Female	6 Participants	8 Participants	7 Participants	21 Participants
Sex: Female, Male Male	26 Participants	22 Participants	25 Participants	73 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 32	0 / 30	0 / 32
other Total, other adverse events	16 / 32	11 / 30	14 / 32
serious Total, serious adverse events	3 / 32	1 / 30	3 / 32

Outcome results

Primary

Crohn's Disease Activity Index (CDAI) Response (Clinical Response or Remission) at Week 6

CDAI Response is presented as the percentage of subjects with clinical response at Week 6 or remission at Week 6. Clinical response is defined as at least a 100-point decrease from the Week 0 CDAI score, where change = (CDAI score at Week 6) - (CDAI score at Week 0). Remission is defined as a CDAI of \<= 150 at Week 6.

Time frame: Baseline, Week 6

Population: Full Analysis Set defined as subjects randomized and allocated to study medication, excluding the following subjects determined by data review prior to unblinding:~Subjects~* with Good Clinical Practice (GCP) violations~* who were not diagnosed (definitely) with CD~* who received no dose of study medication~* with no data after randomization

Arm	Measure	Value (NUMBER)
Full Analysis Set (Placebo Treated Subjects)	Crohn's Disease Activity Index (CDAI) Response (Clinical Response or Remission) at Week 6	25.0 percentage of subjects
Full Analysis Set (CZP 200 mg Treated Subjects)	Crohn's Disease Activity Index (CDAI) Response (Clinical Response or Remission) at Week 6	43.3 percentage of subjects
Full Analysis Set (CZP 400 mg Treated Subjects)	Crohn's Disease Activity Index (CDAI) Response (Clinical Response or Remission) at Week 6	48.4 percentage of subjects

Secondary