Crohn's Disease
Conditions
Brief summary
A follow-on safety study in subjects with Crohn's Disease who have previously been withdrawn from the double-blind study CDP870-031 \[NCT00152490\] or CDP870-032 \[NCT00152425\] due to an exacerbation of Crohn's Disease.
Interventions
BIOLOGICALCertolizumab Pegol (CDP870)
Liquid for subcutaneous injection, 200 mg/ml. 400 mg at Weeks 0, 2, 4 and thereafter every 4 weeks until Week 360. Up to 84 months of therapy in this study.
Sponsors
UCB Pharma SA
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participation in either of the CDP870-031 \[NCT00152490\] or CDP870-032 \[NCT00152425\] clinical studies in which the subject completed the Week 2 assessment in CDP870-031 \[NCT00152490\] or the Week 6 randomization in CDP870-032 \[NCT00152425\] but whose Crohn's Disease was significantly worse as determined by the investigator and whose Clinical Disease Activity Index (CDAI) score at entry to this study is either (subjects may have received active or placebo treatment): 1. At least 70 points higher then Baseline (Week 0 CDP870-031 \[NCT00152490\]; Week 6 CDP870 032 \[NCT00152425\] responders) OR 2. Higher than Baseline (Week 0 CDP870-031 \[NCT00152490\]; Week 6 CDP870-032 \[NCT00152425\] responders) with an absolute score of at least 350 points * Subjects must be able to understand the information provided to them and give written informed consent
Exclusion criteria
* Any exclusion criterion that would have prevented the subject's participation in the qualifying pivotal study (CDP870-031 \[NCT00152490\] or CDP870-032 \[NCT00152425\]), although the upper limit of 450 in the CDAI score is not applicable. In addition the criterion that excludes previous participation in a clinical trial of Certolizumab Pegol does not apply
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With at Least One Adverse Event (AE) During the Duration of This Study CDP870-034 (up to 84 Months) | Up to 84 months from Study Entry (Week 0) to the Study End (Week 362 ) and the Safety Follow-up (Week 372) | An AE is defined as any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. |
| Percentage of Subjects With at Least One Serious Adverse Event (SAE) During the Duration of This Study CDP870-034 (up to 84 Months) | Up to 84 months from Study Entry (Week 0) to the Study End (Week 362 ) and the Safety Follow-up (Week 372) | An SAE is defined as any untoward medical occurrence that occurs at any dose which results in death, is life threatening requires hospitalization, results in persistent/significant disability/incapacity, is an infection that requires parenteral antibiotics, is a congenital anomaly/birth defect, or is an important medical event. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects in Harvey Bradshaw Index (HBI) Response (HBI Change ≥ 3) at Study Completion Visit or (Early) Withdrawal Visit From Week 0 of CDP870-034 | From Week 0 of study CDP870-034 to Study Completion Visit (Week 362) or (Early) Withdrawal Visit (up to 84 months) | Response is defined as decrease in total Harvey Bradshaw Index (HBI) score of 3 or more points. HBI score consists of clinical parameters of general well-being (0 to 4), abdominal pain (0 to 3), number of liquid stools per day, abdominal mass (0 to 3), and complications (8 items, score 1 per item) lower scores indicating better well being. The first three parameters are scored for the previous day. |
| Plasma Concentration of Certolizumab Pegol at Study Completion Visit or (Early) Withdrawal Visit | Study Completion Visit (Week 362) / (Early) Withdrawal Visit | Plasma Samples for determination of Certolizumab Pegol were taken prior to Certolizumab Pegol administration. |
| Percentage of Subjects Achieving Harvey Bradshaw Index (HBI) Remission (HBI ≤ 4) at Study Completion Visit or (Early) Withdrawal Visit | Study Completion Visit (Week 362) / (Early) Withdrawal Visit | HBI remission is defined as total HBI score of 4 points or less. HBI score consists of clinical parameters of general well-being (0 to 4), abdominal pain (0 to 3), number of liquid stools per day, abdominal mass (0 to 3), and complications (8 items, score 1 per item) lower scores indicating better well being. The first three parameters are scored for the previous day. |
| C-Reactive Protein (CRP) Level at Study Completion Visit or (Early) Withdrawal Visit | Study Completion Visit (Week 362) / (Early) Withdrawal Visit | — |
| Fecal Calprotectin Level at Week 256 or (Early) Withdrawal Visit, if it is Earlier Than Week 256 | Week 256 / (Early) Withdrawal Visit, if it is earlier than Week 256 | — |
| Percentage of Subjects With Positive Anti-CZP Anti-body Status at Any Time From Week 0 of the Feeder Studies CDP870-031 or CDP870-032 to the Study Completion Visit in CDP870-034 | From Week 0 of study CDP870-031 [NCT00152490] or CDP870-032 [NCT00152425] up to Study Completion Visit (Week 362) of CDP870-034 (up to 90 months) | Subjects are counted as antibody positive to Certolizumab Pegol if they have at least one positive result from Week 0 in one of the previous studies CDP870-031 \[NCT00152490\] or CDP870-032 \[NCT00152425\] to the last Visit in this study. A positive result is defined as Anti-CZP antibody levels \> 2.4 units/mL. |
| Percentage of Subjects in Harvey Bradshaw Index (HBI) Response (HBI Change ≥ 3) at Study Completion Visit or (Early) Withdrawal Visit From Week 0 of Feeder Study CDP870-031 or CDP870-032 | From Baseline of study CDP870-031 [NCT00152490] or CDP870-032 [NCT00152425] to Study Completion Visit (Week 362) or (Early) Withdrawal Visit of this study (up to 90 months) | Response is defined as decrease in total Harvey Bradshaw Index (HBI) score of 3 or more points. HBI score consists of clinical parameters of general well-being (0 to 4), abdominal pain (0 to 3), number of liquid stools per day, abdominal mass (0 to 3), and complications (8 items, score 1 per item) lower scores indicating better well being. The first three parameters are scored for the previous day. |
Countries
Australia, Austria, Belarus, Belgium, Bulgaria, Canada, Czechia, Denmark, Estonia, Germany, Hungary, Israel, Italy, New Zealand, Norway, Poland, Russia, Serbia, Singapore, Slovenia, South Africa, Spain, Ukraine, United States
Participant flow
Recruitment details
This multicenter study started to enroll subjects in February 2004 in order to end up with 141 centers in 24 countries with enrolled subjects. Participant Flow refers to the Safety Population, including all enrolled subjects who received at least one injection of study treatment in feeder study C87031 \[NCT00152490\] or C87032 \[NCT00152425\].
Pre-assignment details
Subjects who withdrew from feeder studies for worsening of Crohn's Disease entered study C87034. Subjects in study C87031 were eligible for entry into C87034 at any time after completing the Week 2 assessment, subjects in study C87032 at any time after completing the Week 6 randomisation.
Participants by arm
| Arm | Count |
|---|---|
| Certolizumab Pegol 3-dose induction regimen of Certolizumab Pegol 400 mg at Weeks 0, 2, 4. Subsequently continue on 4-weekly treatment with Certolizumab Pegol 400 mg until Week 360.
Certolizumab Pegol (CDP870) : Liquid for subcutaneous injection, 200 mg/ml. 400 mg at Weeks 0, 2, 4 and thereafter every 4 weeks until Week 360.
Up to 84 months of therapy in this study. | 310 |
| Total | 310 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 53 |
| Overall Study | Adverse Event and Other Reason | 105 |
| Overall Study | Lack of Efficacy | 42 |
| Overall Study | Lack of Efficacy and Other | 1 |
| Overall Study | Lost to Follow-up | 4 |
| Overall Study | Lost to Follow-up and Other | 1 |
| Overall Study | Other Reason | 11 |
| Overall Study | Physician Decision | 10 |
| Overall Study | Physician Decision and Other | 3 |
| Overall Study | Protocol Violation | 3 |
| Overall Study | Withdrawal by Subject | 41 |
| Overall Study | Withdrawal by Subject and Other | 12 |
Baseline characteristics
| Characteristic | Certolizumab Pegol |
|---|---|
| Age, Categorical <=18 years | 2 Participants |
| Age, Categorical >=65 years | 9 Participants |
| Age, Categorical Between 18 and 65 years | 299 Participants |
| Age, Continuous | 36.5 years STANDARD_DEVIATION 11.67 |
| Region of Enrollment Australia | 43 participants |
| Region of Enrollment Austria | 7 participants |
| Region of Enrollment Belarus | 2 participants |
| Region of Enrollment Belgium | 8 participants |
| Region of Enrollment Bulgaria | 1 participants |
| Region of Enrollment Canada | 9 participants |
| Region of Enrollment Czech Republic | 10 participants |
| Region of Enrollment Denmark | 11 participants |
| Region of Enrollment Estonia | 5 participants |
| Region of Enrollment Germany | 29 participants |
| Region of Enrollment Hungary | 13 participants |
| Region of Enrollment Israel | 5 participants |
| Region of Enrollment Italy | 5 participants |
| Region of Enrollment New Zealand | 10 participants |
| Region of Enrollment Norway | 7 participants |
| Region of Enrollment Poland | 10 participants |
| Region of Enrollment Russian Federation | 17 participants |
| Region of Enrollment Serbia | 4 participants |
| Region of Enrollment Singapore | 2 participants |
| Region of Enrollment Slovenia | 3 participants |
| Region of Enrollment South Africa | 31 participants |
| Region of Enrollment Spain | 1 participants |
| Region of Enrollment Ukraine | 3 participants |
| Region of Enrollment United States | 74 participants |
| Sex: Female, Male Female | 179 Participants |
| Sex: Female, Male Male | 131 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 248 / 310 |
| serious Total, serious adverse events | 138 / 310 |
Outcome results
Primary
Percentage of Subjects With at Least One Adverse Event (AE) During the Duration of This Study CDP870-034 (up to 84 Months)
An AE is defined as any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
Time frame: Up to 84 months from Study Entry (Week 0) to the Study End (Week 362 ) and the Safety Follow-up (Week 372)
Population: All 310 subjects in the Safety Population are included in the analysis of this outcome measure. Safety Population includes all enrolled subjects who received at least one injection of study treatment in feeder study C87031 \[NCT00152490\] or C87032 \[NCT00152425\].
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol | Percentage of Subjects With at Least One Adverse Event (AE) During the Duration of This Study CDP870-034 (up to 84 Months) | 94.2 percentage of subjects |
Primary
Percentage of Subjects With at Least One Serious Adverse Event (SAE) During the Duration of This Study CDP870-034 (up to 84 Months)
An SAE is defined as any untoward medical occurrence that occurs at any dose which results in death, is life threatening requires hospitalization, results in persistent/significant disability/incapacity, is an infection that requires parenteral antibiotics, is a congenital anomaly/birth defect, or is an important medical event.
Time frame: Up to 84 months from Study Entry (Week 0) to the Study End (Week 362 ) and the Safety Follow-up (Week 372)
Population: All 310 subjects in the Safety Population are included in the analysis of this outcome measure. Safety Population includes all enrolled subjects who received at least one injection of study treatment in feeder study C87031 \[NCT00152490\] or C87032 \[NCT00152425\].
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol | Percentage of Subjects With at Least One Serious Adverse Event (SAE) During the Duration of This Study CDP870-034 (up to 84 Months) | 44.5 percentage of subjects |
Secondary
C-Reactive Protein (CRP) Level at Study Completion Visit or (Early) Withdrawal Visit
Time frame: Study Completion Visit (Week 362) / (Early) Withdrawal Visit
Population: All 309 subjects in the Intention-To-Treat (ITT) Population are included in the analysis of this outcome measure. ITT Population includes all subjects of the Safety Population who provide at least one efficacy measurement after Week 0 of this study.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Certolizumab Pegol | C-Reactive Protein (CRP) Level at Study Completion Visit or (Early) Withdrawal Visit | 10.78 mg/L |
Secondary
Fecal Calprotectin Level at Week 256 or (Early) Withdrawal Visit, if it is Earlier Than Week 256
Time frame: Week 256 / (Early) Withdrawal Visit, if it is earlier than Week 256
Population: Of the 309 subjects in the Intention-To-Treat (ITT) Population, 280 subjects are included in the analysis of this outcome measure. ITT Population includes all subjects of the Safety Population who provide at least one efficacy measurement after Week 0 of this study.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Certolizumab Pegol | Fecal Calprotectin Level at Week 256 or (Early) Withdrawal Visit, if it is Earlier Than Week 256 | 460.784 µg/g stool |
Secondary
Percentage of Subjects Achieving Harvey Bradshaw Index (HBI) Remission (HBI ≤ 4) at Study Completion Visit or (Early) Withdrawal Visit
HBI remission is defined as total HBI score of 4 points or less. HBI score consists of clinical parameters of general well-being (0 to 4), abdominal pain (0 to 3), number of liquid stools per day, abdominal mass (0 to 3), and complications (8 items, score 1 per item) lower scores indicating better well being. The first three parameters are scored for the previous day.
Time frame: Study Completion Visit (Week 362) / (Early) Withdrawal Visit
Population: All 309 subjects in the Intention-To-Treat (ITT) Population are included in the analysis of this outcome measure. ITT Population includes all subjects of the Safety Population who provide at least one efficacy measurement after Week 0 of this study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol | Percentage of Subjects Achieving Harvey Bradshaw Index (HBI) Remission (HBI ≤ 4) at Study Completion Visit or (Early) Withdrawal Visit | 34.6 percentage of subjects |
Secondary
Percentage of Subjects in Harvey Bradshaw Index (HBI) Response (HBI Change ≥ 3) at Study Completion Visit or (Early) Withdrawal Visit From Week 0 of CDP870-034
Response is defined as decrease in total Harvey Bradshaw Index (HBI) score of 3 or more points. HBI score consists of clinical parameters of general well-being (0 to 4), abdominal pain (0 to 3), number of liquid stools per day, abdominal mass (0 to 3), and complications (8 items, score 1 per item) lower scores indicating better well being. The first three parameters are scored for the previous day.
Time frame: From Week 0 of study CDP870-034 to Study Completion Visit (Week 362) or (Early) Withdrawal Visit (up to 84 months)
Population: Of the 309 subjects in the Intention-To-Treat (ITT) Population, 299 subjects are included in the analysis of this outcome measure. ITT Population includes all subjects of the Safety Population who provide at least one efficacy measurement after Week 0 of this study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol | Percentage of Subjects in Harvey Bradshaw Index (HBI) Response (HBI Change ≥ 3) at Study Completion Visit or (Early) Withdrawal Visit From Week 0 of CDP870-034 | 65.6 percentage of subjects |
Secondary
Percentage of Subjects in Harvey Bradshaw Index (HBI) Response (HBI Change ≥ 3) at Study Completion Visit or (Early) Withdrawal Visit From Week 0 of Feeder Study CDP870-031 or CDP870-032
Response is defined as decrease in total Harvey Bradshaw Index (HBI) score of 3 or more points. HBI score consists of clinical parameters of general well-being (0 to 4), abdominal pain (0 to 3), number of liquid stools per day, abdominal mass (0 to 3), and complications (8 items, score 1 per item) lower scores indicating better well being. The first three parameters are scored for the previous day.
Time frame: From Baseline of study CDP870-031 [NCT00152490] or CDP870-032 [NCT00152425] to Study Completion Visit (Week 362) or (Early) Withdrawal Visit of this study (up to 90 months)
Population: Of the 309 subjects in the Intention-To-Treat (ITT) Population, 307 subjects are included in the analysis of this outcome measure. ITT Population includes all subjects of the Safety Population who provide at least one efficacy measurement after Week 0 of this study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol | Percentage of Subjects in Harvey Bradshaw Index (HBI) Response (HBI Change ≥ 3) at Study Completion Visit or (Early) Withdrawal Visit From Week 0 of Feeder Study CDP870-031 or CDP870-032 | 52.8 percentage of subjects |
Secondary
Percentage of Subjects With Positive Anti-CZP Anti-body Status at Any Time From Week 0 of the Feeder Studies CDP870-031 or CDP870-032 to the Study Completion Visit in CDP870-034
Subjects are counted as antibody positive to Certolizumab Pegol if they have at least one positive result from Week 0 in one of the previous studies CDP870-031 \[NCT00152490\] or CDP870-032 \[NCT00152425\] to the last Visit in this study. A positive result is defined as Anti-CZP antibody levels \> 2.4 units/mL.
Time frame: From Week 0 of study CDP870-031 [NCT00152490] or CDP870-032 [NCT00152425] up to Study Completion Visit (Week 362) of CDP870-034 (up to 90 months)
Population: Of the 310 subjects in the Safety Population, 309 subjects are included in the analysis of this outcome measure. Safety Population includes all enrolled subjects who received at least one injection of study treatment in feeder study C87031 \[NCT00152490\] or C87032 \[NCT00152425\].
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol | Percentage of Subjects With Positive Anti-CZP Anti-body Status at Any Time From Week 0 of the Feeder Studies CDP870-031 or CDP870-032 to the Study Completion Visit in CDP870-034 | 23.6 percentage of subjects |
Secondary
Plasma Concentration of Certolizumab Pegol at Study Completion Visit or (Early) Withdrawal Visit
Plasma Samples for determination of Certolizumab Pegol were taken prior to Certolizumab Pegol administration.
Time frame: Study Completion Visit (Week 362) / (Early) Withdrawal Visit
Population: Of the 310 subjects in the Safety Population, 307 subjects are included in the analysis of this outcome measure. Safety Population includes all enrolled subjects who received at least one injection of study treatment in feeder study C87031 \[NCT00152490\] or C87032 \[NCT00152425\].
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Certolizumab Pegol | Plasma Concentration of Certolizumab Pegol at Study Completion Visit or (Early) Withdrawal Visit | 5.870 µg/mL |