Crohn Disease
Conditions
Keywords
CDP 870, Certolizumab Pegol, CIMZIA, Crohn's Disease, Crohn Disease, CD Induction, Induction, Clinical response, Clinical remission
Brief summary
The primary objective of the study is to assess the safety of long term therapy with Certolizumab Pegol in those subjects participating in study C87085 \[NCT00552058\].
Detailed description
This study consisted of: * Induction Period (dosing at Weeks 0, 2, and 4) * Maintenance Dosing (dosing every 4 weeks up to Week 260) * End of Treatment Visit that occurred at Week 262/Withdrawal Visit and a Safety Follow-up Visit (SFU; 12 weeks after final dose)
Interventions
BIOLOGICALCimzia
* Active substance: Certolizumab Pegol * Pharmaceutical form:first reconstituted, lyophilized powder formulation of CZP and after implementation of Amendment 2 (after 401 subjects were enrolled) prefilled syringe * Concentration: 200 mg/ml * Route of Administration: Subcutaneous use
Sponsors
PPD Development, LP
UCB BIOSCIENCES GmbH
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Subject participated in study C87085 \[NCT00552058\] in which the subject completed the study at Week 6 * Subject is capable of providing informed consent, which must be obtained prior to any study related procedures * Have a chest X-ray taken at Visit 1 that is read by a qualified radiologist or pulmonary physician, with no evidence of current active Tuberculosis (TB) or old inactive TB * Subject has taken a TB survey and is committed to comply with TB prophylaxis if applicable
Exclusion criteria
* Subject is experiencing an ongoing serious adverse event assessed as being related to study medication or is experiencing a serious adverse event that is still not assessable * Subject has an intercurrent illness that requires termination of treatment, such as a serious infection (e.g. TB, pneumonia, sepsis, pyelonephritis, fistula abscess) * Subject is non-compliant with TB prophylactic treatment (if applicable) * Subject has had a chest X-ray at Visit 1 that shows an abnormality suggestive of a malignancy or active infection, including TB * Female who is pregnant or breast feeding * Female of child bearing age or post puberty males not practicing effective birth control * Subject is expecting to receive any live virus or bacterial vaccination within 3 months of first Study Medication administration, during the trial or 3 months after last dose of study drug
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With at Least One Adverse Event (AE) During the Duration of the Study C87088 (up to 272 Weeks) | From study start to the end of the Safety Follow-up Period (up to 272 weeks) | 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 the Study C87088 (up to 272 Weeks) | From study start to the end of the Safety Follow-up Period (up to 272 weeks) | 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 Achieving Harvey Bradshaw Index (HBI) Remission (HBI ≤ 4) at Study Completion Visit (Week 262) | Week 262 | 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. |
| Percentage of Subjects Achieving Inflamatory Bowel Disease Questionnaire (IBDQ) Remission (IBDQ ≥ 170) at Study Completion Visit (Week 262) | Week 262 | IBDQ remission is defined as having a total IBDQ score of 170 points or greater. IBDQ score consists of 32 questions eaching having a score of 1 to 7. Overall scores range from 32 to 224. |
| Plasma Concentration of Certolizumab Pegol After 1 Year (Week 52) | Week 52 | Plasma samples for determination of Certolizumab Pegol were taken prior to Certolizumab Pegol administration. |
| Percentage of Subjects With Positive Anti-CZP Anti-body Status at Any Time From Week 0 of the Feeder Study C87085 to the Study Completion Visit in C87088 | From Week 0 of study C87085 [NCT00552058] to Study Completion Visit (Week 262) of C87088 (up to 268 weeks) | Subjects are counted as antibody positive to Certolizumab Pegol if they have at least one positive result from Week 0 in the previous study C87085 \[NCT00552058\] to the Last Visit in this study. A positive result is defined as Anti-CZP antibody levels \> 2.4 units/mL. |
Countries
Australia, Austria, Belgium, Brazil, Canada, Czechia, Estonia, Germany, Hungary, Israel, Italy, Latvia, New Zealand, Poland, Romania, Russia, Ukraine, United States
Participant flow
Recruitment details
The study started to enroll patients in May 2008 and concluded in Dec 2014. Participant Flow refers to the Safety Population including all enrolled subjects who received at least 1 open-label injection of study medication.
Pre-assignment details
406 subjects were screened: 3 subjects were considered as screen failures and were not enrolled. 403 subjects entered the study from C87085. 1 subject was enrolled in this study, but did not receive any open-label study medication and was withdrawn from the study; this subject was, therefore, not included in any of the analyses.
Participants by arm
| Arm | Count |
|---|---|
| Certolizumab Pegol Certolizumab Pegol 200 mg/vial; 400 mg subcutaneously at Week 0, 2 and 4, thereafter 400 mg subcutaneously at every 4 weeks. | 402 |
| Total | 402 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | AE, non-serious non-fatal | 38 |
| Overall Study | Lack of Efficacy | 55 |
| Overall Study | Loss of efficacy | 75 |
| Overall Study | Lost to Follow-up | 8 |
| Overall Study | Other Reason | 22 |
| Overall Study | SAE, fatal + AE, non-serious non-fatal | 1 |
| Overall Study | SAE, non-fatal | 6 |
| Overall Study | SAE,non-fatal+AE,non-serious non-fatal | 62 |
| Overall Study | Withdrawal by Subject | 48 |
Baseline characteristics
| Characteristic | Certolizumab Pegol |
|---|---|
| Age, Continuous | 37.3 years STANDARD_DEVIATION 12.68 |
| Age, Customized 18 - < 65 years | 393 Participants |
| Age, Customized 65 - < 85 years | 9 Participants |
| Age, Customized >= 85 years | 0 Participants |
| Sex: Female, Male Female | 221 Participants |
| Sex: Female, Male Male | 181 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 351 / 402 |
| serious Total, serious adverse events | 149 / 402 |
Outcome results
Primary
Percentage of Subjects With at Least One Adverse Event (AE) During the Duration of the Study C87088 (up to 272 Weeks)
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: From study start to the end of the Safety Follow-up Period (up to 272 weeks)
Population: Safety Population including all enrolled subjects who received at least 1 open-label injection of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol | Percentage of Subjects With at Least One Adverse Event (AE) During the Duration of the Study C87088 (up to 272 Weeks) | 89.6 percentage of subjects |
Primary
Percentage of Subjects With at Least One Serious Adverse Event (SAE) During the Duration of the Study C87088 (up to 272 Weeks)
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: From study start to the end of the Safety Follow-up Period (up to 272 weeks)
Population: Safety Population including all enrolled subjects who received at least 1 open-label injection of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol | Percentage of Subjects With at Least One Serious Adverse Event (SAE) During the Duration of the Study C87088 (up to 272 Weeks) | 37.1 percentage of subjects |
Secondary
Percentage of Subjects Achieving Harvey Bradshaw Index (HBI) Remission (HBI ≤ 4) at Study Completion Visit (Week 262)
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: Week 262
Population: Intention-to-Treat (ITT) population including all enrolled subjects irrespective of any protocol deviations who received at least 1 open-label injection of study treatment and who had at least 1 efficacy measurement after the first open-label injection.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol | Percentage of Subjects Achieving Harvey Bradshaw Index (HBI) Remission (HBI ≤ 4) at Study Completion Visit (Week 262) | 11.6 percentage of subjects |
Secondary
Percentage of Subjects Achieving Inflamatory Bowel Disease Questionnaire (IBDQ) Remission (IBDQ ≥ 170) at Study Completion Visit (Week 262)
IBDQ remission is defined as having a total IBDQ score of 170 points or greater. IBDQ score consists of 32 questions eaching having a score of 1 to 7. Overall scores range from 32 to 224.
Time frame: Week 262
Population: Intention-to-Treat (ITT) population including all enrolled subjects irrespective of any protocol deviations who received at least 1 open-label injection of study treatment and who had at least 1 efficacy measurement after the first open-label injection.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol | Percentage of Subjects Achieving Inflamatory Bowel Disease Questionnaire (IBDQ) Remission (IBDQ ≥ 170) at Study Completion Visit (Week 262) | 7.8 percentage of subjects |
Secondary
Percentage of Subjects With Positive Anti-CZP Anti-body Status at Any Time From Week 0 of the Feeder Study C87085 to the Study Completion Visit in C87088
Subjects are counted as antibody positive to Certolizumab Pegol if they have at least one positive result from Week 0 in the previous study C87085 \[NCT00552058\] 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 C87085 [NCT00552058] to Study Completion Visit (Week 262) of C87088 (up to 268 weeks)
Population: Safety Population including all enrolled subjects who received at least 1 open-label injection of study medication.
| 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 Study C87085 to the Study Completion Visit in C87088 | 10.2 percentage of subjects |
Secondary
Plasma Concentration of Certolizumab Pegol After 1 Year (Week 52)
Plasma samples for determination of Certolizumab Pegol were taken prior to Certolizumab Pegol administration.
Time frame: Week 52
Population: Safety Population including all enrolled subjects who received at least 1 open-label injection of study medication.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Certolizumab Pegol | Plasma Concentration of Certolizumab Pegol After 1 Year (Week 52) | 6.317 μg/mL |