Crohn's Disease
Conditions
Keywords
certolizumab pegol, Cimzia, Crohn's Disease, Inflammatory Bowel Disease
Brief summary
The current study is designed to measure the corticosteroid-sparing effect of certolizumab pegol using a defined schedule of corticosteroid tapering in subjects with moderate to severe Crohn's disease. Subjects had to be in remission (CDAI\<=150) and receiving corticosteroids at a dose no higher than 30 mg/day prednisone or equivalent during the week prior to randomization.
Interventions
BIOLOGICALcertolizumab pegol 400 mg
Certolizumab pegol 400 mg provided in solution for subcutaneous injection (2 x 200 mg/mL) in single-use vials for administration at Weeks 0, 2, 4 and then every 4 weeks until Week 36. Two vials will be required for each dosing.
OTHERPlacebo
Placebo (commercially available sodium chloride 0.9% (preservative free)) provided for subcutaneous injection in single-use vials for administration at Weeks 0, 2, 4 and then every 4 weeks until Week 36. Two vials will be required for each dosing.
Sponsors
UCB Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men and women * Age 18 years or older with moderate to severe Crohn's disease (Crohn's Disease Activity Index (CDAI) score of ≥ 220 ≤450)
Exclusion criteria
* Active or draining fistula present at screening * Lactating and/or pregnant female subjects * A history of any health condition that could potentially interfere with the disease and/or the treatment * A history of an adverse reaction to polyethylene glycol (PEG) or a protein medicinal product * Any other condition which in the Investigator's judgment would make the patient unsuitable for inclusion in the study * History of drug or alcohol abuse in the prior year * Receipt of any experimental therapy within or outside a clinical trial in the 3 months prior to Visit 0
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Who Have Been Withdrawn From Prednisone or Prednisolone Therapy According to the Corticosteroid Tapering Schedule and Have Remained Off Corticosteroids and in Disease Remission at Week 38 | Week 38 | The Crohn's Disease Activity Index (CDAI) is used to quantify the symptoms of subjects with Crohn's disease. A CDAI score of 150 or below indicates disease remission and a score above 450 indicates extremely severe disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Percentage of Subjects With Relapse/Treatment Failure at Week 38 | Week 38 | A subject with relapse/ treatment failure has a Crohn's Disease Activity Index (CDAI) \> 150 and an increase in CDAI of \>= 70 points versus Week 0. \[The CDAI is used to quantify the symptoms of subjects with Crohn's disease. A score of 150 or below indicates disease remission and a score above 450 indicates extremely severe disease.\] |
| Time to Relapse/Treatment Failure During the 38-week Double-blind Treatment Period | During the 38-week double-blind treatment period | A subject with relapse/ treatment failure has a Crohn's Disease Activity Index (CDAI) \> 150 and an increase in CDAI of \>= 70 points versus Week 0. \[The CDAI is used to quantify the symptoms of subjects with Crohn's disease. A score of 150 or below indicates disease remission and a score above 450 indicates extremely severe disease.\] |
| Per-subject Median Weekly Dose of Corticosteroids Over the 38-week Double-blind Treatment Period | Over the 38-week double-blind treatment period | The median weekly dose of corticosteroids is calculated for each subject, and these per-subject median values are further summarized by treatment group. The mean of the per-subject median doses in each treatment group is presented here. |
| Per-subject Cumulative Dose of Corticosteroids Over the 48-week Study Period | Over the 48-week study period | The cumulative dose of corticosteroids over the 48-week study period is calculated for each subject individually. The mean of these values for each treatment group is presented here. |
| Percentage of Subjects With Continuous Remission Off Steroids at Week 38 | Week 38 | The Crohn's Disease Activity Index (CDAI) is used to quantify the symptoms of subjects with Crohn's disease. A CDAI score of 150 or below indicates disease remission and a score above 450 indicates extremely severe disease. A subject with continuous remission off steroids at Week 38 is a subject in remission (CDAI =\< 150) from the visit when he stops taking steroids to Week 38 and is off corticosteroids until Week 38. |
| Crohn's Disease Activity Index (CDAI) Score at Week 38 | Week 38 | 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. |
| Change From Baseline in CDAI Score at Week 38 | Week 0, Week 38 | 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. |
| Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Week 38 | Week 38 | The total IBDQ score will be derived 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. IBDQ remission is defined as a subject having an IBDQ total score \>= 170 points. |
| Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Week 38 | Week 0, Week 38 | The total IBDQ score will be derived 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 scores indicates a better quality of life. IBDQ response is defined as an increase from baseline in the IBDQ total score \>= 16 points. |
| Change From the 6-week run-in Period in Per-subject Median Weekly Dose of Corticosteroids Over the 38-week Double-blind Treatment Period | 6-week run-in period, 38-week double-blind treatment period | The run in period lasted a minimum of 1 week and a maximum of 6 weeks. During this period subjects were treated with any dose or type of systemic corticosteroids the Investigator felt was appropriate. To be eligible for study randomization, subjects must have been in remission (CDAI ≤150 points) and receiving corticosteroids at a dose no higher than 30 mg/day prednisone or equivalent during the week prior to randomization. Subjects who did not meet these criteria were not randomized and were withdrawn from the study. |
Countries
Canada, Germany, United States
Participant flow
Recruitment details
A Randomized Trial to Examine the Corticosteroid-sparing Effect of Certolizumab Pegol in Subjects With Moderate to Severe Crohn's Disease from November 2006 to July 2009
Participants by arm
| Arm | Count |
|---|---|
| Certolizumab Pegol 400 mg Certolizumab pegol 400 mg provided in a solution for subcutaneous injection (2 x 200 mg/mL) in single-use vials for administration at Weeks 0, 2, 4 and then every 4 weeks until Week 36 | 87 |
| Placebo Placebo provided for subcutaneous injection in 2 single-use vials for administration at Weeks 0, 2, 4 and then every 4 weeks until Week 36 | 87 |
| Total | 174 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 8 | 12 |
| Overall Study | Lack of Efficacy | 37 | 42 |
| Overall Study | Lost to Follow-up | 4 | 2 |
| Overall Study | Other:History of squamous cell carcinoma | 1 | 0 |
| Overall Study | Other: Inadvertently unblinded | 1 | 0 |
| Overall Study | Other: Ineligible | 1 | 0 |
| Overall Study | Other: Non compliance | 0 | 1 |
| Overall Study | Other: Patient's steroid use | 1 | 0 |
| Overall Study | Other: Patient stopped steroids | 0 | 1 |
| Overall Study | Other: Required exclusionary medication | 0 | 1 |
| Overall Study | Personal reasons | 6 | 5 |
Baseline characteristics
| Characteristic | Certolizumab Pegol 400 mg | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 2 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 85 Participants | 85 Participants | 170 Participants |
| Age, Continuous | 40.77 years STANDARD_DEVIATION 13.2 | 39.73 years STANDARD_DEVIATION 13.31 | 40.25 years STANDARD_DEVIATION 13.23 |
| Region of Enrollment Canada | 18 participants | 11 participants | 29 participants |
| Region of Enrollment Germany | 4 participants | 8 participants | 12 participants |
| Region of Enrollment United States | 65 participants | 68 participants | 133 participants |
| Sex: Female, Male Female | 52 Participants | 45 Participants | 97 Participants |
| Sex: Female, Male Male | 35 Participants | 42 Participants | 77 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 70 / 87 | 73 / 87 |
| serious Total, serious adverse events | 9 / 87 | 8 / 87 |
Outcome results
Primary
Percentage of Subjects Who Have Been Withdrawn From Prednisone or Prednisolone Therapy According to the Corticosteroid Tapering Schedule and Have Remained Off Corticosteroids and in Disease Remission at Week 38
The Crohn's Disease Activity Index (CDAI) is used to quantify the symptoms of subjects with Crohn's disease. A CDAI score of 150 or below indicates disease remission and a score above 450 indicates extremely severe disease.
Time frame: Week 38
Population: Intention-to-treat (ITT) population which consists of all randomized subjects who received at least one injection of study medication. In the analyses of remission rates, subjects for whom it is impossible to assess the remission status will be conservatively considered as non-remitters in the calculations.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol 400 mg | Percentage of Subjects Who Have Been Withdrawn From Prednisone or Prednisolone Therapy According to the Corticosteroid Tapering Schedule and Have Remained Off Corticosteroids and in Disease Remission at Week 38 | 26.4 percentage of subjects |
| Placebo | Percentage of Subjects Who Have Been Withdrawn From Prednisone or Prednisolone Therapy According to the Corticosteroid Tapering Schedule and Have Remained Off Corticosteroids and in Disease Remission at Week 38 | 21.8 percentage of subjects |
Secondary
Change From Baseline in CDAI Score at Week 38
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.
Time frame: Week 0, Week 38
Population: Of the 87 (Placebo) and 87 (Certolizumab pegol 400 mg) subjects randomized, 22 and 27 subjects respectively had available values at Baseline and at Week 38 and are included in the summary based on the intention-to-treat (ITT) population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol 400 mg | Change From Baseline in CDAI Score at Week 38 | -25.50 score on a scale | Standard Deviation 53.48 |
| Placebo | Change From Baseline in CDAI Score at Week 38 | -18.36 score on a scale | Standard Deviation 75.97 |
Secondary
Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Week 38
The total IBDQ score will be derived 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 scores indicates a better quality of life. IBDQ response is defined as an increase from baseline in the IBDQ total score \>= 16 points.
Time frame: Week 0, Week 38
Population: Of the 87 (Placebo) and 87 (Certolizumab Pegol 400 mg) subjects randomized, 23 and 26 subjects respectively had available values at Baseline and Week 38 and are included in the summary based on the intention-to-treat (ITT) population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol 400 mg | Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Week 38 | 12.6 score on a scale | Standard Deviation 23.2 |
| Placebo | Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Week 38 | 1.5 score on a scale | Standard Deviation 21.5 |
Secondary
Change From the 6-week run-in Period in Per-subject Median Weekly Dose of Corticosteroids Over the 38-week Double-blind Treatment Period
The run in period lasted a minimum of 1 week and a maximum of 6 weeks. During this period subjects were treated with any dose or type of systemic corticosteroids the Investigator felt was appropriate. To be eligible for study randomization, subjects must have been in remission (CDAI ≤150 points) and receiving corticosteroids at a dose no higher than 30 mg/day prednisone or equivalent during the week prior to randomization. Subjects who did not meet these criteria were not randomized and were withdrawn from the study.
Time frame: 6-week run-in period, 38-week double-blind treatment period
Population: Of the 87 (Placebo) and 87 (Certolizumab pegol 400 mg) subjects randomized, 86 in each group had available values at the 6-week run-in period and over the 38-week double-blind treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol 400 mg | Change From the 6-week run-in Period in Per-subject Median Weekly Dose of Corticosteroids Over the 38-week Double-blind Treatment Period | -111.20 mg per week | Standard Deviation 64.6 |
| Placebo | Change From the 6-week run-in Period in Per-subject Median Weekly Dose of Corticosteroids Over the 38-week Double-blind Treatment Period | -78.04 mg per week | Standard Deviation 202.55 |
Secondary
Crohn's Disease Activity Index (CDAI) Score at Week 38
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.
Time frame: Week 38
Population: Of the 87 (Placebo) and 87 (Certolizumab pegol 400 mg) subjects randomized, 22 and 27 subjects respectively are included in the summary of the Week 38, based on the intention-to-treat (ITT) population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol 400 mg | Crohn's Disease Activity Index (CDAI) Score at Week 38 | 78.90 score on a scale | Standard Deviation 65.05 |
| Placebo | Crohn's Disease Activity Index (CDAI) Score at Week 38 | 73.42 score on a scale | Standard Deviation 61.09 |
Secondary
Cumulative Percentage of Subjects With Relapse/Treatment Failure at Week 38
A subject with relapse/ treatment failure has a Crohn's Disease Activity Index (CDAI) \> 150 and an increase in CDAI of \>= 70 points versus Week 0. \[The CDAI is used to quantify the symptoms of subjects with Crohn's disease. A score of 150 or below indicates disease remission and a score above 450 indicates extremely severe disease.\]
Time frame: Week 38
Population: Of 87 (Placebo) and 87 (Certolizumab pegol 400 mg) subjects randomized, 85 and 87 subjects respectively are included in summary of Week 38, based on conditional intention-to-treat population, consisting of all randomized subjects who received at least one injection of study medication, excluding those who were not in remission (CDAI\>150) at Week 0
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol 400 mg | Cumulative Percentage of Subjects With Relapse/Treatment Failure at Week 38 | 57.5 percentage of subjects |
| Placebo | Cumulative Percentage of Subjects With Relapse/Treatment Failure at Week 38 | 56.5 percentage of subjects |
Secondary
Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Week 38
The total IBDQ score will be derived 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. IBDQ remission is defined as a subject having an IBDQ total score \>= 170 points.
Time frame: Week 38
Population: Of the 87 (Placebo) and 87 (Certolizumab pegol 400 mg) subjects randomized, 23 and 27 subjects respectively had available values at Week 38 and are included in the summary based on the intention-to-treat (ITT) population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol 400 mg | Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Week 38 | 174.7 score on a scale | Standard Deviation 25.7 |
| Placebo | Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Week 38 | 168.6 score on a scale | Standard Deviation 23.4 |
Secondary
Percentage of Subjects With Continuous Remission Off Steroids at Week 38
The Crohn's Disease Activity Index (CDAI) is used to quantify the symptoms of subjects with Crohn's disease. A CDAI score of 150 or below indicates disease remission and a score above 450 indicates extremely severe disease. A subject with continuous remission off steroids at Week 38 is a subject in remission (CDAI =\< 150) from the visit when he stops taking steroids to Week 38 and is off corticosteroids until Week 38.
Time frame: Week 38
Population: Intention-to-treat (ITT) population which consists of all randomized subjects who received at least one injection of study medication. In the analyses of remission rates, subjects for whom it is impossible to assess the remission status will be conservatively considered as non-remitters in the calculations.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol 400 mg | Percentage of Subjects With Continuous Remission Off Steroids at Week 38 | 16.1 percentage of subjects |
| Placebo | Percentage of Subjects With Continuous Remission Off Steroids at Week 38 | 14.9 percentage of subjects |
Secondary
Per-subject Cumulative Dose of Corticosteroids Over the 48-week Study Period
The cumulative dose of corticosteroids over the 48-week study period is calculated for each subject individually. The mean of these values for each treatment group is presented here.
Time frame: Over the 48-week study period
Population: 87 (Placebo) and 87 (Certolizumab pegol 400 mg) subjects randomized are included in the summary based on the intention-to-treat (ITT) population. Of the 87 subjects in the placebo group, 1 subject taking a daily dose of 3g with a rectal route has been excluded from the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol 400 mg | Per-subject Cumulative Dose of Corticosteroids Over the 48-week Study Period | 792.68 mg | Standard Deviation 438.14 |
| Placebo | Per-subject Cumulative Dose of Corticosteroids Over the 48-week Study Period | 1294.96 mg | Standard Deviation 4459.27 |
Secondary
Per-subject Median Weekly Dose of Corticosteroids Over the 38-week Double-blind Treatment Period
The median weekly dose of corticosteroids is calculated for each subject, and these per-subject median values are further summarized by treatment group. The mean of the per-subject median doses in each treatment group is presented here.
Time frame: Over the 38-week double-blind treatment period
Population: 87 (Placebo) and 87 (Certolizumab pegol 400 mg) subjects randomized are included in the summary based on the intention-to-treat (ITT) population. Of the 87 subjects in the placebo group, 1 subject taking a daily dose of 3g with a rectal route has been excluded from the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol 400 mg | Per-subject Median Weekly Dose of Corticosteroids Over the 38-week Double-blind Treatment Period | 88.66 mg per week | Standard Deviation 38.72 |
| Placebo | Per-subject Median Weekly Dose of Corticosteroids Over the 38-week Double-blind Treatment Period | 122.47 mg per week | Standard Deviation 210.15 |
Secondary
Time to Relapse/Treatment Failure During the 38-week Double-blind Treatment Period
A subject with relapse/ treatment failure has a Crohn's Disease Activity Index (CDAI) \> 150 and an increase in CDAI of \>= 70 points versus Week 0. \[The CDAI is used to quantify the symptoms of subjects with Crohn's disease. A score of 150 or below indicates disease remission and a score above 450 indicates extremely severe disease.\]
Time frame: During the 38-week double-blind treatment period
Population: Of 87 (Placebo) and 87 (Certolizumab pegol 400 mg) subjects randomized, 85 and 87 subjects respectively are included in summary of Week 38, based on conditional intention-to-treat population, consisting of all randomized subjects who received at least one injection of study medication, excluding those who were not in remission (CDAI\>150) at Week 0
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol 400 mg | Time to Relapse/Treatment Failure During the 38-week Double-blind Treatment Period | 83.5 days | Standard Deviation 61.8 |
| Placebo | Time to Relapse/Treatment Failure During the 38-week Double-blind Treatment Period | 81.9 days | Standard Deviation 70.4 |