Corticosteroid Sparing Effect of Certolizumab in Crohn's Disease

Study Overview
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Brief Summary
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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.

Official Title
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A Phase IIIb Multicenter, Double-blind, Placebo-controlled,Randomized Trial to Examine the Corticosteroid-sparing Effect of Certolizumab Pegol in Patients With Moderate to Severe Crohn's Disease.

Conditions
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Crohn's Disease

Intervention / Treatment
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* Biological: certolizumab pegol 400 mg
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Certolizumab pegol 400 mg<br>Certolizumab pegol 400 mg | Biological: certolizumab pegol 400 mg<br>* 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.<br>* Other names: CZP;|
| Placebo Comparator: Placebo<br>Placebo | Other: Placebo<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Week 38 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Week 38 | 
| 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.] | Week 38 | 
| 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.] | During the 38-week double-blind treatment period | 
| 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. | Over the 38-week double-blind treatment period | 
| 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. | Over the 48-week study period | 
| 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. | 6-week run-in period, 38-week double-blind treatment period | 
| 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. | Week 38 | 
| 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. | Week 0, Week 38 | 
| 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. | Week 38 | 
| 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. | Week 0, Week 38 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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certolizumab pegol, Cimzia, Crohn's Disease, Inflammatory Bowel Disease