Certolizumab in Crohn's Disease Patients With Loss of Response or Intolerance to Infliximab

Study Overview
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Brief Summary
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To assess the clinical efficacy of subcutaneous (sc) certolizumab pegol administration over 26 weeks in patients suffering from Crohn's Disease (CD) and previously treated with infliximab

Official Title
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Phase IIIb Open-label Induction and Double-blind Comparison of 2 Maintenance Schedules Evaluating Clinical Benefit and Tolerability of Certolizumab Pegol in Crohn's Disease Patients With Prior Loss of Response or Intolerance to Infliximab

Conditions
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Crohn's Disease

Intervention / Treatment
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* Biological: Certolizumab pegol
* Biological: Certolizumab pegol
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with Crohn's Disease Previous treatment failure to Infliximab (intolerance and/or no response) Exclusion Criteria: Obstructive intestinal strictures Recent bowel resection Proctocolectomy or total colectomy Current total parenteral nutrition Short bowel syndrome All concomitant diseases or pathological conditions that could interfere with Crohn's disease assessment or to be harmful for the well being of the patient Previous clinical trials and previous biological therapy that could interfere with the results in the present clinical trial

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: Active 1<br>Q4W regimen - every 4 weeks: alternatively placebo and 400mg Certolizumab Pegol | Biological: Certolizumab pegol<br>* 400mg Certolizumab Pegol, Q4W, administered 4-weekly<br>* Other names: Cimzia;Other: Placebo<br>* placebo administered 4-weekly in Active 1<br>|
| Experimental: Active 2<br>Q2W regimen - every 2 weeks: 400 mg Certolizumab Pegol | Biological: Certolizumab pegol<br>* 400mg Certolizumab Pegol, Q2W, administered 2-weekly<br>* Other names: Cimzia;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Status With Response Defined as at Least 100 Point Decrease in Crohn's Disease Activity Score (CDAI Score) From Baseline in the Induction Phase | Response is defined as at least 100 point decrease in Crohn's Disease Activity Score (CDAI score) from baseline, otherwise there is a non-response. The CDAI score is used to quantify the symptoms of subjects with Crohn's Disease. A score of 150 or below indicates remission and a score above 450 indicates extremely severe disease. A decrease in CDAI over time indicates improvement in disease activity. | Baseline to Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Status With Response Defined as at Least 100 Point Decrease in CDAI Score From Baseline in the Randomized Maintenance Phase | Response is defined as at least 100 point decrease in CDAI score from baseline. The CDAI score is used to quantify the symptoms of subjects with Crohn's Disease. A score of 150 or below indicates remission and a score above 450 indicates extremely severe disease. A decrease in CDAI over time indicates improvement in disease activity. | Baseline to Week 26 | 
| Response Status With Response Defined as at Least 70 Points Reduction in CDAI Score in the Induction Phase | Response is defined as at least 70 points reduction in CDAI score. The CDAI score is used to quantify the symptoms of subjects with Crohn's Disease. A score of 150 or below indicates remission and a score above 450 indicates extremely severe disease. A decrease in CDAI over time indicates improvement in disease activity. | Baseline to Week 6 | 
| Response Status With Response Defined as at Least 70 Points Reduction in CDAI Score in the Randomized Maintenance Phase | Response is defined as at least 70 points reduction in CDAI score. The CDAI score is used to quantify the symptoms of subjects with Crohn's Disease. A score of 150 or below indicates remission and a score above 450 indicates extremely severe disease. A decrease in CDAI over time indicates improvement in disease activity. | Baseline to Week 26 | 
| Remission Status With Remission Defined as CDAI Score ≤ 150 in the Induction Phase | Remission is defined as CDAI score ≤ 150. The CDAI score is used to quantify the symptoms of subjects with Crohn's Disease. A score of 150 or below indicates remission and a score above 450 indicates extremely severe disease. A decrease in CDAI over time indicates improvement in disease activity. | Week 6 | 
| Remission Status With Remission Defined as CDAI Score ≤ 150 in the Randomized Maintenance Phase | Remission is defined as CDAI score ≤ 150. The CDAI score is used to quantify the symptoms with Crohn's Disease. A score of 150 or below indicates remission and a score above 450 indicates extremely severe disease. A decrease in CDAI over time indicates improvement in disease activity. | Week 26 | 
| CDAI Score at Week 2 of the Induction Phase | The CDAI score is used to quantify the symptoms of subjects with Crohn's Disease. A score of 150 or below indicates remission and a score above 450 indicates extremely severe disease. A decrease in CDAI over time indicates improvement in disease activity. | Week 2 | 
| CDAI Score at Week 4 of the Induction Phase | The CDAI score is used to quantify the symptoms of subjects with Crohn's Disease. A score of 150 or below indicates remission and a score above 450 indicates extremely severe disease. A decrease in CDAI over time indicates improvement in disease activity. | Week 4 | 
| CDAI Score at Week 6 of the Induction Phase | The CDAI score is used to quantify the symptoms of subjects with Crohn's Disease. A score of 150 or below indicates remission and a score above 450 indicates extremely severe disease. A decrease in CDAI over time indicates improvement in disease activity. | Week 6 | 
| CDAI Score at Week 8 in the Randomized Maintenance Phase | The CDAI score is used to quantify the symptoms of subjects with Crohn's Disease. A score of 150 or below indicates remission and a score above 450 indicates extremely severe disease. A decrease in CDAI over time indicates improvement in disease activity. | Week 8 | 
| CDAI Score at Week 10 in the Randomized Maintenance Phase | The CDAI score is used to quantify the symptoms of subjects with Crohn's Disease. A score of 150 or below indicates remission and a score above 450 indicates extremely severe disease. A decrease in CDAI over time indicates improvement in disease activity. | Week 10 | 
| CDAI Score at Week 12 in the Randomized Maintenance Phase | The CDAI score is used to quantify the symptoms of subjects with Crohn's Disease. A score of 150 or below indicates remission and a score above 450 indicates extremely severe disease. A decrease in CDAI over time indicates improvement in disease activity. | Week 12 | 
| CDAI Score at Week 14 in the Randomized Maintenance Phase | The CDAI score is used to quantify the symptoms of subjects with Crohn's Disease. A score of 150 or below indicates remission and a score above 450 indicates extremely severe disease. A decrease in CDAI over time indicates improvement in disease activity. | Week 14 | 
| CDAI Score at Week 16 in the Randomized Maintenance Phase | The CDAI score is used to quantify the symptoms of subjects with Crohn's Disease. A score of 150 or below indicates remission and a score above 450 indicates extremely severe disease. A decrease in CDAI over time indicates improvement in disease activity. | Week 16 | 
| CDAI Score at Week 18 in the Randomized Maintenance Phase | The CDAI score is used to quantify the symptoms of subjects with Crohn's Disease. A score of 150 or below indicates remission and a score above 450 indicates extremely severe disease. A decrease in CDAI over time indicates improvement in disease activity. | Week 18 | 
| CDAI Score at Week 20 in the Randomized Maintenance Phase | The CDAI score is used to quantify the symptoms of subjects with Crohn's Disease. A score of 150 or below indicates remission and a score above 450 indicates extremely severe disease. A decrease in CDAI over time indicates improvement in disease activity. | Week 20 | 
| CDAI Score at Week 22 in the Randomized Maintenance Phase | The CDAI score is used to quantify the symptoms of subjects with Crohn's Disease. A score of 150 or below indicates remission and a score above 450 indicates extremely severe disease. A decrease in CDAI over time indicates improvement in disease activity. | Week 22 | 
| CDAI Score at Week 24 in the Randomized Maintenance Phase | The CDAI score is used to quantify the symptoms of subjects with Crohn's Disease. A score of 150 or below indicates remission and a score above 450 indicates extremely severe disease. A decrease in CDAI over time indicates improvement in disease activity. | Week 24 | 
| CDAI Score at Week 26 in the Randomized Maintenance Phase | The CDAI score is used to quantify the symptoms of subjects with Crohn's Disease. A score of 150 or below indicates remission and a score above 450 indicates extremely severe disease. A decrease in CDAI over time indicates improvement in disease activity. | Week 26 | 
| Change From Baseline in CDAI Score at Week 2 of the Induction Phase | The CDAI score is used to quantify the symptoms of subjects with Crohn's Disease. A score of 150 or below indicates remission and a score above 450 indicates extremely severe disease. A decrease in CDAI over time indicates improvement in disease activity. | Baseline to Week 2 | 
| Change From Baseline in CDAI Score at Week 4 of the Induction Phase | The CDAI score is used to quantify the symptoms of subjects with Crohn's Disease. A score of 150 or below indicates remission and a score above 450 indicates extremely severe disease. A decrease in CDAI over time indicates improvement in disease activity. | Baseline to Week 4 | 
| Change From Baseline in CDAI Score at Week 6 of the Induction Phase | The CDAI score is used to quantify the symptoms of subjects with Crohn's Disease. A score of 150 or below indicates remission and a score above 450 indicates extremely severe disease. A decrease in CDAI over time indicates improvement in disease activity. | Baseline to Week 6 | 
| Change From Baseline in CDAI Score at Week 8 in the Randomized Maintenance Phase | The CDAI score is used to quantify the symptoms of subjects with Crohn's Disease. A score of 150 or below indicates remission and a score above 450 indicates extremely severe disease. A decrease in CDAI over time indicates improvement in disease activity. | Baseline to Week 8 | 
| Change From Baseline in CDAI Score at Week 10 in the Randomized Maintenance Phase | The CDAI score is used to quantify the symptoms of subjects with Crohn's Disease. A score of 150 or below indicates remission and a score above 450 indicates extremely severe disease. A decrease in CDAI over time indicates improvement in disease activity. | Baseline to Week 10 | 
| Change From Baseline in CDAI Score at Week 12 in the Randomized Maintenance Phase | The CDAI score is used to quantify the symptoms of subjects with Crohn's Disease. A score of 150 or below indicates remission and a score above 450 indicates extremely severe disease. A decrease in CDAI over time indicates improvement in disease activity. | Baseline to Week 12 | 
| Change From Baseline in CDAI Score at Week 14 in the Randomized Maintenance Phase | The CDAI score is used to quantify the symptoms of subjects with Crohn's Disease. A score of 150 or below indicates remission and a score above 450 indicates extremely severe disease. A decrease in CDAI over time indicates improvement in disease activity. | Baseline to Week 14 | 
| Change From Baseline in CDAI Score at Week 16 in the Randomized Maintenance Phase | The CDAI score is used to quantify the symptoms of subjects with Crohn's Disease. A score of 150 or below indicates remission and a score above 450 indicates extremely severe disease. A decrease in CDAI over time indicates improvement in disease activity. | Baseline to Week 16 | 
| Change From Baseline in CDAI Score at Week 18 in the Randomized Maintenance Phase | The CDAI score is used to quantify the symptoms of subjects with Crohn's Disease. A score of 150 or below indicates remission and a score above 450 indicates extremely severe disease. A decrease in CDAI over time indicates improvement in disease activity. | Baseline to Week 18 | 
| Change From Baseline in CDAI Score at Week 20 in the Randomized Maintenance Phase | The CDAI score is used to quantify the symptoms of subjects with Crohn's Disease. A score of 150 or below indicates remission and a score above 450 indicates extremely severe disease. A decrease in CDAI over time indicates improvement in disease activity. | Baseline to Week 20 | 
| Change From Baseline in CDAI Score at Week 22 in the Randomized Maintenance Phase | The CDAI score is used to quantify the symptoms of subjects with Crohn's Disease. A score of 150 or below indicates remission and a score above 450 indicates extremely severe disease. A decrease in CDAI over time indicates improvement in disease activity. | Baseline to Week 22 | 
| Change From Baseline in CDAI Score at Week 24 in the Randomized Maintenance Phase | The CDAI score is used to quantify the symptoms of subjects with Crohn's Disease. A score of 150 or below indicates remission and a score above 450 indicates extremely severe disease. A decrease in CDAI over time indicates improvement in disease activity. | Baseline to Week 24 | 
| Change From Baseline in CDAI Score at Week 26 in the Randomized Maintenance Phase | The CDAI score is used to quantify the symptoms of subjects with Crohn's Disease. A score of 150 or below indicates remission and a score above 450 indicates extremely severe disease. A decrease in CDAI over time indicates improvement in disease activity. | Baseline to Week 26 | 
| Number of Patients Able to Taper and Discontinue Steroids While Maintaining Remission at Week 10 in the Randomized Maintenance Phase in the Subset of Patients Taking Steroids at Baseline. | Remission is defined as CDAI score ≤ 150. | Week 10 | 
| Number of Patients Able to Taper and Discontinue Steroids While Maintaining Remission at Week 12 in the Randomized Maintenance Phase in the Subset of Patients Taking Steroids at Baseline. | Remission is defined as CDAI score ≤ 150. | Week 12 | 
| Number of Patients Able to Taper and Discontinue Steroids While Maintaining Remission at Week 14 in the Randomized Maintenance Phase in the Subset of Patients Taking Steroids at Baseline. | Remission is defined as CDAI score ≤ 150. | Week 14 | 
| Number of Patients Able to Taper and Discontinue Steroids While Maintaining Remission at Week 16 in the Randomized Maintenance Phase in the Subset of Patients Taking Steroids at Baseline. | Remission is defined as CDAI score ≤ 150. | Week 16 | 
| Number of Patients Able to Taper and Discontinue Steroids While Maintaining Remission at Week 18 in the Randomized Maintenance Phase in the Subset of Patients Taking Steroids at Baseline. | Remission is defined as CDAI score ≤ 150. | Week 18 | 
| Number of Patients Able to Taper and Discontinue Steroids While Maintaining Remission at Week 20 in the Randomized Maintenance Phase in the Subset of Patients Taking Steroids at Baseline. | Remission is defined as CDAI score ≤ 150. | Week 20 | 
| Number of Patients Able to Taper and Discontinue Steroids While Maintaining Remission at Week 22 in the Randomized Maintenance Phase in the Subset of Patients Taking Steroids at Baseline. | Remission is defined as CDAI score ≤ 150. | Week 22 | 
| Number of Patients Able to Taper and Discontinue Steroids While Maintaining Remission at Week 24 in the Randomized Maintenance Phase in the Subset of Patients Taking Steroids at Baseline. | Remission is defined as CDAI score ≤ 150. | Week 24 | 
| Number of Patients Able to Taper and Discontinue Steroids While Maintaining Remission at Week 26 in the Randomized Maintenance Phase in the Subset of Patients Taking Steroids at Baseline. | Remission is defined as CDAI score ≤ 150. | Week 26 | 
| Number of Patients Able to Taper and Discontinue Steroids While Maintaining Response at Week 10 in the Randomized Maintenance Phase in the Subset of Patients Taking Steroids at Baseline. | Response is defined as at least 100 point decrease in Crohn's Disease Activity Score (CDAI score). | Week 10 | 
| Number of Patients Able to Taper and Discontinue Steroids While Maintaining Response at Week 12 in the Randomized Maintenance Phase in the Subset of Patients Taking Steroids at Baseline. | Response is defined as at least 100 point decrease in Crohn's Disease Activity Score (CDAI score). | Week 12 | 
| Number of Patients Able to Taper and Discontinue Steroids While Maintaining Response at Week 14 in the Randomized Maintenance Phase in the Subset of Patients Taking Steroids at Baseline. | Response is defined as at least 100 point decrease in Crohn's Disease Activity Score (CDAI score). | Week 14 | 
| Number of Patients Able to Taper and Discontinue Steroids While Maintaining Response at Week 16 in the Randomized Maintenance Phase in the Subset of Patients Taking Steroids at Baseline. | Response is defined as at least 100 point decrease in Crohn's Disease Activity Score (CDAI score). | Week 16 | 
| Number of Patients Able to Taper and Discontinue Steroids While Maintaining Response at Week 18 in the Randomized Maintenance Phase in the Subset of Patients Taking Steroids at Baseline. | Response is defined as at least 100 point decrease in Crohn's Disease Activity Score (CDAI score). | Week 18 | 
| Number of Patients Able to Taper and Discontinue Steroids While Maintaining Response at Week 20 in the Randomized Maintenance Phase in the Subset of Patients Taking Steroids at Baseline. | Response is defined as at least 100 point decrease in Crohn's Disease Activity Score (CDAI score). | Week 20 | 
| Number of Patients Able to Taper and Discontinue Steroids While Maintaining Response at Week 22 in the Randomized Maintenance Phase in the Subset of Patients Taking Steroids at Baseline. | Response is defined as at least 100 point decrease in Crohn's Disease Activity Score (CDAI score). | Week 22 | 
| Number of Patients Able to Taper and Discontinue Steroids While Maintaining Response at Week 24 in the Randomized Maintenance Phase in the Subset of Patients Taking Steroids at Baseline. | Response is defined as at least 100 point decrease in Crohn's Disease Activity Score (CDAI score). | Week 24 | 
| Number of Patients Able to Taper and Discontinue Steroids While Maintaining Response at Week 26 in the Randomized Maintenance Phase in the Subset of Patients Taking Steroids at Baseline. | Response is defined as at least 100 point decrease in Crohn's Disease Activity Score (CDAI score). | Week 26 | 
| C - Reactive Protein (CRP) Level at Baseline (Week 0) of the Induction Phase | High CRP levels are defined as greater or equal 5 mg/L, normal or low levels are below 5 mg/L. | Week 0 | 
| CRP Level at Week 2 of the Induction Phase | High CRP levels are defined as greater or equal 5 mg/L, normal or low levels are below 5 mg/L. | Week 2 | 
| CRP Level at Week 4 of the Induction Phase | High CRP levels are defined as greater or equal 5 mg/L, normal or low levels are below 5 mg/L. | Week 4 | 
| CRP Level at Week 6 of the Induction Phase | High CRP levels are defined as greater or equal 5 mg/L, normal or low levels are below 5 mg/L. | Week 6 | 
| CRP Level at Week 8 in the Randomized Maintenance Phase | High CRP levels are defined as greater or equal 5 mg/L, normal or low levels are below 5 mg/L. | Week 8 | 
| CRP Level at Week 10 in the Randomized Maintenance Phase | High CRP levels are defined as greater or equal 5 mg/L, normal or low levels are below 5 mg/L. | Week 10 (optional measurement) | 
| CRP Level at Week 12 in the Randomized Maintenance Phase | High CRP levels are defined as greater or equal 5 mg/L, normal or low levels are below 5 mg/L. | Week 12 | 
| CRP Level at Week 14 in the Randomized Maintenance Phase | High CRP levels are defined as greater or equal 5 mg/L, normal or low levels are below 5 mg/L. | Week 14 (optional measurement) | 
| CRP Level at Week 16 in the Randomized Maintenance Phase | High CRP levels are defined as greater or equal 5 mg/L, normal or low levels are below 5 mg/L. | Week 16 | 
| CRP Level at Week 18 in the Randomized Maintenance Phase | High CRP levels are defined as greater or equal 5 mg/L, normal or low levels are below 5 mg/L. | Week 18 (optional measurement) | 
| CRP Level at Week 20 in the Randomized Maintenance Phase | High CRP levels are defined as greater or equal 5 mg/L, normal or low levels are below 5 mg/L. | Week 20 | 
| CRP Level at Week 22 in the Randomized Maintenance Phase | High CRP levels are defined as greater or equal 5 mg/L, normal or low levels are below 5 mg/L. | Week 22 (optional measurement) | 
| CRP Level at Week 24 in the Randomized Maintenance Phase | High CRP levels are defined as greater or equal 5 mg/L, normal or low levels are below 5 mg/L. | Week 24 | 
| CRP Level at Week 26 in the Randomized Maintenance Phase | High CRP levels are defined as greater or equal 5 mg/L, normal or low levels are below 5 mg/L. | Week 26 | 
| CRP Level at Endpoint (Last Visit) in the Randomized Maintenance Phase | High CRP levels are defined as greater or equal 5 mg/L, normal or low levels are below 5 mg/L. Endpoint is the visit when the last observation was taken, either at week 26 or at a visit before in case of early dropout. | Last visit on or before Week 26 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Crohn's Disease, Certolizumab pegol