Mucosal Healing Study in Crohn's Disease (CD)

Study Overview
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Brief Summary
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The aim of the study will be to investigate the effect of certolizumab pegol on the intestinal mucosa in active Crohn's disease.

Official Title
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A Phase IIIB Multicentre Open Label 54 Weeks Clinical Trial Evaluating Certolizumab Pegol, a PEGylated Fab Fragment of Humanized Antibody to Tumor Necrosis Factor Alpha (TNFα) on Endoscopic and Mucosal Healing in Patients Suffering From Active Crohn's Disease.

Conditions
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Crohn's Disease

Intervention / Treatment
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* Biological: Certolizumab pegol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients suffering from active Crohn's disease [Crohn's Disease Activity Index(CDAI) ≥ 220 and ≤ 450] and at least 2 segments with endoscopic ulcerative lesions with Baseline Crohn's Disease Endoscopic Index of Severity (CDEIS) ≥ 8 Patients who need to be treated by anti-tumor necrosis factor (anti-TNF) therapy Exclusion Criteria: Obstructive intestinal strictures, bowel resection, proctocolectomy or total colectomy, current total parenteral nutrition, short bowel syndrome History of tuberculosis or positive tests for tuberculosis at screening All the 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CDP870 400 mg<br>Certolizumab pegol (CDP870) 400 mg | Biological: Certolizumab pegol<br>* Certolizumab pegol (CDP870) 400 mg administered subcutaneously (sc) at Weeks 0, 2 and 4 (induction doses), then every 4 weeks (Q4W) until Week 52. Investigators can escalate dosage to CDP870 400 mg 2-weekly (Q2W) at any time after Week 10 for lack of response/remission. After Week 52 patients can continue to receive treatment until study drug end, either Q4W or Q2W, according to their administration frequency at Week 52.<br>* Other names: CDP870;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in CDEIS (Crohn's Disease Endoscopic Index of Severity) Score at Week 10 Using Local Non-blinded Assessments | The CDEIS (Crohn's Disease Endoscopic Index of Severity) score provides a measure of mucosal inflammation. Generally, scores range from 0-30. A higher score indicates more severe mucosal inflammation, thus a negative change from Baseline (i.e., Week 10 score minus Baseline score) indicates improvement. | Baseline, Week 10 | 
| Mean Change From Baseline in CDEIS (Crohn's Disease Endoscopic Index of Severity) Score at Week 10 Using Central Blinded Assessments | The CDEIS (Crohn's Disease Endoscopic Index of Severity) score provides a measure of mucosal inflammation. Generally, scores range from 0-30. A higher score indicates more severe mucosal inflammation, thus a negative change from Baseline (i.e., Week 10 score minus Baseline score) indicates improvement. | Baseline, Week 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Achieving Mucosal Healing at Week 10 Using Local Non-blinded Assessments | Mucosal healing is defined as complete absence of ulceration contribution in the CDEIS (Crohn's Disease Endoscopic Index of Severity) score | Week 10 | 
| Percentage of Patients Achieving Mucosal Healing at Week 10 Using Central Blinded Assessments | Mucosal healing is defined as complete absence of ulceration contribution in the CDEIS (Crohn's Disease Endoscopic Index of Severity) score | Week 10 | 
| Percentage of Patients Achieving Mucosal Healing at Week 54 Using Local Non-blinded Assessments | Mucosal healing is defined as complete absence of ulceration contribution in the CDEIS (Crohn's Disease Endoscopic Index of Severity) score | Week 54 | 
| Percentage of Patients Achieving Mucosal Healing at Week 54 Using Central Blinded Assessments | Mucosal healing is defined as complete absence of ulceration contribution in the CDEIS (Crohn's Disease Endoscopic Index of Severity) score | Week 54 | 
| Percentage of Patients With Endoscopic Response (Crohn's Disease Endoscopic Index of Severity (CDEIS) Decrease From Baseline of More Than 5 Points) at Week 10 Using Local Non-blinded Assessments | The CDEIS (Crohn's Disease Endoscopic Index of Severity) score provides a measure of mucosal inflammation. Generally, scores range from 0-30. A higher score indicates more severe mucosal inflammation. | Baseline, Week 10 | 
| Percentage of Patients With Endoscopic Response (Crohn's Disease Endoscopic Index of Severity (CDEIS) Decrease From Baseline of More Than 5 Points) at Week 10 Using Central Blinded Assessments | The CDEIS (Crohn's Disease Endoscopic Index of Severity) score provides a measure of mucosal inflammation. Generally, scores range from 0-30. A higher score indicates more severe mucosal inflammation. | Baseline, Week 10 | 
| Percentage of Patients With Endoscopic Response (Crohn's Disease Endoscopic Index of Severity (CDEIS) Decrease From Baseline of More Than 5 Points) at Week 54 Using Local Non-blinded Assessments | The CDEIS (Crohn's Disease Endoscopic Index of Severity) score provides a measure of mucosal inflammation. Generally, scores range from 0-30. A higher score indicates more severe mucosal inflammation. | Baseline, Week 54 | 
| Percentage of Patients With Endoscopic Response (Crohn's Disease Endoscopic Index of Severity (CDEIS) Decrease From Baseline of More Than 5 Points) at Week 54 Using Central Blinded Assessments | The CDEIS (Crohn's Disease Endoscopic Index of Severity) score provides a measure of mucosal inflammation. Generally, scores range from 0-30. A higher score indicates more severe mucosal inflammation. | Baseline, Week 54 | 
| Percentage of Patients With Endoscopic Remission (Crohn's Disease Endoscopic Index of Severity (CDEIS) Score Below 6) at Week 10 Using Local Non-blinded Assessments | The CDEIS (Crohn's Disease Endoscopic Index of Severity) score provides a measure of mucosal inflammation. Generally, scores range from 0-30. A higher score indicates more severe mucosal inflammation. | Week 10 | 
| Percentage of Patients With Endoscopic Remission (Crohn's Disease Endoscopic Index of Severity (CDEIS) Score Below 6) at Week 10 Using Central Blinded Assessments | The CDEIS (Crohn's Disease Endoscopic Index of Severity) score provides a measure of mucosal inflammation. Generally, scores range from 0-30. A higher score indicates more severe mucosal inflammation. | Week 10 | 
| Percentage of Patients With Endoscopic Remission (Crohn's Disease Endoscopic Index of Severity (CDEIS) Score Below 6) at Week 54 Using Local Non-blinded Assessments | The CDEIS (Crohn's Disease Endoscopic Index of Severity) score provides a measure of mucosal inflammation. Generally, scores range from 0-30. A higher score indicates more severe mucosal inflammation. | Week 54 | 
| Percentage of Patients With Endoscopic Remission (Crohn's Disease Endoscopic Index of Severity (CDEIS) Score Below 6) at Week 54 Using Central Blinded Assessments | The CDEIS (Crohn's Disease Endoscopic Index of Severity) score provides a measure of mucosal inflammation. Generally, scores range from 0-30. A higher score indicates more severe mucosal inflammation. | Week 54 | 
| Percentage of Patients With Endoscopic Complete Remission (Crohn's Disease Endoscopic Index of Severity (CDEIS) Score Below 3) at Week 10 Using Local Non-blinded Assessments | The CDEIS (Crohn's Disease Endoscopic Index of Severity) score provides a measure of mucosal inflammation. Generally, scores range from 0-30. A higher score indicates more severe mucosal inflammation. | Week 10 | 
| Percentage of Patients With Endoscopic Complete Remission (Crohn's Disease Endoscopic Index of Severity (CDEIS) Score Below 3) at Week 10 Using Central Blinded Assessments | The CDEIS (Crohn's Disease Endoscopic Index of Severity) score provides a measure of mucosal inflammation. Generally, scores range from 0-30. A higher score indicates more severe mucosal inflammation. | Week 10 | 
| Percentage of Patients With Endoscopic Complete Remission (Crohn's Disease Endoscopic Index of Severity (CDEIS) Score Below 3) at Week 54 Using Local Non-blinded Assessments | The CDEIS (Crohn's Disease Endoscopic Index of Severity) score provides a measure of mucosal inflammation. Generally, scores range from 0-30. A higher score indicates more severe mucosal inflammation. | Week 54 | 
| Percentage of Patients With Endoscopic Complete Remission (Crohn's Disease Endoscopic Index of Severity (CDEIS) Score Below 3) at Week 54 Using Central Blinded Assessments | The CDEIS (Crohn's Disease Endoscopic Index of Severity) score provides a measure of mucosal inflammation. Generally, scores range from 0-30. A higher score indicates more severe mucosal inflammation. | Week 54 | 
| Change From Baseline in Histological Crohn's Disease Score at Week 10 Using Central Blinded Assessment | The histological Crohn's disease score combines active inflammatory changes: infiltration of mononuclear cells, polymorphonuclear cells, presence of erosions and/or ulcers, and chronic architectural changes. Scores range from 0 to 44, with higher scores indicating greater disease. | Baseline, Week 10 | 
| Change From Baseline in Histological Crohn's Disease Score at Week 54 Using Central Blinded Assessment | The histological Crohn's disease score combines active inflammatory changes: infiltration of mononuclear cells, polymorphonuclear cells, presence of erosions and/or ulcers, and chronic architectural changes. Scores range from 0 to 44, with higher scores indicating greater disease. | Baseline, Week 54 | 
| Percentage of Patients Achieving Crohn's Disease Activity Index (CDAI) Response (Defined as a Decrease of at Least 100 Points in CDAI Score From Baseline) at Week 10 | Crohn's disease activity index (CDAI) responders are patients achieving clinical response (a reduction in CDAI score of at least 100 points from Baseline). CDAI is used to quantify the symptoms of Crohn's disease. A score of 150 or below indicates remission and a score above 450 indicates extremely severe disease. | Baseline, Week 10 | 
| Percentage of Patients Achieving Crohn's Disease Activity Index (CDAI) Response (Defined as a Decrease of at Least 100 Points in CDAI Score From Baseline) at Week 54 | Crohn's disease activity index (CDAI) responders are patients achieving clinical response (a reduction in CDAI score of at least 100 points from Baseline). CDAI is used to quantify the symptoms of Crohn's disease. A score of 150 or below indicates remission and a score above 450 indicates extremely severe disease. | Baseline, Week 54 | 
| Percentage of Patients Achieving Crohn's Disease Activity Index (CDAI) Remission (Defined as a CDAI Score Less Than or Equal to 150) at Week 10 | Crohn's disease activity index (CDAI) responders are patients achieving clinical response (a reduction in CDAI score of at least 100 points from Baseline). CDAI is used to quantify the symptoms of Crohn's disease. A score of 150 or below indicates remission and a score above 450 indicates extremely severe disease. | Week 10 | 
| Percentage of Patients Achieving Crohn's Disease Activity Index (CDAI) Remission (Defined as a CDAI Score Less Than or Equal to 150) at Week 54 | Crohn's disease activity index (CDAI) responders are patients achieving clinical response (a reduction in CDAI score of at least 100 points from Baseline). CDAI is used to quantify the symptoms of Crohn's disease. A score of 150 or below indicates remission and a score above 450 indicates extremely severe disease. | Week 54 | 
| Geometric Mean C-Reactive Protein (CRP) Level (mg/L) at Week 10 |  | Week 10 | 
| Ratio to Baseline of C-Reactive Protein (CRP) Level (mg/L) at Week 10 | Ratio is calculated as the Week 10 value divided by the Baseline value for patients with data at both timepoints. | Baseline, Week 10 | 
| Geometric Mean C-Reactive Protein (CRP) Level (mg/L) at Week 52 |  | Week 52 | 
| Ratio to Baseline of C-Reactive Protein (CRP) Level (mg/L) at Week 52 | The ratio is calculated as the Week 52 value divided by Baseline value for patients with data at both timepoints. | Baseline, Week 52 | 
| Correlation Between Mean C-Reactive Protein (CRP) Plasma Level and Crohn's Disease Activity Index (CDAI) Score at Week 10 | Crohn's disease activity index (CDAI) responders are patients achieving clinical response (a reduction in CDAI score of at least 100 points from Baseline). CDAI is used to quantify the symptoms of Crohn's disease. A score of 150 or below indicates remission and a score above 450 indicates extremely severe disease. | Week 10 | 
| Correlation Between Mean C-Reactive Protein (CRP) Plasma Level and Crohn's Disease Endoscopic Index of Severity (CDEIS) Score at Week 10 Using Local Non-blinded Assessment | The CDEIS (Crohn's Disease Endoscopic Index of Severity) score provides a measure of mucosal inflammation. Generally, scores range from 0-30. A higher score indicates more severe mucosal inflammation. | Week 10 | 
| Correlation Between Mean C-Reactive Protein (CRP) Plasma Level and Crohn's Disease Endoscopic Index of Severity (CDEIS) Score at Week 10 Using Central Blinded Assessment | The CDEIS (Crohn's Disease Endoscopic Index of Severity) score provides a measure of mucosal inflammation. Generally, scores range from 0-30. A higher score indicates more severe mucosal inflammation. | Week 10 | 
| Correlation Between Mean C-Reactive Protein (CRP) Plasma Level and Histological Crohn's Disease Score at Week 10 Using Central Blinded Assessment | The histological Crohn's disease score combines active inflammatory changes: infiltration of mononuclear cells, polymorphonuclear cells, presence of erosions and/or ulcers, and chronic architectural changes. Scores range from 0 to 44, with higher scores indicating greater disease | Week 10 | 
| Change From Baseline in Crohn's Disease Endoscopic Index of Severity (CDEIS) Score at Week 54 Using Local Non-blinded Assessment | The CDEIS (Crohn's Disease Endoscopic Index of Severity) score provides a measure of mucosal inflammation. Generally, scores range from 0-30. A higher score indicates more severe mucosal inflammation. | Baseline, Week 54 | 
| Change From Baseline in Crohn's Disease Endoscopic Index of Severity (CDEIS) Score at Week 54 Using Central Blinded Assessment | The CDEIS (Crohn's Disease Endoscopic Index of Severity) score provides a measure of mucosal inflammation. Generally, scores range from 0-30. A higher score indicates more severe mucosal inflammation. | Baseline, Week 54 | 
| Change From Baseline in Crohn's Disease Activity Index (CDAI) Score at Week 10 | Crohn's disease activity index (CDAI) responders are patients achieving clinical response (a reduction in CDAI score of at least 100 points from Baseline). CDAI is used to quantify the symptoms of Crohn's disease. A score of 150 or below indicates remission and a score above 450 indicates extremely severe disease. | Baseline, Week 10 | 
| Change From Baseline in Crohn's Disease Activity Index (CDAI) Score at Week 54 | Crohn's disease activity index (CDAI) responders are patients achieving clinical response (a reduction in CDAI score of at least 100 points from Baseline). CDAI is used to quantify the symptoms of Crohn's disease. A score of 150 or below indicates remission and a score above 450 indicates extremely severe disease. | Baseline, Week 54 | 

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