Mucosal Healing Study in Crohn's Disease (CD) (MUSIC)

• ClinicalTrials.gov Identifier: NCT00297648
• Recruitment Status: Completed
• First Posted: February 28, 2006
• Results First Posted: January 18, 2010
• Last Update Posted: August 31, 2011
• Sponsor: UCB Pharma
• Information provided by (Responsible Party): UCB Pharma

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Crohn's Disease	Biological: Certolizumab pegol	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 89 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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.
• Study Start Date: February 2006
• Actual Primary Completion Date: January 2008
• Actual Study Completion Date: December 2009

Arms and Interventions

Arm

Intervention/treatment

Experimental: CDP870 400 mg; Certolizumab pegol (CDP870) 400 mg

Biological: Certolizumab pegol; 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.; Other Names: Cimzia; CZP; CDP870

Outcome Measures

Primary Outcome Measures :

1. Mean Change From Baseline in CDEIS (Crohn's Disease Endoscopic Index of Severity) Score at Week 10 Using Local Non-blinded Assessments [ Time Frame: Baseline, Week 10 ]
   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.
2. Mean Change From Baseline in CDEIS (Crohn's Disease Endoscopic Index of Severity) Score at Week 10 Using Central Blinded Assessments [ Time Frame: Baseline, Week 10 ]
   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.

Secondary Outcome Measures :

1. Percentage of Patients Achieving Mucosal Healing at Week 10 Using Local Non-blinded Assessments [ Time Frame: Week 10 ]
   Mucosal healing is defined as complete absence of ulceration contribution in the CDEIS (Crohn's Disease Endoscopic Index of Severity) score
2. Percentage of Patients Achieving Mucosal Healing at Week 10 Using Central Blinded Assessments [ Time Frame: Week 10 ]
   Mucosal healing is defined as complete absence of ulceration contribution in the CDEIS (Crohn's Disease Endoscopic Index of Severity) score
3. Percentage of Patients Achieving Mucosal Healing at Week 54 Using Local Non-blinded Assessments [ Time Frame: Week 54 ]
   Mucosal healing is defined as complete absence of ulceration contribution in the CDEIS (Crohn's Disease Endoscopic Index of Severity) score
4. Percentage of Patients Achieving Mucosal Healing at Week 54 Using Central Blinded Assessments [ Time Frame: Week 54 ]
   Mucosal healing is defined as complete absence of ulceration contribution in the CDEIS (Crohn's Disease Endoscopic Index of Severity) score
5. 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 [ Time Frame: Baseline, Week 10 ]
   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.
6. 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 [ Time Frame: Baseline, Week 10 ]
   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.
7. 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 [ Time Frame: Baseline, Week 54 ]
   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.
8. 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 [ Time Frame: Baseline, Week 54 ]
   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.
9. 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 [ Time Frame: Week 10 ]
   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.
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 [ Time Frame: Week 10 ]
    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.
11. 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 [ Time Frame: Week 54 ]
    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.
12. Percentage of Patients With Endoscopic Remission (Crohn's Disease Endoscopic Index of Severity (CDEIS) Score Below 6) at Week 54 Using Central Blinded Assessments [ Time Frame: Week 54 ]
    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.
13. 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 [ Time Frame: Week 10 ]
    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.
14. 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 [ Time Frame: Week 10 ]
    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.
15. 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 [ Time Frame: Week 54 ]
    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.
16. 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 [ Time Frame: Week 54 ]
    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.
17. Change From Baseline in Histological Crohn's Disease Score at Week 10 Using Central Blinded Assessment [ Time Frame: Baseline, Week 10 ]
    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.
18. Change From Baseline in Histological Crohn's Disease Score at Week 54 Using Central Blinded Assessment [ Time Frame: Baseline, Week 54 ]
    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.
19. 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 [ Time Frame: Baseline, 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.
20. 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 [ Time Frame: Baseline, 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.
21. 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 [ Time Frame: 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.
22. 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 [ Time Frame: 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.
23. Geometric Mean C-Reactive Protein (CRP) Level (mg/L) at Week 10 [ Time Frame: Week 10 ]
24. Ratio to Baseline of C-Reactive Protein (CRP) Level (mg/L) at Week 10 [ Time Frame: Baseline, Week 10 ]
    Ratio is calculated as the Week 10 value divided by the Baseline value for patients with data at both timepoints.
25. Geometric Mean C-Reactive Protein (CRP) Level (mg/L) at Week 52 [ Time Frame: Week 52 ]
26. Ratio to Baseline of C-Reactive Protein (CRP) Level (mg/L) at Week 52 [ Time Frame: Baseline, Week 52 ]
    The ratio is calculated as the Week 52 value divided by Baseline value for patients with data at both timepoints.
27. Correlation Between Mean C-Reactive Protein (CRP) Plasma Level and Crohn's Disease Activity Index (CDAI) Score at Week 10 [ Time Frame: 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.
28. 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 [ Time Frame: Week 10 ]
    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.
29. 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 [ Time Frame: Week 10 ]
    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.
30. Correlation Between Mean C-Reactive Protein (CRP) Plasma Level and Histological Crohn's Disease Score at Week 10 Using Central Blinded Assessment [ Time Frame: Week 10 ]
    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
31. Change From Baseline in Crohn's Disease Endoscopic Index of Severity (CDEIS) Score at Week 54 Using Local Non-blinded Assessment [ Time Frame: Baseline, Week 54 ]
    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.
32. Change From Baseline in Crohn's Disease Endoscopic Index of Severity (CDEIS) Score at Week 54 Using Central Blinded Assessment [ Time Frame: Baseline, Week 54 ]
    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.
33. Change From Baseline in Crohn's Disease Activity Index (CDAI) Score at Week 10 [ Time Frame: Baseline, 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.
34. Change From Baseline in Crohn's Disease Activity Index (CDAI) Score at Week 54 [ Time Frame: Baseline, 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Belgium

Bonheiden, Belgium

Brussels, Belgium

Edegem, Belgium

Leuven, Belgium

France

Amiens, France

Besancon, France

Chambray-Les-Tours, France

Clichy, France

Grenoble, France

Lille, France

Marseille, France

Nice, France

Paris, France

Reims, France

Rouen, France

Strasbourg, France

Vandoeuvre Les Nancy, France

Germany

Berlin, Germany

Bonn, Germany

Sponsors and Collaborators

UCB Pharma

Investigators

• Study Director: UCB Clinical Trial Call Center; +1 877 822 9493 (UCB)

More Information

Additional Information:

Product Information 

FDA Safety Alerts and Recalls 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Colombel JF, Sandborn WJ, Allez M, Dupas JL, Dewit O, D'Haens G, Bouhnik Y, Parker G, Pierre-Louis B, Hébuterne X. Association between plasma concentrations of certolizumab pegol and endoscopic outcomes of patients with Crohn's disease. Clin Gastroenterol Hepatol. 2014 Mar;12(3):423-31.e1. doi: 10.1016/j.cgh.2013.10.025. Epub 2013 Nov 1.

Hébuterne X, Lémann M, Bouhnik Y, Dewit O, Dupas JL, Mross M, D'Haens G, Mitchev K, Ernault É, Vermeire S, Brixi-Benmansour H, Moreels TG, Mary JY, Marteau P, Colombel JF. Endoscopic improvement of mucosal lesions in patients with moderate to severe ileocolonic Crohn's disease following treatment with certolizumab pegol. Gut. 2013 Feb;62(2):201-8. doi: 10.1136/gutjnl-2012-302262. Epub 2012 Apr 23.

• Responsible Party: UCB Pharma
• ClinicalTrials.gov Identifier: NCT00297648
• Other Study ID Numbers: C87043; EudraCT Number 2005-003977-25 ( Other Identifier: EudraCT )
• First Posted: February 28, 2006
• Results First Posted: January 18, 2010
• Last Update Posted: August 31, 2011
• Last Verified: February 2011

Keywords provided by UCB Pharma:

Certolizumab pegol; Crohn's disease; Mucosal healing

Additional relevant MeSH terms:

Crohn Disease; Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Certolizumab Pegol; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents