Evaluation of Efficacy and Safety of Tralokinumab in Patients With Active, Moderate-to-severe Ulcerative Colitis
Primary Purpose
Ulcerative Colitis
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
tralokinumab
placebo
Sponsored by
About this trial
This is an interventional treatment trial for Ulcerative Colitis focused on measuring tralokinumab, inflammatory bowel disease, moderate to severe ulcerative colitis
Eligibility Criteria
Inclusion Criteria:
- Diagnosed ulcerative colitis at least 90 days prior randomisation.
- Men or women age 18 - 75 years.
- Non-hospitalized patients with moderate-severe ulcerative colitis treated with stable background UC therapy (e.g. containing 5-aminosalicylates, and/or low dose of glucocorticosteroids, and/or purine analogue) prior to randomization.
- Females of childbearing potential who are sexually active with a nonsterilized male partner must use highly effective contraception from Day1.
- Nonsterilized males or sterilized males who are ≤1 year post-vasectomy who are sexually active with a female partner of childbearing potential must use a highly effective method of contraception.
Exclusion Criteria:
- Pregnant or breastfeeding women.
- History of colostomy.
- Current diagnosis of indeterminate colitis, Crohn's disease, ischemic colitis, fulminant colitis and/or toxic megacolon and patients with ulcerative colitis limited to the rectum (ulcerative proctitis).
- Hepatitis B, C or HIV.
- History of cancer.
Sites / Locations
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Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
1
2
Arm Description
tralokinumab (CAT-354) sc injection
placebo sc injection
Outcomes
Primary Outcome Measures
Clinical Response at Week 8 Based on Mayo Score
Clinical response was measured as a decrease in Mayo score of ≥3 points from baseline, decrease in the total Mayo score from baseline ≥30 percentage and a decrease in the sub score for rectal bleeding ≥1 or absolute sub score for rectal bleeding of 0 or 1 point. Mayo score is sum of four sub-scores: stool frequency, rectal bleeding, endoscopy findings and the physician's global assessment. The total Mayo score ranges from 0-12, with higher scores indicating a more severe disease.
Secondary Outcome Measures
Change in Mayo Score From Baseline to Week 8
Mayo score is sum of four sub-scores: stool frequency, rectal bleeding, endoscopy findings and the physician's global assessment. The total Mayo score ranges from 0-12, with higher scores indicating a more severe disease. Change from baseline: Mayo score at week 8 minus the Mayo score at baseline.
Mucosal Healing at Week 8 Based on Mayo Score
Improvement of the endoscopy sub score (from the Mayo score) from 3 or 2 to 0 or 1 point, or from 1 to 0 points.
Clinical Remission at Week 8 Based on Mayo Score
Participants were classified as in remission if Mayo score of ≤2 with no individual sub score exceeding 1 point. Mayo score is sum of four sub-scores: stool frequency, rectal bleeding, endoscopy findings and the physician's global assessment. The total Mayo score ranges from 0-12, with higher scores indicating a more severe disease.
Change From Baseline in Partial Mayo Score
The partial Mayo score is the sum of the three sub-score areas: stool frequency, rectal bleeding, and the physician's global assessment.The partial Mayo score ranges from 0-9, with higher scores indicating a more severe disease. Change from baseline: Mayo score at each post-baseline timepoint (week 4, 8, 12, 16, 20, and 24) minus the Mayo score at baseline.
Change From Baseline in Modified Riley Score
Modified Riley score is biopsy grade which range from 0-5; where 0: Normal mucosa, 1: Infiltration of lymphocytes and plasma cells in the lamina propria, 2: Infiltration of neutrophils and eosinophils in the lamina propria, 3: Infiltration of neutrophils in the epithelium, 4: Crypt destruction, 5: Erosion and/or ulceration.
Change From Baseline in C - Reactive Protein
Change From Baseline in Albumin
Change From Baseline in Calprotectin
Serum Concentration of Tralokinumab
Immunogenicity
Incidence of anti-drug antibodies (ADA) to tralokinumab in serum.
Full Information
NCT ID
NCT01482884
First Posted
November 29, 2011
Last Updated
March 7, 2016
Sponsor
AstraZeneca
Collaborators
MedImmune Ltd
1. Study Identification
Unique Protocol Identification Number
NCT01482884
Brief Title
Evaluation of Efficacy and Safety of Tralokinumab in Patients With Active, Moderate-to-severe Ulcerative Colitis
Official Title
A Phase IIa, Randomised, Double-blind, Placebo-controlled, Parallel-arm, Multicenter Study to Evaluate the Efficacy and Safety of Tralokinumab (CAT-354), a Recombinant Human Monoclonal Antibody Directed Against Interleukin-13 (IL-13), as add-on Therapy, on Clinical Response in Patients With Active, Moderate-to-severe, Ulcerative Colitis
Study Type
Interventional
2. Study Status
Record Verification Date
March 2016
Overall Recruitment Status
Completed
Study Start Date
March 2012 (undefined)
Primary Completion Date
March 2013 (Actual)
Study Completion Date
June 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
Collaborators
MedImmune Ltd
4. Oversight
5. Study Description
Brief Summary
The study is designed to evaluate the clinical efficacy and safety of tralokinumab as compared to placebo. Investigational product will be administered as subcutaneous injection. All patients will continue background therapy for ulcerative colitis as per local standards of care in addition to investigational product.
Detailed Description
A phase IIa, randomised, double-blind, placebo-controlled, parallel-arm, multicenter study to evaluate the efficacy and safety of tralokinumab (CAT-354), a recombinant human monoclonal antibody directed against interleukin-13 (IL-13), as add-on therapy, on clinical response in patients with active, moderate-to-severe, ulcerative colitis
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ulcerative Colitis
Keywords
tralokinumab, inflammatory bowel disease, moderate to severe ulcerative colitis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
147 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
tralokinumab (CAT-354) sc injection
Arm Title
2
Arm Type
Placebo Comparator
Arm Description
placebo sc injection
Intervention Type
Drug
Intervention Name(s)
tralokinumab
Intervention Description
2 sc injections of every 2 weeks for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
2 sc injections of every 2 weeks for 12 weeks.
Primary Outcome Measure Information:
Title
Clinical Response at Week 8 Based on Mayo Score
Description
Clinical response was measured as a decrease in Mayo score of ≥3 points from baseline, decrease in the total Mayo score from baseline ≥30 percentage and a decrease in the sub score for rectal bleeding ≥1 or absolute sub score for rectal bleeding of 0 or 1 point. Mayo score is sum of four sub-scores: stool frequency, rectal bleeding, endoscopy findings and the physician's global assessment. The total Mayo score ranges from 0-12, with higher scores indicating a more severe disease.
Time Frame
Eight week treatment period
Secondary Outcome Measure Information:
Title
Change in Mayo Score From Baseline to Week 8
Description
Mayo score is sum of four sub-scores: stool frequency, rectal bleeding, endoscopy findings and the physician's global assessment. The total Mayo score ranges from 0-12, with higher scores indicating a more severe disease. Change from baseline: Mayo score at week 8 minus the Mayo score at baseline.
Time Frame
Eight week treatment period
Title
Mucosal Healing at Week 8 Based on Mayo Score
Description
Improvement of the endoscopy sub score (from the Mayo score) from 3 or 2 to 0 or 1 point, or from 1 to 0 points.
Time Frame
Eight week treatment period
Title
Clinical Remission at Week 8 Based on Mayo Score
Description
Participants were classified as in remission if Mayo score of ≤2 with no individual sub score exceeding 1 point. Mayo score is sum of four sub-scores: stool frequency, rectal bleeding, endoscopy findings and the physician's global assessment. The total Mayo score ranges from 0-12, with higher scores indicating a more severe disease.
Time Frame
Eight week treatment period
Title
Change From Baseline in Partial Mayo Score
Description
The partial Mayo score is the sum of the three sub-score areas: stool frequency, rectal bleeding, and the physician's global assessment.The partial Mayo score ranges from 0-9, with higher scores indicating a more severe disease. Change from baseline: Mayo score at each post-baseline timepoint (week 4, 8, 12, 16, 20, and 24) minus the Mayo score at baseline.
Time Frame
From baseline to Week 4, 8, 12, 16, 20, and 24.
Title
Change From Baseline in Modified Riley Score
Description
Modified Riley score is biopsy grade which range from 0-5; where 0: Normal mucosa, 1: Infiltration of lymphocytes and plasma cells in the lamina propria, 2: Infiltration of neutrophils and eosinophils in the lamina propria, 3: Infiltration of neutrophils in the epithelium, 4: Crypt destruction, 5: Erosion and/or ulceration.
Time Frame
Eight week treatment period
Title
Change From Baseline in C - Reactive Protein
Time Frame
From baseline to Week 4, 8, 12, 16, 20, and 24.
Title
Change From Baseline in Albumin
Time Frame
From baseline to Week 4, 8, 12, 16, 20, and 24.
Title
Change From Baseline in Calprotectin
Time Frame
From baseline to Week 4, 8, 12, 16, 20, and 24.
Title
Serum Concentration of Tralokinumab
Time Frame
Pre-dose sampling at baseline, Week 4, 8, 12, 16, 20, and 24.
Title
Immunogenicity
Description
Incidence of anti-drug antibodies (ADA) to tralokinumab in serum.
Time Frame
Pre-dose sampling at baseline, Week 8, 12, 16, and 24.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosed ulcerative colitis at least 90 days prior randomisation.
Men or women age 18 - 75 years.
Non-hospitalized patients with moderate-severe ulcerative colitis treated with stable background UC therapy (e.g. containing 5-aminosalicylates, and/or low dose of glucocorticosteroids, and/or purine analogue) prior to randomization.
Females of childbearing potential who are sexually active with a nonsterilized male partner must use highly effective contraception from Day1.
Nonsterilized males or sterilized males who are ≤1 year post-vasectomy who are sexually active with a female partner of childbearing potential must use a highly effective method of contraception.
Exclusion Criteria:
Pregnant or breastfeeding women.
History of colostomy.
Current diagnosis of indeterminate colitis, Crohn's disease, ischemic colitis, fulminant colitis and/or toxic megacolon and patients with ulcerative colitis limited to the rectum (ulcerative proctitis).
Hepatitis B, C or HIV.
History of cancer.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark Berner Hansen, MD, PhD
Organizational Affiliation
AstraZeneca R&D Mölndal Pepparedsleden 1, S-431 83 Mölndal, Sweden
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Silvio Danese, MD, PhD
Organizational Affiliation
IBD Center, Instituto Clinico Humanitas, Department of Gastroenterology, Via Manzoni 56, 20089 Rozzano, Milan, Italy
Official's Role
Principal Investigator
Facility Information:
Facility Name
Research Site
City
Ceske Budejovice
Country
Czech Republic
Facility Name
Research Site
City
Hradec Kralove
Country
Czech Republic
Facility Name
Research Site
City
Olomouc
Country
Czech Republic
Facility Name
Research Site
City
Praha 1
Country
Czech Republic
Facility Name
Research Site
City
Praha 5
Country
Czech Republic
Facility Name
Research Site
City
Praha 7
Country
Czech Republic
Facility Name
Research Site
City
Amiens Cedex 1
Country
France
Facility Name
Research Site
City
Caen
Country
France
Facility Name
Research Site
City
Clichy
Country
France
Facility Name
Research Site
City
Nice Cedex 3
Country
France
Facility Name
Research Site
City
Pessac
Country
France
Facility Name
Research Site
City
Rouen
Country
France
Facility Name
Research Site
City
Vandoeuvre Les Nancy
Country
France
Facility Name
Research Site
City
Ludwigshafen
Country
Germany
Facility Name
Research Site
City
Oelde
Country
Germany
Facility Name
Research Site
City
Potsdam
Country
Germany
Facility Name
Research Site
City
Wangen
Country
Germany
Facility Name
Research Site
City
Firenze
Country
Italy
Facility Name
Research Site
City
Padova
Country
Italy
Facility Name
Research Site
City
Roma
Country
Italy
Facility Name
Research Site
City
Rozzano
Country
Italy
Facility Name
Research Site
City
Bydgoszcz
Country
Poland
Facility Name
Research Site
City
Częstochowa
Country
Poland
Facility Name
Research Site
City
Sopot
Country
Poland
Facility Name
Research Site
City
Warszawa
Country
Poland
Facility Name
Research Site
City
Łódź
Country
Poland
Facility Name
Research Site
City
Cambridge
Country
United Kingdom
Facility Name
Research Site
City
Coventry
Country
United Kingdom
Facility Name
Research Site
City
Oxford
Country
United Kingdom
Facility Name
Research Site
City
Shrewsbury
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
25304132
Citation
Danese S, Rudzinski J, Brandt W, Dupas JL, Peyrin-Biroulet L, Bouhnik Y, Kleczkowski D, Uebel P, Lukas M, Knutsson M, Erlandsson F, Hansen MB, Keshav S. Tralokinumab for moderate-to-severe UC: a randomised, double-blind, placebo-controlled, phase IIa study. Gut. 2015 Feb;64(2):243-9. doi: 10.1136/gutjnl-2014-308004. Epub 2014 Oct 10.
Results Reference
result
Links:
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=1241&filename=D2211C00001_Protocol_Redacted.pdf
Description
D2211C00001_Protocol_Redacted
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=1241&filename=D2211C00001_Study_Synopsis_with_changes.pdf
Description
D2211C00001_Study_Synopsis
Learn more about this trial
Evaluation of Efficacy and Safety of Tralokinumab in Patients With Active, Moderate-to-severe Ulcerative Colitis
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