Evaluation of Efficacy and Safety of Tralokinumab in Patients With Active, Moderate-to-severe Ulcerative Colitis

Phase 2

Completed

• Conditions: Ulcerative Colitis
• Interventions: Drug: placebo; Drug: tralokinumab

• Registration Number: NCT01482884
• Lead Sponsor: AstraZeneca

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

Study Timeline

• Study First Submitted: 2011-11-29
• Study First Submitted QC: 2011-11-30
• Study First Posted: 2011-12-01
• Study Start: 2012-03
• Primary Completion: 2013-03
• Study Completion: 2013-06
• Disposition First Submitted: 2015-01-12
• Disposition First Submitted QC: 2015-01-12
• Results First Submitted: 2015-01-20
• Disposition First Posted: 2015-01-21
• Status Verified: 2016-03
• Results First Submitted QC: 2016-03-07
• Last Update Submitted: 2016-03-07
• Results First Posted: 2016-04-05
• Last Update Posted: 2016-04-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 147

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2	placebo	placebo sc injection
1	tralokinumab	tralokinumab (CAT-354) sc injection

Primary Outcome Measures

Name	Time	Method
Clinical Response at Week 8 Based on Mayo Score	Eight week treatment period	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

Name	Time	Method
Change From Baseline in C - Reactive Protein	From baseline to Week 4, 8, 12, 16, 20, and 24.
Change in Mayo Score From Baseline to Week 8	Eight week treatment period	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	Eight week treatment period	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	Eight week treatment period	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	From baseline to Week 4, 8, 12, 16, 20, and 24.	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	Eight week treatment period	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 Albumin	From baseline to Week 4, 8, 12, 16, 20, and 24.
Change From Baseline in Calprotectin	From baseline to Week 4, 8, 12, 16, 20, and 24.
Serum Concentration of Tralokinumab	Pre-dose sampling at baseline, Week 4, 8, 12, 16, 20, and 24.
Immunogenicity	Pre-dose sampling at baseline, Week 8, 12, 16, and 24.	Incidence of anti-drug antibodies (ADA) to tralokinumab in serum.

Trial Locations

Locations (1)

Research Site; 🇬🇧 Shrewsbury, United Kingdom