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

Study Overview
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Brief Summary
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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
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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

Official Title
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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

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: tralokinumab
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>tralokinumab (CAT-354) sc injection | Drug: tralokinumab<br>* 2 sc injections of every 2 weeks for 12 weeks.<br>|
| Placebo Comparator: 2<br>placebo sc injection | Drug: placebo<br>* 2 sc injections of every 2 weeks for 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Eight week treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Eight week treatment period | 
| 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. | Eight week treatment period | 
| 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. | Eight week treatment period | 
| 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. | From baseline to Week 4, 8, 12, 16, 20, and 24. | 
| 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. | Eight week treatment period | 
| Change From Baseline in C - Reactive Protein |  | From baseline to Week 4, 8, 12, 16, 20, and 24. | 
| 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 | Incidence of anti-drug antibodies (ADA) to tralokinumab in serum. | Pre-dose sampling at baseline, Week 8, 12, 16, and 24. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tralokinumab, inflammatory bowel disease, moderate to severe ulcerative colitis