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

This study has been completed.
Sponsor:
Collaborator:
MedImmune Ltd
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01482884
First received: November 29, 2011
Last updated: March 7, 2016
Last verified: March 2016
  Purpose
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.

Condition Intervention Phase
Ulcerative Colitis
Drug: tralokinumab
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Clinical Response at Week 8 Based on Mayo Score [ Time Frame: Eight week treatment period ] [ Designated as safety issue: No ]
    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 [ Time Frame: Eight week treatment period ] [ Designated as safety issue: No ]
    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 [ Time Frame: Eight week treatment period ] [ Designated as safety issue: No ]
    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 [ Time Frame: Eight week treatment period ] [ Designated as safety issue: No ]
    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 [ Time Frame: From baseline to Week 4, 8, 12, 16, 20, and 24. ] [ Designated as safety issue: No ]
    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 [ Time Frame: Eight week treatment period ] [ Designated as safety issue: No ]
    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 [ Time Frame: From baseline to Week 4, 8, 12, 16, 20, and 24. ] [ Designated as safety issue: No ]
  • Change From Baseline in Albumin [ Time Frame: From baseline to Week 4, 8, 12, 16, 20, and 24. ] [ Designated as safety issue: No ]
  • Change From Baseline in Calprotectin [ Time Frame: From baseline to Week 4, 8, 12, 16, 20, and 24. ] [ Designated as safety issue: No ]
  • Serum Concentration of Tralokinumab [ Time Frame: Pre-dose sampling at baseline, Week 4, 8, 12, 16, 20, and 24. ] [ Designated as safety issue: No ]
  • Immunogenicity [ Time Frame: Pre-dose sampling at baseline, Week 8, 12, 16, and 24. ] [ Designated as safety issue: No ]
    Incidence of anti-drug antibodies (ADA) to tralokinumab in serum.


Enrollment: 147
Study Start Date: March 2012
Study Completion Date: June 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
tralokinumab (CAT-354) sc injection
Drug: tralokinumab
2 sc injections of every 2 weeks for 12 weeks.
Placebo Comparator: 2
placebo sc injection
Drug: placebo
2 sc injections of every 2 weeks for 12 weeks.

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
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01482884

Locations
Czech Republic
Research Site
Ceske Budejovice, Czech Republic
Research Site
Hradec Kralove, Czech Republic
Research Site
Olomouc, Czech Republic
Research Site
Praha 1, Czech Republic
Research Site
Praha 5, Czech Republic
Research Site
Praha 7, Czech Republic
France
Research Site
Amiens Cedex 1, France
Research Site
Caen, France
Research Site
Clichy, France
Research Site
Nice Cedex 3, France
Research Site
Pessac, France
Research Site
Rouen, France
Research Site
Vandoeuvre Les Nancy, France
Germany
Research Site
Ludwigshafen, Germany
Research Site
Oelde, Germany
Research Site
Potsdam, Germany
Research Site
Wangen, Germany
Italy
Research Site
Firenze, Italy
Research Site
Padova, Italy
Research Site
Roma, Italy
Research Site
Rozzano, Italy
Poland
Research Site
Bydgoszcz, Poland
Research Site
Częstochowa, Poland
Research Site
Sopot, Poland
Research Site
Warszawa, Poland
Research Site
Łódź, Poland
United Kingdom
Research Site
Cambridge, United Kingdom
Research Site
Coventry, United Kingdom
Research Site
Oxford, United Kingdom
Research Site
Shrewsbury, United Kingdom
Sponsors and Collaborators
AstraZeneca
MedImmune Ltd
Investigators
Study Director: Mark Berner Hansen, MD, PhD AstraZeneca R&D Mölndal Pepparedsleden 1, S-431 83 Mölndal, Sweden
Principal Investigator: Silvio Danese, MD, PhD IBD Center, Instituto Clinico Humanitas, Department of Gastroenterology, Via Manzoni 56, 20089 Rozzano, Milan, Italy
  More Information

Additional Information:
Publications:
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01482884     History of Changes
Other Study ID Numbers: D2211C00001  EudraCT number 2011-004812-40 
Study First Received: November 29, 2011
Results First Received: January 20, 2015
Last Updated: March 7, 2016
Health Authority: Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Paul-Ehrlich-Institut
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by AstraZeneca:
tralokinumab
inflammatory bowel disease
moderate to severe ulcerative colitis

Additional relevant MeSH terms:
Colitis
Ulcer
Colitis, Ulcerative
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases

ClinicalTrials.gov processed this record on September 23, 2016