Evaluation of Safety, Efficacy, Pharmacokinetic and Pharmacodynamic of Bertilimumab in Patients With Active Moderate to Severe Ulcerative Colitis

Study Identifier:
Immune/BRT/UC-01
ClinicalTrials.gov Identifier:
NCT01671956
EudraCT Identifier:
N/A
EU CT ID:
N/A
Sponsor:
Alexion Pharmaceuticals, Inc.
Study Contact Information:
N/A
Other

Available Documents

ProtocolStatistical Analysis Plan

Study Details

Medical Condition
  • Unmapped
Study Drug
  • Biological: Bertilimumab
  • Biological: Placebo
Date
Jul 2015 - Aug 2018
Phase 1
Phase 2
Phase 3
Phase 4
N/A
Patient Requirements
Sex: Female & Male
Age: 18 - 70 Years
Requirements Information
Inclusion and Exclusion Criteria
Inclusion Criteria
  • Males or females, 18 to 70 years of age inclusive.
  • Diagnosed with active moderate to severe UC per standard diagnostic criteria for a minimum of 3 months:
  • Mayo score of 6-12 (inclusive) at the Screening Visit
  • Endoscopic evidence of active mucosal disease, as assessed by flexible sigmoidoscopy, with an Endoscopic Finding Sub-score of ≥2 (assessed centrally)
  • Rectal Bleeding Sub-score of ≥1
  • Physician's Global Assessment (PGA) Sub-score of ≥2.
  • Levels of eotaxin-1 in biopsied colon tissue of ≥100 pg/mg protein.
  • Adequate cardiac, renal and hepatic function as determined by the Investigator and demonstrated by screening laboratory evaluations and physical examination results; these findings must all be within normal limits or judged not clinically significant by the Investigator.
Exclusion Criteria
  • History of colonic or rectal surgery other than hemorrhoidal surgery or appendectomy.
  • Currently receiving total parenteral nutrition (TPN).
  • Positive Clostridium difficile toxin stool assay.
  • Tested positive for active/latent mycobacterium tuberculosis (TB) infection.
  • Pregnant or breast-feeding, or plan to become pregnant during the study.
  • Males who are young and childless or planning to have more children in the future.
  • Known hypersensitivity to bertilimumab or any of the drug excipients.
  • History of infection requiring administration of any IV antibiotic, antiviral or antifungal medication within 30 days of Screening or any oral anti-infective agent within 14 days of Screening.
  • Severe UC evidenced by the following signs of toxicity: heart rate \>100 beats/min at rest, temperature \>37.8°C, hemoglobin \<10.0 g/dL.
  • Ulcerative proctitis, defined as disease limited to less than 15 cm from the anal verge.
  • Received a vaccine or other immunostimulator within 4 weeks prior to screening.
  • Use of \>4.8 g mesalazine or equivalent within 2 weeks prior to the screening visit. Mesalazine ≤4.8 g is allowed if the dose during the 2 weeks prior to the screening visit was stable.
  • Use of systemic corticosteroids exceeding the equivalent of 20 mg/day of prednisone within four weeks prior to the screening visit (see Section 6.9.1).
  • Change in dose of immunosuppressive drugs (e.g., corticosteroids, 6-mercaptopurine \[6-MP\], azathioprine) within four weeks prior to the screening visit.
  • Use of TNF-blockers (e.g., infliximab or adalimumab) within 60 days of the screening visit.
  • Use of chronic non-steroidal anti-inflammatory (NSAID) therapy. Occasional use of NSAIDs or acetaminophen for headache, arthritis, myalgias, menstrual cramps, etc., or daily use of low dose (81-162 mg) aspirin for cardiovascular prophylaxis is allowed.
  • Patients diagnosed with:
  • Crohn's disease
  • Diverticulitis or diverticulosis
  • Indeterminate colitis (inability to distinguish between UC and Crohn's disease \[as assessed by the Investigator\])
  • Microscopic colitis (collagenous or lymphocytic colitis)
  • Ischemic or infectious colitis
  • Clostridium difficile colitis within 90 days of the screening visit
  • Parasitic disease within 90 days of the screening visit
  • Systemic fungal infection within 90 days of the screening visit.
  • History of positive serology of hepatitis B or C, or human immunodeficiency virus (HIV) infection.
  • Congenital or acquired immunodeficiency (e.g., common variable immunodeficiency, organ transplantation).
  • Clinically significant abnormal laboratory test results, unless regarded by the Investigator as related to UC, including but not limited to:
  • Hemoglobin level \<10.0 g/dL
  • White blood cell count \< 3 x 103/µL
  • Lymphocyte count \< 0.5 x 103/µL
  • Platelet count \<100 x 103/µL or \>1200 x 103/µL
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>3 the upper limit of normal (ULN)
  • Alkaline phosphatase \>3 ULN
  • Serum creatinine \>2 ULN.
  • Active abuse of alcohol or drugs.
  • Known malignancy or history of malignancy that could reduce life expectancy.
  • Any condition, which in the opinion of the Investigator, would place the patient at an unacceptable risk if participating in the study protocol.
  • Participation in a clinical trial of an investigational (unapproved) product
Sex
Female & Male
Age
18 - 70 Years

Study Details

Medical Condition
  • Unmapped
Study Drug
  • Biological: Bertilimumab
  • Biological: Placebo
Date
Jul 2015 - Aug 2018
Phase 1
Phase 2
Phase 3
Phase 4
N/A
Patient Requirements
Sex: Female & Male
Age: 18 - 70 Years years
Requirements Information
Inclusion and Exclusion Criteria
Inclusion Criteria
  • Males or females, 18 to 70 years of age inclusive.
  • Diagnosed with active moderate to severe UC per standard diagnostic criteria for a minimum of 3 months:
  • Mayo score of 6-12 (inclusive) at the Screening Visit
  • Endoscopic evidence of active mucosal disease, as assessed by flexible sigmoidoscopy, with an Endoscopic Finding Sub-score of ≥2 (assessed centrally)
  • Rectal Bleeding Sub-score of ≥1
  • Physician's Global Assessment (PGA) Sub-score of ≥2.
  • Levels of eotaxin-1 in biopsied colon tissue of ≥100 pg/mg protein.
  • Adequate cardiac, renal and hepatic function as determined by the Investigator and demonstrated by screening laboratory evaluations and physical examination results; these findings must all be within normal limits or judged not clinically significant by the Investigator.
Exclusion Criteria
  • History of colonic or rectal surgery other than hemorrhoidal surgery or appendectomy.
  • Currently receiving total parenteral nutrition (TPN).
  • Positive Clostridium difficile toxin stool assay.
  • Tested positive for active/latent mycobacterium tuberculosis (TB) infection.
  • Pregnant or breast-feeding, or plan to become pregnant during the study.
  • Males who are young and childless or planning to have more children in the future.
  • Known hypersensitivity to bertilimumab or any of the drug excipients.
  • History of infection requiring administration of any IV antibiotic, antiviral or antifungal medication within 30 days of Screening or any oral anti-infective agent within 14 days of Screening.
  • Severe UC evidenced by the following signs of toxicity: heart rate \>100 beats/min at rest, temperature \>37.8°C, hemoglobin \<10.0 g/dL.
  • Ulcerative proctitis, defined as disease limited to less than 15 cm from the anal verge.
  • Received a vaccine or other immunostimulator within 4 weeks prior to screening.
  • Use of \>4.8 g mesalazine or equivalent within 2 weeks prior to the screening visit. Mesalazine ≤4.8 g is allowed if the dose during the 2 weeks prior to the screening visit was stable.
  • Use of systemic corticosteroids exceeding the equivalent of 20 mg/day of prednisone within four weeks prior to the screening visit (see Section 6.9.1).
  • Change in dose of immunosuppressive drugs (e.g., corticosteroids, 6-mercaptopurine \[6-MP\], azathioprine) within four weeks prior to the screening visit.
  • Use of TNF-blockers (e.g., infliximab or adalimumab) within 60 days of the screening visit.
  • Use of chronic non-steroidal anti-inflammatory (NSAID) therapy. Occasional use of NSAIDs or acetaminophen for headache, arthritis, myalgias, menstrual cramps, etc., or daily use of low dose (81-162 mg) aspirin for cardiovascular prophylaxis is allowed.
  • Patients diagnosed with:
  • Crohn's disease
  • Diverticulitis or diverticulosis
  • Indeterminate colitis (inability to distinguish between UC and Crohn's disease \[as assessed by the Investigator\])
  • Microscopic colitis (collagenous or lymphocytic colitis)
  • Ischemic or infectious colitis
  • Clostridium difficile colitis within 90 days of the screening visit
  • Parasitic disease within 90 days of the screening visit
  • Systemic fungal infection within 90 days of the screening visit.
  • History of positive serology of hepatitis B or C, or human immunodeficiency virus (HIV) infection.
  • Congenital or acquired immunodeficiency (e.g., common variable immunodeficiency, organ transplantation).
  • Clinically significant abnormal laboratory test results, unless regarded by the Investigator as related to UC, including but not limited to:
  • Hemoglobin level \<10.0 g/dL
  • White blood cell count \< 3 x 103/µL
  • Lymphocyte count \< 0.5 x 103/µL
  • Platelet count \<100 x 103/µL or \>1200 x 103/µL
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>3 the upper limit of normal (ULN)
  • Alkaline phosphatase \>3 ULN
  • Serum creatinine \>2 ULN.
  • Active abuse of alcohol or drugs.
  • Known malignancy or history of malignancy that could reduce life expectancy.
  • Any condition, which in the opinion of the Investigator, would place the patient at an unacceptable risk if participating in the study protocol.
  • Participation in a clinical trial of an investigational (unapproved) product

Protocol Summary

This is a randomized, double blind, placebo-controlled, parallel group multi-center study in adult participants with active moderate to severe UC.

Trial Locations

Location
Status
Location
Research Site
Afula, Israel
Status
N/A
Location
Research Site
Holon, Israel, 58100
Status
N/A
Location
Research Site
Jerusalem, Israel, 91031
Status
N/A
Location
Research Site
Kfar Saba, Israel, 44299
Status
N/A
Location
Research Site
Tel Aviv, Israel, 64239
Status
N/A