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

A Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multi-Center Study Designed to Evaluate the Safety, Efficacy, Pharmacokinetic and Pharmacodynamic Profile of Bertilimumab in Patients With Active Moderate to Severe Ulcerative Colitis

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

Study Overview

• Status: Terminated
• Conditions: Ulcerative Colitis, Active Severe; Ulcerative Colitis, Active Moderate
• Intervention / Treatment: Biological: Bertilimumab; Biological: Placebo

Detailed Description

This is a randomized, double blind, placebo-controlled, parallel group multi-center study in adult patients with active moderate to severe UC . Eligible patients will be randomly assigned in a 2:1 ratio to one of two treatment groups, bertilimumab 10 mg/kg or matching placebo, respectively.

The study will consist of three periods: a screening period of up to two weeks, a 4-week double-blind treatment period (three IV infusions at 2-week intervals), and a safety and efficacy follow-up period of approximately 9 weeks.

Bertilimumab is a recombinant human IgG4 monoclonal antibody that neutralizes human eotaxin-1 (eotaxin). Bertilimumab will be administered every other week for 4-weeks, by IV infusion over 30 minutes.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2

Contacts and Locations

Study Locations

• Israel
  • Afula, Israel
    • Research Site
  • Holon, Israel, 58100
    • Research Site
  • Jerusalem, Israel, 91031
    • Research Site
  • Jerusalem, Israel, 91120
    • Research Site
  • Kfar Saba, Israel, 44299
    • Research Site
  • Tel Aviv, Israel, 64239
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Males or females, 18 to 70 years of age inclusive.

2. 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.
3. Levels of eotaxin-1 in biopsied colon tissue of ≥100 pg/mg protein.
4. 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:

1. History of colonic or rectal surgery other than hemorrhoidal surgery or appendectomy.
2. Currently receiving total parenteral nutrition (TPN).
3. Positive Clostridium difficile toxin stool assay.
4. Tested positive for active/latent mycobacterium tuberculosis (TB) infection.
5. Pregnant or breast-feeding, or plan to become pregnant during the study.
6. Males who are young and childless or planning to have more children in the future.
7. Known hypersensitivity to bertilimumab or any of the drug excipients.
8. 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.
9. 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.
10. Ulcerative proctitis, defined as disease limited to less than 15 cm from the anal verge.
11. Received a vaccine or other immunostimulator within 4 weeks prior to screening.
12. 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.
13. 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).
14. Change in dose of immunosuppressive drugs (e.g., corticosteroids, 6-mercaptopurine [6-MP], azathioprine) within four weeks prior to the screening visit.
15. Use of TNF-blockers (e.g., infliximab or adalimumab) within 60 days of the screening visit.
16. 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.

17. 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.
18. History of positive serology of hepatitis B or C, or human immunodeficiency virus (HIV) infection.
19. Congenital or acquired immunodeficiency (e.g., common variable immunodeficiency, organ transplantation).

20. 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.
21. Active abuse of alcohol or drugs.
22. Known malignancy or history of malignancy that could reduce life expectancy.
23. Any condition, which in the opinion of the Investigator, would place the patient at an unacceptable risk if participating in the study protocol.
24. Participation in a clinical trial of an investigational (unapproved) product

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bertilimumab; Bertilimumab 10 mg/kg will be administered by IV infusion over 30 minutes	Biological: Bertilimumab; IV infusion over 30 minutes, at Day 0, Day 14 and Day 28
Placebo Comparator: Placebo; Phosphate buffered saline (PBS) placebo will be administered by IV infusion over 30 minutes.	Biological: Placebo; IV infusion over 30 minutes, at Day 0, Day 14 and Day 28

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Total Mayo Score at Day 56	The Total Mayo score is an instrument designed to measure disease activity of ulcerative colitis and ranged from 0 (normal or inactive disease) to 12 (severe disease). It is a composite of 4 sub-scores: Stool frequency sub-score, rectal bleeding sub-score, endoscopic finding sub-score, and physician's global assessment sub-score, each of which ranges from 0 (normal) to 3 (severe disease). The sub-scores were summed to give a total score that ranged from 0-12. Change in mayo score was calculated as the sum of scores at Day 56 minus the sum of scores at Baseline divided by 14 for bertilimumab arm and sum of scores at Day 56 minus the sum of scores at Baseline divided by 6 for placebo arm.	Baseline, Day 56

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Ulcerative Colitis Endoscopic Index of Severity (UCEIS) Score at Day 56	The UCEIS is the validated index for the assessment of overall endoscopic activity. The model incorporated the vascular pattern score (0-2), the presence of bleeding score (0-3) and the presence of erosions and ulcers score (0-3). The total score ranged from 0-8. Higher scores indicated more severe disease. Change in mayo score was calculated as the sum of scores at Day 56 minus the sum of scores at Baseline divided by 15 for bertilimumab arm and sum of scores at Day 56 minus the sum of scores at Baseline divided by 6 for placebo arm.	Baseline, Day 56

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
PHARMACOKINETICS	PK analysis for bertilimumab concentration: blood samples will be collected on dosing days (pre-dose and at 30 minutes and 4 hours following initiation of study drug infusion) and at the follow-up visits. The following PK parameters will be calculated, to the degree possible given the number of timepoints: Cmax, Tmax, Cavg, Cmin and t1/2. Additional standard and exploratory PK parameters will be calculated if deemed necessary	Throughout the study
PHARMACODYNAMIC	Fecal calprotectin change from Day 0 (baseline) to all scheduled measurement timepoints.; PD analysis of eosinophil shape change: blood samples will be collected on dosing days (pre-dose and on Day 0 only, at 4 hours following initiation of study drug infusion), and at the follow-up visits.; Change in eosinophil count, serum eotaxin-1 and hs-CRP from Day 0 to all scheduled measurement timepoints.; Change in eotaxin-1 concentration and eosinophil count in biopsy tissue from Screening to Day 56	Throughout the study
Safety	Adverse events (AE); Injection site reactions; Physical examination; Vital signs (blood pressure, heart rate, temperature and respiratory rate); ECG; Concomitant medications; Laboratory evaluation (hematology, biochemistry, anti-bertilimumab antibodies).	Throughout the study

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals, Inc.
• Collaborators: Immune Pharmaceuticals
• Investigators: Principal Investigator: Dov Wengrower, MD, Shaare Zedek Medical Center, Jerusalem, Israel

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2015
• Primary Completion (Actual): August 31, 2018
• Study Completion (Actual): November 14, 2018

Study Registration Dates

• First Submitted: August 9, 2012
• First Submitted That Met QC Criteria: August 21, 2012
• First Posted (Estimated): August 24, 2012

Study Record Updates

• Last Update Posted (Estimated): November 25, 2025
• Last Update Submitted That Met QC Criteria: November 14, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Ulcerative Colitis; IBD; Colitis; UC
• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: Immune/BRT/UC-01