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
Overview
- Phase
- Phase 2
- Intervention
- Bertilimumab
- Conditions
- Ulcerative Colitis, Active Moderate
- Sponsor
- Alexion Pharmaceuticals, Inc.
- Enrollment
- 32
- Locations
- 1
- Primary Endpoint
- Change From Baseline in Total Mayo Score at Day 56
- Status
- Terminated
- Last Updated
- 5 months ago
Overview
Brief Summary
This is a randomized, double blind, placebo-controlled, parallel group multi-center study in adult participants with active moderate to severe UC.
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.
Investigators
Eligibility 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 ≥
- •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.
Arms & Interventions
Bertilimumab
Bertilimumab 10 mg/kg will be administered by IV infusion over 30 minutes
Intervention: Bertilimumab
Placebo
Phosphate buffered saline (PBS) placebo will be administered by IV infusion over 30 minutes.
Intervention: Placebo
Outcomes
Primary Outcomes
Change From Baseline in Total Mayo Score at Day 56
Time Frame: Baseline, 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.
Secondary Outcomes
- Change From Baseline in Ulcerative Colitis Endoscopic Index of Severity (UCEIS) Score at Day 56(Baseline, Day 56)