Evaluation of Safety, Efficacy, Pharmacokinetic and Pharmacodynamic of Bertilimumab in Patients With Active Moderate to Severe Ulcerative Colitis
Ulcerative Colitis, Active Moderate
Ulcerative Colitis, Active Severe
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||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|
- Clinical response [ Time Frame: Day 56 ] [ Designated as safety issue: No ]
- A decrease in Mayo score from baseline of at least 3 points and at least 30% AND
- Either a decrease in the sub-score for rectal bleeding of at least 1 point, or rectal bleeding sub-score of 0 or 1.
- Change in UCEIS score from screening to Day 56 [ Time Frame: Da 56 ] [ Designated as safety issue: No ]
- Clinical remission at Day 56, defined as a total Mayo score of 2 points or lower, with no individual sub-score exceeding 1 point [ Time Frame: Day 56 ] [ Designated as safety issue: No ]
- Mucosal healing at Day 56, defined as an absolute sub-score for endoscopy of 0 or 1. [ Time Frame: Day 56 ] [ Designated as safety issue: No ]
- Change in partial Mayo score from Day 0 to all scheduled measurement timepoints (efficacy follow up). [ Time Frame: Throughout the study ] [ Designated as safety issue: No ]
- PHARMACOKINETICS [ Time Frame: Throughout the study ] [ Designated as safety issue: No ]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
- PHARMACODYNAMIC [ Time Frame: Throughout the study ] [ Designated as safety issue: No ]
- 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
- Safety [ Time Frame: Throughout the study ] [ Designated as safety issue: Yes ]
- Adverse events (AE)
- Injection site reactions
- Physical examination
- Vital signs (blood pressure, heart rate, temperature and respiratory rate)
- Concomitant medications
- Laboratory evaluation (hematology, biochemistry, anti-bertilimumab antibodies).
|Study Start Date:||July 2015|
|Estimated Study Completion Date:||November 2016|
|Estimated Primary Completion Date:||October 2016 (Final data collection date for primary outcome measure)|
Bertilimumab 10 mg/kg will be administered by IV infusion over 30 minutes
Placebo Comparator: Placebo
Phosphate buffered saline (PBS) placebo will be administered by IV infusion over 30 minutes.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01671956
|Rambam Medical Center||Not yet recruiting|
|Haifa, Israel, 31096|
|Contact: Mati Waterman 972-50-2061361 firstname.lastname@example.org|
|Contact: Daliya Katz, Study Cordinator 972-4-8541777 email@example.com|
|Principal Investigator: Mati Waterman, Dr|
|Wolfson Medical Center||Not yet recruiting|
|Holon, Israel, 58100|
|Contact: Yona Avni, Dr 972-3-5028499 firstname.lastname@example.org|
|Contact: Orit Shevah, Study Cordunator 972-50-2562560 email@example.com|
|Principal Investigator: Yona Avni, Dr|
|Hadassah Ein Kerem||Recruiting|
|Jerusalem, Israel, 91120|
|Contact: Eran Israeli, Dr 972-2-6776848 firstname.lastname@example.org|
|Contact: Galina Gerber, Study Cordinator 972-50-5172626 email@example.com|
|Principal Investigator: Eran Israeli, Dr|
|Shaare Tzedek Medical Central||Not yet recruiting|
|Jerusalem, Israel, 91031|
|Contact: Eran Goldin, Prof. 02-6555916 firstname.lastname@example.org|
|Contact: Chava Kaniel, Study Cordinator 972-2-6666916 email@example.com|
|Principal Investigator: Eran Goldin, Prof|
|Meir Medical Center||Recruiting|
|Kfar-Saba, Israel, 44299|
|Contact: Fred Konikoff, Prof 972-09-7472523 Fred.Konikoff@clalit.org.il|
|Contact: Lee Graidy, Study Cordinator 972-9-7471017 firstname.lastname@example.org|
|Principal Investigator: Fred Kinikoff, Prof|
|Sourasky-Ichilov Tel Aviv Medical Center||Not yet recruiting|
|Tel- Aviv, Israel, 64239|
|Contact: Sigal Fishman, Dr 972-52-4262625 email@example.com|
|Contact: Liana Shmialov, Study Cordinator 972-52-6608388 firstname.lastname@example.org|
|Principal Investigator: Sigal Fishman, Dr|
|Principal Investigator:||Eran Goldin, Prof||Shaare Zedek Medical Center|