Evaluation of Safety, Efficacy, Pharmacokinetic and Pharmacodynamic of Bertilimumab in Patients With Active Moderate to Severe Ulcerative Colitis
- Conditions
- Ulcerative Colitis, Active ModerateUlcerative Colitis, Active Severe
- Interventions
- Biological: BertilimumabBiological: Placebo
- Registration Number
- NCT01671956
- Lead Sponsor
- Immune Pharmaceuticals
- Brief Summary
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
- 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 42
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Males or females, 18 to 70 years of age inclusive.
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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.
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Levels of eotaxin-1 in biopsied colon tissue of ≥100 pg/mg protein.
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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.
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History of colonic or rectal surgery other than hemorrhoidal surgery or appendectomy.
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Currently receiving total parenteral nutrition (TPN).
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Positive Clostridium difficile toxin stool assay.
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Tested positive for active/latent mycobacterium tuberculosis (TB) infection.
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Pregnant or breast-feeding, or plan to become pregnant during the study.
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Males who are young and childless or planning to have more children in the future.
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Known hypersensitivity to bertilimumab or any of the drug excipients.
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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.
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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.
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Ulcerative proctitis, defined as disease limited to less than 15 cm from the anal verge.
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Received a vaccine or other immunostimulator within 4 weeks prior to screening.
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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.
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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).
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Change in dose of immunosuppressive drugs (e.g., corticosteroids, 6-mercaptopurine [6-MP], azathioprine) within four weeks prior to the screening visit.
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Use of TNF-blockers (e.g., infliximab or adalimumab) within 60 days of the screening visit.
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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.
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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.
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History of positive serology of hepatitis B or C, or human immunodeficiency virus (HIV) infection.
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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.
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Active abuse of alcohol or drugs.
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Known malignancy or history of malignancy that could reduce life expectancy.
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Any condition, which in the opinion of the Investigator, would place the patient at an unacceptable risk if participating in the study protocol.
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Participation in a clinical trial of an investigational (unapproved) product
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Bertilimumab Bertilimumab Bertilimumab 10 mg/kg will be administered by IV infusion over 30 minutes Placebo Placebo Phosphate buffered saline (PBS) placebo will be administered by IV infusion over 30 minutes.
- Primary Outcome Measures
Name Time Method Clinical response Day 56 * 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.
- Secondary Outcome Measures
Name Time Method Change in partial Mayo score from Day 0 to all scheduled measurement timepoints (efficacy follow up). Throughout the study Clinical remission at Day 56, defined as a total Mayo score of 2 points or lower, with no individual sub-score exceeding 1 point Day 56 Mucosal healing at Day 56, defined as an absolute sub-score for endoscopy of 0 or 1. Day 56 Change in UCEIS score from screening to Day 56 Da 56
Trial Locations
- Locations (6)
HaEmek Medical Center
🇮🇱Afula, Israel
Wolfson Medical Center
🇮🇱Holon, Israel
Shaare Zedek Medical Central
🇮🇱Jerusalem, Israel
Hadassah Ein Kerem
🇮🇱Jerusalem, Israel
Meir Medical Center
🇮🇱Kfar-Saba, Israel
Sourasky-Ichilov Tel Aviv Medical Center
🇮🇱Tel- Aviv, Israel