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
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Change From Baseline in Total Mayo Score at Day 56
研究概览
简要总结
This is a randomized, double blind, placebo-controlled, parallel group multi-center study in adult participants with active moderate to severe UC.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
Bertilimumab
Bertilimumab 10 mg/kg will be administered by IV infusion over 30 minutes
干预措施: Bertilimumab (Biological)
Placebo
Phosphate buffered saline (PBS) placebo will be administered by IV infusion over 30 minutes.
干预措施: Placebo (Biological)
结局指标
主要结局
Change From Baseline in Total Mayo Score at Day 56
时间窗: 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.
次要结局
- Change From Baseline in Ulcerative Colitis Endoscopic Index of Severity (UCEIS) Score at Day 56(Baseline, Day 56)