Randomized Placebo Controlled Pilot Trial to determine the efficacy of an IL22 agonist (F-652) in patients with Alcoholic Hepatitis

随机安慰剂对照预试验以确定 IL22 激动剂 (F-652) 对酒精性肝炎患者的疗效

• 批准号: 10202402
• 负责人: VIJAY H. SHAH
• 金额: $ 7.5万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-22 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10202402
• 关键词: Adrenal Cortex Hormones; Agonist; Alcoholic Hepatitis; Antioxidants; Apoptotic; Cessation of life; Clinic; Clinical Research; Conduct Clinical Trials; Data; Development; Disease; Dose; Drug Kinetics; Environment; Future; Group Practice; Investigation; Link; Liver; Morbidity - disease rate; Patient Recruitments; Patients; Pattern; Pentoxifylline; Pharmacodynamics; Phase; Pilot Projects; Placebo Control; Placebos; Positioning Attribute; Prednisone; Randomized; Randomized Controlled Trials; Research; Research Personnel; Safety; Serious Adverse Event; Signal Transduction; Steroids; System; Testing; antimicrobial; arm; base; clinical investigation; drug efficacy; follow-up; improved; innovation; interleukin-22; liver cell proliferation; liver transplantation; mortality; novel; novel therapeutics; pharmacokinetics and pharmacodynamics; phase 3 study; pilot trial; primary endpoint; randomized placebo controlled study; secondary endpoint; success; therapeutic development; therapeutically effective

PROJECT SUMMARY/ABSTRACT Alcoholic hepatitis (AH) is a leading cause of liver-related morbidity and mortality with a remarkable paucity of effective therapeutics. F-652, an IL-22 agonist, is a promising agent to treat patients with AH because of its antioxidant, anti-apoptotic, anti-steatotic, anti-microbial, and pro-proliferative effects that have been demonstrated in various experimental systems. A pilot study from our group in patients with AH has confirmed safety and suggested efficacy of F-652, with no worrisome pharmacodynamic or pharmacokinetic patterns. Based on the encouraging results from the pilot study, this application represents the next step to confirm efficacy of the IL-22 agonist in patients with AH. The aims of this proposal are: 1. Determine the efficacy and confirm the safety of an IL-22 agonist (F-652) in a randomized, placebo-controlled study in patients with AH and MELD score 11-20 as demonstrated by improved MELD scores at 90 days. Patients with AH and MELD score 11-20 (thus not candidates for the trial described in our linked application to RFA-AA-18-002) will undergo a 1:1 randomization into an IL-22 agonist arm or a placebo (control) arm. Three doses of the IL-22 agonist or placebo will be administered at approximately 5-day intervals. The primary endpoint is improvement (reduction) in MELD score by >25% at 90 days. Secondary endpoints include 30- and 90-day survival; Lille score; and safety as determined by absence of serious adverse events (SAE) at 90 days. 2. Determine the efficacy and confirm the safety of an IL-22 agonist (F-652) in a randomized, placebo-controlled study in patients with AH and MELD score 21-28 as demonstrated by improved MELD scores at 90 days. Patients with AH with contraindication to steroids (thus not candidates for the trial described in our linked application to RFA-AA 18-002) and MELD score 21-28 will undergo a 2:1 randomization into an IL-22 agonist arm or a placebo (control) arm. Three doses of the IL-22 agonist or placebo will be administered at approximately 5-day intervals. Secondary endpoints include 30- and 90-day survival; Lille score; and safety as determined by absence of SAE up to 90 days. We believe a pilot randomized controlled trial is a logical extension of our preliminary studies which demonstrated safety and possible efficacy of the IL-22 agonist in patients with AH. The investigators are uniquely positioned to perform the proposed study given substantial breadth and depth of expertise related to AH, clinical trial conduct, and therapeutic development.

项目总结/文摘