A Multicenter Randomized, Double-Blinded, Placebo-Controlled Study of Posaconazole in Genetically-Defined Patients With Active Crohn's Disease
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Number of Subjects With Medically Defined Endoscopic Response
研究概览
简要总结
This trial is designed to evaluate the effects of oral antifungal treatment with posaconazole on active Crohn's disease (CD) activity and the burden of Malassezia spp. in CD patients with the caspase recruitment domain family member 9 (CARD9) S12N risk allele. Further, this project will investigate the hypothesis that the microbial changes induced by antifungal treatment are associated with dampened downstream immune responses in those with a genetic predisposition to developing strong immune responses to Malassezia.
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
- Triple (Participant, Care Provider, Outcomes Assessor)
盲法说明
Both subject and clinical staff will be masked to treatment group assigned.
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patients aged 18 years and older, inclusive based on the date of the screening visit.
- •A diagnosis of CD with minimum disease duration of 6 months with involvement of the ileum and/or colon documented on colonoscopy
- •Have an endoscopically-confirmed active Crohn's disease with active disease defined by SES-CD > 6 (>4 if ileal only), AND active symptoms of Crohn's disease (CDAI score >220)
- •Homozygous for CARD9 S12N risk allele, without the protective exon 11 polymorphism
- •Subjects receiving oral aminosalicylates (at a stable dose for 2 weeks prior to baseline), immunomodulators (at a stable dose for 4 weeks prior to baseline), anti-TNF, anti IL12/23, or anti-integrin therapy (at stable maintenance doses for > 8 weeks) may continue their use during the study.
- •Subjects receiving oral corticosteroids may continue their use during the study provided the dose (prednisone up to 20 mg/day, budesonide up to 9 mg/day) has been stable for two weeks prior to screening.
- •Have had age-appropriate and disease-duration-appropriate colon cancer screening1 without unresected dysplasia.
- •Women of childbearing age, excluding those with prior bilateral tubal ligation or at least one-year post-menopause, must not be pregnant, lactating, or planning to become pregnant. They must agree to use effective contraception throughout the study period.
- •Subjects must be able to provide informed consent and understand, agree with, and be able to adhere to daily diary entries, all scheduled visits, tests, procedures, and protocol in English.
排除标准
- •Known hypersensitivity or allergy to posaconazole or other azole antifungal agents
- •Concomitant medications primarily metabolized by CY3PA4 including: a) Hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors, primarily metabolized by CY3PA4 (increases risk of rhabdomyolysis), b) Sirolimus, c) Ergot alkaloids, d) vincristine
- •Proarrhythmic conditions
- •Moderate or severe renal impairment (Cr Clearance <50)
- •Current diagnosis of ulcerative colitis, indeterminate colitis, ischemic colitis, infectious colitis, or microscopic colitis.
- •Fulminant colitis, toxic megacolon, peritonitis, ileostomy or colostomy.
- •Stool sample positive for pathogens including ova and parasites, Salmonella, Shigella, and C. difficile at screening.
- •History of any clinically significant neurological, renal, hepatic, gastrointestinal, pulmonary, metabolic, cardiovascular, psychiatric, endocrine, hematological disorder or disease or any other medical condition that, in the Investigators opinion, would prevent the subject from participation in the study.
- •Treatment with antibiotics, antifungal agents, probiotics, or prebiotics within two weeks of screening.
- •Alcohol or drug abuse (in the opinion of the Investigator) that would interfere with compliance.
- •Any other investigational therapy or treatment within four weeks of screening.
研究组 & 干预措施
Posaconazole
Subjects administered posaconazole (Noxafil®, Merck) 300mg twice daily for 1 day followed by 300mg daily for 12 weeks
干预措施: Posaconazole Delayed Release Oral Tablet (Drug)
Placebo
Subjects administered three matching placebo tablets twice daily for 1 day followed by three tablets daily for 12 weeks
干预措施: Matching Placebo Tablet (Drug)
结局指标
主要结局
Number of Subjects With Medically Defined Endoscopic Response
时间窗: Week 12
Defined as ≥ 50% reduction from baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD). The SES-CD evaluates 4 endoscopic variables: ulcer size, ulcerated surface, affected surface, and presence of narrowings. The total SES-CD is calculated as the sum of the 4 variables for the 5 bowel segments: rectum, left colon, transverse colon, right colon, and ileum. Scores range from 0 to 60, with higher scores indicating more severe disease.
次要结局
- Induction of Clinical Remission(Week 12)
- Change in Amount of Concomitant Medications(Week 12)
- Proportion of Subjects in Endoscopic Remission(Week 12)
研究者
Gil Melmed
Principal Investigator
Cedars-Sinai Medical Center