Phase 1, Open Label Study to Evaluate Safety and Tolerability of NTR-101 in Patients With Acute Alcohol-Associated Hepatitis
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Frequency of adverse events
研究概览
简要总结
The goal of this clinical trial is to learn about the safety and tolerability of NTR-101 in adult participants suffering from acute alcohol-associated hepatitis (AH).
The drug is intended for use in the treatment of AH where the presence of specific strains of E. faecalis play a contributing role.
The main questions it aims to answer are:
Are multiple doses of NTR-101 in participants with acute AH safe and well tolerated? What medical problems do participants have when taking NTR-101? Researchers will administer the drug and monitor participants in an inpatient center.
Participants will:
Be administered multiple ascending dose frequencies of NTR-101 every day for 7 days.
Stay in the clinic for 9 days (7 days of treatment) and present to clinic once every week for checkups and tests for 35 days.
Keep a diary of their symptoms until the checkups and tests are completed.
详细描述
Alcohol-associated hepatitis (AH) is a severe inflammatory liver disease that can progress to liver failure, with high morbidity and mortality rates. Emerging studies indicate a significant role of gut-derived pathogens, particularly Enterococcus faecalis (E faecalis), in exacerbating liver damage through bacterial translocation and the release of toxins.
Cytolysin-positive E. faecalis strains exhibit high virulence and resistance to standard antibiotics.
NTR-101 is a product developed for oral delivery and composed of natural bacteriophages that specifically target cytolysin-positive E. faecalis.
The targeted activity of NTR-101 against E. faecalis in AH patients has the potential to address the underlying bacterial trigger, offering a novel approach to mitigate liver inflammation and reduce disease progression. For patients who do not respond to traditional treatments like corticosteroids or experience reduced antibiotic therapy efficacy, NTR-101 represents a novel, targeted approach that leverages bacteriophages' specificity for bacterial strains in this target population, offering a potential alternative or complement to traditional antibiotics.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
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
- •Diagnostic definition of acute alcohol-associated hepatitis based on well established standard disease markers
- •Able to provide written informed consent (either from patient or patient's legally authorized representative)
- •Male and female patients aged ≥18 years and ≤ 70 years of age
- •BMI ≥ 20 to ≤ 40 kg/m2
- •Enterococcus faecalis testing
- •Susceptibility to NTR-101
- •Women of child-bearing potential and male patients must agree to use a medically acceptable method of contraception/ birth control throughout the study duration.
排除标准
- •Participants considered at high risk for alcohol withdrawal according to the clinical institute withdrawal assessment (CIWA-Ar) protocol
- •Participants taking systemic corticosteroids for a specified duration
- •Platelet count below specified ranges
- •INR and Serum creatinine levels above specified ranges
- •Active bacterial or viral infections
- •Other or concomitant cause(s) of liver disease as a result of other conditions
- •Co-infection with HIV
- •Positive urine drug screen
- •Any significant systemic or major illness other than liver disease that, in the opinion of the investigator, would preclude the patient from participating in and completing the study or might complicated or exacerbated by the proposed treatments or might confound assessment of investigational product
- •If female, known pregnancy, or has a positive serum pregnancy test, or lactating/ breastfeeding
研究组 & 干预措施
Cohort 1
Dose 1
干预措施: Bacteriophage preparation (Drug)
Cohort 2
Dose 2
干预措施: Bacteriophage preparation (Drug)
Cohort 3
Dose 3
干预措施: Bacteriophage preparation (Drug)
Cohort 4
Dose 4
干预措施: Bacteriophage preparation (Drug)
结局指标
主要结局
Frequency of adverse events
时间窗: AEs will be recorded daily for 7 days, then weekly on days 14, 21, 28 and 35
The number of adverse events (AEs) will be recorded.
Changes in liver function will be evaluated
时间窗: Assessments will be recorded daily for 7 days, then weekly on days 14, 21, 28 and 35
ALT (alanine transaminase) and AST (aspartate aminotransferase) enzymes will be evaluated
次要结局
- Preliminary assessment of NTR-101 efficacy and viability(Stool samples will be collected daily for 7 days, then weekly on days 14, 21, 28 and 35 to evaluate the presence of the target pathogen and NTR-101 viability)