NCT04607655撤回1 期
GULLIVER-1 - A Randomised, Double-Blind, Placebo Controlled, Phase Ib, 12-week Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Orally Administered GB1211 in Participants With Suspected or Confirmed Non-alcoholic Steatohepatitis (NASH) and Liver Fibrosis
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 主要终点
- Safety and Tolerability of GB1211
研究概览
简要总结
This study is a randomised, double-blind, placebo controlled, phase Ib trial in subjects with suspected or confirmed non-alcoholic steatohepatitis (NASH) and liver fibrosis
详细描述
This study is designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of orally administered GB1211 a gelectin-3 inhibitor over 12 weeks. Participants will receive two doses of GB1211, each given twice per day and compared to placebo in participants with fibrotic NASH
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)
盲法说明
This study is a double-blind study. The blinding will be maintained throughout the study.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males or females, of any race, ≥ 18 and ≤ 75 years of age at enrolment.
- •Body mass index (BMI) of ≥ 25.0 and ≤45.0 kg/m2
- •Diagnosis of suspected NASH and liver fibrosis (Chalasani et al. 2012):
- •a. Evidence of hepatic steatosis within the 24 weeks prior to Screening: i. magnetic resonance imaging (MRI PDFF) suggesting liver fat ≥ 8% or ii. ultrasound (US) indicating fatty liver or iii. FibroScan Controlled Attenuation Parameter (CAP) > 270 dB/m. iv. in participants without a documented history of fatty liver, a FibroScan CAP or US can be performed at Screening. Participants with FibroScan CAP > 270 dB/m or US indicating fatty liver are eligible AND b. Metabolic risk factors: i. Metabolic syndrome (Adult Treatment Panel III definition) requires three or more of the following five disorders (Grundy et al. 2005):
- •elevated waist circumference (≥102 cm in men and ≥88 cm in women),
- •hypertriglyceridemia (≥1.7 mmol/l),
- •low HDL cholesterol level (<1.03 mmol/l in men and <1.3 mmol/l in women),
- •high blood pressure (systolic blood pressure ≥130 mmHg and/or diastolic blood pressure ≥85 mmHg and/or pharmacological treatment)
- •elevated fasting glucose (≥5.6 mmol/l and/or pharmacological treatment) ii. OR T2DM (defined as stable diabetes with glycosylated haemoglobin [HbA1c] ≤ 9.5%) OR A diagnosis of confirmed NASH and liver fibrosis based on a biopsy within 12-months of Screening
- •Liver stiffness as measured by transient elastography (FibroScan) ≥ 8.5 KPa
- •Women of non-childbearing potential defined as permanently sterile (see Appendix 4) or postmenopausal (see Appendix 4) or Women considered to be of childbearing potential who agree to use highly effective birth control methods until 90 days after the Follow-up visit (see Appendix 4)
- •Males will agree to use contraception throughout the study and until 90-days after the Follow-up visit
- •Male participants must agree to refrain from sperm donation and females should refrain from ova donation from the date of Randomisation (Day -1) until 90 days after the Follow up visit
- •Able to comprehend and willing to sign an ICF and to abide by the study restrictions
排除标准
- •Any other causes for secondary hepatic fat accumulation such as significant alcohol consumption, use of steatogenic medication or hereditary disorders
- •The following clinical laboratory results at Screening:
- •ALT > 200 U/L
- •AST > 200 U/L
- •History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy, cholecystectomy, and hernia repair will be allowed)
- •Positive alcohol breath test result or positive urine drug screen (confirmed by repeat) at Screening or Randomisation
- •Positive hepatitis panel and/or positive HIV test
- •Evidence of acute Hepatitis A virus (HAV) and a positive serological test for anti-HAV IgM antibodies
- •Estimated glomerular filtration rate (eGFR) < 60 mL/[min*1.73 m²] at Screening
- •Use or intend to use slow release medications/products considered to still be active within 14 days prior to Randomisation, unless deemed acceptable by the Investigator (or Designee)
- •Participant taking any antidiabetic medications, with the exception of metformin and sulfonylureas within 3 months prior to Screening
- •Have previously completed or withdrawn from this study investigating GB1211 and have previously received the investigational product
- •Participant who, in the opinion of the Investigator (or Designee), should not participate in this study
- •Vulnerable/institutionalised patients
- •Patients related to PI/site staff
研究组 & 干预措施
Oral GB1211, 100 mg, twice a day
Experimental
GB1211 is a galectin-3 inhibitor an orally available small molecule anti-fibrotic. It is administered orally twice a day.
干预措施: GB1211 (Drug)
Oral GB1211, 10 mg, twice a day
Experimental
GB1211 is a galectin-3 inhibitor an orally available small molecule anti-fibrotic. It is administered orally twice a day.
干预措施: GB1211 (Drug)
Oral GB1211, Placebo, twice a day
Placebo Comparator
Placebo is administered as inhalation once a day
干预措施: Placebo (Drug)
结局指标
主要结局
Safety and Tolerability of GB1211
时间窗: 12 Weeks
Physical examination abnormalities measured by vital signs and 12 lead ECG
次要结局
- Pharmacokinetics of GB1211(12 Weeks)
研究者
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