NCT04887766Unknown不适用
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study Assessing the Effect of GS300 on Nonalcoholic Fatty Liver Disease
适应症
试验速览
- 阶段
- 不适用
- 入组人数
- 250
- 主要终点
- Relative reduction in liver fat
研究概览
简要总结
To determine the efficacy of GS300 when administered for 24 weeks in patients with Nonalcoholic Fatty Liver Disease (NAFLD).
详细描述
This is a multicenter, randomized, placebo-controlled, double-blinded, parallel-group study. Patients will be randomized 1:1 to receive either GS300 or placebo. The study includes an up to 6 weeks screening period, a 24-week treatment period, and a 1-week follow-up period.
Approximately 250 patients (125 patients per arm) will be enrolled (at least 40% from each gender and at least 40% from US and 40% from Europe).
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, Investigator)
入排标准
- 年龄范围
- 22 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 22 years and ≤ 65 years
- •Body Mass Index (BMI) ≥ 27 and ≤ 40 kilogram (kg)/meter2 (m2)
- •Negative for Hepatitis B, C and Human Immunodeficiency Virus (HIV) within 6 months of screening [HbsAg negative and Hepatitis C Virus (HCV) RNA negative; subjects treated and cured of HCV must have completed treatment and tested negative for HCV at least 2 years prior to study enrollment]
- •Fibroscan CAP score > 300 decibels (dB)/m
- •Stable body weight defined as less than 5% change in body weight in the 3 months prior to screening (per patient report)
- •Approximately 250 patients (approximately 125 patients per treatment arm)
- •Prediabetes i) Untreated prediabetic patients with FPG ≥ 100 mg/ dL (≥ 5.6 mmol/L) and < 126 mg/dL (< 7.0 mmol/L) at both Screening Visits with HbA1c ≤ 6.4% (≤ 46 mmol/mol) - if only one value is within this range, the other value should not be ≥ 126 mg/dL (≥ 7.0 mmol/L) and HbA1c should be ≥ 5.7% (≥ 39 mmol/mol) and ≤ 6.4% (≤ 46 mmol/mol) ii) Drug-treated (metformin) prediabetic patients with FPG ≥ 70 mg/dL (≥ 3.9 mmol/L) and < 126 mg/dL (< 7.0 mmol/L) at both Screening Visits
- •Type 2 Diabetes i) Untreated type 2 diabetic patients with FPG ≤ 200 mg/dL (≤ 11.2 mmol/L) at both Screening Visits and either FPG ≥ 126 mg/dL (≥ 7.0 mmol/L) at both Screening Visits or FPG < 126 mg/dL (< 7.0 mmol/L) at one or both Screening Visits with HbA1c ≥ 6.5% (≥ 48 mmol/mol) ii) Drug-treated [metformin and/or dipeptidyl peptidase-4 (DPP-4) inhibitors, and/or insulin] type 2 diabetic patients with FPG ≥ 70 mg/dL (≥ 3.9 mmol/L) and ≤ 270 mg/dL (≤ 15.1 mmol/L) at both Screening Visits Note, approximately 10% to 20% of enrolled Type 2 diabetic patients will be on insulin therapy
- •Normoglycemia (up to approximately 10% of patients) Normoglycemic patients with FPG ≥ 70 mg/dL (≥ 3.9 mmol/L) and < 100 mg/ dL (< 5.6 mmol/L) at both Screening Visits with HbA1c < 5.7% (< 39 mmol/mol) and HOMA-IR ≥ 3.0
- •MRI PDFF ≥ 10%
- •Willing to sign the ICF prior to any study related procedures
排除标准
- •Self-reported alcohol intake > 20 gram (g)/day for women and > 30 g/day for men (on average per day) as per medical history
- •Alcohol Use Disorders Identification Test (AUDIT) questionnaire: AUDIT-C score of ≥ 4 in men and ≥ 3 in women will be followed by a full AUDIT questionnaire by interview with patients excluded for score ≥ 8
- •Prior liver transplant
- •Liver cirrhosis as evidenced by any of the following:
- •Serum albumin < 3.5 g/dL (0.53 mmol/L)
- •INR > 1.3 (unless due to anticoagulant therapy)
- •AST/ALT ratio ≥ 2
- •Direct bilirubin > 0.3 mg/dL (5.13 micromol (micromol)/L)
- •Platelet count < 150,000/microL
- •History or evidence of other chronic liver diseases, including, but not limited to the following:
- •Current active autoimmune hepatitis
- •Primary biliary cholangitis (PBC)
- •Primary sclerosing cholangitis
- •Wilson's disease
- •Alpha-1-antitrypsin (A1AT) deficiency
- •Hemochromatosis
- •Drug-induced liver disease, as defined on the basis of typical exposure and history
- •Bile duct obstruction
- •Suspected or proven liver cancer
- •History of hepatic encephalopathy
- •Portal hypertension (esophageal varices, ascites, splenomegaly)
- •History of gastric surgery (up to 10% patients with history of gastric bypass or sleeve gastrectomy may be enrolled if the surgery occurred more than 6 months prior to enrollment and patients had a weight change < 5% during the 3 months prior to enrollment)
- •Angina, coronary bypass, or myocardial infarction within 6 months prior to Screening Visit
- •Inflammatory bowel disease, celiac disease, or other significant gastrointestinal disease - for example, a history of bowel obstruction without surgical correction (patients with irritable bowel syndrome may be enrolled)
- •Absence of medically approved contraceptive methods in females of childbearing potential (e.g., hysterectomy, oral contraceptives, non-oral contraceptive medications or intrauterine device combined with a barrier method, two combined barrier methods such as diaphragm and condom or spermicide, or condom and spermicide; bilateral tubal ligation and vasectomy are not acceptable methods)
- •Type 1 Diabetes
- •HbA1c > 8.5% (> 69 mmol/mol)
- •Serum LDL-C ≥ 160 mg/dL (≥ 4.15 mmol/L)
- •Serum triglycerides ≥ 350 mg/dL (≥ 3.96 mmol/L)
- •Use of any medications for the treatment of diabetes within 3 months prior to enrollment. Note, metformin, DPP-4 inhibitors, and insulin at a stable dose over the last 3 months are allowed. Insulin dose variance of 20% (decrease or increase) is allowed.
- •Any change in standard of care or background therapy for liver disease or other ongoing chronic conditions within 3 months prior to enrollment, including changes in the following:
- •Antidiabetic medications (metformin, DPP-4 inhibitors, insulin)
- •Thyroid hormones
- •Medications treating depression
- •Medications treating dyslipidemia
- •Medications treating hypertension
- •Vitamin E
- •Regular/daily use of any of the following within 3 months prior to enrollment or anticipated regular/daily use during the study period:
- •High dose nonsteroidal anti-inflammatory drugs (NSAIDS) (equivalent of > 3,200 mg/day ibuprofen)
- •Systemic corticosteroids, anabolic steroids
- •Methotrexate, amiodarone, tamoxifen, tetracyclines, estrogens at doses greater than those used for hormone replacement, valproic acid
- •Probiotic supplements (yogurt is allowed)
- •Addictive, non-prescribed medications including amphetamines, barbiturates, cocaine, opiates, methadone and phencyclidine as per medical history or regular daily use of cannabinoids
- •Use of any anti-obesity medications (including herbal preparations) within 2 months prior to enrollment or any anticipated use during the study period
- •History of allergic reaction to carboxymethylcellulose (CMC), citric acid, sodium stearyl fumarate, raw cane sugar, gelatin, or titanium dioxide
- •Currently enrolled in another investigational device or drug study, or less than 3 months since ending another investigational device or drug study(s), or receiving other investigational treatment(s)
- •Any disease or condition that, in the opinion of the investigator or Sponsor, would interfere with study participation
结局指标
主要结局
Relative reduction in liver fat
时间窗: 24 Weeks
Relative reduction in liver fat from Baseline to Week 24, as measured by hepatic Magnetic Resonance Imaging Proton Density Fat Fraction (MRI PDFF).
Placebo-adjusted percent change in weight from Baseline to Week 24
时间窗: 24 Weeks
Placebo-adjusted percent change in weight from Baseline to Week 24.
Weight loss ≥ 5%
时间窗: 24 Weeks
Proportion of patients with weight loss ≥ 5% at Week 24.
次要结局
- Weight loss ≥ 7.5%(24 Weeks)
- To assess placebo-adjusted waist circumference reduction(24 Weeks)
- Weight loss ≥ 10%(24 Weeks)
- To evaluate the percentage of patients with ≥ 30% relative reduction in liver fat(24 Weeks)
- To assess the impact of GS300 on glycemic control in patients with NAFLD(24 Weeks)
- To assess the impact of GS300 on liver enzymes in patients with NAFLD(24 Weeks)
研究者
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