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临床试验/NCT03371355
NCT03371355已完成2 期

A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Dose Finding Study of ISIS 703802 (AKCEA-ANGPTL3-LRx) Administered Subcutaneously to Subjects With Hypertriglyceridemia, Type 2 Diabetes Mellitus (T2DM), and Nonalcoholic Fatty Liver Disease (NAFLD)

Akcea Therapeutics2 个研究点 分布在 2 个国家目标入组 105 人开始时间: 2017年12月21日最近更新:
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适应症
干预措施
相关药物

试验速览

阶段
2 期
状态
已完成
入组人数
105
试验地点
2
主要终点
Percent Change From Baseline in Fasting Triglycerides Level at the Primary Analysis Time Point
研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This is a multicenter, randomized, double-blind, placebo-controlled, dose-ranging study to evaluate the safety, including tolerability, of ISIS 703802 and to assess the efficacy of different doses and dosing regimens of ISIS 703802 on glucose and lipid metabolism, and liver fat in participants with hypertriglyceridemia, Type 2 diabetes mellitus (T2DM), and nonalcoholic fatty liver disease (NAFLD).

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, Investigator, Outcomes Assessor)

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

  • •Plasma triglycerides (TG) at Screening greater than (>)150 milligrams per deciliter (mg/dL) and at qualification of >150 mg/dL.
  • •Documented history of hepatic steatosis with baseline magnetic resonance imaging (MRI) indicating hepatic fat fraction (HFF) greater than (>) 8%.
  • •Diagnosis of Type 2 diabetes mellitus with hemoglobin A1c (HbA1c) >6.5 and less than or equal to (≤) 10% at Screening.
  • •Must have been on a stable dose of oral antidiabetic therapy for a minimum of 3 months prior to Screening.
  • •Body mass index between 27- 40 kilograms per meter square (kg/m^2), inclusive, at Screening.

排除标准

  • •Type 1 diabetes mellitus.
  • •Active chronic liver disease, alcoholic liver disease, Wilson's disease hemochromatosis, primary biliary cirrhosis, primary sclerosing cholangitis, genetic hemochromatosis, known or suspected hepatocellular carcinoma, history of or planned liver transplant for end-stage liver disease of any etiology.
  • •Documented history of advanced liver fibrosis.
  • •History of cirrhosis and/or hepatic decompensation including ascites, hepatic encephalopathy, or variceal bleeding.
  • •History of clinically significant acute cardiac event within 6 months before Screening.
  • •History of heart failure with New York Heart Association (NYHA) greater than Class II.
  • •Use of Insulin or insulin analogs, glucagon-like peptide-1 (GLP-1) agonists, and peroxisome proliferator-activated receptor gamma (PPARᵞ) agonists (pioglitazone or rosiglitazone).
  • •Weight change >5% within 3 months before Screening.
  • •Conditions contraindicated for magnetic resonance imaging (MRI) procedures including any metal implant (example, heart pacemaker, rods, screws, aneurysm clips).

研究组 & 干预措施

Pooled Placebo

Placebo Comparator

Participants from each cohort received placebo at a dose-matched volume of study drug, subcutaneously (SC).

干预措施: Placebo (Drug)

Cohort B: ISIS 703802, 40 mg Q4W

Experimental

Participants received ISIS 703802, 40 milligrams (mg) SC once every 4 weeks for 6 doses.

干预措施: ISIS 703802 40 mg (Drug)

Cohort C: ISIS 703802, 80 mg Q4W

Experimental

Participants received ISIS 703802, 80 mg SC once every 4 weeks for 6 doses.

干预措施: ISIS 703802 80 mg (Drug)

Cohort A: ISIS 703802, 20 mg QW

Experimental

Participants received ISIS 703802, 20 mg once every week for 26 doses.

干预措施: ISIS 703802 20 mg (Drug)

结局指标

主要结局

Percent Change From Baseline in Fasting Triglycerides Level at the Primary Analysis Time Point

时间窗: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

An ANCOVA model was performed on the log ratio of Primary Analysis Time Point to Baseline. The estimate of the log ratio was converted back to the original scale and percent change was calculated using formula: = (ratio of Primary Analysis Time Point to Baseline - 1) × 100.

次要结局

  • Change From Baseline in Free Fatty Acid (FFA) at Primary Analysis Time Point(Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C)
  • Change From Baseline in Weight at the Primary Analysis Time Point(Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C)
  • Change From Baseline in Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) at the Primary Analysis Time Point(Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C)
  • Change From Baseline in Subcutaneous Adipose Tissue (SAT) and Visceral Adipose Tissue (VAT) by Single Slice MRI at the Primary Analysis Timepoint(Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C)
  • Change From Baseline in Angiopoietin-Like 3 Protein at the Primary Analysis Time Point(Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C)
  • Change From Baseline in Hemoglobin A1c (HbA1c) at the Primary Analysis Time Point(Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C)
  • Change From Baseline in and HOMA-IR at the Primary Analysis Time Point(Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C)
  • Change From Baseline in TC, LDL-C, HDL-C, VLDL-C, Non-HDL-C, ApoB (ApoB-48, ApoB-100), ApoCIII, and ApoAI at the Primary Analysis Time Point(Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C)
  • Change From Baseline in Lipoprotein(a) (Lp[a]) at the Primary Analysis Time Point(Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C)
  • Change From Baseline in Fasting Plasma Glucose at the Primary Analysis Time Point(Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C)
  • Change From Baseline in Leptin at the Primary Analysis Time Point(Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C)
  • Change From Baseline in Adiponectin at the Primary Analysis Time Point(Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C)
  • Percent Change From Baseline in ANGPTL3, TC, LDL-C, HDL-C, VLDL-C, Non-HDL-C, ApoB (ApoB-48, ApoB-100), ApoCIII, ApoAI, FFA, and Lp(a) at Primary Analysis Time Point(Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C)
  • Percent Change From Baseline in Weight, SBP and DBP at Primary Analysis Time Point(Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C6)
  • Percent Change From Baseline in Hepatic Fat Fraction (HFF) by Magnetic Resonance Imaging-Derived Proton Density Fat Fraction (MRI-PDFF) at the Primary Analysis Time Point(Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C)
  • Percentage of Participants With HFF ≤ 8% by MRI-PDFF at the Primary Analysis Time Point(Week 27 for Cohort A, and Week 25 for Cohorts B and C)
  • Change From Baseline in Fasting Insulin at the Primary Analysis Time Point(Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C)
  • Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Primary Analysis Time Point(Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C)
  • Change From Baseline in Fatty Liver Index (FLI) at the Primary Analysis Time Point(Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C)
  • Change From Baseline in Waist to Hip Ratio (WHR) at the Primary Analysis Timepoint(Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C)
  • Number of Participants With Treatment-emergent Adverse Events (TEAEs)(Up to 13 weeks post treatment period (up to 39 weeks))
  • Change From Baseline in Fructosamine at Primary Analysis Time Point(Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C)
  • Change From Baseline in Glycated Albumin at the Primary Analysis Time Point(Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C)
  • Change From Baseline in Hepatic Fat Fraction (HFF) by Magnetic Resonance Imaging-Derived Proton Density Fat Fraction (MRI-PDFF) at the Primary Analysis Time Point(Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C)
  • Change From Baseline in Waist Circumference by Single Slice MRI at the Primary Analysis Timepoint(Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C)
  • Change From Baseline in Body Mass Index (BMI) at the Primary Analysis Timepoint(Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C)

研究者

申办方类型
Industry
责任方
Sponsor

研究点 (2)

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