Study of ISIS 703802 in Participants With Hypertriglyceridemia, Type 2 Diabetes Mellitus, and Nonalcoholic Fatty Liver Disease
Condition: NAFLD; Diabetes Mellitus, Type 2; Hypertriglyceridemia; Fatty Liver, Nonalcoholic
MeSH terms: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypertriglyceridemia
Intervention: Placebo; ISIS 703802 40 mg; ISIS 703802 80 mg; ISIS 703802 20 mg
Intervention description: Placebo (Matched with ISIS 703802); ISIS 703802 40 mg, administered via SC injection, once every 4 weeks for 6 doses.; ISIS 703802 80 mg, administered via SC injection, once every 4 weeks for 6 doses.; ISIS 703802 20 mg, administered via SC injection, once every week for 26 doses.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 105.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Type 2 Diabetes; Hepatic Steatosis; Triglycerides; AKCEA-ANGPTL3-Lrx; IONIS-ANGPTL3-Lrx; Fatty Liver; Fatty Liver Without Mention of Alcohol; Liver Fat; Liver Diseases; Diabetes Mellitus Type 2 in Nonobese; Diabetes Mellitus; Triglycerides High; High Triglycerides; Metabolic Disease; Endocrine System Diseases; Digestive System Disease; Glucose Metabolism Disorders; Vupanorsen

Summary:

      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).
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  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.

        Key Exclusion Criteria:

          -  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).