Study of ISIS 703802 in Participants With Hypertriglyceridemia, Type 2 Diabetes Mellitus, and Nonalcoholic Fatty Liver Disease

Akcea Therapeutics

Status and phase: Completed; Phase 2

Conditions: Fatty Liver, Nonalcoholic; Hypertriglyceridemia; NAFLD; Diabetes Mellitus, Type 2

Treatments: Drug: ISIS 703802 20 mg; Drug: ISIS 703802 40 mg; Drug: ISIS 703802 80 mg; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03371355

ISIS 703802-CS2

Details and patient eligibility

About

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).

Enrollment: 105 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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105 participants in 4 patient groups, including a placebo group

Pooled Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

Cohort B: ISIS 703802, 40 mg Q4W

Experimental group

Description:

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

Treatment:

Drug: ISIS 703802 40 mg

Cohort C: ISIS 703802, 80 mg Q4W

Experimental group

Description:

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

Treatment:

Drug: ISIS 703802 80 mg

Cohort A: ISIS 703802, 20 mg QW

Experimental group

Description:

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

Treatment:

Drug: ISIS 703802 20 mg