Safety, Tolerability, and Pharmacodynamics of IONIS-DGAT2Rx in Adult Patients With Type 2 Diabetes

A Double-Blind, Randomized, Placebo-Controlled, Phase 2 Study to Evaluate the Safety, Tolerability and Pharmacodynamics of ISIS 484137 (IONIS-DGAT2Rx, an Antisense Inhibitor of Diacylglycerol Acyltransferase 2) Administered Once-Weekly for 13 Weeks in Adult Patients With Type 2 Diabetes

The purpose is to assess the Safety, Tolerability, and Pharmacodynamics effect of IONIS DGAT2Rx in up to 45 Adult Patients with Type 2 Diabetes.

This short-term study will assess changes in hepatic steatosis over a 13-week treatment period in a patient population with higher risk for development of Nonalcoholic fatty liver disease (NAFLD) and Nonalcoholic steatohepatitis (NASH), obese type 2 diabetes mellitus (T2DM) with elevated HbA1c.

Inclusion Criteria:

• Must have given written informed consent and be able to comply with all study requirements.
• Males or females aged 18-75, inclusive, at the time of Informed Consent.
• Females must be non-pregnant and non-lactating, and either surgically sterile or post- menopausal.
• Males must be surgically sterile, abstinent or using an acceptable contraceptive method.
• Body mass index (BMI) ≥ 27.0 - ≤ 39.0 kilograms per square meter (kg/m^2).
• Diagnosis of Type 2 Diabetes Mellitus with an Hemoglobin A1C (HbA1c) ≥7.3% and ≤9.5% at screening.
• Must have been on a stable dose of Oral Antidiabetic Therapy for a minimum of 3 months prior to Screening.
• ≥ 10% liver fat prior to randomization assessed by MRI-PDFF.
• Stable body weight for at least 3 months before screening.

Exclusion Criteria:

• Clinically-significant abnormalities in medical history or physical examination.
• Clinically-significant abnormalities in screening laboratory values that would render a participant unsuitable for inclusion, per Sponsor.
• Evidence of uncorrected hypothyroidism or hyperthyroidism results at Screening.
• History of solid organ transplantation or renal dialysis.
• Clinically-significant complications of diabetes.
• Treatment with another Study Drug, biological agent, or device within one-month of screening.
• Known history or evidence of liver disease with a positive test for human immunodeficiency virus (HIV), Hepatitis C virus (HCV), or chronic Hepatitis B virus (HBV), or chronic liver disease other than NASH.
• Recent history of, or current drug or alcohol abuse.
• Current use of concomitant medications known to significantly impact body weight or that may cause liver toxicity, per Investigator
• Use of anticoagulant/Antiplatelet agents unless the dose has been stable for 4 weeks prior to the first dose of study drug]
• Use of non-steroidal anti-inflammatory drug nimesulide or any other drug influencing coagulation (except lose-dose aspirin).
• Use of obeticholic acid or ursodeoxycholic acid
• Considered unsuitable for inclusion by the Principal Investigator