Safety, Tolerability, and Pharmacodynamics of IONIS-DGAT2Rx in Adult Patients With Type 2 Diabetes
Condition: Hepatic Steatosis
MeSH terms: Fatty Liver; Diabetes Mellitus, Type 2
Intervention: IONIS DGAT2Rx; Placebo
Intervention description: Single Dose of DGAT2Rx administered subcutaneously once weekly for 13 weeks; Saline 0.9%
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 44.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Hepatic Steatosis; IONIS-DGAT2Rx; Type 2 Diabetes

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

Eligibility criteria:

        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