A Study to Assess the Safety, Efficacy, and Pharmacokinetics of Multiple Doses of ION224

• Status: Recruiting
• Trial end date: 2023-09-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to assess the effect of multiple ION224 doses when administered by subcutaneous (SC) injection for 49 weeks (end of the treatment [EOT]) on non-alcoholic steatohepatitis (NASH) histologic improvement and to assess the effect on liver steatosis by magnetic resonance imaging-determined proton density fat fraction (MRI-PDFF), additional changes in NASH histologic features, liver biochemistry tests, and plasma lipid profile.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Ionis Pharmaceuticals, Inc.

Criteria

Inclusion Criteria:

• Males or females greater than or equal to (≥) 18 and less than or equal to (≤) 75 years old at the time of informed consent.

• Body mass index ≥ 25 Kg/m2 as assessed during screening

• Liver fat ≥ 10% as assessed by MRI-PDFF before randomization.

• Presence of NASH confirmed by centrally read liver biopsy

• Weight loss < 5% after historical biopsy. Otherwise, weight loss < 5% in the previous 3 months prior to randomization.

• ALT and AST ≤ 200 units per liter (U/L) and confirmed to be stable.

• Total Bilirubin ≤ 1.3 miligrams per deciliter (mg/dL) and confirmed to be stable.

Exclusion Criteria:

• Prior or planned (during the Study Period) bariatric surgery

• History of solid organ transplant

• Screening laboratory values that would render a participant unsuitable for inclusion, including but not limited to:

• Clinically significant albuminuria or proteinuria

• Positive test for blood on urinalysis

• Estimated glomerular filtration rate (eGFR) < 60 milliliters (mL)/minute (min)/1.73 square meter (m^2)

• Hemoglobin A1c (HbA1c) > 9.5%

• Platelet count < 170 × 10^9/liter (L)

• Diagnosis of Gilbert's syndrome

• Known history of or evidence of liver disease other than NASH.

• Clinical evidence of liver decompensation

• Active SARS-CoV-2 infection (COVID-19) or confirmed SARS-CoV-2 infection-related complication within 8 weeks of Screening

• Uncontrolled arterial hypertension

• History of bleeding diathesis or coagulopathy

• Participants with known intolerance to magnetic resonance imaging (MRI) or with conditions contraindicated for MRI Procedures

• History of, or current hard drug or alcohol abuse within 2 years prior to Screening

• Use of drugs historically associated with NAFLD for more than 2 weeks in the year prior to Screening.

• Use of obeticholic acid, ursodeoxycholic acid, icosapent ethyl, niacin, PCSK9 inhibitors, and bile acid sequestrants

• Participants taking the following medicines UNLESS on a stable dose:

• Anti-diabetic medications

• statins, fenofibrate, and ezetimibe

• Estrogen containing contraceptives

• Glucagon-like peptide (GLP)-1 agonists

• Pioglitazone

• Vitamin E at doses ≤ 800 international unit (IU)/day

• Herbal medicines, other prescription medicines, vitamins or supplements known to affect lipid metabolism

• Other protocol-defined inclusion/exclusion criteria could apply