A Phase 3 study of investigational drug ISIS 678354 administered under skin to patients with severely increased amount of triglycerides in blood.

Phase 1

Conditions: Severe hypertryglyceridemia
MedDRA version: 20.0Level: PTClassification code 10059183Term: Familial hypertriglyceridaemiaSystem Organ Class: 10010331 - Congenital, familial and genetic disorders
Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
MedDRA version: 20.1Level: LLTClassification code 10020607Term: HyperchylomicronemiaSystem Organ Class: 100000004861

Registration Number: EUCTR2021-002192-19-PT

Lead Sponsor: Ionis Pharmaceuticals, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 540

Inclusion Criteria

- Fasting TG = 500 mg/dL (5.65 mmol/L) at Screening and Qualification
- Patients must be on lipid-lowering therapy that should adhere to standard of care (SOC) per local guidelines. Lipid-lowering medications should be optimized and stabilized for at least 4 weeks prior to Screening to minimize changes in these medications during the study.

Other protocol defined criteria will apply.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 490
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion Criteria

Hemoglobin A1c (HbA1c) = 9.5% at Screening
Alanine aminotransferase or aspartate aminotransferase > 3.0 × upper limit of normal
Total bilirubin > upper limit of normal unless due to Gilbert's syndrome
Estimated GFR < 30 mL/min/1.73 m^2

Other Protocol defined exclusion criteria will apply.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy of olezarsen as compared to placebo on the percent change in fasting TG from Baseline;Secondary Objective: To evaluate the efficacy of olezarsen as compared to placebo on:<br><br>1/ Proportion of patients who achieve fasting TG < 500 mg/dL (5.65 mmol/L)<br>2/ Proportion of patients who achieve fasting TG < 880 mg/dL (10 mmol/L)<br>3/ Proportion of patients who achieve fasting TG < 1000 mg/dL (11.29 mmol/L)<br>4/ Adjudicated acute pancreatitis event rate in patients with = 2 events of adjudicated acute pancreatitis in 5 years prior to enrollment <br>5/ Adjudicated acute pancreatitis event rate;Primary end point(s): The primary endpoint is the percent change in fasting TG from Baseline at Month 6 (average of Weeks 25 and 27) compared to placebo.;Timepoint(s) of evaluation of this end point: baseline, 6 months

Secondary Outcome Measures