Study of ISIS 678354 (AKCEA-APOCIII-LRx) in Participants With Hypertriglyceridemia and Established Cardiovascular Disease (CVD)

Akcea Therapeutics114 enrolled

Overview

This was a multicenter, randomized, double-blind, placebo-controlled, dose-ranging study to evaluate the safety, including tolerability, of ISIS 678354 and to assess the efficacy of different doses and dosing regimens of ISIS 678354 for reduction of serum triglyceride (TG) levels in participants with hypertriglyceridemia and established CVD or at a high risk for CVD.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

114

Conditions

Hypertriglyceridemia Cardiovascular Diseases

Interventions

ISIS 678354DRUG

ISIS 678354 solution for SC injection.

PlaceboDRUG

Sterile Normal Saline (0.9% NaCl).

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * Clinical diagnosis of CVD (defined as documented coronary artery disease, stroke, or peripheral artery disease). * Fasting serum triglycerides (TG) greater than or equal to (≥) 200 milligrams per deciliter (mg/dL) (≥ 2.3 millimoles per liter (mmol/L)) and less than or equal to (≤) 500 mg/dL (≥ 5.7 mmol/L) at Screening. * Fasting TG ≥ 200 mg/dL and ≤ 500 mg/dL at Qualification visit. * Must be on standard-of-care preventative therapy for known CVD risk factors. Key Exclusion Criteria: * Within 6 months of Screening: acute coronary syndrome, major cardiac surgery, or stroke/transient ischemic attack (TIA). * Within 3 months of Screening: coronary, carotid, or peripheral arterial revascularization, major non-cardiac surgery, or lipoprotein apheresis. * Heart failure New York Heart Association (NYHA) class IV. * Type 1 diabetes mellitus. * Type 2 diabetes mellitus with any of the following: * Newly diagnosed within 12 weeks of Screening. * Glycated hemoglobin (HbA1c) ≥ 9.0% at Screening. * Recent change in anti-diabetic pharmacotherapy (change in dosage or addition of new medication within 12 weeks of Screening \[with the exception of ± 10 units of insulin\]. * Body Mass Index (BMI) greater than (\>) 40 kilograms per square meter (kg/m\^2).

Locations (31)

Outcomes

Primary Outcomes

Percent Change From Baseline in Fasting Triglycerides (TG) at the Primary Analysis Time Point

An analysis of covariance (ANCOVA) model was performed on the log ratio of TG value at the Primary Analysis Time Point to TG value at Baseline. The estimate of the log ratio was converted back to the original scale and percent change was calculated using formula: (ratio of TG value at the Primary Analysis Time Point to TG value at Baseline - 1) × 100.

Time frame: Baseline and Month 6 (Week 25 for Cohorts A and B and Week 27 for Cohorts C and D)

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

An adverse event (AE) was defined as any unfavorable and unintended sign (including a clinically-significant abnormal laboratory finding, for example), symptom, or disease temporally associated with the study or use of investigational drug product, whether or not the AE was considered to be related to the investigational drug product. A TEAE was defined as any AE starting on or after the first dose of the study drug.

Time frame: Up to the 13-week post-treatment follow-up period (Up to approximately 15 months)

Secondary Outcomes

Percent Change From Baseline in ApoC-III, TC, LDL-C, HDL-C, Non-HDL-C, VLDL-C, ApoB, and ApoA-I at the Primary Analysis Time Point

An ANCOVA model was performed on the log ratio of Primary Analysis Time Point value to Baseline value for ApoC-III, TC, LDL-C, HDL-C, Non-HDL-C, VLDL-C, ApoB, and ApoA-I. The estimate of the log ratio was converted back to the original scale and percent change for each lipid parameter was calculated using formula: (ratio of Primary Analysis Time Point value to Baseline value - 1) × 100.

Time frame: Baseline and Month 6 (Week 25 for Cohorts A and B and Week 27 for Cohorts C and D)

Percentage of Participants Who Achieved Fasting Triglycerides (TG) <= 150 mg/dL (<= 1.7 Millimoles Per Liter [mmol/L])

The percentage of participants who achieved \<= 150 mg/dL or \<= 1.7 mmol/L of fasting TG levels at the primary analysis time point were compared between each ISIS 678354 treatment group and pooled placebo group using a logistic regression model with log-transformed baseline TG value as a covariate.

Data from ClinicalTrials.gov

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