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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03385239
Other study ID # ISIS 678354-CS2
Secondary ID
Status Completed
Phase Phase 2
First received
Last updated
Start date January 30, 2018
Est. completion date February 25, 2020

Study information

Verified date December 2022
Source Akcea Therapeutics
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


Recruitment information / eligibility

Status Completed
Enrollment 114
Est. completion date February 25, 2020
Est. primary completion date November 25, 2019
Accepts healthy volunteers No
Gender All
Age group 18 Years to 80 Years
Eligibility 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).

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
ISIS 678354
ISIS 678354 solution for SC injection.
Placebo
Sterile Normal Saline (0.9% NaCl).

Locations

Country Name City State
Canada Clinical Site Brossard Quebec
Canada Clinical Site Cambridge Ontario
Canada Clinical Site Chicoutimi Quebec
Canada Clinical Site Gatineau Quebec
Canada Clinical Site Montréal Quebec
Canada Clinical Site Québec Quebec
Canada Clinical Site Sudbury Ontario
United States Clinical Site Ames Iowa
United States Clinical Site Boca Raton Florida
United States Clinical Site Carmichael California
United States Clinical Site Cooperstown New York
United States Clinical Site Cottonwood Arizona
United States Clinical Site Fall River Massachusetts
United States Clinical Site Fresno California
United States Clinical Site Greer South Carolina
United States Clinical Site High Point North Carolina
United States Clinical Site Houston Texas
United States Clinical Site Jacksonville Florida
United States Clinical Site Kansas City Kansas
United States Clinical Site La Jolla California
United States Clinical Site Lansdale Pennsylvania
United States Clinical Site Little Rock Arkansas
United States Clinical Site Long Beach California
United States Clinical Site Louisville Kentucky
United States Clinical Site Milwaukee Wisconsin
United States Clinical Site Montclair California
United States Clinical Site Munster Indiana
United States Clinical Site New Port Richey Florida
United States Clinical Site Portland Oregon
United States Clinical Site Providence Rhode Island
United States Clinical Site Wilmington Delaware

Sponsors (2)

Lead Sponsor Collaborator
Akcea Therapeutics Ionis Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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. Baseline and Month 6 (Week 25 for Cohorts A and B and Week 27 for Cohorts C and D)
Primary 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. Up to the 13-week post-treatment follow-up period (Up to approximately 15 months)
Secondary 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. Baseline and Month 6 (Week 25 for Cohorts A and B and Week 27 for Cohorts C and D)
Secondary 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. Baseline and Month 6 (Week 25 for Cohorts A and B and Week 27 for Cohorts C and D)
Secondary Percentage of Participants Who Achieved Fasting Triglycerides (TG) <= 100 mg/dL (<= 1.13 mmol/L) The percentage of participants who achieved <= 100 mg/dL or <= 1.13 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. Baseline and Month 6 (Week 25 for Cohorts A and B and Week 27 for Cohorts C and D)
Secondary Maximum Plasma Concentration (Cmax) of ISIS 678354 Predose, 1, 2, 4, 8, 24 hours post the first dose (Day 1), Week 21 (for Cohorts A and B) and Week 25 (for Cohorts C and D)
Secondary Time to Reach Maximum Plasma Concentration (Tmax) of ISIS 678354 Predose, 1, 2, 4, 8, 24 hours post the first dose (Day 1), Week 21 (for Cohorts A and B) and Week 25 (for Cohorts C and D)
Secondary Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours (AUC0-24) of ISIS 678354 Predose, 1, 2, 4, 8, 24 hours post the first dose (Day 1), Week 21 (for Cohorts A and B) and Week 25 (for Cohorts C and D)
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