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

Akcea Therapeutics

Status and phase

Completed

Phase 2

Conditions

Hypertriglyceridemia

Cardiovascular Diseases

Treatments

Drug: Placebo

Drug: ISIS 678354

Study type

Interventional

Funder types

Industry

Identifiers

NCT03385239

ISIS 678354-CS2

Details and patient eligibility

About

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.

Enrollment

114 patients

Sex

All

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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).

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Triple Blind

114 participants in 5 patient groups, including a placebo group

Pooled Placebo

Placebo Comparator group

Description:

Participants in each cohort (A, B, C and D) were randomized to receive placebo at a dose-matched volume of study drug (ISIS 678354).

Treatment:

Drug: Placebo

Cohort A: ISIS 678354: 10 mg Q4W

Experimental group

Description:

Cohort A participants received 10 milligrams (mg) ISIS 678354, subcutaneous (SC) injection, once every 4 weeks (Q4W), for up to 49 weeks and a maximum of 13 doses.

Treatment:

Drug: ISIS 678354

Cohort C: ISIS 678354: 15 mg Q2W

Experimental group

Description:

Cohort C participants received 15 mg ISIS 678354, SC injection, once every 2 weeks (Q2W) for up to 51 weeks and a maximum of 26 doses.

Treatment:

Drug: ISIS 678354

Cohort D: ISIS 678354: 10 mg QW

Experimental group

Description:

Cohort D participants received 10 mg ISIS 678354, SC injection, once weekly (QW) for up to 52 weeks and a maximum of 52 doses.