Phase 2
N=114
Study of ISIS 678354 (AKCEA-APOCIII-LRx) in Participants With Hypertriglyceridemia and Established Cardiovascular Disease (CVD)
Hypertriglyceridemia · Cardiovascular Diseases
Bottom Line
View on ClinicalTrials.gov: NCT03385239 ↗Enrolled (actual)
114
Serious AEs
11.4%
Results posted
Jan 2023
Primary outcome: Primary: Percent Change From Baseline in Fasting Triglycerides (TG) at the Primary Analysis Time Point — 6; -23; -56; -60 percent change — p=0.0042
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- ISIS 678354 (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Akcea Therapeutics
- Primary completion
- Nov 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percent Change From Baseline in Fasting Triglycerides (TG) at the Primary Analysis Time Point |
6; -23; -56; -60; -60 | 0.0042 sig |
| PRIMARY Number of Participants With Treatment-Emergent Adverse Events (TEAEs) |
20; 17; 20; 22; 21 | — |
| 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 |
2; -29; -68; -73; -74; 1 | 0.0123 sig |
| SECONDARY Percentage of Participants Who Achieved Fasting Triglycerides (TG) <= 150 mg/dL (<= 1.7 Millimoles Per Liter [mmol/L]) |
4.2; 13.6; 65.2; 73.9; 90.9 | 0.2591 |
| SECONDARY Percentage of Participants Who Achieved Fasting Triglycerides (TG) <= 100 mg/dL (<= 1.13 mmol/L) |
0; 0; 30.4; 26.1; 45.5 | 0.9119 |
| SECONDARY Maximum Plasma Concentration (Cmax) of ISIS 678354 |
53.7; 45.9; 35.8; 48.8; 41.0; 48.0 | — |
| SECONDARY Time to Reach Maximum Plasma Concentration (Tmax) of ISIS 678354 |
1.08; 2.00; 3.03; 1.50; 2.00; 2.08 | — |
| SECONDARY Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours (AUC0-24) of ISIS 678354 |
618; 499; 411; 563; 468; 499 | — |
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.
Eligibility 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).
Data sourced from ClinicalTrials.gov (NCT03385239). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.