Phase 2
Completed N=286
Phase 2 Study of ISIS 681257 (AKCEA-APO(a)-LRx) in Participants With Hyperlipoproteinemia(a) and Cardiovascular Disease
Elevated Lipoprotein(a) · Cardiovascular Disease
Source: ClinicalTrials.gov NCT03070782 ↗
Enrolled (actual)
286
Serious AEs
10.8%
Results posted
Oct 2020
Primary outcomePrimary: Percent Change From Baseline in Fasting Lipoprotein A [Lp(a)] at the Primary Analysis Time Point — -35; -56; -72; -58 percent change — p=0.0032
Summary
This is a multicenter, randomized, double-blind, placebo-controlled, dose-ranging study to evaluate the safety, including tolerability, of ISIS 681257 and to assess the efficacy of different doses and dosing regimens of ISIS 681257 for reduction of plasma Lipoprotein(a) [Lp(a)] levels in participants with hyperlipoproteinemia(a) and established cardiovascular disease (CVD).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percent Change From Baseline in Fasting Lipoprotein A [Lp(a)] at the Primary Analysis Time Point |
-35; -56; -72; -58; -80; -6 | 0.0032 sig |
| PRIMARY Number of Participants With Treatment Emergent Adverse Events (TEAEs) |
46; 43; 43; 41; 44; 41 | — |
| PRIMARY Number of Participants With TEAEs by Maximum Severity |
20; 21; 16; 24; 21; 22 | — |
| PRIMARY Number of Participants With TEAEs Leading to Study Discontinuation |
3; 0; 3; 1; 6; 2 | — |
| SECONDARY Percent Change From Baseline in Fasting Low-Density Lipoprotein Cholesterol (LDL-C) |
-7; -26; -16; -17; -23; -1 | 0.4407 |
| SECONDARY Percentage of Participants Who Achieved Plasma Lp(a) ≤ 125 Nanomoles Per Liter (Nmol/L) or ≤ 50 Milligrams Per Deciliter (mg/dL) |
22.9; 62.5; 80.9; 64.6; 97.9; 6.4 | 0.0286 sig |
| SECONDARY Percentage of Participants Who Achieved Plasma Lp(a) ≤ 75 Nmol/L or ≤ 30 mg/dL |
6.3; 25.0; 53.2; 33.3; 70.8; 0 | 0.2007 |
| SECONDARY Percent Change From Baseline in the Plasma Levels of Apolipoprotein B (apoB) |
-3; -15; -8; -9; -16; 1 | 0.4022 |
| SECONDARY Percent Change From Baseline in the Plasma Levels of Oxidized Phospholipids (OxPL) on Apolipoprotein(a) [OxPL-apo(a)] |
-28; -49; -63; -45; -70; -20 | 0.4956 |
| SECONDARY Percent Change From Baseline in the Plasma Levels of Oxidized Phospholipids (OxPL) on Apolipoprotein B (OxPL-apoB) |
-37; -57; -79; -64; -88; 14 | 0.0020 sig |
Eligibility Criteria
Key Inclusion Criteria
- Clinical diagnosis of CVD defined as documented coronary artery disease, stroke, or peripheral artery disease
- Lp(a) plasma level ≥ 60 mg/dL
- Must be on standard-of-care preventative therapy for other than elevated Lp(a) CVD risk factors
Key Exclusion Criteria
- Within 6 months of Screening: acute coronary syndrome, major cardiac surgery, or stroke/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
Data sourced from ClinicalTrials.gov (NCT03070782). 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. Informational only — not medical advice.