Phase 2
Completed N=312
Study of Efficacy and Safety of Inclisiran in Japanese Participants With High Cardiovascular Risk and Elevated LDL-C
Hypercholesterolemia · Heterozygous Familial Hypercholesterolemia
Source: ClinicalTrials.gov NCT04666298 ↗
Enrolled (actual)
312
Serious AEs
7.0%
Results posted
May 2023
Primary outcomePrimary: Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) to Day 180 — 9.0; -47.6; -51.9; -56.3 percent change in LDL-C — p=<.0001
Summary
This was a placebo-controlled, double-blind, randomized trial in Japanese participants with history of coronary artery disease (CAD) or participants categorized in 'high risk' by JAS 2017 guideline, or Japanese participants with heterozygous familial hypercholesterolemia (HeFH) and elevated Low-density lipoprotein cholesterol (LDL-C) despite maximum tolerated dose of statin(s) to evaluate the efficacy, safety, tolerability, and PK of subcutaneous inclisiran injection(s).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) to Day 180 |
9.0; -47.6; -51.9; -56.3 | <.0001 sig |
| SECONDARY Percent Change From Baseline in PCSK9 by Visit |
4.79; -55.42; -65.64; -69.56; 1.92; -66.45 | — |
| SECONDARY Percent Change From Baseline in LDL-C by Visit |
1.68; -37.15; -42.08; -47.60; 1.29; -52.20 | — |
| SECONDARY Absolute Change in LDL-C From Baseline at Day 180 |
13.2; -49.3; -53.9; -57.7 | — |
| SECONDARY Proportion of Participants With LDL-C Greater Than 80% of Baseline Value at Day 180 |
35; 0; 0; 0 | — |
| SECONDARY Proportion of Participants With Greater or Equal to 50% LDL-C Reduction From Baseline by Visit |
1; 17; 40; 45; 0; 31 | — |
| SECONDARY Percent Change From Baseline in Cholesterol by Visit |
0.87; -21.94; -24.71; -28.60; 0.89; -30.92 | — |
| SECONDARY Percent Change From Baseline in Triglycerides by Visit |
5.49; 1.24; -1.16; -7.19; 7.76; -4.72 | — |
| SECONDARY Percent Change From Baseline in HDL Cholesterol by Visit |
1.73; 3.00; 5.93; 4.38; 1.94; 4.86 | — |
| SECONDARY Percent Change From Baseline in Non-HDL Cholesterol by Visit |
1.13; -31.37; -35.68; -41.16; 1.03; -44.72 | — |
| SECONDARY Percent Change From Baseline in VLDL-C by Visit |
5.55; -2.96; -5.56; -12.41; 6.69; -9.01 | — |
| SECONDARY Percent Change From Baseline in Apo- A1 by Visit |
0.04; 3.64; 2.29; 3.98; 0.90; 2.70 | — |
| SECONDARY Percent Change From Baseline in Apo- B by Visit |
1.09; -28.16; -32.45; -37.12; 2.16; -39.72 | — |
| SECONDARY Percent Change From Baseline in Lipoprotein-a by Visit |
3.33; -21.77; -16.63; -22.84; 0.92; -28.09 | — |
| SECONDARY Proportion of Participants Who Attain Lipid Control Target Pre-specified by JAS 2017 Guidelines for Their Level of Cardiovascular Risk at Day 180 |
5; 50; 87; 91 | — |
| SECONDARY Number of Participants With LDL-C Levels of <25 mg/dL, <50 mg/dL, <70 mg/dL, and <100 mg/dL by Visit |
0; 1; 5; 10; 1; 19 | — |
Eligibility Criteria
Inclusion Criteria
- Participants with history of CAD or participants categorized in 'high risk' by Japan Atherosclerosis Society (JAS) 2017 guidelines or participants with heterozygous familial hypercholesterolemia (HeFH)
- As per the JAS 2017 guideline, participants not meeting the LDL-C management targets.
- Participants on statins should be receiving a maximally tolerated dose.
- Participants not receiving statins must have documented evidence of intolerance to at least one statin.
- The lipid-lowering therapy should have remained stable for ≥ 30 days before screening with no planned medication/ dose change until Day 180
Exclusion Criteria
- Participants diagnosed with homozygous familial hypercholesterolemia (HoFH).
- Treatment (within 90 days of screening) with monoclonal antibodies directed towards PCSK9.
- New York Heart Association (NYHA) class IV heart failure or last known left ventricular ejection fraction 160 mmHg or diastolic blood pressure >100 mmHg prior to randomization despite antihypertensive therapy.
- Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver or unexplained elevations in alanine aminotransferase (ALT), aspartate aminotransferase (AST), >3x the upper limit of normal (ULN), or total bilirubin >2x ULN at screening.
- Severe concomitant non-cardiovascular disease that carries the risk of reducing life expectancy to less than 2 years.
Data sourced from ClinicalTrials.gov (NCT04666298). 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.