Study of Efficacy and Safety of Inclisiran in Japanese Participants With High Cardiovascular Risk and Elevated LDL-C (ORION-15)

Novartis

Status and phase: Completed; Phase 2

Conditions: Hypercholesterolemia; Heterozygous Familial Hypercholesterolemia

Treatments: Drug: Inclisiran sodium; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT04666298

CKJX839A11201

Details and patient eligibility

About

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).

Full description

The expected duration of the participants' involvement in the study was approximately 374 days which included screening (up to 14 days), Day 1 study drug administration, two additional injections on Day 90 and Day 270, and the follow-up period to Day 360.

The primary analysis was conducted after all participants had finished Day 180 visit assessments or discontinued before Day 180 visit.

After the primary analysis, double-blind treatment period were maintained to Day 360, although specific sponsor members (except for blinded monitors) were unblinded for the regulatory submission in Japan.

Enrollment: 312 patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

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 <25%.
• Cardiac arrhythmia within 3 months prior to randomization that is not controlled by medication or via ablation.
• Uncontrolled hypertension: systolic blood pressure >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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

312 participants in 4 patient groups, including a placebo group

300 mg inclisiran sodium

Experimental group

Description:

Subcutaneous injection

Treatment:

Drug: Inclisiran sodium

200 mg inclisiran sodium

Experimental group

Description:

Subcutaneous injection

Treatment:

Drug: Inclisiran sodium

100 mg inclisiran sodium

Experimental group

Description:

Subcutaneous injection

Treatment:

Drug: Inclisiran sodium

Placebo

Placebo Comparator group

Description:

Subcutaneous injection

Treatment:

Drug: Placebo