Study to Evaluate Efficacy and Safety of Inclisiran in Adolescents With Heterozygous Familial Hypercholesterolemia (ORION-16)

Novartis

Status and phase: Completed; Phase 3

Conditions: Familial Hypercholesterolemia - Heterozygous

Treatments: Drug: Placebo; Drug: Inclisiran

Study type: Interventional

Funder types: Industry

Identifiers

NCT04652726

CKJX839C12301

2020-002757-18 (EudraCT Number)

Details and patient eligibility

About

This is a pivotal phase III study designed to evaluate safety, tolerability, and efficacy of inclisiran in adolescents with heterozygous familial hypercholesterolemia (HeFH) and elevated low density lipoprotein cholesterol (LDL-C).

Full description

This is a two-part (1 year double-blind inclisiran versus placebo / 1 year open-label inclisiran) multicenter study designed to evaluate safety, tolerability, and efficacy of inclisiran in adolescents with heterozygous familial hypercholesterolemia (HeFH) and elevated low density lipoprotein cholesterol (LDL-C) on stable standard of care background lipid-lowering therapy. The primary objective is to demonstrate superiority of inclisiran compared to placebo in reducing LDL-C (percent change) at Day 330.

Enrollment: 141 patients

Sex: All

Ages: 12 to 17 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Heterozygous Familial Hypercholesterolemia (HeFH) diagnosed either by genetic testing or on phenotypic criteria
• Fasting LDL-C >130 mg/dL (3.4 mmol/L) at screening
• Fasting triglycerides <400 mg/dL (4.5 mmol/L) at screening
• On maximally tolerated dose of statin (investigator's discretion) with or without other lipid-lowering therapy; stable for ≥ 30 days before screening
• Estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m2 at screening

Exclusion criteria

• Homozygous familial hypercholesterolemia (HoFH)
• Active liver disease
• Secondary hypercholesterolemia, e.g. hypothyroidism or nephrotic syndrome
• Major adverse cardiovascular events within 3 months prior to randomization
• Previous treatment with monoclonal antibodies directed towards PCSK9 (within 90 days of screening)
• Recent and/or planned use of other investigational medicinal products or devices

Other protocol-defined inclusion/exclusion criteria may apply

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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141 participants in 2 patient groups, including a placebo group

Inclisiran

Experimental group

Description:

Year 1 - inclisiran sodium 300 mg subcutaneous injection (given at Days 1, 90, and 270) Day 360 only - placebo subcutaneous injection Year 2 - inclisiran sodium 300 mg subcutaneous injection (given at Days 450 and 630)

Treatment:

Drug: Inclisiran

Placebo

Placebo Comparator group

Description:

Year 1 - placebo subcutaneous injection (given at Days 1, 90 and 270) Year 2 - inclisiran sodium 300 mg subcutaneous injection (given at Days 360, 450, and 630)

Treatment:

Drug: Placebo