Study to Evaluate Efficacy and Safety of Inclisiran in Adolescents With Homozygous Familial Hypercholesterolemia (ORION-13)

Novartis

Status and phase: Completed; Phase 3

Conditions: Familial Hypercholesterolemia - Homozygous

Treatments: Drug: Inclisiran; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT04659863

2020-002755-38 (EudraCT Number)

CKJX839C12302

Details and patient eligibility

About

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

Full description

This was a two-part (double-blind, inclisiran versus placebo [Year 1] followed by open-label inclisiran [Year 2]) multicenter study in adolescents (aged 12 to < 18 years) with HoFH and elevated LDL-C (> 130 mg/dL; 3.4 mmol/L) on stable, individualized, optimal standard of care (SoC) background lipid-lowering therapy (including maximally tolerated statin treatment, at the Investigator's discretion) to evaluate the safety, tolerability, and efficacy of inclisiran in this pediatric patient population.

Following an approximately 4-week screening/run-in period, the study had 2 sequential parts as follows:

Part 1/Year 1: 12 months double-blind, parallel group period, in which participants were randomized in a 2:1 ratio to receive either inclisiran sodium 300 mg subcutaneous (s.c.) or placebo. The primary endpoint was assessed at Day 330.

Part 2/Year 2: 12 months single arm, open-label follow-up period, with all participants receiving inclisiran sodium 300 mg s.c.

Enrollment: 13 patients

Sex: All

Ages: 12 to 17 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Homozygous Familial Hypercholesterolemia (HoFH) diagnosed by genetic confirmation
• Fasting LDL-C >130 mg/dL (3.4 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
• Male or female participants >=12 to <18 years of age at screening

Exclusion criteria

• Documented evidence of a null (negative) mutation in both LDLR alleles
• Heterozygous familial hypercholesterolemia (HeFH)
• Active liver disease
• Secondary hypercholesterolemia, e.g. hypothyroidism or nephrotic syndrome
• Previous treatment with monoclonal antibodies directed towards PCSK9 (within 90 days of screening)
• Treatment with mipomersen or lomitapide (within 5 months of screening)
• Recent and/or planned use of other investigational medicinal products or devices

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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13 participants in 3 patient groups, including a placebo group

Part 1 - Inclisiran

Experimental group

Description:

Inclisiran sodium 300 mg subcutaneous (sc) injection (given at Days 1, 90 and 270)

Treatment:

Drug: Inclisiran

Part 1 - Placebo

Placebo Comparator group

Description:

Placebo sc injection (given at Day 1, 90 and 270)

Treatment:

Drug: Placebo

Part 2 - Inclisiran (Total)

Experimental group

Description:

Inclisiran sodium 300 mg sc injection (given at Days 450 and 630). In addition, participants assigned to placebo in Part 1 received inclisiran sodium 300 mg sc injection on Day 360, while participants assigned to inclisiran in Part 1 received placebo sc injection on Day 360.

Treatment:

Drug: Inclisiran