Study to Evaluate Safety, Tolerability and Efficacy of Inclisiran in Children With Homozygous Familial Hypercholesterolemia (ORION-19)

Novartis

Status and phase: Begins enrollment in 3 months; Phase 3

Conditions: Familial Hypercholesterolemia - Homozygous

Treatments: Drug: Placebo; Drug: Inclisiran

Study type: Interventional

Funder types: Industry

Identifiers

NCT06597006

2024-514595-41 (EudraCT Number)

CKJX839C12304

Details and patient eligibility

About

This is a pivotal phase III study designed to evaluate safety, tolerability, and efficacy of inclisiran in children (aged 2 to <12 years) with homozygous familial hypercholesterolemia (HoFH) and elevated low density lipoprotein cholesterol (LDLC).

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 children (aged 2 to <12 years) with homozygous familial hypercholesterolemia (HoFH) and elevated low density lipoprotein cholesterol (LDL-C) on stable standard of care background lipid-lowering therapy.

Enrollment: 9 estimated patients

Sex: All

Ages: 2 to 11 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or female participants, 2 to <12 years of age at screening

• HoFH diagnosed by genetic confirmation

  • Note: Participants with known null (negative) mutations in both LDLR alleles are not eligible (see also exclusion criteria)

• Fasting LDL-C >130 mg/dL (3.4 mmol/L) at screening

• On an optimal dose of statin (investigator's discretion), unless statin intolerant, with or without other lipid-lowering therapy (e.g. ezetimibe)

• Participants on lipid-lowering therapies (such as e.g. statins, ezetimibe) must be on a stable dose for ≥30 days before screening with no planned medication or dose changes during study participation

• Participants on a documented regimen of LDL-apheresis for ≥ 3 months before screening will be allowed to continue the apheresis during the study, if needed. The apheresis schedule/settings/duration must be stable prior to screening, are not allowed to change during the double-blind period of the trial and must permit that an apheresis coincides with each study visit.

Exclusion criteria

• Documented evidence of a null (negative) mutation in both LDLR alleles
• Previous treatment (within 90 days of screening) with monoclonal antibodies directed towards PCSK9
• History of poor response to therapy with any monoclonal antibody directed towards PCSK9 (e.g. <15% reduction in LDL-C)
• Treatment with mipomersen or lomitapide (within 5 months of screening)
• Secondary hypercholesterolemia, e.g. hypothyroidism or nephrotic syndrome
• Heterozygous familial hypercholesterolemia (HeFH)
• Body weight (at the screening and/or randomization (Day 1) visit) <16 kg for participants 6 to <12 years (at screening) or <11 kg for participants 2 to <6 years (at screening)
• Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver or unexplained alanine aminotransferase (ALT), aspartate aminotransferase (AST) elevation >3x ULN, or total bilirubin elevation >2x ULN (except patients with Gilbert's syndrome)
• Pregnant or nursing females
• 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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9 participants in 2 patient groups, including a placebo group

Inclisiran

Experimental group

Description:

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

Treatment:

Drug: Placebo