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NCT06597006PHASE3Recruiting

Study to Evaluate Safety, Tolerability and Efficacy of Inclisiran in Children With Homozygous Familial Hypercholesterolemia

Novartis Pharmaceuticals

Start Date

2/28/2025

Completion Date

4/15/2029

Summary

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).

Detailed 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.

Eligibility Criteria

Age Range: 2 years to 11 years

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

Interventions

DRUG

Inclisiran

DRUG

Placebo

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Conditions

Familial Hypercholesterolemia - Homozygous

Locations

UC San Francisco Medical Center

San Francisco, California 94143-0348

United States

Childrens National Hospital

Washington D.C., District of Columbia 20010

United States

Washington Univ School Of Medicine

St Louis, Missouri 63110

United States

Primary Childrens Medical Center

Salt Lake City, Utah 84113

United States

Novartis Investigative Site

Vienna, 1090

Austria

Novartis Investigative Site

Beijing, Beijing Municipality 100013

China

Novartis Investigative Site

Frankfurt am Main, Hesse 60590

Germany

Novartis Investigative Site

Ioannina, 455 00

Greece

Novartis Investigative Site

Thessaloniki, 546 42

Greece

Novartis Investigative Site

Kota Bharu, Kelantan 16150

Malaysia

Novartis Investigative Site

Amsterdam, North Holland 1105 AZ

Netherlands

Novartis Investigative Site

Bloemfontein, Free State 9301

South Africa

Novartis Investigative Site

Johannesburg, Gauteng 2193

South Africa

Novartis Investigative Site

Taichung, 407219

Taiwan

Novartis Investigative Site

Taipei, 111045

Taiwan

Novartis Investigative Site

Adana, Saricam 01330

Turkey (Türkiye)

Novartis Investigative Site

Ankara, Yenimahalle 06500

Turkey (Türkiye)

Novartis Investigative Site

Izmir, 35100

Turkey (Türkiye)

Novartis Investigative Site

Southampton, SO16 6YD

United Kingdom