Study to Evaluate Efficacy and Safety of Inclisiran in Children With Heterozygous Familial Hypercholesterolemia

Official title

Two Part (Double-blind Inclisiran Versus Placebo [Year 1] Followed by Open-label Inclisiran [Year 2]) Randomized Multicenter Study to Evaluate Safety, Tolerability and Efficacy of Inclisiran in Children (6 to Less Than 12 Years) With Heterozygous Familial Hypercholesterolemia and Elevated LDL- Cholesterol

Overview

This is a pivotal phase III study designed to evaluate safety, tolerability, and efficacy of inclisiran in children (aged 6 to \<12 years) with heterozygous familial hypercholesterolemia (HeFH) 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 6 to \<12 years) with heterozygous familial hypercholesterolemia (HeFH) and elevated low density lipoprotein cholesterol (LDL-C) on stable standard of care background lipid-lowering therapy.

Interventions

• Drug Inclisiran
  Inclisiran (inclisiran sodium 300 mg subcutaneous (s.c.) for participants with body weight ≥23 kg and inclisiran sodium 180 mg s.c. for participants with body weight \<23 kg. The dose level is based on the participant's body weight on Day 1 (for Part 1) and Day 360 (for Part 2), respectively.
• Drug Placebo
  Sterile normal saline (0.9% sodium chloride in water for subcutaneous injection)

Primary outcome measures

• Percentage change in LDL-C from baseline to Day 330 (Year 1) [Time frame: Baseline and Day 330]

Secondary outcome measures (12)

• Time-adjusted percent change in LDL-C from baseline after Day 90 and up to Day 330 (Year 1) [Time frame: Baseline, after Day 90 up to Day 330]
• Absolute change in LDL-C from baseline to Day 330 (Year 1) [Time frame: Baseline and Day 330]
• Percent change in PCSK9 from baseline to Day 330 (Year 1) [Time frame: Baseline and Day 330]
• Percent change in total cholesterol, non-HDL-C from baseline to Day 330 (Year 1) [Time frame: Baseline and Day 330]
• Percent change in Apo B from baseline to Day 330 (Year 1) [Time frame: Baseline and Day 330]
• Percent change in LDLC, total cholesterol, non-HDLC, triglycerides, HDL-C, VLDL-C from baseline to each assessment time up to Day 720 (Year 2) [Time frame: Baseline, up to Day 720]
• Percent change in PCSK9 from baseline to each assessment time up to Day 720 (Year 2) [Time frame: Baseline, up to Day 720]
• Percent change in Apo B, Apo A1 from baseline to each assessment time up to Day 720 (Year 2) [Time frame: Baseline, up to Day 720]
• Absolute change in LDLC, total cholesterol, non-HDLC, triglycerides, HDL-C, VLDL-C from baseline to each assessment time up to Day 720 (Year 2) [Time frame: Baseline, up to Day 720]
• Absolute change in PCSK9 from baseline to each assessment time up to Day 720 (Year 2) [Time frame: Baseline, up to Day 720]
• Absolute change in Apo B, Apo A1 from baseline to each assessment time up to Day 720 (Year 2) [Time frame: Baseline, up to Day 720]
• Percent change in Lp(a) from baseline to each assessment time up to Day 720 (Year 2) [Time frame: Baseline, up to Day 720]

Eligibility criteria

Inclusion criteria

• Male or female participants, 6 to <12 years of age at screening
• HeFH diagnosed either by genetic testing or on phenotypic criteria
• Fasting LDL-C >130 mg/dL (3.4 mmol/L) at screening
• For participants 8 to <12 years, on an optimal dose of statin (investigator's discretion) unless statin intolerant, with or without other lipid-lowering therapy (e.g. ezetimibe). For participants <8 years, the use of background lipid-lowering treatment is based on investigator's discretion.
• Participants on lipid-lowering therapies (such as statin and/or e.g. ezetimibe) must be on a stable dose for ≥30 days before screening with no planned medication or dose changes during study participation.

Exclusion criteria

• Previous treatment (within 90 days of screening) with monoclonal antibodies directed towards PCSK9
• Secondary hypercholesterolemia, e.g. hypothyroidism or nephrotic syndrome
• Homozygous familial hypercholesterolemia (HoFH)
• Body weight <16 kg at the screening and/or randomization (Day 1) visit
• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

United States · 11 centers

• UC San Francisco Medical Center — San Francisco
• UC San Francisco Medical Center — San Francisco
• Children's National Hospital — Washington D.C.
• Childrens National Hospital — Washington D.C.
• Excel Medical Clinical Trials LLC — Boca Raton
• Icahn School of Med at Mt Sinai — New York
• Primary Childrens Medical Center — Salt Lake City
• Primary Childrens Medical Center — Salt Lake City
• … and 3 more centers

Spain · 8 centers

• Novartis Investigative Site — Elche
• Novartis Investigative Site — Cadiz
• Novartis Investigative Site — Badalona
• Novartis Investigative Site — Esplugues
• Novartis Investigative Site — Pamplona
• Novartis Investigative Site — Barcelona
• Novartis Investigative Site — Málaga
• Novartis Investigative Site — Seville

Brazil · 4 centers

• Novartis Investigative Site — Fortaleza
• Novartis Investigative Site — Rio de Janeiro
• Novartis Investigative Site — Porto Alegre
• Novartis Investigative Site — São Paulo

Italy · 4 centers

• Novartis Investigative Site — Milan
• Novartis Investigative Site — Roma
• Novartis Investigative Site — Torino
• Novartis Investigative Site — Verona

Portugal · 4 centers

• Novartis Investigative Site — Coimbra
• Novartis Investigative Site — Lisbon
• Novartis Investigative Site — Porto
• Novartis Investigative Site — Porto

France · 3 centers

• Novartis Investigative Site — Marseille
• Novartis Investigative Site — Nantes
• Novartis Investigative Site — Paris

Germany · 3 centers

• Novartis Investigative Site — Freiburg im Breisgau
• Novartis Investigative Site — Frankfurt am Main
• Novartis Investigative Site — Hanover

Poland · 3 centers

• Novartis Investigative Site — Bialystok
• Novartis Investigative Site — Gdansk
• Novartis Investigative Site — Lodz

Turkey (Türkiye) · 3 centers

• Novartis Investigative Site — Adana
• Novartis Investigative Site — Ankara
• Novartis Investigative Site — Izmir

Argentina · 2 centers

• Novartis Investigative Site — Buenos Aires
• Novartis Investigative Site — CABA

Austria · 2 centers

• Novartis Investigative Site — Salzburg
• Novartis Investigative Site — Vienna

Belgium · 2 centers

• Novartis Investigative Site — Brussels
• Novartis Investigative Site — Leuven

China · 2 centers

• Novartis Investigative Site — Beijing
• Novartis Investigative Site — Shanghai

Czechia · 2 centers

• Novartis Investigative Site — Prague
• Novartis Investigative Site — Prague

Greece · 2 centers

• Novartis Investigative Site — Athens
• Novartis Investigative Site — Ioannina

Israel · 2 centers

• Novartis Investigative Site — Jerusalem
• Novartis Investigative Site — Ramat Gan

Taiwan · 2 centers

• Novartis Investigative Site — Taipei
• Novartis Investigative Site — Taipei

United Kingdom · 2 centers

• Novartis Investigative Site — West Midlands
• Novartis Investigative Site — London

Hong Kong · 1 center

• Novartis Investigative Site — Hong Kong

Hungary · 1 center

• Novartis Investigative Site — Budapest

Malaysia · 1 center

• Novartis Investigative Site — Kuala Lumpur

Netherlands · 1 center

• Novartis Investigative Site — Amsterdam

South Africa · 1 center

• Novartis Investigative Site — Bloemfontein

Identifiers

NCT: NCT06597019 · CKJX839C12303 · 2024-514594-21

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗