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Recruiting NCT06597006

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

Phase III Interventional Familial Hypercholesterolemia - Homozygous

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Inclisiran, Placebo.
Who it may be relevant to
Registry conditions: Familial Hypercholesterolemia - Homozygous. Basic parameters: 2 years — 11 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
United States, Austria, China, Germany, Greece +6
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

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 (2 to Less Than 12 Years) With Homozygous 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 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.

Interventions

  • Drug Inclisiran
    Inclisiran (inclisiran sodium 300 mg subcutaneous (s.c.) for participants with body weight ≥23 kg, inclisiran sodium 180 mg s.c. for participants with body weight \<23 kg to ≥16 kg, or inclisiran sodium 100 mg s.c. for participants with body weight \<16 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 (9)
  • 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]
  • Percent change in LDL-C, total cholesterol, non-HDL-C, 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 LDL-C, total cholesterol, non-HDL-C, 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]
  • Absolute 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, 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

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 · 4 centers
  • UC San Francisco Medical Center — San Francisco
  • Childrens National Hospital — Washington D.C.
  • Washington Univ School Of Medicine — St Louis
  • Primary Childrens Medical Center — Salt Lake City
Turkey (Türkiye) · 3 centers
  • Novartis Investigative Site — Adana
  • Novartis Investigative Site — Ankara
  • Novartis Investigative Site — Izmir
Greece · 2 centers
  • Novartis Investigative Site — Ioannina
  • Novartis Investigative Site — Thessaloniki
South Africa · 2 centers
  • Novartis Investigative Site — Bloemfontein
  • Novartis Investigative Site — Johannesburg
Taiwan · 2 centers
  • Novartis Investigative Site — Taichung
  • Novartis Investigative Site — Taipei
Austria · 1 center
  • Novartis Investigative Site — Vienna
China · 1 center
  • Novartis Investigative Site — Beijing
Germany · 1 center
  • Novartis Investigative Site — Frankfurt am Main
Malaysia · 1 center
  • Novartis Investigative Site — Kota Bharu
Netherlands · 1 center
  • Novartis Investigative Site — Amsterdam
United Kingdom · 1 center
  • Novartis Investigative Site — Southampton

Identifiers

NCT: NCT06597006 · CKJX839C12304 · 2024-514595-41

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗