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).
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
9
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.
Sterile normal saline (0.9% sodium chloride in water for subcutaneous injection)
UC San Francisco Medical Center
San Francisco, California, United States
RECRUITINGPercentage change in LDL-C from baseline to Day 330 (Year 1)
Evaluate the effect of inclisiran compared to placebo on reducing LDL-C \[percent change\] at Day 330
Time frame: Baseline and Day 330
Time-adjusted percent change in LDL-C from baseline after Day 90 and up to Day 330 (Year 1)
Evaluate the effect of inclisiran compared to placebo on reducing LDL-C \[time-adjusted percent change\] over 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)
Evaluate the effect of inclisiran, compared to placebo (for Year 1) and long-term (up to Day 720), on lowering LDL-C, other lipoprotein and lipid parameters, and PCSK9 over time
Time frame: Baseline, up to Day 720
Percent change in PCSK9 from baseline to each assessment time up to Day 720 (Year 2)
Evaluate the effect of inclisiran, compared to placebo (for Year 1) and long-term (up to Day 720), on lowering LDL-C, other lipoprotein and lipid parameters, and PCSK9 over time
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)
Evaluate the effect of inclisiran, compared to placebo (for Year 1) and long-term (up to Day 720), on lowering LDL-C, other lipoprotein and lipid parameters, and PCSK9 over time
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)
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UC San Francisco Medical Center
San Francisco, California, United States
Childrens National Hospital
Washington D.C., District of Columbia, United States
RECRUITINGWashington Univ School Of Medicine
St Louis, Missouri, United States
RECRUITINGNovartis Investigative Site
Vienna, Austria
RECRUITINGNovartis Investigative Site
Beijing, Beijing Municipality, China
RECRUITINGNovartis Investigative Site
Frankfurt am Main, Hesse, Germany
RECRUITINGNovartis Investigative Site
Ioannina, Greece
RECRUITINGNovartis Investigative Site
Kota Bharu, Kelantan, Malaysia
RECRUITINGNovartis Investigative Site
Amsterdam, North Holland, Netherlands
RECRUITING...and 7 more locations
Evaluate the effect of inclisiran, compared to placebo (for Year 1) and long-term (up to Day 720), on lowering LDL-C, other lipoprotein and lipid parameters, and PCSK9 over time
Time frame: Baseline, up to Day 720
Absolute change in PCSK9 from baseline to each assessment time up to Day 720 (Year 2)
Evaluate the effect of inclisiran, compared to placebo (for Year 1) and long-term (up to Day 720), on lowering LDL-C, other lipoprotein and lipid parameters, and PCSK9 over time
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)
Evaluate the effect of inclisiran, compared to placebo (for Year 1) and long-term (up to Day 720), on lowering LDL-C, other lipoprotein and lipid parameters, and PCSK9 over time
Time frame: Baseline, up to Day 720
Percent change in Lp(a) from baseline to each assessment time up to Day 720 (Year 2)
Evaluate the effect of inclisiran, compared to placebo (for Year 1) and long-term (up to Day 720), on lowering LDL-C, other lipoprotein and lipid parameters, and PCSK9 over time
Time frame: Baseline, up to Day 720
Absolute change in Lp(a) from baseline to each assessment time up to Day 720 (Year 2)
Evaluate the effect of inclisiran, compared to placebo (for Year 1) and long-term (up to Day 720), on lowering LDL-C, other lipoprotein and lipid parameters, and PCSK9 over time
Time frame: Baseline, up to Day 720