Familial Hypercholesterolemia - Homozygous
Conditions
Keywords
Homozygous familial hypercholesterolemia (HoFH),, LDL-cholesterol (LDL-C), children, pediatric,, small interfering ribonucleic acid (siRNA),, inclisiran,, Familial Hypercholesterolemia,, Homozygous FH,, Hypercholesterolemia,, Lipoprotein(a),, Hyperlipidemia,, Dyslipidemia,, Cardiovascular Diseases,, Heart Failure,, Cholesterol,, Aortic Stenosis
Brief 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.
Interventions
DRUGInclisiran
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.
DRUGPlacebo
Sterile normal saline (0.9% sodium chloride in water for subcutaneous injection)
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Masked (Year 1) to No Masking (Year 2)
Intervention model description
Parallel (Year 1) to single-group (Year 2)
Eligibility
Sex/Gender
ALL
Age
2 Years to 11 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage change in LDL-C from baseline to Day 330 (Year 1) | Baseline and Day 330 | Evaluate the effect of inclisiran compared to placebo on reducing LDL-C \[percent change\] at Day 330 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time-adjusted percent change in LDL-C from baseline after Day 90 and up to Day 330 (Year 1) | Baseline, after Day 90 up to Day 330 | Evaluate the effect of inclisiran compared to placebo on reducing LDL-C \[time-adjusted percent change\] over Year 1 |
| 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) | Baseline, up to Day 720 | 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 |
| Percent change in PCSK9 from baseline to each assessment time up to Day 720 (Year 2) | Baseline, up to Day 720 | 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 |
| Percent change in Apo B, Apo A1 from baseline to each assessment time up to Day 720 (Year 2) | Baseline, up to Day 720 | 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 |
| 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) | Baseline, up to Day 720 | 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 |
| Absolute change in PCSK9 from baseline to each assessment time up to Day 720 (Year 2) | Baseline, up to Day 720 | 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 |
| Absolute change in Apo B, Apo A1 from baseline to each assessment time up to Day 720 (Year 2) | Baseline, up to Day 720 | 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 |
| Percent change in Lp(a) from baseline to each assessment time up to Day 720 (Year 2) | Baseline, up to Day 720 | 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 |
| Absolute change in Lp(a) from baseline to each assessment time up to Day 720 (Year 2) | Baseline, up to Day 720 | 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 |
Countries
Austria, China, Germany, Greece, Malaysia, Netherlands, South Africa, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTNovartis Pharmaceuticals
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Outcome results
None listed