Study to Evaluate Safety, Tolerability and Efficacy of Inclisiran in Children With Homozygous Familial Hypercholesterolemia
- Conditions
- Familial Hypercholesterolemia - Homozygous
- Interventions
- Drug: Placebo
- Registration Number
- NCT06597006
- Lead Sponsor
- Novartis Pharmaceuticals
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 9
-
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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Inclisiran Inclisiran Year 1 - inclisiran sodium subcutaneous injection (given at Days 1, 90, and 270) Day 360 only - placebo subcutaneous injection Year 2 - inclisiran sodium subcutaneous injection (given at Days 450 and 630) Placebo Placebo Year 1 - placebo subcutaneous injection (given at Days 1, 90 and 270) Year 2 - inclisiran sodium subcutaneous injection (given at Days 360, 450, and 630)
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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
Trial Locations
- Locations (4)
UC San Francisco Medical Center
🇺🇸San Francisco, California, United States
Childrens National Medical Center
🇺🇸Washington, District of Columbia, United States
Washington Univ School Of Medicine
🇺🇸Saint Louis, Missouri, United States
Novartis Investigative Site
🇨🇳Taichung, Taiwan