Study to Evaluate Efficacy and Safety of Inclisiran in Children With Heterozygous Familial Hypercholesterolemia
- Conditions
- Familial Hypercholesterolemia - Heterozygous
- Interventions
- Drug: Placebo
- Registration Number
- NCT06597019
- 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 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 51
- 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.
- 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
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 Demonstrate superiority of inclisiran compared to placebo in 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 Demonstrate superiority of inclisiran compared to placebo in reducing LDL-C \[time-adjusted percent change\] over Year 1
Absolute change in LDL-C from baseline to Day 330 (Year 1) Baseline and Day 330 Demonstrate superiority of inclisiran compared to placebo in reducing LDL-C \[absolute change\] at Day 330 (Year 1)
Percent change in PCSK9 from baseline to Day 330 (Year 1) Baseline and Day 330 Demonstrate superiority of inclisiran compared to placebo in reducing PCSK9, total cholesterol, Apo B, and non-HDL-C \[percent change\] at Day 330 (Year 1)
Percent change in total cholesterol, non-HDL-C from baseline to Day 330 (Year 1) Baseline and Day 330 Demonstrate superiority of inclisiran compared to placebo in reducing PCSK9, total cholesterol, Apo B, and non-HDL-C \[percent change\] at Day 330 (Year 1)
Percent change in Apo B from baseline to Day 330 (Year 1) Baseline and Day 330 Demonstrate superiority of inclisiran compared to placebo in reducing PCSK9, total cholesterol, Apo B, and non-HDL-C \[percent change\] at Day 330 (Year 1)
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) 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 LDLC, total cholesterol, non-HDLC, 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 (7)
Novartis Investigative Site
🇹🇷Ankara, Turkey
Children's National Hospital
🇺🇸Washington, District of Columbia, United States
UC San Francisco Medical Center
🇺🇸San Francisco, California, United States
Excel Medical Clinical Trials LLC
🇺🇸Boca Raton, Florida, United States
Icahn School of Medicine Mt Sinai
🇺🇸New York, New York, United States
Primary Childrens Medical Center
🇺🇸Salt Lake, Utah, United States
West Virginia Children's Hospital
🇺🇸Morgantown, West Virginia, United States