Familial Hypercholesterolemia - Heterozygous
Conditions
Keywords
Heterozygous familial hypercholesterolemia (HeFH),, LDL-cholesterol (LDL-C),, Children,, pediatric,, small interfering ribonucleic acid (siRNA),, inclisiran,, Familial Hypercholesterolemia,, Heterozygous FH,, Hypercholesterolemia,, Lipoprotein(a),, Hyperlipidemia,, Dyslipidemia,, Heart Failure,, Cardiovascular Diseases,, Cholesterol,, Aortic Stenosis
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.
Interventions
DRUGInclisiran
Inclisiran (inclisiran sodium 300 mg subcutaneous (s.c.) for participants with body weight ≥23 kg and inclisiran sodium 180 mg s.c. for participants with body weight \<23 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
6 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 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 |
| 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, 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 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) |
Countries
Argentina, Austria, Belgium, Brazil, China, Czechia, France, Germany, Greece, Hong Kong, Hungary, Israel, Italy, Malaysia, Netherlands, Poland, Portugal, South Africa, Spain, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTNovartis Pharmaceuticals
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Outcome results
None listed