Study to Evaluate Efficacy and Safety of Inclisiran in Adolescents With Heterozygous Familial Hypercholesterolemia

Phase 3

Completed

• Conditions: Familial Hypercholesterolemia - Heterozygous
• Interventions: Drug: Inclisiran; Drug: Placebo

• Registration Number: NCT04652726
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

This was a pivotal phase III study designed to evaluate safety, tolerability, and efficacy of inclisiran in adolescents with heterozygous familial hypercholesterolemia (HeFH) and elevated low density lipoprotein cholesterol (LDL-C).

Detailed Description

This was 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 adolescents with heterozygous familial hypercholesterolemia (HeFH) and elevated low density lipoprotein cholesterol (LDL-C) on stable standard of care background lipid-lowering therapy. The primary objective was to demonstrate superiority of inclisiran compared to placebo in reducing LDL-C (percent change) at Day 330.

Study Timeline

• Study First Submitted: 2020-12-02
• Study First Submitted QC: 2020-12-02
• Study First Posted: 2020-12-03
• Study Start: 2021-01-27
• Primary Completion: 2023-11-09
• Disposition First Submitted: 2024-06-14
• Disposition First Posted: 2024-06-17
• Study Completion: 2024-11-27
• Status Verified: 2025-05
• Results First Submitted: 2025-05-22
• Results First Submitted QC: 2025-05-22
• Last Update Submitted: 2025-05-22
• Results First Posted: 2025-06-10
• Last Update Posted: 2025-06-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 141

Inclusion Criteria

• Heterozygous Familial Hypercholesterolemia (HeFH) diagnosed either by genetic testing or on phenotypic criteria
• Fasting LDL-C >130 mg/dL (3.4 mmol/L) at screening
• Fasting triglycerides <400 mg/dL (4.5 mmol/L) at screening
• On maximally tolerated dose of statin (investigator's discretion) with or without other lipid-lowering therapy; stable for ≥ 30 days before screening

Exclusion Criteria

• Homozygous familial hypercholesterolemia (HoFH)
• Active liver disease
• Secondary hypercholesterolemia, e.g. hypothyroidism or nephrotic syndrome
• Previous treatment with monoclonal antibodies directed towards PCSK9 (within 90 days of screening)
• 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 300 mg subcutaneous injection (given at Days 1, 90, and 270) Day 360 only - placebo subcutaneous injection Year 2 - inclisiran sodium 300 mg 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 300 mg 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 (Part 1/Year 1)	Baseline and Day 330	Percentage change in low-density lipoprotein cholesterol (LDL-C) from baseline to Day 330 (Year 1)

Secondary Outcome Measures

Name	Time	Method
Percent Change in Total Cholesterol From Baseline up to Day 330 (Part 1/Year 1)	Baseline and Day 330	Percentage change in total cholesterol from baseline to Day 330.
Percent Change in LDL-C From Baseline up to Day 720	Baseline, up to Day 720	Percentage change in LDL-C from baseline to each assessment time up to Day 720.
Absolute Change in LDL-C From Baseline up to Day 720	Baseline, up to Day 720	Absolute change in LDL-C from baseline to each assessment time up to Day 720.
Percent Change in Apo B From Baseline up to Day 720	Baseline, up to Day 720	Percentage change in apolipoprotein B (Apo B) from baseline to each assessment time up to Day 720.
Absolute Change in LDL-C From Baseline to up Day 330 (Part 1/Year 1)	Baseline and Day 330	Absolute change in LDL-C from baseline to Day 330.
Percent Change in Apo B From Baseline up to Day 330 (Part 1/Year 1)	Baseline and Day 330	Percentage change in apolipoprotein B (Apo B) from baseline to Day 330.
Percent Change in Lp(a) From Baseline up to Day 330 (Part 1/Year 1)	Baseline and Day 330	Percentage change in lipoprotein (a) \[Lp(a)\] from baseline to Day 330.
Percent Change in Non-HDL-C From Baseline up to Day 330 (Part 1/Year 1)	Baseline and Day 330	Percentage change in non-high density lipoprotein cholesterol (non-HDL-C) from baseline to Day 330.
Absolute Change in Apo B From Baseline up to Day 720	Baseline, up to Day 720	Absolute change in apolipoprotein B (Apo B) from baseline to each assessment time up to Day 720.
Percent Change in Lp(a) From Baseline up to Day 720	Baseline, up to Day 720	Percentage change in lipoprotein (a) \[Lp(a)\] from baseline to each assessment time up to Day 720.
Absolute Change in Lp(a) From Baseline up to Day 720	Baseline, up to Day 720	Absolute change in lipoprotein (a) \[Lp(a)\] from baseline to each assessment time up to Day 720.
Percent Change in Non-HDL-C From Baseline up to Day 720	Baseline, up to Day 720	Percentage change in non-high density lipoprotein cholesterol (non-HDL-C) from baseline to each assessment time up to Day 720.
Absolute Change in Non-HDL-C From Baseline up to Day 720	Baseline, up to Day 720	Absolute change in non-high density lipoprotein cholesterol (non-HDL-C) from baseline to each assessment time up to Day 720.
Percent Change in Total Cholesterol From Baseline up to Day 720	Baseline, up to Day 720	Percentage change in total cholesterol from baseline to each assessment time up to Day 720.
Absolute Change in Total Cholesterol From Baseline up to Day 720	Baseline, up to Day 720	Absolute change in total cholesterol from baseline to each assessment time up to Day 720.
Percent Change in Triglycerides From Baseline up to Day 720	Baseline, up to Day 720	Percentage change in triglycerides from baseline to each assessment time up to Day 720.
Absolute Change in Triglycerides From Baseline up to Day 720	Baseline, up to Day 720	Absolute change in triglycerides from baseline to each assessment time up to Day 720.
Percent Change in HDL-C From Baseline up to Day 720	Baseline, up to Day 720	Percentage change in high density lipoprotein cholesterol (HDL-C) from baseline to each assessment time up to Day 720.
Absolute Change in HDL-C From Baseline up to Day 720	Baseline, up to Day 720	Absolute change in high density lipoprotein cholesterol (HDL-C) from baseline to each assessment time up to Day 720.
Percent Change in VLDL-C From Baseline up to Day 720	Baseline, up to Day 720	Percentage change in very low density lipoprotein cholesterol (VLDL-C) from baseline to each assessment time up to Day 720.
Absolut Change in VLDL-C From Baseline up to Day 720	Baseline, up to Day 720	Absolute change in very low density lipoprotein cholesterol (VLDL-C) from baseline to each assessment time up to Day 720.
Percent Change in Apo A1 From Baseline up to Day 720	Baseline, up to Day 720	Percentage change in apolipoprotein A1 (Apo A1) from baseline to each assessment time up to Day 720.
Absolute Change in Apo A1 From Baseline up to Day 720	Baseline, up to Day 720	Absolute change in apolipoprotein A1 (Apo A1) from baseline to each assessment time up to Day 720.
Percent Change in PCSK9 From Baseline up to Day 720	Baseline, up to Day 720	Percentage change in proprotein convertase subtilisin/kexin type 9 (PCSK9) from baseline to each assessment time up to Day 720.
Absolut Change in PCSK9 From Baseline up to Day 720	Baseline, up to Day 720	Absolute change in proprotein convertase subtilisin/kexin type 9 (PCSK9) from baseline to each assessment time up to Day 720.
Time-adjusted Percent Change in LDL-C From Baseline After Day 90 and up to Day 330 (Part 1/Year 1)	Baseline, after Day 90 up to Day 330	Time-adjusted percent change in LDL-C (after Day 90 and up to Day 330), calculated as the average of percent changes from baseline to Days 150, 270 and 330

Trial Locations

Locations (31)

Tucson Medical Center; 🇺🇸 Tucson, Arizona, United States

Icahn School of Medicine at Mount Sinai; 🇺🇸 New York, New York, United States

Wake Forest U of Health Sciences; 🇺🇸 Winston-Salem, North Carolina, United States

Cincinnati Children's Hospital Medical Center; 🇺🇸 Cincinnati, Ohio, United States

Childrens Hospital Pittsburgh of UPMC; 🇺🇸 Pittsburgh, Pennsylvania, United States

Primary Children's Medical Center; 🇺🇸 Salt Lake City, Utah, United States

Novartis Investigative Site; 🇬🇧 Middlesex, United Kingdom

Unidade de pesquisa clinica - Hospital Universitario Walter Cantidio; 🇧🇷 Fortaleza, Ceara, Brazil

Nucleo de Pesquisa Clinica do Rio Grande do Sul; 🇧🇷 Porto Alegre, RS, Brazil

Setor de Lípides, Aterosclerose e Biologia; 🇧🇷 Sao Paulo, SP, Brazil

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