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 is 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 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 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 is to demonstrate superiority of inclisiran compared to placebo in reducing LDL-C (percent change) at Day 330.

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
Estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m2 at screening

Exclusion Criteria

Homozygous familial hypercholesterolemia (HoFH)
Active liver disease
Secondary hypercholesterolemia, e.g. hypothyroidism or nephrotic syndrome
Major adverse cardiovascular events within 3 months prior to randomization
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

Other protocol-defined inclusion/exclusion criteria may apply

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 low-density lipoprotein cholesterol (LDL-C) from baseline to Day 330	Baseline and Day 330	Demonstrate superiority of inclisiran compared to placebo in reducing LDL-C \[percent change\] at Day 330 (Year 1)

Secondary Outcome Measures

Name	Time	Method
Time-adjusted % change in LDL-C from baseline after Day 90 and up to Day 330	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	Baseline and Day 330	Demonstrate superiority of inclisiran compared to placebo in reducing LDL-C \[absolute change\] at Day 330 (Year 1)
% change in apolipoprotein B (Apo B), lipoprotein (a) [Lp(a)], non-high density lipoprotein cholesterol (non-HDL-C), and total cholesterol from baseline to Day 330	Baseline and Day 330	Demonstrate superiority of inclisiran compared to placebo in reducing Apo B, lipoprotein (a) \[Lp(a)\], non-high density lipoprotein cholesterol (non-HDL-C), and total cholesterol \[percent change\] at Day 330 (Year 1) - Hierarchical testing
% change and absolute change in LDL-C from baseline up to Day 720	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 over time
% change and absolute change in other lipoproteins and lipid parameters from baseline up to Day 720	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 Apo B, Lp(a), non-HDL-C, total cholesterol, triglycerides, high density lipoprotein cholesterol (HDL-C), very low density lipoprotein cholesterol (VLDL-C), apolipoprotein A1 (Apo A1) over time
% change and absolute change in proprotein convertase subtilisin/kexin type 9 (PCSK9) from baseline up to Day 720	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 PCSK9 over time

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
Heart Institute (InCOr) HCMFUSP
🇧🇷
Sao Paulo, SP, Brazil
Universitaetsmedizin Mannheim
🇩🇪
Mannheim, Baden-Wuerttemberg, Germany
KKIM UK Frankfurt/Main
🇩🇪
Frankfurt, Germany
Universitaetsklinikum Freiburg
🇩🇪
Freiburg, Germany
University General Hospital of Ioannina
🇬🇷
Ioannina, GR, Greece
Lipid Research
🇮🇱
Jerusalem, Israel
Hippokrateion General Hospital of Athens Greece
🇬🇷
Athens, Greece
Metropolitan Hospital
🇬🇷
Athens, Greece
Lipids Center Sheba Medical Center, Israel
🇮🇱
Ramat Gan, Israel
Hotel Dieu de France Hospital
🇱🇧
Ashrafieh, Lebanon
UiTM Sungai Buloh
🇲🇾
Sungai Buloh, Selangor Darul Ehsan, Malaysia
Institute of the complex problems of cardiovascular disease
🇷🇺
Kemerovo, Russian Federation
Institute of Internal Prev. Med.
🇷🇺
Novosibirsk, Russian Federation
University Medical Centre Ljubljana, Div. of Pediatric Dept. of Endocrinology, Diabetes and Metabolic Diseases
🇸🇮
Ljubljana, Slovenia
Hospital Reina Sofia
🇪🇸
Cordoba, Andalucia, Spain
Hospital Virgen de la Vcitoria
🇪🇸
Malaga, Andalucia, Spain
Hospital Central de Asturias
🇪🇸
Oviedo, Asturias, Spain
Hospital Abente y Lago
🇪🇸
A Coruna, Spain
Far Eastern Memorial Hospital
🇨🇳
New Taipei, Taiwan
Taipei Veterans General Hospital
🇨🇳
Taipei, Taiwan
Gazi University Medical Faculty
🇹🇷
Ankara, Turkey