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

Familial Hypercholesterolemia - Heterozygous Clinical Trial

— ORION-16  

Official title:

Two Part (Double-blind Inclisiran Versus Placebo [Year 1] Followed by Open-label Inclisiran [Year 2]) Randomized Multicenter Study to Evaluate Safety, Tolerability, and Efficacy of Inclisiran in Adolescents (12 to Less Than 18 Years) With Heterozygous Familial Hypercholesterolemia and Elevated LDL-cholesterol (ORION-16)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04652726
• Other study ID #: CKJX839C12301
• Secondary ID: 2020-002757-18
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: January 27, 2021
• Est. completion date: December 2, 2024

Study information

• Verified date: June 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 141
• Est. completion date: December 2, 2024
• Est. primary completion date: November 9, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Familial Hypercholesterolemia - Heterozygous
• Hypercholesterolemia
• Hyperlipoproteinemia Type II

Intervention

Drug:
• Inclisiran
Inclisiran sodium 300 mg (equivalent to 284 mg inclisiran) in 1.5 mL solution for subcutaneous injection
• Placebo
Sterile normal saline (0.9% sodium chloride in water for subcutaneous injection)

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Ciudad de Formosa	Formosa
Brazil	Unidade de pesquisa clinica - Hospital Universitario Walter Cantidio	Fortaleza	Ceara
Brazil	Nucleo de Pesquisa Clinica do Rio Grande do Sul	Porto Alegre	RS
Brazil	Heart Institute (InCOr) HCMFUSP	Sao Paulo	SP
Brazil	Setor de Lípides, Aterosclerose e Biologia	Sao Paulo	SP
Canada	Novartis Investigative Site	Quebec
Czechia	Novartis Investigative Site	Praha 2
Czechia	Novartis Investigative Site	Praha 5
France	Novartis Investigative Site	Besancon Cedex
France	Novartis Investigative Site	Bron Cedex
France	Novartis Investigative Site	Toulouse Cedex
Germany	KKIM UK Frankfurt/Main	Frankfurt
Germany	Universitaetsklinikum Freiburg	Freiburg
Germany	Universitaetsmedizin Mannheim	Mannheim	Baden-Wuerttemberg
Greece	Hippokrateion General Hospital of Athens Greece	Athens
Greece	Metropolitan Hospital	Athens
Greece	University General Hospital of Ioannina	Ioannina	GR
Hungary	Novartis Investigative Site	Pecs
Israel	Lipid Research	Jerusalem
Israel	Lipids Center Sheba Medical Center, Israel	Ramat Gan
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Modena	MO
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Roma	RM
Jordan	Novartis Investigative Site	Irbid
Lebanon	Hotel Dieu de France Hospital	Ashrafieh
Malaysia	UiTM Sungai Buloh	Sungai Buloh	Selangor Darul Ehsan
Netherlands	Novartis Investigative Site	Amsterdam
Netherlands	Novartis Investigative Site	Rotterdam	Zuid Holland
Norway	Novartis Investigative Site	Oslo
Poland	Novartis Investigative Site	Gdansk
Poland	Novartis Investigative Site	Lodz
Russian Federation	Institute of the complex problems of cardiovascular disease	Kemerovo
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Institute of Internal Prev. Med.	Novosibirsk
Slovakia	Novartis Investigative Site	Poprad
Slovenia	University Medical Centre Ljubljana, Div. of Pediatric Dept. of Endocrinology, Diabetes and Metabolic Diseases	Ljubljana
South Africa	Novartis Investigative Site	Bloemfontein	Free State
South Africa	Novartis Investigative Site	Cape Town
South Africa	Novartis Investigative Site	Somerset West	Western Cape
Spain	Hospital Abente y Lago	A Coruna
Spain	Hospital Reina Sofia	Cordoba	Andalucia
Spain	Hospital Virgen de la Vcitoria	Malaga	Andalucia
Spain	Hospital Central de Asturias	Oviedo	Asturias
Spain	Novartis Investigative Site	Pamplona	Navarra
Switzerland	Novartis Investigative Site	Geneve 14
Taiwan	Far Eastern Memorial Hospital	New Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Turkey	Novartis Investigative Site	Adana
Turkey	Gazi University Medical Faculty	Ankara
Turkey	Novartis Investigative Site	Istanbul	TUR
Turkey	Novartis Investigative Site	Izmir
United Kingdom	Novartis Investigative Site	Middlesex
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Childrens Hospital Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	Primary Children's Medical Center	Salt Lake City	Utah
United States	Tucson Medical Center	Tucson	Arizona
United States	Wake Forest U of Health Sciences	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Canada,  Czechia,  France,  Germany,  Greece,  Hungary,  Israel,  Italy,  Jordan,  Lebanon,  Malaysia,  Netherlands,  Norway,  Poland,  Russian Federation,  Slovakia,  Slovenia,  South Africa,  Spain,  Switzerland,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage (%) change in low-density lipoprotein cholesterol (LDL-C) from baseline to Day 330	Demonstrate superiority of inclisiran compared to placebo in reducing LDL-C [percent change] at Day 330 (Year 1)	Baseline and Day 330
Secondary	Time-adjusted % change in LDL-C from baseline after Day 90 and up to Day 330	Demonstrate superiority of inclisiran compared to placebo in reducing LDL-C [time-adjusted percent change] over Year 1	Baseline, after Day 90 up to Day 330
Secondary	Absolute change in LDL-C from baseline to Day 330	Demonstrate superiority of inclisiran compared to placebo in reducing LDL-C [absolute change] at Day 330 (Year 1)	Baseline and Day 330
Secondary	% 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	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	Baseline and Day 330
Secondary	% change and absolute change in LDL-C from 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	Baseline, up to Day 720
Secondary	% change and absolute change in other lipoproteins and lipid parameters from 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	Baseline, up to Day 720
Secondary	% change and absolute change in proprotein convertase subtilisin/kexin type 9 (PCSK9) from 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	Baseline, up to Day 720