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

Familial Hypercholesterolemia - Homozygous Clinical Trial

— ORION-13  

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 Homozygous Familial Hypercholesterolemia and Elevated LDL-cholesterol (ORION-13)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04659863
• Other study ID #: CKJX839C12302
• Secondary ID: 2020-002755-38
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: February 16, 2021
• Est. completion date: December 2, 2024

Study information

• Verified date: March 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 homozygous familial hypercholesterolemia (HoFH) 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 homozygous familial hypercholesterolemia (HoFH) and elevated low density lipoprotein cholesterol (LDL-C) on stable standard of care background lipid-lowering therapy. The primary objective is to evaluate the effect of inclisiran compared to placebo in reducing LDL-C (percent change) at Day 330.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 13
• Est. completion date: December 2, 2024
• Est. primary completion date: October 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 17 Years

Eligibility

Inclusion Criteria:

• Homozygous Familial Hypercholesterolemia (HoFH) diagnosed by genetic confirmation
• Fasting LDL-C >130 mg/dL (3.4 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:

• Documented evidence of a null (negative) mutation in both LDLR alleles
• Heterozygous familial hypercholesterolemia (HeFH)
• Active liver disease
• Secondary hypercholesterolemia, e.g. hypothyroidism or nephrotic syndrome
• Major adverse cardiovascular events within 1 month prior to randomization
• Previous treatment with monoclonal antibodies directed towards PCSK9 (within 90 days of screening)
• Treatment with mipomersen or lomitapide (within 5 months 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 - Homozygous
• Homozygous Familial Hypercholesterolemia
• 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 injection) for subcutaneous injection

Locations

Country	Name	City	State
Canada	Novartis Investigative Site	Quebec
France	Novartis Investigative Site	Bron Cedex
Greece	Metropolitan Hospital	Athens
Greece	University General Hospital of Ioannina	Ioannina	GR
Lebanon	Hotel Dieu de France Hospital	Ashrafieh
Lebanon	American University of Beirut Medical Center	Beirut
Malaysia	Novartis Investigative Site	Kuala Lumpur
Netherlands	Novartis Investigative Site	Amsterdam
Turkey	Novartis Investigative Site	Istanbul	TUR
Turkey	Novartis Investigative Site	Izmir
United States	Excel Medical Clinical Trials LLC	Boca Raton	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada,  France,  Greece,  Lebanon,  Malaysia,  Netherlands,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage (%) change in low-density lipoprotein cholesterol (LDL-C) from baseline to Day 330	Evaluate the effect of inclisiran compared to placebo on reducing LDL-C [percent change] at Day 330 (Year 1)	Baseline and Day 330
Secondary	Time-adjusted percent change in LDL-C from baseline after Day 90 and up to Day 330	Evaluate the effect of inclisiran compared to placebo on reducing LDL-C [time-adjusted percent change] over Year 1	Baseline, after Day 90 up to 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 lipoprotein and lipid parameters from baseline up to Day 720	Evaluate the effect of inclisiran compared to placebo (up to Day 330) and long-term (up to Day 720), on lowering apolipoprotein B (Apo B), lipoprotein (a) [Lp(a)], non-high density lipoprotein cholesterol (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	Baselne, 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 (up to Day 330) and long-term (up to Day 720), on lowering PCSK9 over time	Baseline, up to Day 720