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

Phase 3

Active, not recruiting

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

• Registration Number: NCT04659863
• 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 homozygous familial hypercholesterolemia (HoFH) 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 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.

Study Timeline

• Study First Submitted: 2020-12-02
• Study First Submitted QC: 2020-12-02
• Study First Posted: 2020-12-09
• Study Start: 2021-02-16
• Primary Completion: 2023-10-30
• Status Verified: 2024-06
• Disposition First Submitted: 2024-06-14
• Last Update Submitted: 2024-06-14
• Disposition First Posted: 2024-06-17
• Last Update Posted: 2024-06-17
• Study Completion: 2024-12-02

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 13

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

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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

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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	Evaluate the effect of inclisiran compared to placebo on reducing LDL-C \[percent change\] at Day 330 (Year 1)

Secondary Outcome Measures

Name	Time	Method
% 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 (up to Day 330) and long-term (up to Day 720), on lowering PCSK9 over time
Time-adjusted percent change in LDL-C from baseline after Day 90 and up to Day 330	Baseline, after Day 90 up to Day 330	Evaluate the effect of inclisiran compared to placebo on reducing LDL-C \[time-adjusted percent change\] over Year 1
% 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 lipoprotein and lipid parameters from baseline up to Day 720	Baselne, 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

Trial Locations

Locations (6)

Excel Medical Clinical Trials LLC; 🇺🇸 Boca Raton, Florida, United States

Hotel Dieu de France Hospital; 🇱🇧 Ashrafieh, Lebanon

Novartis Investigative Site; 🇹🇷 Izmir, Turkey

University General Hospital of Ioannina; 🇬🇷 Ioannina, GR, Greece

Metropolitan Hospital; 🇬🇷 Athens, Greece

American University of Beirut Medical Center; 🇱🇧 Beirut, Lebanon