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

Novartis Pharmaceuticals13 enrolled

Overview

This was 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).

This was a two-part (double-blind, inclisiran versus placebo \[Year 1\] followed by open-label inclisiran \[Year 2\]) multicenter study in adolescents (aged 12 to \< 18 years) with HoFH and elevated LDL-C (\> 130 mg/dL; 3.4 mmol/L) on stable, individualized, optimal standard of care (SoC) background lipid-lowering therapy (including maximally tolerated statin treatment, at the Investigator's discretion) to evaluate the safety, tolerability, and efficacy of inclisiran in this pediatric patient population. Following an approximately 4-week screening/run-in period, the study had 2 sequential parts as follows: Part 1/Year 1: 12 months double-blind, parallel group period, in which participants were randomized in a 2:1 ratio to receive either inclisiran sodium 300 mg subcutaneous (s.c.) or placebo. The primary endpoint was assessed at Day 330. Part 2/Year 2: 12 months single arm, open-label follow-up period, with all participants receiving inclisiran sodium 300 mg s.c.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Familial Hypercholesterolemia - Homozygous

Interventions

InclisiranDRUG

Inclisiran sodium 300 mg (equivalent to 284 mg inclisiran) in 1.5 mL solution for subcutaneous injection

PlaceboDRUG

Sterile normal saline (0.9% sodium chloride in water for injection) for subcutaneous injection

Eligibility

Sex: ALLMin age: 12 YearsMax age: 17 Years

Medical Language ↔ Plain English

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 * Male or female participants \>=12 to \<18 years of age 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 * 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

Locations (11)

Excel Medical Clinical Trials LLC

Boca Raton, Florida, United States

Novartis Investigative Site

Québec, Quebec, Canada

Novartis Investigative Site

Bron, France

Outcomes

Primary Outcomes

Percentage Change in LDL-C From Baseline to Day 330 (Part 1/Year 1)

Percentage change in low-density lipoprotein cholesterol (LDL-C) from baseline to Day 330 (Year 1)

Time frame: Baseline and Day 330

Secondary Outcomes

Time-adjusted Percent Change in LDL-C From Baseline After Day 90 and up to Day 330 (Part 1/Year 1)

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

Time frame: Baseline, after Day 90 up to Day 330

Percent Change in LDL-C From Baseline up to Day 720

Percentage change in LDL-C from baseline to each assessment time up to Day 720.

Time frame: Baseline, up to Day 720

Absolute Change in LDL-C From Baseline up to Day 720

Absolute change in LDL-C from baseline to each assessment time up to Day 720.

Time frame: Baseline, up to Day 720

Percent Change in Apo B From Baseline up to Day 720

Percentage change in apolipoprotein B (Apo B) from baseline to each assessment time up to Day 720.

Time frame: Baseline, up to Day 720

Absolute Change in Apo B From Baseline up to Day 720

Absolute change in apolipoprotein B (Apo B) from baseline to each assessment time up to Day 720.

Time frame: Baseline, up to Day 720

Percent Change in Lp(a) From Baseline up to Day 720

Percentage change in lipoprotein (a) \[Lp(a)\] from baseline to each assessment time up to Day 720.

Data from ClinicalTrials.gov

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University General Hospital of Ioannina

Ioannina, GR, Greece

Metropolitan Hospital

Athens, Greece

American University of Beirut Medical Center

Beirut, Lebanon

Hotel Dieu de France Hospital

El Achrafiyé, Lebanon

Novartis Investigative Site

Kuala Lumpur, Malaysia

Novartis Investigative Site

Amsterdam, Netherlands

Novartis Investigative Site

Istanbul, TUR, Turkey (Türkiye)

...and 1 more locations

Time frame: Baseline, up to Day 720

Absolute Change in Lp(a) From Baseline up to Day 720

Absolute change in lipoprotein (a) \[Lp(a)\] from baseline to each assessment time up to Day 720.

Time frame: Baseline, up to Day 720

Percent Change in Non-HDL-C From 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.

Time frame: Baseline, up to Day 720

Absolute Change in Non-HDL-C From 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.

Time frame: Baseline, up to Day 720

Percent Change in Total Cholesterol From Baseline up to Day 720

Percentage change in total cholesterol from baseline to each assessment time up to Day 720.

Time frame: Baseline, up to Day 720

Absolute Change in Total Cholesterol From Baseline up to Day 720

Absolute change in total cholesterol from baseline to each assessment time up to Day 720.

Time frame: Baseline, up to Day 720

Percent Change in Triglycerides From Baseline up to Day 720

Percentage change in triglycerides from baseline to each assessment time up to Day 720.

Time frame: Baseline, up to Day 720

Absolute Change in Triglycerides From Baseline up to Day 720

Absolute change in triglycerides from baseline to each assessment time up to Day 720.

Time frame: Baseline, up to Day 720

Percent Change in HDL-C From Baseline up to Day 720

Percentage change in high density lipoprotein cholesterol (HDL-C) from baseline to each assessment time up to Day 720.

Time frame: Baseline, up to Day 720

Absolute Change in HDL-C From Baseline up to Day 720

Absolute change in high density lipoprotein cholesterol (HDL-C) from baseline to each assessment time up to Day 720.

Time frame: Baseline, up to Day 720

Percent Change in VLDL-C From 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.

Time frame: Baseline, up to Day 720

Absolut Change in VLDL-C From 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.

Time frame: Baseline, up to Day 720

Percent Change in Apo A1 From Baseline up to Day 720

Percentage change in apolipoprotein A1 (Apo A1) from baseline to each assessment time up to Day 720.

Time frame: Baseline, up to Day 720

Absolute Change in Apo A1 From Baseline up to Day 720

Absolute change in apolipoprotein A1 (Apo A1) from baseline to each assessment time up to Day 720.

Time frame: Baseline, up to Day 720

Percent Change in PCSK9 From 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.

Time frame: Baseline, up to Day 720

Absolut Change in PCSK9 From 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 frame: Baseline, up to Day 720