Clinical trial NCT06597019: Study to Evaluate Efficacy and Safety of Inclisiran in Children With Heterozygous Familial Hypercholesterolemia
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 Children (6 to Less Than 12 Years) With Heterozygous Familial Hypercholesterolemia and Elevated LDL- Cholesterol
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Familial Hypercholesterolemia - Heterozygous
Keywords: Heterozygous familial hypercholesterolemia (HeFH),
LDL-cholesterol (LDL-C),
Children,
pediatric,
small interfering ribonucleic acid (siRNA),
inclisiran,
Familial Hypercholesterolemia,
Heterozygous FH,
Hypercholesterolemia,
Lipoprotein(a),
Hyperlipidemia,
Dyslipidemia,
Heart Failure,
Cardiovascular Diseases,
Cholesterol,
Aortic Stenosis
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2024-09-19
Enrollment: 51
Sex: ALL
Minimum age (years): 6
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel (Year 1) to single-group (Year 2)
Primary purpose: TREATMENT

Brief summary: This is a pivotal phase III study designed to evaluate safety, tolerability, and efficacy of inclisiran in children (aged 6 to \<12 years) with heterozygous familial hypercholesterolemia (HeFH) and elevated low density lipoprotein cholesterol (LDLC).

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 children (aged 6 to \<12 years) with heterozygous familial hypercholesterolemia (HeFH) and elevated low density lipoprotein cholesterol (LDL-C) on stable standard of care background lipid-lowering therapy.

Eligibility criteria: Inclusion Criteria:

* Male or female participants, 6 to \<12 years of age at screening
* HeFH diagnosed either by genetic testing or on phenotypic criteria
* Fasting LDL-C \>130 mg/dL (3.4 mmol/L) at screening
* For participants 8 to \<12 years, on an optimal dose of statin (investigator's discretion) unless statin intolerant, with or without other lipid-lowering therapy (e.g. ezetimibe). For participants \<8 years, the use of background lipid-lowering treatment is based on investigator's discretion.
* Participants on lipid-lowering therapies (such as statin and/or e.g. ezetimibe) must be on a stable dose for ≥30 days before screening with no planned medication or dose changes during study participation.

Exclusion Criteria:

* Previous treatment (within 90 days of screening) with monoclonal antibodies directed towards PCSK9
* Secondary hypercholesterolemia, e.g. hypothyroidism or nephrotic syndrome
* Homozygous familial hypercholesterolemia (HoFH)
* Body weight \<16 kg at the screening and/or randomization (Day 1) visit
* Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver or unexplained alanine aminotransferase (ALT), aspartate aminotransferase (AST) elevation \>3x ULN, or total bilirubin elevation \>2x ULN (except patients with Gilbert's syndrome)
* Pregnant or nursing females
* Recent and/or planned use of other investigational medicinal products or devices

Primary outcomes:
measure: Percentage change in LDL-C from baseline to Day 330 (Year 1)
timeFrame: Baseline and Day 330
Secondary outcomes:
measure: Time-adjusted percent change in LDL-C from baseline after Day 90 and up to Day 330 (Year 1)
timeFrame: Baseline, after Day 90 up to Day 330
measure: Absolute change in LDL-C from baseline to Day 330 (Year 1)
timeFrame: Baseline and Day 330
measure: Percent change in PCSK9 from baseline to Day 330 (Year 1)
timeFrame: Baseline and Day 330
measure: Percent change in total cholesterol, non-HDL-C from baseline to Day 330 (Year 1)
timeFrame: Baseline and Day 330
measure: Percent change in Apo B from baseline to Day 330 (Year 1)
timeFrame: Baseline and Day 330
measure: Percent change in LDLC, total cholesterol, non-HDLC, triglycerides, HDL-C, VLDL-C from baseline to each assessment time up to Day 720 (Year 2)
timeFrame: Baseline, up to Day 720
measure: Percent change in PCSK9 from baseline to each assessment time up to Day 720 (Year 2)
timeFrame: Baseline, up to Day 720
measure: Percent change in Apo B, Apo A1 from baseline to each assessment time up to Day 720 (Year 2)
timeFrame: Baseline, up to Day 720
measure: Absolute change in LDLC, total cholesterol, non-HDLC, triglycerides, HDL-C, VLDL-C from baseline to each assessment time up to Day 720 (Year 2)
timeFrame: Baseline, up to Day 720
measure: Absolute change in PCSK9 from baseline to each assessment time up to Day 720 (Year 2)
timeFrame: Baseline, up to Day 720
measure: Absolute change in Apo B, Apo A1 from baseline to each assessment time up to Day 720 (Year 2)
timeFrame: Baseline, up to Day 720
measure: Percent change in Lp(a) from baseline to each assessment time up to Day 720 (Year 2)
timeFrame: Baseline, up to Day 720
measure: Absolute change in Lp(a) from baseline to each assessment time up to Day 720 (Year 2)
timeFrame: Baseline, up to Day 720
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UC San Francisco Medical Center
state: California
city: Washington
country: United States
facility: Children's National Hospital
state: District of Columbia
city: Boca Raton
country: United States
facility: Excel Medical Clinical Trials LLC
state: Florida
city: New York
country: United States
facility: Icahn School of Med at Mt Sinai
state: New York
city: New York
country: United States
facility: Icahn School of Medicine Mt Sinai
state: New York
city: Salt Lake
country: United States
facility: Primary Childrens Medical Center
state: Utah
city: Morgantown
country: United States
facility: West Virginia Children's Hospital
state: West Virginia
city: Morgantown
country: United States
facility: West Virginia Childrens Hospital
state: West Virginia
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Salzburg
country: Austria
facility: Novartis Investigative Site
city: Wien
country: Austria
facility: Novartis Investigative Site
city: Porto Alegre
country: Brazil
facility: Novartis Investigative Site
state: RS
city: Beijing
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Praha 5
country: Czechia
facility: Novartis Investigative Site
city: Praha
country: Czechia
facility: Novartis Investigative Site
city: Marseille
country: France
facility: Novartis Investigative Site
city: Nantes Cedex 1
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Ioannina
country: Greece
facility: Novartis Investigative Site
state: GR
city: Athens
country: Greece
facility: Novartis Investigative Site
city: Hong Kong
country: Hong Kong
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Jerusalem
country: Israel
facility: Novartis Investigative Site
city: Ramat Gan
country: Israel
facility: Novartis Investigative Site
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Torino
country: Italy
facility: Novartis Investigative Site
state: TO
city: Verona
country: Italy
facility: Novartis Investigative Site
state: VR
city: Kuala Lumpur
country: Malaysia
facility: Novartis Investigative Site
state: Wilayah Persekutuan
city: Bialystok
country: Poland
facility: Novartis Investigative Site
city: Gdansk
country: Poland
facility: Novartis Investigative Site
city: Lodz
country: Poland
facility: Novartis Investigative Site
city: Lisboa
country: Portugal
facility: Novartis Investigative Site
city: Porto
country: Portugal
facility: Novartis Investigative Site
city: Elche
country: Spain
facility: Novartis Investigative Site
state: Alicante
city: Cadiz
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Malaga
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Pamplona
country: Spain
facility: Novartis Investigative Site
state: Navarra
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Izmir
country: Turkey
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: