Clinical trial NCT06597006: Study to Evaluate Safety, Tolerability and Efficacy of Inclisiran in Children With Homozygous 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 (2 to Less Than 12 Years) With Homozygous Familial Hypercholesterolemia and Elevated LDL-cholesterol
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Familial Hypercholesterolemia - Homozygous
Keywords: Homozygous familial hypercholesterolemia (HoFH),
LDL-cholesterol (LDL-C), children, pediatric,
small interfering ribonucleic acid (siRNA),
inclisiran,
Familial Hypercholesterolemia,
Homozygous FH,
Hypercholesterolemia,
Lipoprotein(a),
Hyperlipidemia,
Dyslipidemia,
Cardiovascular Diseases,
Heart Failure,
Cholesterol,
Aortic Stenosis
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2024-09-19
Enrollment: 9
Sex: ALL
Minimum age (years): 2
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 2 to \<12 years) with homozygous familial hypercholesterolemia (HoFH) 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 2 to \<12 years) with homozygous familial hypercholesterolemia (HoFH) 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, 2 to \<12 years of age at screening
* HoFH diagnosed by genetic confirmation

  - Note: Participants with known null (negative) mutations in both LDLR alleles are not eligible (see also exclusion criteria)
* Fasting LDL-C \>130 mg/dL (3.4 mmol/L) at screening
* On an optimal dose of statin (investigator's discretion), unless statin intolerant, with or without other lipid-lowering therapy (e.g. ezetimibe)
* Participants on lipid-lowering therapies (such as e.g. statins, ezetimibe) must be on a stable dose for ≥30 days before screening with no planned medication or dose changes during study participation
* Participants on a documented regimen of LDL-apheresis for ≥ 3 months before screening will be allowed to continue the apheresis during the study, if needed. The apheresis schedule/settings/duration must be stable prior to screening, are not allowed to change during the double-blind period of the trial and must permit that an apheresis coincides with each study visit.

Exclusion Criteria:

* Documented evidence of a null (negative) mutation in both LDLR alleles
* Previous treatment (within 90 days of screening) with monoclonal antibodies directed towards PCSK9
* History of poor response to therapy with any monoclonal antibody directed towards PCSK9 (e.g. \<15% reduction in LDL-C)
* Treatment with mipomersen or lomitapide (within 5 months of screening)
* Secondary hypercholesterolemia, e.g. hypothyroidism or nephrotic syndrome
* Heterozygous familial hypercholesterolemia (HeFH)
* Body weight (at the screening and/or randomization (Day 1) visit) \<16 kg for participants 6 to \<12 years (at screening) or \<11 kg for participants 2 to \<6 years (at screening)
* 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: Percent change in LDL-C, total cholesterol, non-HDL-C, 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 LDL-C, total cholesterol, non-HDL-C, 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: Childrens National Medical Center
state: District of Columbia
city: Saint Louis
country: United States
facility: Washington Univ School Of Medicine
state: Missouri
city: Beijing
country: China
facility: Novartis Investigative Site
city: Kota Bahru
country: Malaysia
facility: Novartis Investigative Site
state: Kelantan
city: Taichung
country: Taiwan
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: