Phase 3
N=13
Study to Evaluate Efficacy and Safety of Inclisiran in Adolescents With Homozygous Familial Hypercholesterolemia
Familial Hypercholesterolemia - Homozygous
Bottom Line
View on ClinicalTrials.gov: NCT04659863 ↗Enrolled (actual)
13
Serious AEs
0.0%
Results posted
May 2025
Primary outcome: Primary: Percentage Change in LDL-C From Baseline to Day 330 (Part 1/Year 1) — -21.6; 11.7 percent change in LDL-C
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Inclisiran (Drug); Placebo (Drug)
- Age
- Pediatric · 12+ yrs
- Sex
- All
- Sponsor
- Novartis Pharmaceuticals
- Primary completion
- Oct 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage Change in LDL-C From Baseline to Day 330 (Part 1/Year 1) |
-21.6; 11.7 | — |
| SECONDARY Time-adjusted Percent Change in LDL-C From Baseline After Day 90 and up to Day 330 (Part 1/Year 1) |
-21.0; 13.0 | — |
| SECONDARY Percent Change in LDL-C From Baseline up to Day 720 |
-26.1; 6.8; -24.1; 17.0; -17.3; 10.2 | — |
| SECONDARY Absolute Change in LDL-C From Baseline up to Day 720 |
-70.6; 16.5; -66.1; 20.3; -47.1; -9.3 | — |
| SECONDARY Percent Change in Apo B From Baseline up to Day 720 |
-20.3; 10.0; -18.5; 4.5; -14.8; 10.6 | — |
| SECONDARY Absolute Change in Apo B From Baseline up to Day 720 |
-37.3; 7.5; -35.8; 0.3; -28.7; 12.0 | — |
| SECONDARY Percent Change in Lp(a) From Baseline up to Day 720 |
-0.7; -4.4; -0.3; -16.5; -1.7; -12.1 | — |
| SECONDARY Absolute Change in Lp(a) From Baseline up to Day 720 |
8.9; -0.3; 2.8; 5.3; 5.8; 0.5 | — |
| SECONDARY Percent Change in Non-HDL-C From Baseline up to Day 720 |
-24.0; 19.0; -23.3; 9.4; -20.1; 7.1 | — |
| SECONDARY Absolute Change in Non-HDL-C From Baseline up to Day 720 |
-73.8; 28.8; -74.4; 4.3; -60.0; 6.0 | — |
| SECONDARY Percent Change in Total Cholesterol From Baseline up to Day 720 |
-19.0; 16.0; -19.1; 8.7; -16.1; 6.8 | — |
| SECONDARY Absolute Change in Total Cholesterol From Baseline up to Day 720 |
-69.7; 29.5; -71.4; 8.8; -57.3; 10.0 | — |
| SECONDARY Percent Change in Triglycerides From Baseline up to Day 720 |
0.3; -15.7; -9.6; -5.8; 11.4; 14.1 | — |
| SECONDARY Absolute Change in Triglycerides From Baseline up to Day 720 |
-3.4; -15.0; -9.4; -2.3; 8.7; 28.0 | — |
| SECONDARY Percent Change in HDL-C From Baseline up to Day 720 |
10.0; -0.1; 7.5; 10.9; 6.7; 9.2 | — |
| SECONDARY Absolute Change in HDL-C From Baseline up to Day 720 |
4.1; 0.8; 3.0; 4.5; 2.7; 4.0 | — |
| SECONDARY Percent Change in VLDL-C From Baseline up to Day 720 |
-7.0; 74.5; -29.0; 2.0; -17.0; 34.6 | — |
| SECONDARY Absolut Change in VLDL-C From Baseline up to Day 720 |
-7.7; 8.5; -11.6; -7.5; -9.2; 10.3 | — |
| SECONDARY Percent Change in Apo A1 From Baseline up to Day 720 |
-0.9; -1.3; -2.1; 9.0; 3.1; 13.7 | — |
| SECONDARY Absolute Change in Apo A1 From Baseline up to Day 720 |
-1.2; -1.3; -2.7; 10.3; 4.2; 16.0 | — |
| SECONDARY Percent Change in PCSK9 From Baseline up to Day 720 |
-56.8; -17.3; -60.4; -1.7; -65.3; -5.1 | — |
| SECONDARY Absolut Change in PCSK9 From Baseline up to Day 720 |
-278.7; -98.5; -296.3; -6.1; -323.1; -35.3 | — |
Summary
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).
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT04659863). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.