Phase 3
N=141
Study to Evaluate Efficacy and Safety of Inclisiran in Adolescents With Heterozygous Familial Hypercholesterolemia
Familial Hypercholesterolemia - Heterozygous
Bottom Line
View on ClinicalTrials.gov: NCT04652726 ↗Enrolled (actual)
141
Serious AEs
3.6%
Results posted
Jun 2025
Primary outcome: Primary: Percentage Change in LDL-C From Baseline to Day 330 (Part 1/Year 1) — -27.14; 1.40 percent change in LDL-C — p=<.0001
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
- Nov 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage Change in LDL-C From Baseline to Day 330 (Part 1/Year 1) |
-27.14; 1.40 | <.0001 sig |
| SECONDARY Time-adjusted Percent Change in LDL-C From Baseline After Day 90 and up to Day 330 (Part 1/Year 1) |
-26.04; 3.26 | <.0001 sig |
| SECONDARY Absolute Change in LDL-C From Baseline to up Day 330 (Part 1/Year 1) |
-50.54; -0.55 | <.0001 sig |
| SECONDARY Percent Change in Apo B From Baseline up to Day 330 (Part 1/Year 1) |
-21.46; 4.24 | <.0001 sig |
| SECONDARY Percent Change in Lp(a) From Baseline up to Day 330 (Part 1/Year 1) |
-5.04; 1.14 | 0.1419 |
| SECONDARY Percent Change in Non-HDL-C From Baseline up to Day 330 (Part 1/Year 1) |
-25.04; 1.76 | <.0001 sig |
| SECONDARY Percent Change in Total Cholesterol From Baseline up to Day 330 (Part 1/Year 1) |
-18.72; 0.48 | <.0001 sig |
| SECONDARY Percent Change in LDL-C From Baseline up to Day 720 |
-23.9; -0.1; -32.5; 6.4; -19.0; 2.1 | — |
| SECONDARY Absolute Change in LDL-C From Baseline up to Day 720 |
-45.4; -3.0; -61.0; 6.6; -38.4; 1.0 | — |
| SECONDARY Percent Change in Apo B From Baseline up to Day 720 |
-25.1; 2.2; -21.9; 3.9; -19.3; 1.7 | — |
| SECONDARY Absolute Change in Apo B From Baseline up to Day 720 |
-33.3; 0.0; -29.2; 2.9; -26.1; -0.6 | — |
| SECONDARY Percent Change in Lp(a) From Baseline up to Day 720 |
-13.4; 5.4; -7.2; 1.1; -9.3; 3.6 | — |
| SECONDARY Absolute Change in Lp(a) From Baseline up to Day 720 |
-12.5; 3.2; -9.5; 5.3; -10.2; 4.4 | — |
| SECONDARY Percent Change in Non-HDL-C From Baseline up to Day 720 |
-29.0; 5.1; -25.7; 1.8; -24.0; 1.2 | — |
| SECONDARY Absolute Change in Non-HDL-C From Baseline up to Day 720 |
-60.2; 5.7; -52.6; 0.5; -49.7; -3.0 | — |
| SECONDARY Percent Change in Total Cholesterol From Baseline up to Day 720 |
-22.6; 4.4; -19.2; 0.6; -18.5; 0.6 | — |
| SECONDARY Absolute Change in Total Cholesterol From Baseline up to Day 720 |
-59.0; 6.6; -49.4; -0.9; -48.2; -3.1 | — |
| SECONDARY Percent Change in Triglycerides From Baseline up to Day 720 |
16.2; 2.8; 1.8; 9.7; 1.7; 3.8 | — |
| SECONDARY Absolute Change in Triglycerides From Baseline up to Day 720 |
6.9; -4.8; -2.9; 3.5; -3.1; -1.7 | — |
| SECONDARY Percent Change in HDL-C From Baseline up to Day 720 |
3.6; 3.6; 7.4; -1.9; 4.4; 0.9 | — |
| SECONDARY Absolute Change in HDL-C From Baseline up to Day 720 |
1.2; 0.9; 3.2; -1.4; 1.5; -0.1 | — |
| SECONDARY Percent Change in VLDL-C From Baseline up to Day 720 |
11.8; 3.3; 0.6; 10.0; 1.0; 4.7 | — |
| SECONDARY Absolut Change in VLDL-C From Baseline up to Day 720 |
0.7; -0.9; -0.7; 0.8; -0.7; -0.2 | — |
| SECONDARY Percent Change in Apo A1 From Baseline up to Day 720 |
3.7; 0.4; 5.2; -1.5; 3.0; -1.5 | — |
| SECONDARY Absolute Change in Apo A1 From Baseline up to Day 720 |
3.3; 0.0; 6.1; -2.8; 2.7; -2.6 | — |
| SECONDARY Percent Change in PCSK9 From Baseline up to Day 720 |
-67.8; 11.6; -72.3; 3.8; -72.9; 4.8 | — |
| SECONDARY Absolut Change in PCSK9 From Baseline up to Day 720 |
-259.6; 2.1; -274.8; -27.7; -278.2; -23.9 | — |
Summary
This was a pivotal phase III study designed to evaluate safety, tolerability, and efficacy of inclisiran in adolescents with heterozygous familial hypercholesterolemia (HeFH) and elevated low density lipoprotein cholesterol (LDL-C).
Eligibility Criteria
Inclusion Criteria
- Heterozygous Familial Hypercholesterolemia (HeFH) diagnosed either by genetic testing or on phenotypic criteria
- Fasting LDL-C >130 mg/dL (3.4 mmol/L) at screening
- Fasting triglycerides <400 mg/dL (4.5 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
Exclusion Criteria
- Homozygous familial hypercholesterolemia (HoFH)
- Active liver disease
- Secondary hypercholesterolemia, e.g. hypothyroidism or nephrotic syndrome
- Previous treatment with monoclonal antibodies directed towards PCSK9 (within 90 days of screening)
- Recent and/or planned use of other investigational medicinal products or devices
Data sourced from ClinicalTrials.gov (NCT04652726). 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.