Trial results for the Phase 3 study (NCT04652726) evaluating inclisiran in adolescents with heterozygous familial hypercholesterolemia (HeFH) were posted on ClinicalTrials.gov on 2025-06-10. The study demonstrated that inclisiran reduced LDL-C by -27.14% from baseline to Day 330, compared to a 1.40% increase with placebo.
Background
The study NCT04652726, titled "Study to Evaluate Efficacy and Safety of Inclisiran in Adolescents With Heterozygous Familial Hypercholesterolemia," was a pivotal Phase 3 study. It was designed to evaluate the safety, tolerability, and efficacy of inclisiran in adolescents diagnosed with heterozygous familial hypercholesterolemia (HeFH) who also had elevated low-density lipoprotein cholesterol (LDL-C).
Trial design
The study NCT04652726 was a Phase 3 trial that enrolled 141 participants. The study investigated inclisiran in adolescents with heterozygous familial hypercholesterolemia. Participants received either inclisiran or placebo.
Key results
The trial results showed a significant reduction in lipid parameters for participants treated with inclisiran compared to placebo.
- For "Percentage Change in LDL-C From Baseline to Day 330 (Part 1/Year 1)": inclisiran showed a least squares mean change of -27.14%, while placebo showed 1.40%.
- For "Time-adjusted Percent Change in LDL-C From Baseline After Day 90 and up to Day 330 (Part 1/Year 1)": inclisiran showed a least squares mean change of -26.04%, while placebo showed 3.26%.
- For "Absolute Change in LDL-C From Baseline to up Day 330 (Part 1/Year 1)": inclisiran showed a least squares mean change of -50.54 mg/dL, while placebo showed -0.55 mg/dL.
- For "Percent Change in Apo B From Baseline up to Day 330 (Part 1/Year 1)": inclisiran showed a least squares mean change of -21.46%, while placebo showed 4.24%.
- For "Percent Change in Lp(a) From Baseline up to Day 330 (Part 1/Year 1)": inclisiran showed a least squares mean change of -5.04%, while placebo showed 1.14%.
- For "Percent Change in Non-HDL-C From Baseline up to Day 330 (Part 1/Year 1)": inclisiran showed a least squares mean change of -25.04%, while placebo showed 1.76%.
Key analyses further supported these findings:
- An ANCOVA analysis for the percentage change in LDL-C showed an LS Mean difference of -28.54 (95.0% CI: -35.81 to -21.27) with a p-value of 0.0001.
- A Mixed Models for Repeated Measures (MMRM) analysis for the time-adjusted percentage change in LDL-C showed an LS Mean difference of -29.3 (95.0% CI: -36.24 to -22.36) with a p-value of 0.0001.
- An ANCOVA analysis for the absolute change in LDL-C showed an LS Mean difference of -49.99 (95.0% CI: -63.18 to -36.81) with a p-value of 0.0001.
- An ANCOVA analysis for the percentage change in Apo B showed an LS Mean difference of -25.7 (95.0% CI: -31.68 to -19.73) with a p-value of 0.0001.
- An ANCOVA analysis for the percentage change in Lp(a) showed an LS Mean difference of -6.18 (95.0% CI: -17.48 to 5.12) with a p-value of 0.1419.
- An ANCOVA analysis for the percentage change in Non-HDL-C showed an LS Mean difference of -26.8 (95.0% CI: -33.63 to -19.97) with a p-value of 0.0001.
What this means
The results from this Phase 3 trial indicate that inclisiran significantly reduces LDL-C and other atherogenic lipid markers in adolescents with heterozygous familial hypercholesterolemia. The substantial reductions observed in LDL-C, Apo B, and Non-HDL-C suggest that inclisiran could be an effective therapeutic option for managing dyslipidemia in this young patient population. These findings contribute important data for clinicians considering treatment strategies for HeFH in adolescents.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT04652726, titled "Study to Evaluate Efficacy and Safety of Inclisiran in Adolescents With Heterozygous Familial Hypercholesterolemia," were posted on 2025-06-10 on clinicaltrials.gov.