Study to Evaluate Efficacy and Safety of Inclisiran in Adolescents With Homozygous Familial Hypercholesterolemia

NCT04659863 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: CKJX839C123022020-002755-38
• Study Type: interventional
• Target: 13
• Locations: 8 countries
• Sites: 11

Brief 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).

Conditions

Familial Hypercholesterolemia - Homozygous

Keywords

Homozygous familial hypercholesterolemia (HoFH); LDL-cholesterol (LDL-C); adolescents; pediatric; small interfering ribonucleic acid (siRNA)

Outcome Measures

Primary Outcomes (1)

• Percentage Change in LDL-C From Baseline to Day 330 (Part 1/Year 1)

  Percentage change in low-density lipoprotein cholesterol (LDL-C) from baseline to Day 330 (Year 1)

  Baseline and Day 330

Secondary Outcomes (21)

• Time-adjusted Percent Change in LDL-C From Baseline After Day 90 and up to Day 330 (Part 1/Year 1)

  Baseline, after Day 90 up to Day 330

• Percent Change in LDL-C From Baseline up to Day 720

  Baseline, up to Day 720

• Absolute Change in LDL-C From Baseline up to Day 720

  Baseline, up to Day 720

• Percent Change in Apo B From Baseline up to Day 720

  Baseline, up to Day 720

• Absolute Change in Apo B From Baseline up to Day 720

  Baseline, up to Day 720

Study Arms (3)

Part 1 - Inclisiran

EXPERIMENTAL

Inclisiran sodium 300 mg subcutaneous (sc) injection (given at Days 1, 90 and 270)

Drug: Inclisiran

Part 1 - Placebo

PLACEBO COMPARATOR

Placebo sc injection (given at Day 1, 90 and 270)

Drug: Placebo

Part 2 - Inclisiran (Total)

EXPERIMENTAL

Inclisiran sodium 300 mg sc injection (given at Days 450 and 630). In addition, participants assigned to placebo in Part 1 received inclisiran sodium 300 mg sc injection on Day 360, while participants assigned to inclisiran in Part 1 received placebo sc injection on Day 360.

Drug: Inclisiran

Interventions

Inclisiran DRUG

Inclisiran sodium 300 mg (equivalent to 284 mg inclisiran) in 1.5 mL solution for subcutaneous injection

Also known as: KJX839

Part 1 - Inclisiran; Part 2 - Inclisiran (Total)

Placebo DRUG

Sterile normal saline (0.9% sodium chloride in water for injection) for subcutaneous injection

Also known as: Saline solution

Part 1 - Placebo

Eligibility Criteria

• Age: 12 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (11)

Excel Medical Clinical Trials LLC

Boca Raton, Florida, 33434, United States

Location

Novartis Investigative Site

Québec, Quebec, G1V 4W2, Canada

Location

Novartis Investigative Site

Bron, 69677, France

Location

University General Hospital of Ioannina

Ioannina, GR, 455 00, Greece

Location

Metropolitan Hospital

Athens, 18547, Greece

Location

American University of Beirut Medical Center

Beirut, 1107 2020, Lebanon

Location

Hotel Dieu de France Hospital

El Achrafiyé, 166830, Lebanon

Location

Novartis Investigative Site

Kuala Lumpur, 59100, Malaysia

Location

Novartis Investigative Site

Amsterdam, 1105 AZ, Netherlands

Location

Novartis Investigative Site

Istanbul, TUR, 34098, Turkey (Türkiye)

Location

Novartis Investigative Site

Izmir, 35100, Turkey (Türkiye)

Location

Related Publications (3)

• Wiegman A, Peterson AL, Hegele RA, Bruckert E, Schweizer A, Lesogor A, Wang Y, Defesche J. Efficacy and Safety of Inclisiran in Adolescents With Genetically Confirmed Homozygous Familial Hypercholesterolemia: Results From the Double-Blind, Placebo-Controlled Part of the ORION-13 Randomized Trial. Circulation. 2025 Jun 24;151(25):1758-1766. doi: 10.1161/CIRCULATIONAHA.124.073233. Epub 2025 May 20.

  PMID: 40391436 DERIVED

• Reijman MD, Schweizer A, Peterson ALH, Bruckert E, Stratz C, Defesche JC, Hegele RA, Wiegman A. Rationale and design of two trials assessing the efficacy, safety, and tolerability of inclisiran in adolescents with homozygous and heterozygous familial hypercholesterolaemia. Eur J Prev Cardiol. 2022 Jul 20;29(9):1361-1368. doi: 10.1093/eurjpc/zwac025.

  PMID: 35175352 DERIVED

• Warden BA, Duell PB. Inclisiran: A Novel Agent for Lowering Apolipoprotein B-containing Lipoproteins. J Cardiovasc Pharmacol. 2021 Aug 1;78(2):e157-e174. doi: 10.1097/FJC.0000000000001053.

  PMID: 33990512 DERIVED

Related Links

• A Plain Language Trial Summary is available on www.novctrd.com
• A Pediatric Plain Language Trial Summary is available on www.novctrd.com

MeSH Terms

Conditions

Homozygous Familial Hypercholesterolemia

Interventions

ALN-PCS; Saline Solution

Condition Hierarchy (Ancestors)

Hyperlipoproteinemia Type II; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

+ 1 862 778 8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Masked (Year 1) to No Masking (Year 2)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Parallel (Year 1) to single-group (Year 2)

Study Record Dates

• First Submitted: December 2, 2020
• First Posted: December 9, 2020
• Study Start: February 16, 2021
• Primary Completion: October 30, 2023
• Study Completion: November 18, 2024
• Last Updated: January 13, 2026
• Results First Posted: May 31, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

MY (1); TU (2); CA (1); LE (2); FR (1); GR (2); NL (1); US (1)