Study to Evaluate Efficacy and Safety of Inclisiran in Adolescents With Heterozygous Familial Hypercholesterolemia
ORION-16
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 Adolescents (12 to Less Than 18 Years) With Heterozygous Familial Hypercholesterolemia and Elevated LDL-cholesterol (ORION-16)
2 other identifiers
interventional
141
25 countries
58
Brief 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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Jan 2021
Typical duration for phase_3
58 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 2, 2020
CompletedFirst Posted
Study publicly available on registry
December 3, 2020
CompletedStudy Start
First participant enrolled
January 27, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 9, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
November 27, 2024
CompletedResults Posted
Study results publicly available
June 10, 2025
CompletedJanuary 13, 2026
December 1, 2025
2.8 years
December 2, 2020
May 22, 2025
December 18, 2025
Conditions
Keywords
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 (26)
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
Absolute Change in LDL-C From Baseline to up Day 330 (Part 1/Year 1)
Baseline and Day 330
Percent Change in Apo B From Baseline up to Day 330 (Part 1/Year 1)
Baseline and Day 330
Percent Change in Lp(a) From Baseline up to Day 330 (Part 1/Year 1)
Baseline and Day 330
Percent Change in Non-HDL-C From Baseline up to Day 330 (Part 1/Year 1)
Baseline and Day 330
- +21 more secondary outcomes
Study Arms (2)
Inclisiran
EXPERIMENTALYear 1 - inclisiran sodium 300 mg subcutaneous injection (given at Days 1, 90, and 270) Day 360 only - placebo subcutaneous injection Year 2 - inclisiran sodium 300 mg subcutaneous injection (given at Days 450 and 630)
Placebo
PLACEBO COMPARATORYear 1 - placebo subcutaneous injection (given at Days 1, 90 and 270) Year 2 - inclisiran sodium 300 mg subcutaneous injection (given at Days 360, 450, and 630)
Interventions
Inclisiran sodium 300 mg (equivalent to 284 mg inclisiran) in 1.5 mL solution for subcutaneous injection
Sterile normal saline (0.9% sodium chloride in water for subcutaneous injection)
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (59)
Tucson Medical Center
Tucson, Arizona, 85712, United States
Icahn School of Medicine at Mount Sinai
New York, New York, 10029, United States
Wake Forest U of Health Sciences
Winston-Salem, North Carolina, 27157, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229-3039, United States
Childrens Hospital Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224, United States
Primary Children's Medical Center
Salt Lake City, Utah, 84113, United States
Novartis Investigative Site
Formosa, Formosa Province, P3600, Argentina
Unidade de pesquisa clinica - Hospital Universitario Walter Cantidio
Fortaleza, Ceará, 60430275, Brazil
Nucleo de Pesquisa Clinica do Rio Grande do Sul
Porto Alegre, Rio Grande do Sul, 90430-001, Brazil
Setor de Lípides, Aterosclerose e Biologia
São Paulo, São Paulo, 04023-900, Brazil
Heart Institute (InCOr) HCMFUSP
São Paulo, São Paulo, 05403 000, Brazil
Novartis Investigative Site
Québec, Quebec, G1V 4W2, Canada
Novartis Investigative Site
Prague, 12808, Czechia
Novartis Investigative Site
Prague, 150 06, Czechia
Novartis Investigative Site
Besançon, 25030, France
Novartis Investigative Site
Bron, 69677, France
Novartis Investigative Site
Toulouse, 31059, France
Universitaetsmedizin Mannheim
Mannheim, Baden-Wurttemberg, 68305, Germany
KKIM UK Frankfurt/Main
Frankfurt, 60590, Germany
Universitaetsklinikum Freiburg
Freiburg im Breisgau, 79106, Germany
University General Hospital of Ioannina
Ioannina, GR, 455 00, Greece
Hippokrateion General Hospital of Athens Greece
Athens, 115 27, Greece
Metropolitan Hospital
Athens, 18547, Greece
Novartis Investigative Site
Pécs, 7623, Hungary
Lipid Research
Jerusalem, 9112001, Israel
Lipids Center Sheba Medical Center, Israel
Ramat Gan, 52621, Israel
Novartis Investigative Site
Milan, MI, 20162, Italy
Novartis Investigative Site
Modena, MO, 41124, Italy
Novartis Investigative Site
Roma, RM, 00161, Italy
Novartis Investigative Site
Roma, RM, 00165, Italy
Novartis Investigative Site
Irbid, 22110, Jordan
Hotel Dieu de France Hospital
El Achrafiyé, 166830, Lebanon
UiTM Sungai Buloh
Sungai Buloh, Selangor, 47000, Malaysia
Novartis Investigative Site
Rotterdam, South Holland, 3015 GD, Netherlands
Novartis Investigative Site
Amsterdam, 1105 AZ, Netherlands
Novartis Investigative Site
Oslo, 0514, Norway
Novartis Investigative Site
Gdansk, 80 952, Poland
Novartis Investigative Site
Lodz, 93-338, Poland
Institute of the complex problems of cardiovascular disease
Kemerovo, 650002, Russia
Novartis Investigative Site
Moscow, 127412, Russia
Institute of Internal Prev. Med.
Novosibirsk, 630090, Russia
Novartis Investigative Site
Poprad, 058 01, Slovakia
University Medical Centre Ljubljana, Div. of Pediatric Dept. of Endocrinology, Diabetes and Metabolic Diseases
Ljubljana, 1000, Slovenia
Novartis Investigative Site
Bloemfontein, Free State, 9301, South Africa
Novartis Investigative Site
Somerset West, Western Cape, 7130, South Africa
Novartis Investigative Site
Cape Town, 7925, South Africa
Hospital Reina Sofia
Córdoba, Andalusia, 14004, Spain
Hospital Virgen de la Vcitoria
Málaga, Andalusia, 29010, Spain
Novartis Investigative Site
Pamplona, Navarre, 31008, Spain
Hospital Central de Asturias
Oviedo, Principality of Asturias, 33011, Spain
Hospital Abente y Lago
A Coruña, 15001, Spain
Novartis Investigative Site
Geneva, 1211, Switzerland
Far Eastern Memorial Hospital
New Taipei City, 22060, Taiwan
Taipei Veterans General Hospital
Taipei, 11217, Taiwan
Novartis Investigative Site
Istanbul, TUR, 34098, Turkey (Türkiye)
Novartis Investigative Site
Adana, 01330, Turkey (Türkiye)
Gazi University Medical Faculty
Ankara, 06500, Turkey (Türkiye)
Novartis Investigative Site
Izmir, 35100, Turkey (Türkiye)
Novartis Investigative Site
Middlesex, UB9 6JH, United Kingdom
Related Publications (3)
Wiegman A, Peterson AL, Bruckert E, Defesche JC, Schweizer A, Bergeron J, Chueca MJ, Roeters van Lennep JE, Santos RD, Schwab KO, Lesogor A, Zhang S, Hegele RA. Efficacy and safety of inclisiran in adolescents with heterozygous familial hypercholesterolaemia (ORION-16): a two-part, randomised, multicentre clinical trial. Lancet Diabetes Endocrinol. 2026 Mar;14(3):233-242. doi: 10.1016/S2213-8587(25)00351-1. Epub 2026 Jan 27.
PMID: 41616799DERIVEDReijman 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: 35175352DERIVEDWarden 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: 33990512DERIVED
Related Links
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Novartis Pharmaceuticals
Study Officials
- STUDY DIRECTOR
Novartis Pharmaceuticals
Novartis Pharmaceuticals
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
Study Record Dates
First Submitted
December 2, 2020
First Posted
December 3, 2020
Study Start
January 27, 2021
Primary Completion
November 9, 2023
Study Completion
November 27, 2024
Last Updated
January 13, 2026
Results First Posted
June 10, 2025
Record last verified: 2025-12
Data Sharing
- IPD Sharing
- Will share
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.