Study of Efficacy and Safety of Inclisiran in Asian Participants With Atherosclerotic Cardiovascular Disease (ASCVD) or ASCVD High Risk and Elevated Low Density Lipoprotein Cholesterol (LDL-C)
A Multicenter, Randomized, Double-blind, Parallel Group, Placebo-controlled Study to Evaluate the Efficacy and Safety of Inclisiran in Asian Patients With ASCVD or ASCVD High Risk and Elevated Low-density Lipoprotein Cholesterol as an Adjunct to Diet and Maximally Tolerated Statins With or Without Additional Lipid-lowering Therapy (ORION-18)
1 other identifier
interventional
345
4 countries
45
Brief Summary
A multicenter study to evaluate safety and efficacy of inclisiran in Asian patients with ASCVD or ASCVD high risk and elevated LDL-C
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Mar 2021
Longer than P75 for phase_3
45 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
February 5, 2021
CompletedFirst Posted
Study publicly available on registry
February 21, 2021
CompletedStudy Start
First participant enrolled
March 1, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 9, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
December 28, 2026
ExpectedDecember 30, 2025
December 1, 2025
1.3 years
February 5, 2021
December 22, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Core: Percentage change in low- density lipoprotein cholesterol (LDL-C)
Superiority of inclisiran compared to placebo in reducing LDL-C from baseline to Day 330
Baseline, Day 330
Extension: Number of participants with Adverse Events
Evaluation of the safety and tolerability of inclisiran, treatment emergent Adverse events and Serious Adverse Events
Day 360 until study completion, an average of 3 years
Secondary Outcomes (10)
Core: Time adjusted percentage change in LDL-C
From baseline after Day 90 and up to Day 360
Core: Absolute change in LDL-C
From baseline to Day 330
Core: Time adjusted absolute change in LDL-C
From baseline after Day 90 and up to Day 360
Core: Percentage change in PCSK9
From baseline to Day 330
Core: Absolute change in PCSK9
From baseline to Day 330
- +5 more secondary outcomes
Study Arms (2)
inclisiran sodium 300 mg
EXPERIMENTALSubcutaneous injection
Placebo
PLACEBO COMPARATORSubcutaneous injection
Interventions
Subcutaneously injected on Day 1, 90 and 270 (Core Part). Subcutaneously injected on Day 360 and every 6 months thereafter until EOS visit (Extension Part)
Eligibility Criteria
You may qualify if:
- At screening participants with: ASCVD (including acute coronary syndrome (ACS), stable coronary heart disease, post revascularization, ischemic cardiomyopathy, ischemic stroke, transient ischemic attack (TIA), and peripheral atherosclerosis) and Serum LDL-C ≥1.8 mmol/L (≥70 mg/dL) OR ASCVD high risk (LDL-C ≥4.9 mmol/L, diabetes, high 10-year ASCVD risk assessed by Chinese ASCVD Risk Assessment Flow Chart , or high risk per local guidelines with a target LDL-C of \<100 mg/dL) and Serum LDL-C ≥2.6 mmol/L (≥100 mg/dL)
- Fasting triglyceride \< 400 mg/dL (\< 4.52 mmol/L) at screening.
- Participants on statins should be receiving a maximally tolerated dose . Maximum tolerated dose is defined as the maximum dose of statin that can be taken on a regular basis without intolerable AE. Intolerance to any dose of statin must be documented as historical AEs attributed to the statin in question on the source documentation and on the Medical history page of the eCRF
- Participants not receiving statin must have a documented evidence of intolerance to all doses of at least 2 different statins(or the corresponding local definition of complete intolerance to statins)
- Participants following lifestyle modification should be on the therapy of LDL-C lowering (such as statin monotherapy, or statin incombination with ezetimibe) with a stable dose for ≥30 days before screening and have no planned medication or dose change during study participation.
- Participants are willing and able to give informed consent before initiation of any study related procedures and willing to comply with all required study procedures.
You may not qualify if:
- New York Heart Association (NYHA) class IV heart failure or last known left ventricular ejection fraction \<25%.
- Cardiac arrhythmia with clinical significance within 3 months prior to randomization that is not controlled by medication or via ablation.
- Major adverse cardiovascular event within 3 months prior to randomization.
- Uncontrolled severe hypertension: systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg prior to randomization despite antihypertensive therapy.
- Calculated glomerular filtration rate ≤30 mL/min by estimated glomerular filtration rate (eGFR) using standardized clinical methodology.
- Severe concomitant non-cardiovascular disease that carries the risk of reducing life expectancy to less than 2 years.
- History of malignancy that required surgery (excluding local and wide-local excision), radiation therapy and/or systemic therapy during the three years prior to randomization.
- Barrier method: Condom or Occlusive cap (e.g. diaphragm or cervical/vault caps).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (45)
Novartis Investigative Site
Lanzhou, Gansu, 730030, China
Novartis Investigative Site
Foshan, Guangdong, 528000, China
Novartis Investigative Site
Guangzhou, Guangdong, 510080, China
Novartis Investigative Site
Shijiazhuang, Hebei, 050000, China
Novartis Investigative Site
Baotou, Inner Mongolia, 014040, China
Novartis Investigative Site
Hohhot, Inner Mongolia, 010017, China
Novartis Investigative Site
Nanjing, Jiangsu, 210008, China
Novartis Investigative Site
Nanjing, Jiangsu, 211166, China
Novartis Investigative Site
Nantong, Jiangsu, 226000, China
Novartis Investigative Site
Suzhou, Jiangsu, 215004, China
Novartis Investigative Site
Xuzhou, Jiangsu, 221003, China
Novartis Investigative Site
Changchun, Jilin, 130000, China
Novartis Investigative Site
Changchun, Jilin, 130021, China
Novartis Investigative Site
Jinan, Shandong, 250013, China
Novartis Investigative Site
Zhujing, Shanghai Municipality, 201508, China
Novartis Investigative Site
Taiyuan, Shanxi, 030002, China
Novartis Investigative Site
Xian, Shanxi, 710061, China
Novartis Investigative Site
Tianjin, Tianjin Municipality, 300121, China
Novartis Investigative Site
Hangzhou, Zhejiang, 310014, China
Novartis Investigative Site
Beijing, 100034, China
Novartis Investigative Site
Beijing, 100039, China
Novartis Investigative Site
Beijing, 100050, China
Novartis Investigative Site
Beijing, 100191, China
Novartis Investigative Site
Shanghai, 200032, China
Novartis Investigative Site
Shanghai, 200040, China
Novartis Investigative Site
Shanghai, 200080, China
Novartis Investigative Site
Shanghai, 200120, China
Novartis Investigative Site
Tianjin, 300052, China
Novartis Investigative Site
Tianjin, 300140, China
Novartis Investigative Site
Xiamen, 361004, China
Novartis Investigative Site
Singapore, 119074, Singapore
Novartis Investigative Site
Singapore, 169609, Singapore
Novartis Investigative Site
Wŏnju, Gangwon-do, 26427, South Korea
Novartis Investigative Site
Incheon, Korea, 405 760, South Korea
Novartis Investigative Site
Seoul, Korea, 02841, South Korea
Novartis Investigative Site
Seoul, Korea, 03080, South Korea
Novartis Investigative Site
Seoul, Seoul, 06351, South Korea
Novartis Investigative Site
Seoul, South Korea, 110-746, South Korea
Novartis Investigative Site
Gwangju, 61469, South Korea
Novartis Investigative Site
Seoul, 03722, South Korea
Novartis Investigative Site
Seoul, 05505, South Korea
Novartis Investigative Site
Kaohsiung City, 80756, Taiwan
Novartis Investigative Site
Taipei, 10002, Taiwan
Novartis Investigative Site
Taipei, 11217, Taiwan
Novartis Investigative Site
Taipei, 11220, Taiwan
Related Publications (1)
Huo Y, Lesogor A, Lee CW, Chiang CE, Mena-Madrazo J, Poh KK, Jeong MH, Maheux P, Zhang M, Wei S, Han Y, Li Y. Efficacy and Safety of Inclisiran in Asian Patients: Results From ORION-18. JACC Asia. 2023 Nov 14;4(2):123-134. doi: 10.1016/j.jacasi.2023.09.006. eCollection 2024 Feb.
PMID: 38371290DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 5, 2021
First Posted
February 21, 2021
Study Start
March 1, 2021
Primary Completion
June 9, 2022
Study Completion (Estimated)
December 28, 2026
Last Updated
December 30, 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