HypercholesterolemiaPhase 3NCT04765657
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 Phase 3 study testing inclisiran sodium in people with Hypercholesterolemia, run by Novartis Pharmaceuticals at 45 sites in 4 countries.
Trial summary
A multicenter study to evaluate safety and efficacy of inclisiran in Asian patients with ASCVD or ASCVD high risk and elevated LDL-C Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Hypercholesterolemia
- What is being tested?
- inclisiran sodium
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 345 participants
- Where
- 45 sitesin 4 countries
- Study dates
- 1 Mar 2021to 28 Dec 2026
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- -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.
Who cannot join
- 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.
Show all 9Show fewer
- 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).
- Other protocol-defined inclusion/exclusion criteria may apply.
Trial locations and contacts
45 sites in 4 countries.
45 sites in 4 countries
China30 sites
Novartis Investigative Site
Baotou, Inner Mongolia, 014040
Novartis Investigative Site
Beijing, 100034
Novartis Investigative Site
Beijing, 100039
Novartis Investigative Site
Beijing, 100050
Novartis Investigative Site
Beijing, 100191
Novartis Investigative Site
Changchun, Jilin, 130000
Novartis Investigative Site
Changchun, Jilin, 130021
Novartis Investigative Site
Foshan, Guangdong, 528000
Novartis Investigative Site
Guangzhou, Guangdong, 510080
Novartis Investigative Site
Hangzhou, Zhejiang, 310014
Novartis Investigative Site
Hohhot, Inner Mongolia, 010017
Novartis Investigative Site
Jinan, Shandong, 250013
Novartis Investigative Site
Jinshan, Shanghai Municipality, 201508
Novartis Investigative Site
Lanzhou, Gansu, 730030
Novartis Investigative Site
Nanjing, Jiangsu, 210008
Novartis Investigative Site
Nanjing, Jiangsu, 211166
Novartis Investigative Site
Nantong, Jiangsu, 226000
Novartis Investigative Site
Shanghai, 200032
Novartis Investigative Site
Shanghai, 200040
Novartis Investigative Site
Shanghai, 200080
Novartis Investigative Site
Shanghai, 200120
Novartis Investigative Site
Shijiazhuang, Hebei, 050000
Novartis Investigative Site
Suzhou, Jiangsu, 215004
Novartis Investigative Site
Taiyuan, Shanxi, 030002
Novartis Investigative Site
Tianjin, Tianjin Municipality, 300121
Novartis Investigative Site
Tianjin, 300052
Novartis Investigative Site
Tianjin, 300140
Novartis Investigative Site
Xiamen, 361004
Novartis Investigative Site
Xian, Shanxi, 710061
Novartis Investigative Site
Xuzhou, Jiangsu, 221003
South Korea9 sites
Novartis Investigative Site
Gwangju, 61469
Novartis Investigative Site
Incheon, Korea, 405 760
Novartis Investigative Site
Seoul, Korea, 02841
Novartis Investigative Site
Seoul, Korea, 03080
Novartis Investigative Site
Seoul, Seoul, 06351
Novartis Investigative Site
Seoul, South Korea, 110-746
Novartis Investigative Site
Seoul, 03722
Novartis Investigative Site
Seoul, 05505
Novartis Investigative Site
Wŏnju, Gangwon-do, 26427
Taiwan4 sites
Novartis Investigative Site
Kaohsiung City, 80756
Novartis Investigative Site
Taipei, 10002
Novartis Investigative Site
Taipei, 11217
Novartis Investigative Site
Taipei, 11220
Singapore2 sites
Novartis Investigative Site
Singapore, 119074
Novartis Investigative Site
Singapore, 169609
About this study
Official title: 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)
A multicenter study to evaluate safety and efficacy of inclisiran in Asian patients with ASCVD or ASCVD high risk and elevated LDL-C
Read the detailed description
The purpose of the study is to demonstrate the efficacy and safety of inclisiran sodium 300mg to support the indication for LDL-C reduction of inclisiran in Asian patients with atherosclerotic cardiovascular disease (ASCVD) or ASCVD-high risk patients with elevated LDL-C as an adjunct to diet and maximally tolerated dose statins with or without additional lipid-lowering therapy.
A core part (2-week screening period and a 12-month double-blinded treatment period), and an extension part (until reasonable access to the IMP post product launch provided for the participants)
- Conditions
- Hypercholesterolemia
- Being tested
- inclisiran sodium, Placebo
- Keywords
- inclisiran, siRNA, dyslipidemia, KJX839
- Medical subject headings
- Hypercholesterolemia, Dyslipidemias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
inclisiran sodiumDrug
Also called KJX839
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)
PlaceboDrug
Subcutaneously injected on Day 1, 90, and 270.
| Study group | Role | What they receive |
|---|---|---|
| inclisiran sodium 300 mg | Experimental | Subcutaneous injection Receives: Drug: inclisiran sodium |
| Placebo | Placebo comparator | Subcutaneous injection Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: Day 360 until study completion, an average of 3 years
Secondary outcomes (10)
Core: Time adjusted percentage change in LDL-C
The superiority of inclisiran compared to placebo in reducing LDL-C from baseline to Day 330 and over time
Measured: From baseline after Day 90 and up to Day 360
Core: Absolute change in LDL-C
The superiority of inclisiran compared to placebo in reducing LDL-C from baseline to Day 330 and over time
Measured: From baseline to Day 330
Core: Time adjusted absolute change in LDL-C
The superiority of inclisiran compared to placebo in reducing LDL-C from baseline to Day 330 and over time
Measured: From baseline after Day 90 and up to Day 360
Core: Percentage change in PCSK9
The superiority of inclisiran compared to placebo in reducing PCSK9 from baseline to Day 330
Measured: From baseline to Day 330
Core: Absolute change in PCSK9
The superiority of inclisiran compared to placebo in reducing PCSK9 from baseline to Day 330
Measured: From baseline to Day 330
Core: Proportion of participants reaching LDL-C levels of <25 mg/dL, <50 mg/dL, <70 mg/dL, and <100 mg/dL
The superiority of inclisiran compared to placebo in individual response rate for lipid controlling
Measured: Day 330
Core: Proportion of participants in each group with ≥ 50% LDL-C reduction
The superiority of inclisiran compared to placebo in individual response rate for lipid controlling
Measured: From baseline to Day 330
Core: Proportion of participants in each group who attain global lipid targets for their level of ASCVD risk (55mg/dl for ASCVD patients, 70mg/dl for ASCVD high risk patients)
The superiority of inclisiran compared to placebo in individual response rate for lipid controlling
Measured: Day 330
Core: Percentage change in total cholesterol, ApoB, non-HDL-C, ApoA1, HDL-C, Lp(a) and triglycerides
The superiority of inclisiran compared to placebo in reducing other lipids, lipoproteins and apolipoproteins
Measured: From baseline to Day 330
Core: Absolute change in total cholesterol, ApoB, non-HDL-C, ApoA1, HDL-C, Lp(a) and triglycerides
The superiority of inclisiran compared to placebo in reducing other lipids, lipoproteins and apolipoproteins
Measured: From baseline to Day 330
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2021
- Study start1 Mar 2021
- Primary completion9 Jun 2022
- Study completion28 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HypercholesterolemiaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 345 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04765657
- Sponsor's protocol ID
- CKJX839A12307
- Status last verified
- Dec 2025
- First submitted
- 5 Feb 2021
- Last updated
- 30 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Publications
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.
PubMed 38371290
Study at a glance
From the registry record, last updated by the sponsor on 30 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT04765657
- Acronym / sponsor ID
- CKJX839A12307
- Conditions
- Hypercholesterolemia
- Keywords
- inclisiran, siRNA, dyslipidemia, KJX839
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 345 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 1 Mar 2021 (actual)
- Primary completion
- 9 Jun 2022 (actual)
- Study completion
- 28 Dec 2026 (estimated)
- First posted
- 21 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A multicenter study to evaluate safety and efficacy of inclisiran in Asian patients with ASCVD or ASCVD high risk and elevated LDL-C
Detailed description
The purpose of the study is to demonstrate the efficacy and safety of inclisiran sodium 300mg to support the indication for LDL-C reduction of inclisiran in Asian patients with atherosclerotic cardiovascular disease (ASCVD) or ASCVD-high risk patients with elevated LDL-C as an adjunct to diet and maximally tolerated dose statins with or without additional lipid-lowering therapy.
A core part (2-week screening period and a 12-month double-blinded treatment period), and an extension part (until reasonable access to the IMP post product launch provided for the participants)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| inclisiran sodium 300 mg | Experimental | Drug: inclisiran sodiumSubcutaneous injection |
| Placebo | Placebo comparator | Drug: PlaceboSubcutaneous injection |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- -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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| inclisiran sodiumAlso: KJX839Subcutaneously injected on Day 1, 90 and 270 (Core Part). Subcutaneously injected on Day 360 and every 6 months thereafter until EOS visit (Extension Part) | Drug | inclisiran sodium 300 mg |
| PlaceboSubcutaneously injected on Day 1, 90, and 270. | Drug | Placebo |
Primary outcome
Core: Percentage change in low- density lipoprotein cholesterol (LDL-C)
Time frame: Baseline, Day 330
Superiority of inclisiran compared to placebo in reducing LDL-C from baseline to Day 330
Extension: Number of participants with Adverse Events
Time frame: Day 360 until study completion, an average of 3 years
Evaluation of the safety and tolerability of inclisiran, treatment emergent Adverse events and Serious Adverse Events
10 secondary outcomes
Core: Time adjusted percentage change in LDL-C
Time frame: From baseline after Day 90 and up to Day 360
Core: Absolute change in LDL-C
Time frame: From baseline to Day 330
Core: Time adjusted absolute change in LDL-C
Time frame: From baseline after Day 90 and up to Day 360
Core: Percentage change in PCSK9
Time frame: From baseline to Day 330
Core: Absolute change in PCSK9
Time frame: From baseline to Day 330
Core: Proportion of participants reaching LDL-C levels of <25 mg/dL, <50 mg/dL, <70 mg/dL, and <100 mg/dL
Time frame: Day 330
Core: Proportion of participants in each group with ≥ 50% LDL-C reduction
Time frame: From baseline to Day 330
Core: Proportion of participants in each group who attain global lipid targets for their level of ASCVD risk (55mg/dl for ASCVD patients, 70mg/dl for ASCVD high risk patients)
Time frame: Day 330
Core: Percentage change in total cholesterol, ApoB, non-HDL-C, ApoA1, HDL-C, Lp(a) and triglycerides
Time frame: From baseline to Day 330
Core: Absolute change in total cholesterol, ApoB, non-HDL-C, ApoA1, HDL-C, Lp(a) and triglycerides
Time frame: From baseline to Day 330
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Dec 2025.
- Derived from this study: PubMed 38371290Huo 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.
- Individual participant dataSharing planned: Yes. 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
Related trials for Hypercholesterolemia
Active, not recruitingObservational study
Study Evaluating LDL-C Change and Adherence to Inclisiran Lipid-lowering Therapy in ASCVD
Primary Hypercholesterolemia, Mixed Dyslipidemia
Active, not recruitingPhase 3
A Study of Inclisiran to Prevent Cardiovascular Events in High-risk Primary Prevention Patients.
Primary Prevention of Atherosclerotic Cardiovascular Disease
RecruitingObservational study
Causes and Natural History of Dyslipidemias
Hypercholesterolemia, Atherosclerosis
Active, not recruitingObservational study
Early Detection of Familial Hypercholesterolaemia in Pre-school Children ( CzeCH-IT)
Familial Hypercholesterolaemia
Not yet recruiting
Penn Family Screening for Familial Hypercholesterolemia (NHLBI R33) Trial 3
Familial Hypercholesterolemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
45 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing inclisiran sodium in people with Hypercholesterolemia, run by Novartis Pharmaceuticals at 45 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 30 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 45 sites in China, South Korea, Taiwan, Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Core: Percentage change in low- density lipoprotein cholesterol (LDL-C) (time frame: Baseline, Day 330). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04765657, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Dec 2025.