HyperlipidemiaPhase 1ORION-14NCT04774003

Study of Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Inclisiran in Chinese Participants With Elevated Serum LDL-C

A Phase 1 study testing 100 mg inclisiran sodium (equivalent to 94.5 mg inclisiran) and 300 mg inclisiran sodium (equivalent to 284 mg inclisiran) in people with Hyperlipidemia, run by Novartis Pharmaceuticals at 3 sites in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Study to evaluate the pharmacokinetics and pharmacodynamics of inclisiran treatment given as single subcutaneous injection in Chinese participants with elevated low-density lipoprotein cholesterol (LDL-C) despite treatment with LDL-C lowering therapies Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Hyperlipidemia
What is being tested?: 100 mg inclisiran sodium (equivalent to 94.5 mg inclisiran) and 300 mg inclisiran sodium (equivalent to 284 mg inclisiran)
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 40 participants
Where: 3 sitesChina
Study dates: 26 Feb 2021to 18 Oct 2021
Phase: Phase 1
Are there results?: None posted in the registry

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 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Written informed consent must be obtained before any assessment is performed.
Male or female participants ≥ 18 years of age at screening
Participants should meet fasting serum LDL-C ≥ 100 mg/dL (≥ 2.6 mmol/L) at screening
Participants should meet fasting triglyceride < 400 mg/dL (< 4.52 mmol/L) at screening
Participants should be receiving a maximally tolerated dose of statin#.
For all participants, all the lipid-lowering therapy/ies (such as but not limited to statins and/or ezetimibe) should have remained stable (stable dose and no medication change) for ≥ 30 days before screening with no planned medication or dose change during study participation. #Maximum tolerated dose was defined as the maximum dose of statin that could be taken on a regular basis without intolerable AEs.
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)

Who cannot join

Participants diagnosed with any of following: homozygous familial hypercholesterolemia, New York Heart Association class III \& IV heart failure, Type 2 diabetes, severe hypertension, active liver disease, HIV infection or any uncontrolled or serious disease;
History of drug abuse or unhealthy alcohol use, malignancy of any organ system, or or allergy to the investigational compound/compound class;
Major adverse cardiovascular event within 3 months prior to randomization;
Calculated glomerular filtration rate ≤30 mL/min by estimated glomerular filtration rate (eGFR) using standardized clinical methodology;
Use of other investigational drugs or planned use of other investigational products or devices;
Women of child-bearing potential unless they are using basic methods of contraception during dosing of investigational drug (total abstinence, sterilization, barrier methods, hormonal contraception, intrauterine device);
Treatment with monoclonal antibodies inhibiting PCSK9 within 90 days prior to screening.
Other protocol-defined inclusion/exclusion criteria may apply

Trial locations and contacts

3 sites in 1 country.

China3 sites

Novartis Investigative Site
Beijing, 100029
Novartis Investigative Site
Changsha, Hunan, 410003
Novartis Investigative Site
Chengdu, Sichuan, 610041

Other trials in China

About this study

Official title: A Placebo-controlled, Participant, Investigator and Sponsor Blinded, Randomized Study to Evaluate the Pharmacokinetics and Pharmacodynamics of Inclisiran Treatment Given as Single Subcutaneous Injection in Chinese Participants With Elevated Low-density Lipoprotein Cholesterol (LDL-C) Despite Treatment With LDL-C Lowering Therapies (ORION-14)

Read the detailed description

The purpose of the study is to characterize pharmacokinetics, pharmacodynamics, safety and tolerability of inclisiran in Chinese participants with elevated serum LDL-C to support inclisiran registration in China.Inclisiran is a long acting RNA therapeutic agent that inhibits the synthesis of PCSK9, leading to reduced circulating LDL-C levels. Three pivotal Phase III studies have been conducted primarily in non-Asian participants to support New Drug Application/Marketing Authorization Application approval of inclisiran globally. This study design is based on the hypothesis that the global inclisiran clinical data primarily obtained in Caucasian participants could be appropriately extrapolated to Chinese participants.

Conditions: Hyperlipidemia
Being tested: 100 mg inclisiran sodium (equivalent to 94.5 mg inclisiran), Placebo, 300 mg inclisiran sodium (equivalent to 284 mg inclisiran)
Keywords: Inclisiran, KJX839, LDL-C, Pharmacokinetics and pharmacodynamics, Chinese participants with elevated serum LDL-C
Medical subject headings: Hyperlipidemias

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

100 mg inclisiran sodium (equivalent to 94.5 mg inclisiran)Drug
Also called KJX839
100 mg inclisiran sodium (equivalent to 94.5 mg inclisiran) in 0.5 mL solution. Subcutaneous administration at Day 1
PlaceboDrug
Inclisiran sodium 0mg (equivalent to inclisiran 0 mg) in 1.5 mL solution. Subcutaneous administration at Day 1
300 mg inclisiran sodium (equivalent to 284 mg inclisiran)Drug
Also called KJX839
300 mg inclisiran sodium (equivalent to 284 mg inclisiran) in 1.5 mL solution. Subcutaneous administration at Day 1

Study groups in NCT04774003
Study group	Role	What they receive
300 mg inclisiran sodium (equivalent to 284 mg inclisiran)	Experimental	300 mg inclisiran sodium (equivalent to 284 mg inclisiran) x 1 dose (n=15) at Day 1 Receives: Drug: 300 mg inclisiran sodium (equivalent to 284 mg inclisiran)
100 mg inclisiran sodium (equivalent to 94.5 mg inclisiran)	Experimental	100 mg inclisiran sodium (equivalent to 94.5 mg inclisiran) x 1 dose (n=15) at Day 1 Receives: Drug: 100 mg inclisiran sodium (equivalent to 94.5 mg inclisiran)
Placebo	Placebo comparator	Placebo x 1 dose (n=10) at Day 1 Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

PK parameters (Cmax) maximum peak observed plasma inclisiran concentration in treated participants
Pharmacokinetics parameters of inclisiran
Measured: 0-48 hours post-dose
PK parameters (Tmax) time to reach maximum peak plasma inclisiran concentration in treated participants
Pharmacokinetics parameters of inclisiran
Measured: 0-48 hours post-dose
PK parameters (T1/2) the elimination half-life associated with the terminal slope of a semi-logarithmic concentration-time curve in inclisiran treated participants
Pharmacokinetics parameters of inclisiran
Measured: 0-48 hours post-dose
PK parameters (AUC) area under the plasma concentration-time curve in inclisiran treated participants
Pharmacokinetics parameters of inclisiran
Measured: 0-48 hours post-dose
Percentage change in Proprotein convertase subtilisin kexin 9 (PCSK9) from baseline overtime
Pharmacodynamics effects of inclisiran
Measured: Baseline to Days 5, 8, 15, 30, 60 and 90
Percentage change in Low density lipoprotein cholesterol (LDL-C) from baseline overtime
Pharmacodynamics effects of inclisiran
Measured: Baseline to Days 5, 8, 15, 30, 60 and 90

Secondary outcomes (3)

Percent change from baseline to Days 30, 60 and 90 in PD parameter Proprotein convertase subtilisin kexin 9 (PCSK9)
Pharmacodynamics differences between inclisiran and placebo
Measured: Baseline to Days 30, 60 and 90
Percent change from baseline to Days 30, 60 and 90 in PD parameter Low density lipoprotein cholesterol (LDL-C)
Pharmacodynamics differences between inclisiran and placebo
Measured: Baseline to Days 30, 60 and 90
Rate of formation of anti-drug antibodies to Inclisiran
Immunogenicity of inclisiran
Measured: Baseline, Days 30 and 90

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

26 Feb 202118 Oct 2021

First posted26 Feb 2021
Study start26 Feb 2021
Primary completion18 Oct 2021
Study completion18 Oct 2021

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 HyperlipidemiaStudies 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 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: This is a placebo-controlled study of inclisiran sodium given as a single subcutaneous injection of either 100 mg and 300 mg.
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 40 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04774003
Sponsor's protocol ID: CKJX839A12105
Acronym: ORION-14
Status last verified: Mar 2025
First submitted: 18 Feb 2021
Last updated: 25 Mar 2025
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Luo Z, Huang Z, Sun F, Guo F, Wang Y, Kao S, Yang G, Huang J, Li J, Zhao S, He Y. The clinical effects of inclisiran, a first-in-class LDL-C lowering siRNA therapy, on the LDL-C levels in Chinese patients with hypercholesterolemia. J Clin Lipidol. 2023 May-Jun;17(3):392-400. doi: 10.1016/j.jacl.2023.04.010. Epub 2023 Apr 29.
PubMed 37164838

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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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
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All Hyperlipidemia trials

Study at a glance

From the registry record, last updated by the sponsor on 25 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Placebo-controlled, Participant, Investigator and Sponsor Blinded, Randomized Study to Evaluate the Pharmacokinetics and Pharmacodynamics of Inclisiran Treatment Given as Single Subcutaneous Injection in Chinese Participants With Elevated Low-density Lipoprotein Cholesterol (LDL-C) Despite Treatment With LDL-C Lowering Therapies (ORION-14)
ClinicalTrials.gov ID: NCT04774003
Acronym / sponsor ID: ORION-14 / CKJX839A12105
Conditions: Hyperlipidemia
Keywords: Inclisiran, KJX839, LDL-C, Pharmacokinetics and pharmacodynamics, Chinese participants with elevated serum LDL-C
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 40 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: 26 Feb 2021 (actual)
Primary completion: 18 Oct 2021 (actual)
Study completion: 18 Oct 2021 (actual)
First posted: 26 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.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 3
Model description: This is a placebo-controlled study of inclisiran sodium given as a single subcutaneous injection of either 100 mg and 300 mg.

Arm	Type	Receives
300 mg inclisiran sodium (equivalent to 284 mg inclisiran)	Experimental	Drug: 300 mg inclisiran sodium (equivalent to 284 mg inclisiran)300 mg inclisiran sodium (equivalent to 284 mg inclisiran) x 1 dose (n=15) at Day 1
100 mg inclisiran sodium (equivalent to 94.5 mg inclisiran)	Experimental	Drug: 100 mg inclisiran sodium (equivalent to 94.5 mg inclisiran)100 mg inclisiran sodium (equivalent to 94.5 mg inclisiran) x 1 dose (n=15) at Day 1
Placebo	Placebo comparator	Drug: PlaceboPlacebo x 1 dose (n=10) at Day 1

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

Written informed consent must be obtained before any assessment is performed.
Male or female participants ≥ 18 years of age at screening
Participants should meet fasting serum LDL-C ≥ 100 mg/dL (≥ 2.6 mmol/L) at screening
Participants should meet fasting triglyceride < 400 mg/dL (< 4.52 mmol/L) at screening
Participants should be receiving a maximally tolerated dose of statin#.

Key exclusion criteria (8 listed)

Participants diagnosed with any of following: homozygous familial hypercholesterolemia, New York Heart Association class III \& IV heart failure, Type 2 diabetes, severe hypertension, active liver disease, HIV infection or any uncontrolled or serious disease;
History of drug abuse or unhealthy alcohol use, malignancy of any organ system, or or allergy to the investigational compound/compound class;
Major adverse cardiovascular event within 3 months prior to randomization;
Calculated glomerular filtration rate ≤30 mL/min by estimated glomerular filtration rate (eGFR) using standardized clinical methodology;
Use of other investigational drugs or planned use of other investigational products or devices;

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
100 mg inclisiran sodium (equivalent to 94.5 mg inclisiran)Also: KJX839100 mg inclisiran sodium (equivalent to 94.5 mg inclisiran) in 0.5 mL solution. Subcutaneous administration at Day 1	Drug	100 mg inclisiran sodium (equivalent to 94.5 mg inclisiran)
PlaceboInclisiran sodium 0mg (equivalent to inclisiran 0 mg) in 1.5 mL solution. Subcutaneous administration at Day 1	Drug	Placebo
300 mg inclisiran sodium (equivalent to 284 mg inclisiran)Also: KJX839300 mg inclisiran sodium (equivalent to 284 mg inclisiran) in 1.5 mL solution. Subcutaneous administration at Day 1	Drug	300 mg inclisiran sodium (equivalent to 284 mg inclisiran)

Primary outcome

PK parameters (Cmax) maximum peak observed plasma inclisiran concentration in treated participants
Time frame: 0-48 hours post-dose
Pharmacokinetics parameters of inclisiran
PK parameters (Tmax) time to reach maximum peak plasma inclisiran concentration in treated participants
Time frame: 0-48 hours post-dose
Pharmacokinetics parameters of inclisiran
PK parameters (T1/2) the elimination half-life associated with the terminal slope of a semi-logarithmic concentration-time curve in inclisiran treated participants
Time frame: 0-48 hours post-dose
Pharmacokinetics parameters of inclisiran
PK parameters (AUC) area under the plasma concentration-time curve in inclisiran treated participants
Time frame: 0-48 hours post-dose
Pharmacokinetics parameters of inclisiran
Percentage change in Proprotein convertase subtilisin kexin 9 (PCSK9) from baseline overtime
Time frame: Baseline to Days 5, 8, 15, 30, 60 and 90
Pharmacodynamics effects of inclisiran
Percentage change in Low density lipoprotein cholesterol (LDL-C) from baseline overtime
Time frame: Baseline to Days 5, 8, 15, 30, 60 and 90
Pharmacodynamics effects of inclisiran

3 secondary outcomes

Percent change from baseline to Days 30, 60 and 90 in PD parameter Proprotein convertase subtilisin kexin 9 (PCSK9)
Time frame: Baseline to Days 30, 60 and 90
Percent change from baseline to Days 30, 60 and 90 in PD parameter Low density lipoprotein cholesterol (LDL-C)
Time frame: Baseline to Days 30, 60 and 90
Rate of formation of anti-drug antibodies to Inclisiran
Time frame: Baseline, Days 30 and 90

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2025.
Derived from this study: PubMed 37164838Luo Z, Huang Z, Sun F, Guo F, Wang Y, Kao S, Yang G, Huang J, Li J, Zhao S, He Y. The clinical effects of inclisiran, a first-in-class LDL-C lowering siRNA therapy, on the LDL-C levels in Chinese patients with hypercholesterolemia. J Clin Lipidol. 2023 May-Jun;17(3):392-400. doi: 10.1016/j.jacl.2023.04.010. Epub 2023 Apr 29.
A Plain Language Trial Summary is available on novctrd.comLink provided by the sponsor.
Results for CKJX839A12105 from the Novartis Clinical Trials WebsiteLink provided by the sponsor.
Individual participant dataSharing planned: No

Related trials for Hyperlipidemia

Not yet recruiting
Plasma Lipids-Dependent Vitamin E Metabolism During Dynamic Hyperlipidemia
Lipid Metabolism Disorders
Active, not recruiting
Developing a Learning COmmunity to Increase eNgagemeNt and Enrollment in Cardiovascular Clinical Trials (CONNECT)
Cardiovascular Diseases, Hypertension
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

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.

Novartis Pharmaceuticals study director

Novartis Pharmaceuticals

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 7 inclusion and 8 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: finished, as of the sponsor's last update on 25 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in China. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

PK parameters (Cmax) maximum peak observed plasma inclisiran concentration in treated participants (time frame: 0-48 hours post-dose). The study lists 6 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 NCT04774003, 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 25 Mar 2025.