- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04774003
Study of Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Inclisiran in Chinese Participants With Elevated Serum LDL-C (ORION-14)
December 2, 2021 updated by: Novartis Pharmaceuticals
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)
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
Study Overview
Status
Completed
Conditions
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.
Study Type
Interventional
Enrollment (Actual)
40
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Beijing, China, 100029
- Novartis Investigative Site
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Hunan
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Changsha, Hunan, China, 410003
- Novartis Investigative Site
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Sichuan
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Chengdu, Sichuan, China, 610041
- Novartis Investigative Site
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 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)
Exclusion Criteria:
- 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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
|
300 mg inclisiran sodium (equivalent to 284 mg inclisiran) in 1.5 mL solution.
Subcutaneous administration at Day 1
Other Names:
|
Experimental: 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
|
100 mg inclisiran sodium (equivalent to 94.5 mg inclisiran) in 0.5 mL solution.
Subcutaneous administration at Day 1
Other Names:
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Placebo Comparator: Placebo
Placebo x 1 dose (n=10) at Day 1
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Inclisiran sodium 0mg (equivalent to inclisiran 0 mg) in 1.5 mL solution.
Subcutaneous administration at Day 1
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
PK parameters (Cmax) maximum peak observed plasma inclisiran concentration in treated participants
Time Frame: 0-48 hours post-dose
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Pharmacokinetics parameters of inclisiran
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0-48 hours post-dose
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PK parameters (Tmax) time to reach maximum peak plasma inclisiran concentration in treated participants
Time Frame: 0-48 hours post-dose
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Pharmacokinetics parameters of inclisiran
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0-48 hours post-dose
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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
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Pharmacokinetics parameters of inclisiran
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0-48 hours post-dose
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PK parameters (AUC) area under the plasma concentration-time curve in inclisiran treated participants
Time Frame: 0-48 hours post-dose
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Pharmacokinetics parameters of inclisiran
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0-48 hours post-dose
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Percentage change in Proprotein convertase subtilisin kexin 9 (PCSK9) from baseline overtime
Time Frame: Baseline to Days 5, 8, 15, 30, 60 and 90
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Pharmacodynamics effects of inclisiran
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Baseline to Days 5, 8, 15, 30, 60 and 90
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Percentage change in Low density lipoprotein cholesterol (LDL-C) from baseline overtime
Time Frame: Baseline to Days 5, 8, 15, 30, 60 and 90
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Pharmacodynamics effects of inclisiran
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Baseline to Days 5, 8, 15, 30, 60 and 90
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
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Pharmacodynamics differences between inclisiran and placebo
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Baseline to Days 30, 60 and 90
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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
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Pharmacodynamics differences between inclisiran and placebo
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Baseline to Days 30, 60 and 90
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Rate of formation of anti-drug antibodies to Inclisiran
Time Frame: Baseline, Days 30 and 90
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Immunogenicity of inclisiran
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Baseline, Days 30 and 90
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
February 26, 2021
Primary Completion (Actual)
October 18, 2021
Study Completion (Actual)
October 18, 2021
Study Registration Dates
First Submitted
February 18, 2021
First Submitted That Met QC Criteria
February 24, 2021
First Posted (Actual)
February 26, 2021
Study Record Updates
Last Update Posted (Actual)
December 6, 2021
Last Update Submitted That Met QC Criteria
December 2, 2021
Last Verified
December 1, 2021
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CKJX839A12105
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
Yes
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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