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

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

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

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:

  1. Written informed consent must be obtained before any assessment is performed.
  2. Male or female participants ≥ 18 years of age at screening
  3. Participants should meet fasting serum LDL-C ≥ 100 mg/dL (≥ 2.6 mmol/L) at screening
  4. Participants should meet fasting triglyceride < 400 mg/dL (< 4.52 mmol/L) at screening
  5. Participants should be receiving a maximally tolerated dose of statin#.
  6. 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.
  7. 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:

  1. 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;
  2. History of drug abuse or unhealthy alcohol use, malignancy of any organ system, or or allergy to the investigational compound/compound class;
  3. Major adverse cardiovascular event within 3 months prior to randomization;
  4. Calculated glomerular filtration rate ≤30 mL/min by estimated glomerular filtration rate (eGFR) using standardized clinical methodology;
  5. Use of other investigational drugs or planned use of other investigational products or devices;
  6. 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);
  7. 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:
  • KJX839
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:
  • KJX839
Placebo Comparator: Placebo
Placebo x 1 dose (n=10) at Day 1
Inclisiran sodium 0mg (equivalent to inclisiran 0 mg) in 1.5 mL solution. Subcutaneous administration at Day 1

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
Pharmacokinetics parameters of inclisiran
0-48 hours post-dose
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
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
Time Frame: 0-48 hours post-dose
Pharmacokinetics parameters of inclisiran
0-48 hours post-dose
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
0-48 hours post-dose
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
Baseline to Days 5, 8, 15, 30, 60 and 90
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
Baseline to Days 5, 8, 15, 30, 60 and 90

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
Pharmacodynamics differences between inclisiran and placebo
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
Pharmacodynamics differences between inclisiran and placebo
Baseline to Days 30, 60 and 90
Rate of formation of anti-drug antibodies to Inclisiran
Time Frame: Baseline, Days 30 and 90
Immunogenicity of inclisiran
Baseline, Days 30 and 90

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

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

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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