search
Back to results

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)

Primary Purpose

Hypercholesterolemia

Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
inclisiran sodium
Placebo
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypercholesterolemia focused on measuring inclisiran, siRNA, dyslipidemia, KJX839

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

-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.

Exclusion Criteria:

  • 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).
  • Other protocol-defined inclusion/exclusion criteria may apply.

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

inclisiran sodium 300 mg

Placebo

Arm Description

Subcutaneous injection

Subcutaneous injection

Outcomes

Primary Outcome Measures

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
Extension: Number of participants with Adverse Events
Evaluation of the safety and tolerability of inclisiran, treatment emergent Adverse events and Serious Adverse Events

Secondary Outcome Measures

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
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
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
Core: Percentage change in PCSK9
The superiority of inclisiran compared to placebo in reducing PCSK9 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
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
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
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
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
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

Full Information

First Posted
February 5, 2021
Last Updated
October 27, 2022
Sponsor
Novartis Pharmaceuticals
search

1. Study Identification

Unique Protocol Identification Number
NCT04765657
Brief Title
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)
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)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 1, 2021 (Actual)
Primary Completion Date
June 9, 2022 (Actual)
Study Completion Date
December 28, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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
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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypercholesterolemia
Keywords
inclisiran, siRNA, dyslipidemia, KJX839

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
345 (Actual)

8. Arms, Groups, and Interventions

Arm Title
inclisiran sodium 300 mg
Arm Type
Experimental
Arm Description
Subcutaneous injection
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Subcutaneous injection
Intervention Type
Drug
Intervention Name(s)
inclisiran sodium
Other Intervention Name(s)
KJX839
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Subcutaneously injected on Day 1, 90, and 270.
Primary Outcome Measure Information:
Title
Core: Percentage change in low- density lipoprotein cholesterol (LDL-C)
Description
Superiority of inclisiran compared to placebo in reducing LDL-C from baseline to Day 330
Time Frame
Baseline, Day 330
Title
Extension: Number of participants with Adverse Events
Description
Evaluation of the safety and tolerability of inclisiran, treatment emergent Adverse events and Serious Adverse Events
Time Frame
Day 360 until study completion, an average of 3 years
Secondary Outcome Measure Information:
Title
Core: Time adjusted percentage change in LDL-C
Description
The superiority of inclisiran compared to placebo in reducing LDL-C from baseline to Day 330 and over time
Time Frame
From baseline after Day 90 and up to Day 360
Title
Core: Absolute change in LDL-C
Description
The superiority of inclisiran compared to placebo in reducing LDL-C from baseline to Day 330 and over time
Time Frame
From baseline to Day 330
Title
Core: Time adjusted absolute change in LDL-C
Description
The superiority of inclisiran compared to placebo in reducing LDL-C from baseline to Day 330 and over time
Time Frame
From baseline after Day 90 and up to Day 360
Title
Core: Percentage change in PCSK9
Description
The superiority of inclisiran compared to placebo in reducing PCSK9 from baseline to Day 330
Time Frame
From baseline to Day 330
Title
Core: Absolute change in PCSK9
Description
The superiority of inclisiran compared to placebo in reducing PCSK9 from baseline to Day 330
Time Frame
From baseline to Day 330
Title
Core: Proportion of participants reaching LDL-C levels of <25 mg/dL, <50 mg/dL, <70 mg/dL, and <100 mg/dL
Description
The superiority of inclisiran compared to placebo in individual response rate for lipid controlling
Time Frame
Day 330
Title
Core: Proportion of participants in each group with ≥ 50% LDL-C reduction
Description
The superiority of inclisiran compared to placebo in individual response rate for lipid controlling
Time Frame
From baseline to Day 330
Title
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)
Description
The superiority of inclisiran compared to placebo in individual response rate for lipid controlling
Time Frame
Day 330
Title
Core: Percentage change in total cholesterol, ApoB, non-HDL-C, ApoA1, HDL-C, Lp(a) and triglycerides
Description
The superiority of inclisiran compared to placebo in reducing other lipids, lipoproteins and apolipoproteins
Time Frame
From baseline to Day 330
Title
Core: Absolute change in total cholesterol, ApoB, non-HDL-C, ApoA1, HDL-C, Lp(a) and triglycerides
Description
The superiority of inclisiran compared to placebo in reducing other lipids, lipoproteins and apolipoproteins
Time Frame
From baseline to Day 330

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: -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. Exclusion Criteria: 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). Other protocol-defined inclusion/exclusion criteria may apply.
Facility Information:
Facility Name
Novartis Investigative Site
City
Lanzhou
State/Province
Gansu
ZIP/Postal Code
730030
Country
China
Facility Name
Novartis Investigative Site
City
Foshan
State/Province
Guangdong
ZIP/Postal Code
528000
Country
China
Facility Name
Novartis Investigative Site
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
51000
Country
China
Facility Name
Novartis Investigative Site
City
Baotou
State/Province
Inner Mongolia
ZIP/Postal Code
014040
Country
China
Facility Name
Novartis Investigative Site
City
Hohhot
State/Province
Inner Mongolia
ZIP/Postal Code
010017
Country
China
Facility Name
Novartis Investigative Site
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210008
Country
China
Facility Name
Novartis Investigative Site
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
211166
Country
China
Facility Name
Novartis Investigative Site
City
Nantong
State/Province
Jiangsu
ZIP/Postal Code
226000
Country
China
Facility Name
Novartis Investigative Site
City
Suzhou
State/Province
Jiangsu
ZIP/Postal Code
215006
Country
China
Facility Name
Novartis Investigative Site
City
Xuzhou
State/Province
Jiangsu
ZIP/Postal Code
221003
Country
China
Facility Name
Novartis Investigative Site
City
Chang Chun
State/Province
Jilin
ZIP/Postal Code
130021
Country
China
Facility Name
Novartis Investigative Site
City
Changchun
State/Province
Jilin
ZIP/Postal Code
130021
Country
China
Facility Name
Novartis Investigative Site
City
Jinan
State/Province
Shandong
ZIP/Postal Code
250013
Country
China
Facility Name
Novartis Investigative Site
City
Jinshan
State/Province
Shanghai
ZIP/Postal Code
201508
Country
China
Facility Name
Novartis Investigative Site
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200032
Country
China
Facility Name
Novartis Investigative Site
City
Taiyuan
State/Province
Shanxi
Country
China
Facility Name
Novartis Investigative Site
City
Xian
State/Province
Shanxi
ZIP/Postal Code
710061
Country
China
Facility Name
Novartis Investigative Site
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300121
Country
China
Facility Name
Novartis Investigative Site
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310014
Country
China
Facility Name
Novartis Investigative Site
City
Beijing
ZIP/Postal Code
100034
Country
China
Facility Name
Novartis Investigative Site
City
Beijing
ZIP/Postal Code
100050
Country
China
Facility Name
Novartis Investigative Site
City
Beijing
ZIP/Postal Code
100191
Country
China
Facility Name
Novartis Investigative Site
City
Beijing
Country
China
Facility Name
Novartis Investigative Site
City
Shanghai
ZIP/Postal Code
200040
Country
China
Facility Name
Novartis Investigative Site
City
Shanghai
ZIP/Postal Code
200080
Country
China
Facility Name
Novartis Investigative Site
City
Shanghai
ZIP/Postal Code
200120
Country
China
Facility Name
Novartis Investigative Site
City
Shijiazhuang
ZIP/Postal Code
050000
Country
China
Facility Name
Novartis Investigative Site
City
Tianjin
ZIP/Postal Code
300052
Country
China
Facility Name
Novartis Investigative Site
City
Tianjin
Country
China
Facility Name
Novartis Investigative Site
City
Xiamen
ZIP/Postal Code
361004
Country
China
Facility Name
Novartis Investigative Site
City
Wonju
State/Province
Gangwon-do
ZIP/Postal Code
26427
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Gwangju
ZIP/Postal Code
61469
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Incheon
ZIP/Postal Code
405 760
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
02841
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
110-746
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Singapore
ZIP/Postal Code
117549
Country
Singapore
Facility Name
Novartis Investigative Site
City
Singapore
ZIP/Postal Code
169609
Country
Singapore
Facility Name
Novartis Investigative Site
City
Kaohsiung
ZIP/Postal Code
80756
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Taipei
ZIP/Postal Code
10002
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Taipei
ZIP/Postal Code
11217
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Taipei
Country
Taiwan

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
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

Learn more about this trial

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)

We'll reach out to this number within 24 hrs