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)

Hypercholesterolemia Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04765657
• Other study ID #: CKJX839A12307
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: March 1, 2021
• Est. completion date: December 28, 2026

Study information

• Verified date: October 2023
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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

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)

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 345
• Est. completion date: December 28, 2026
• Est. primary completion date: June 9, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Hypercholesterolemia

Intervention

Drug:
• inclisiran sodium
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)
• Placebo
Subcutaneously injected on Day 1, 90, and 270.

Locations

Country	Name	City	State
China	Novartis Investigative Site	Baotou	Inner Mongolia
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Chang Chun	Jilin
China	Novartis Investigative Site	Changchun	Jilin
China	Novartis Investigative Site	Foshan	Guangdong
China	Novartis Investigative Site	Guangzhou	Guangdong
China	Novartis Investigative Site	Hangzhou	Zhejiang
China	Novartis Investigative Site	Hohhot	Inner Mongolia
China	Novartis Investigative Site	Jinan	Shandong
China	Novartis Investigative Site	Jinshan	Shanghai
China	Novartis Investigative Site	Lanzhou	Gansu
China	Novartis Investigative Site	Nanjing	Jiangsu
China	Novartis Investigative Site	Nanjing	Jiangsu
China	Novartis Investigative Site	Nantong	Jiangsu
China	Novartis Investigative Site	Shanghai	Shanghai
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Shijiazhuang
China	Novartis Investigative Site	Suzhou	Jiangsu
China	Novartis Investigative Site	Taiyuan	Shanxi
China	Novartis Investigative Site	Tianjin
China	Novartis Investigative Site	Tianjin
China	Novartis Investigative Site	Tianjin	Tianjin
China	Novartis Investigative Site	Xiamen
China	Novartis Investigative Site	Xian	Shanxi
China	Novartis Investigative Site	Xuzhou	Jiangsu
Korea, Republic of	Novartis Investigative Site	Gwangju
Korea, Republic of	Novartis Investigative Site	Incheon
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Wonju	Gangwon-do
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore
Taiwan	Novartis Investigative Site	Kaohsiung
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

China,  Korea, Republic of,  Singapore,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Baseline, Day 330
Primary	Extension: Number of participants with Adverse Events	Evaluation of the safety and tolerability of inclisiran, treatment emergent Adverse events and Serious Adverse Events	Day 360 until study completion, an average of 3 years
Secondary	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	From baseline after Day 90 and up to Day 360
Secondary	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	From baseline to Day 330
Secondary	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	From baseline after Day 90 and up to Day 360
Secondary	Core: Percentage change in PCSK9	The superiority of inclisiran compared to placebo in reducing PCSK9 from baseline to Day 330	From baseline to Day 330
Secondary	Core: Absolute change in PCSK9	The superiority of inclisiran compared to placebo in reducing PCSK9 from baseline to Day 330	From baseline to Day 330
Secondary	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	Day 330
Secondary	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	From baseline to Day 330
Secondary	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	Day 330
Secondary	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	From baseline to Day 330
Secondary	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	From baseline to Day 330