Clinical trial NCT04765657: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Hypercholesterolemia
Keywords: inclisiran
siRNA
dyslipidemia
KJX839
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2021-02-21
Enrollment: 345
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)

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.

Primary outcomes:
measure: Core: Percentage change in low- density lipoprotein cholesterol (LDL-C)
timeFrame: Baseline, Day 330
measure: Extension: Number of participants with Adverse Events
timeFrame: Day 360 until study completion, an average of 3 years
Secondary outcomes:
measure: Core: Time adjusted percentage change in LDL-C
timeFrame: From baseline after Day 90 and up to Day 360
measure: Core: Absolute change in LDL-C
timeFrame: From baseline to Day 330
measure: Core: Time adjusted absolute change in LDL-C
timeFrame: From baseline after Day 90 and up to Day 360
measure: Core: Percentage change in PCSK9
timeFrame: From baseline to Day 330
measure: Core: Absolute change in PCSK9
timeFrame: From baseline to Day 330
measure: Core: Proportion of participants reaching LDL-C levels of <25 mg/dL, <50 mg/dL, <70 mg/dL, and <100 mg/dL
timeFrame: Day 330
measure: Core: Proportion of participants in each group with ≥ 50% LDL-C reduction
timeFrame: From baseline to Day 330
measure: 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)
timeFrame: Day 330
measure: Core: Percentage change in total cholesterol, ApoB, non-HDL-C, ApoA1, HDL-C, Lp(a) and triglycerides
timeFrame: From baseline to Day 330
measure: Core: Absolute change in total cholesterol, ApoB, non-HDL-C, ApoA1, HDL-C, Lp(a) and triglycerides
timeFrame: From baseline to Day 330
Other outcomes:
Locations:
city: Lanzhou
country: China
facility: Novartis Investigative Site
state: Gansu
city: Foshan
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Guangzhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Baotou
country: China
facility: Novartis Investigative Site
state: Inner Mongolia
city: Hohhot
country: China
facility: Novartis Investigative Site
state: Inner Mongolia
city: Nanjing
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Nanjing
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Nantong
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Suzhou
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Xuzhou
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Chang Chun
country: China
facility: Novartis Investigative Site
state: Jilin
city: Changchun
country: China
facility: Novartis Investigative Site
state: Jilin
city: Jinan
country: China
facility: Novartis Investigative Site
state: Shandong
city: Jinshan
country: China
facility: Novartis Investigative Site
state: Shanghai
city: Shanghai
country: China
facility: Novartis Investigative Site
state: Shanghai
city: Taiyuan
country: China
facility: Novartis Investigative Site
state: Shanxi
city: Xian
country: China
facility: Novartis Investigative Site
state: Shanxi
city: Tianjin
country: China
facility: Novartis Investigative Site
state: Tianjin
city: Hangzhou
country: China
facility: Novartis Investigative Site
state: Zhejiang
city: Beijing
country: China
facility: Novartis Investigative Site
city: Beijing
country: China
facility: Novartis Investigative Site
city: Beijing
country: China
facility: Novartis Investigative Site
city: Beijing
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Shijiazhuang
country: China
facility: Novartis Investigative Site
city: Tianjin
country: China
facility: Novartis Investigative Site
city: Tianjin
country: China
facility: Novartis Investigative Site
city: Xiamen
country: China
facility: Novartis Investigative Site
city: Wonju
country: Korea, Republic of
facility: Novartis Investigative Site
state: Gangwon-do
city: Gwangju
country: Korea, Republic of
facility: Novartis Investigative Site
city: Incheon
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Kaohsiung
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
Study officials:
References: