Clinical trial NCT05888103: Efficacy and Safety of Inclisiran as Monotherapy in Chinese Adults With Low or Moderate ASCVD Risk and Elevated Low-density Lipoprotein Cholesterol.
Official title: A 6 Month Randomized, Double-blind, Placebo-controlled Study Followed by a 6 Month Open- Label Extension to Assess the Efficacy and Safety of Inclisiran as Monotherapy in Chinese Adults With Low or Moderate ASCVD Risk and Elevated Low-density Lipoprotein Cholesterol
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Primary Hypercholesterolemia or Mixed Dyslipidemia
Keywords: Inclisiran
LDL-C
monotherapy
atherosclerotic cardiovascular disease
atheroma
Atherosclerosis
lipid
lipid lowering therapy (LLT)
cholesterol
hypercholesteremia
mixed dyslipidemia
TC (total cholesterol)
Apo B
non HDL-C
Lp(a)
PCSK9
PCSK9 inhibitor
siRNA
low ASCVD risk
moderate ASCVD risk
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2023-06-05
Enrollment: 207
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multi-center, randomized, double-blind, placebo-controlled, parallel groups
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to evaluate the efficacy and safety of inclisiran as a monotherapy in Chinese adults with low or moderate atherosclerotic cardiovascular disease (ASCVD) risk and elevated low-density lipoprotein cholesterol (LDL-C) who were not on any lipid lowering therapy.

Detailed description: This study was designed as a randomized, double-blind, multi-center Phase III trial, with a placebo-controlled treatment period and an open label treatment period, to evaluate the efficacy and safety of inclisiran sodium 300 mg s.c. in participants aged 18 to 75 years with a low or moderate ASCVD risk and fasting LDL-C value of ≥ 130 mg/dL but \< 190 mg/dL who were not on any lipid lowering therapy.

The study consisted of 3 parts:

* Screening: the screening period was up to 14 days to allow adequate time for the eligibility evaluations.
* Core Part: a double-blind, placebo-controlled treatment period of 180 days in which eligible participants were randomized 1:1 to receive either inclisiran sodium 300 mg s.c.

(inclisiran group) or matching placebo s.c. (control group) on Day 1 and Day 90. The end of core part (EOC) visit was conducted on Day 180. The database lock for the core part was planned to occur after all randomized participants have completed the EOC visit (or have discontinued from the study before EOC). The primary analysis was conducted after the database lock for the core part.

• Extension Part: an extended treatment period of 180 days. In the extension part, participants originally randomized to inclisiran in the core part were to continue the inclisiran treatment while participants initially randomized to placebo were to transit to the inclisiran. The extension part was to start from the Day 180 treatment dose (placebo in the inclisiran group and inclisiran for participants originally randomized to the control group).

Eligibility criteria: Inclusion Criteria:

* Written informed consent must be obtained before any assessment is performed.
* Fasting LDL-C of ≥ 130 mg/dL but \< 190 mg/dL
* Triglycerides ≤ 400 mg/dL
* Categorized as low or moderate ASCVD risk by the 2016 Chinese Guideline

Exclusion Criteria:

* Use of any LLT within 90 days prior to screening visit
* History of ASCVD
* Diabetes mellitus or fasting plasma glucose of ≥ 7.0 mmol/L or HbA1c ≥ 6.5%
* Secondary hypercholesterolemia, e.g. hypothyroidism or nephrotic syndrome

Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Percentage Change in Low-density Lipoprotein Cholesterol (LDL-C) (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part
timeFrame: Baseline, Day 150
Secondary outcomes:
measure: Absolute Change in LDL-C (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part
timeFrame: Baseline, Day 150
measure: Percentage Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) (ng/mL) From Baseline at Day 150 - Core Analysis: Core Part
timeFrame: Baseline, Day 150
measure: Absolute Change in PCSK9 (ng/mL) From Baseline at Day 150 - Core Analysis: Core Part
timeFrame: Baseline, Day 150
measure: Percentage Change in Total Cholesterol (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part
timeFrame: Baseline, Day 150
measure: Absolute Change in Total Cholesterol (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part
timeFrame: Baseline, Day 150
measure: Percentage Change in High-density Lipoprotein Cholesterol (HDL-C) (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part
timeFrame: Baseline, Day 150
measure: Absolute Change in HDL-C (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part
timeFrame: Baseline, Day 150
measure: Percentage Change in Non-HDL-C (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part
timeFrame: Baseline, Day 150
measure: Absolute Change in Non-HDL-C (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part
timeFrame: Baseline, Day 150
measure: Percentage Change in Apolipoprotein B (ApoB) (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part
timeFrame: Baseline, Day 150
measure: Absolute Change in ApoB (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part
timeFrame: Baseline, Day 150
measure: Percentage Change in Apolipoprotein A-1 (ApoA-1) (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part
timeFrame: Baseline, Day 150
measure: Absolute Change in ApoA-1 (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part
timeFrame: Baseline, Day 150
measure: Percentage Change in Lipoprotein (a) (Lp(a)) (Nmol/L) From Baseline at Day 150 - Core Analysis: Core Part
timeFrame: Baseline, Day 150
measure: Absolute Change in Log-transformed Lp(a) (Nmol/L) From Baseline at Day 150 - Core Analysis: Core Part
timeFrame: Baseline, Day 150
measure: Percentage Change in Triglyceride (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part
timeFrame: Baseline, Day 150
measure: Absolute Change in Triglyceride (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part
timeFrame: Baseline, Day 150
measure: Percentage Change in LDL-C (mg/dL) From Baseline at Day 330 - Final Analysis: Core Part + Extension Part
timeFrame: Baseline, Day 330
measure: Absolute Change in LDL-C (mg/dL) From Baseline at Day 330 - Final Analysis: Core Part + Extension Part
timeFrame: Baseline, Day 330
measure: Number of Participants With Adverse Events (AEs) During Core Part
timeFrame: Core part, from treatment start (Day 1) to Day 150
measure: Number of Participants With Adverse Events (AEs) During Extension Part
timeFrame: Extension part, from Day 181, up to Day 360
measure: Number of Participants With Adverse Events (AEs) - Cumulative Data (Core + Extension Part)
timeFrame: AEs are reported from first dose of study treatment until end of study treatment plus 30 days after the last study visit (or 90 days after the last administration of study drug, whichever is longer) up to a maximum timeframe of approximately 360 days
Other outcomes:
Locations:
city: Fuzhou
country: China
facility: Novartis Investigative Site
state: Fujian
city: Zhongshan
country: China
facility: Novartis Investigative Site
state: Guang Dong
city: Guangzhou City
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Guangzhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Wuhan
country: China
facility: Novartis Investigative Site
state: Hubei
city: Changsha
country: China
facility: Novartis Investigative Site
state: Hunan
city: Changsha
country: China
facility: Novartis Investigative Site
state: Hunan
city: Hohhot
country: China
facility: Novartis Investigative Site
state: Inner Mongolia
city: Changzhou
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Xuzhou
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Nanchang
country: China
facility: Novartis Investigative Site
state: Jiangxi
city: Jinzhou
country: China
facility: Novartis Investigative Site
state: Liaoning
city: Linyi
country: China
facility: Novartis Investigative Site
state: Shandong
city: Taiyuan
country: China
facility: Novartis Investigative Site
state: Shanxi
city: Xian
country: China
facility: Novartis Investigative Site
state: Shanxi
city: Chengdu
country: China
facility: Novartis Investigative Site
state: Sichuan
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: Jinan
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: Tianjin
country: China
facility: Novartis Investigative Site
city: Tianjin
country: China
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: