Efficacy and Safety of Inclisiran as Monotherapy in Patients With Primary Hypercholesterolemia Not Receiving Lipid-lowering Therapy.

Phase 3

Completed

• Conditions: Hypercholesterolemia
• Interventions: Drug: Matching Placebo for Inclisiran; Drug: Inclisiran; Drug: Ezetimibe; Drug: Matching Placebo for Ezetimibe

• Registration Number: NCT05763875
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

CKJX839D12304 is a research study to determine if the study treatment, called inclisiran, in comparison to placebo or ezetimibe can effectively reduce LDL-C as measured by percentage change from baseline to Day 150. This study is being conducted in eligible participants with primary hypercholesterolemia not receiving any lipid-lowering therapy (LLT), with a 10-year Atherosclerotic Cardiovascular Disease (ASCVD) risk of less than 7.5%.

Detailed Description

This study is a randomized, double-blind, placebo- and active comparator-controlled, multicenter study in 300 adult participants with primary hypercholesterolemia not receiving any LLT with a 10-year ASCVD risk score of less than 7.5%. This study will evaluate the efficacy and safety of inclisiran sodium 300 mg, administered as a monotherapy in comparison to ezetimibe and placebo.

The study consists of:

* a screening period of up to 14 days;

* a double-blind treatment period of 150+/- 5 days during which participants will be randomly assigned to either the inclisiran arm, the ezetimibe arm or the placebo arm in a 2:1:1 ratio; and

* a safety follow-up / End of Study visit conducted 30+5 days after the Day 150 visit.

The overall study duration is approximately 190 days.

Study Timeline

• Study First Submitted: 2023-02-28
• Study First Submitted QC: 2023-02-28
• Study First Posted: 2023-03-10
• Study Start: 2023-03-15
• Primary Completion: 2024-06-20
• Study Completion: 2024-06-20
• Status Verified: 2024-09
• Last Update Submitted: 2024-09-29
• Last Update Posted: 2024-10-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 350

Inclusion Criteria

Not provided

Exclusion Criteria

• history of ASCVD
• diabetes mellitus or fasting plasma glucose of >= 7.0 mmol/L or HbA1c >= 6.5%
• secondary hypercholesterolemia, e.g. hypothyroidism (TSH above upper limit of normal)

Other protocol-defined inclusion/exclusion criteria may apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Inclisiran	Matching Placebo for Ezetimibe	Inclisiran s.c and Placebo p.o
Placebo	Matching Placebo for Ezetimibe	Placebo s.c. and Placebo p.o.
Placebo	Matching Placebo for Inclisiran	Placebo s.c. and Placebo p.o.
Ezetimibe	Matching Placebo for Inclisiran	Placebo s.c. and Ezetimibe p.o.
Inclisiran	Inclisiran	Inclisiran s.c and Placebo p.o
Ezetimibe	Ezetimibe	Placebo s.c. and Ezetimibe p.o.

Primary Outcome Measures

Name	Time	Method
Percentage change in LDL-C from Baseline to Day 150 compared with ezetimibe	Baseline, Day 150	Percentage change in LDL-C from Baseline (Day 1) to Day 150 comparing Inclisiran arm versus Ezetimibe arm.
Percentage change in Low-density Lipoprotein Cholesterol (LDL-C) from Baseline to Day 150 compared with placebo	Baseline, Day 150	Percentage change in LDL-C from Baseline (Day 1) to Day 150 comparing Inclisiran arm versus Placebo arm

Secondary Outcome Measures

Name	Time	Method
Absolute change in LDL-C from Baseline to Day 150	Baseline, Day 150	Absolute change in LDL-C from Baseline (Day 1) to Day 150 compared to ezetimibe and placebo
Percentage change in non-High-Density Lipoprotein Cholesterol (non-HDL-C) from Baseline to Day 150	Baseline, Day 150	Percentage change in non-HDL-C from Baseline (Day 1) and Day 150 compared to ezetimibe and placebo
Percentage change in Total Cholesterol (TC)/HDL-C ratio from Baseline to Day 150	Baseline, Day 150	Percentage change in total cholesterol (TC)/HDL-C ratio from Baseline (Day 1) and Day 150 compared to ezetimibe and placebo
Percentage change in Apo B/Apo A-1 ratio from Baseline to Day 150	Baseline, Day 150	Percentage change in Apo B/Apo A-1 ratio from baseline (Day 1) and Day 150 compared to ezetimibe and placebo
Percentage change in Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) from Baseline to Day 150	Baseline, Day 150	Percentage change in PCSK9 from Baseline (Day 1) and Day 150 compared to ezetimibe and placebo
Percentage change in Apolipoprotein B (Apo B) from Baseline to Day 150	Baseline, Day 150	Percentage change in Apo B from Baseline (Day 1) and Day 150 compared to ezetimibe and placebo
Percentage change in Lipoprotein (a) [Lp(a)] from Baseline to Day 150	Baseline, Day 150	Percentage change in Lp(a) from Baseline (Day 1) and Day 150 compared to ezetimibe and placebo

Trial Locations

Locations (9)

Southern Clin Research Clinic .; 🇺🇸 Zachary, Louisiana, United States

Novartis Investigative Site; 🇲🇽 Queretaro, Mexico

Hillcrest Medical Research; 🇺🇸 DeLand, Florida, United States

Inpatient Research Clinical LLC; 🇺🇸 Miami Lakes, Florida, United States

Alma Clinical Research Inc; 🇺🇸 Miami, Florida, United States

Harmony Clinical Research; 🇺🇸 North Miami Beach, Florida, United States

Fam Medical Specialists Of Fl Plc; 🇺🇸 Plant City, Florida, United States

Monroe Biomedical Research .; 🇺🇸 Monroe, North Carolina, United States

Conrad Clinical Research Research; 🇺🇸 Edmond, Oklahoma, United States