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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Double-blind, Randomized, Placebo- and Active-Comparator Controlled Study to Evaluate the Efficacy of Inclisiran as Monotherapy in Patients With Primary Hypercholesterolemia Not Receiving Lipid-Lowering Therapy (VictORION-Mono)

Conditions
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Hypercholesterolemia

Intervention / Treatment
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* Drug: Inclisiran
* Drug: Ezetimibe
* Drug: Matching Placebo for Inclisiran
* Drug: Matching Placebo for Ezetimibe


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria to be met at screening: informed consent must be signed prior to participation in study fasting LDL-C of >= 100mg/dL but < 190mg/dL fasting triglycerides <= 400 mg/dL 10-year ASCVD risk score < 7.5% not on any lipid-lowering therapy within 90 days Key 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multi-center, randomized, double-blind, placebo-controlled, parallel groups
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Inclisiran<br>Inclisiran s.c and Placebo p.o | Drug: Inclisiran<br>* 284 mg (equivalent to 300 mg inclisiran sodium) subcutaneous injection given on Day 1 and Day 90<br>* Other names: KJX839;Drug: Matching Placebo for Ezetimibe<br>* 0mg over-encapsulated placebo tablet taken once a day from Day 1 through Day 149<br>* Other names: Placebo p.o.;|
| Active Comparator: Ezetimibe<br>Placebo s.c. and Ezetimibe p.o. | Drug: Ezetimibe<br>* 10 mg over-encapsulated tablet taken once a day from Day 1 through Day 149<br>* Other names: Sandoz ezetimibe;Drug: Matching Placebo for Inclisiran<br>* 0mg placebo injection solution for subcutaneous injection on Day 1 and Day 90<br>* Other names: Placebo s.c.;|
| Placebo Comparator: Placebo<br>Placebo s.c. and Placebo p.o. | Drug: Matching Placebo for Inclisiran<br>* 0mg placebo injection solution for subcutaneous injection on Day 1 and Day 90<br>* Other names: Placebo s.c.;Drug: Matching Placebo for Ezetimibe<br>* 0mg over-encapsulated placebo tablet taken once a day from Day 1 through Day 149<br>* Other names: Placebo p.o.;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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inclisiran, ezetimibe, LDL-C, monotherapy, primary hypercholesterolemia