V-Mono: Efficacy and Safety of Inclisiran as Monotherapy in Patients With Primary Hypercholesterolemia Not Receiving Lipid-lowering Therapy.
Study Details
Study Description
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%.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
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:
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a screening period of up to 14 days;
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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
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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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Inclisiran Inclisiran s.c and Placebo p.o |
Drug: Inclisiran
284 mg (equivalent to 300 mg inclisiran sodium) subcutaneous injection given on Day 1 and Day 90
Other Names:
Drug: Matching Placebo for Ezetimibe
0mg over-encapsulated placebo tablet taken once a day from Day 1 through Day 149
Other Names:
|
| Active Comparator: Ezetimibe Placebo s.c. and Ezetimibe p.o. |
Drug: Ezetimibe
10 mg over-encapsulated tablet taken once a day from Day 1 through Day 149
Other Names:
Drug: Matching Placebo for Inclisiran
0mg placebo injection solution for subcutaneous injection on Day 1 and Day 90
Other Names:
|
| Placebo Comparator: Placebo Placebo s.c. and Placebo p.o. |
Drug: Matching Placebo for Inclisiran
0mg placebo injection solution for subcutaneous injection on Day 1 and Day 90
Other Names:
Drug: Matching Placebo for Ezetimibe
0mg over-encapsulated placebo tablet taken once a day from Day 1 through Day 149
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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.
Secondary Outcome Measures
- 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 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 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 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 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 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
Eligibility Criteria
Criteria
Inclusion Criteria to be met at screening:
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informed consent must be signed prior to participation in study
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fasting LDL-C of >= 100mg/dL but < 190mg/dL
-
fasting triglycerides <= 400 mg/dL
-
10-year ASCVD risk score < 7.5%
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not on any lipid-lowering therapy within 90 days
Key Exclusion Criteria:
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history of ASCVD
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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.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CKJX839D12304