A Randomized, Multicenter, Open-label Trial Comparing the Effectiveness of Inclisiran to Bempedoic Acid on LDL Cholesterol (LDL-C) Lowering in Participants With Atherosclerotic Cardiovascular Disease (VICTORION-CHALLENGE)
Overview
- Phase
- Phase 4
- Intervention
- Inclisiran sodium
- Conditions
- Hypercholesterolemia
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 402
- Locations
- 53
- Primary Endpoint
- Percent change from baseline in LDL-C levels
- Status
- Completed
- Last Updated
- 3 months ago
Overview
Brief Summary
This study is a phase IV, open-label, randomized study designed to evaluate the efficacy of Inclisiran vs. bempedoic acid (BPA) in 400 adult subjects (≥ 18 years) at very high and high risk for cardiovascular events as defined by the cardiovascular risk categories in the 2019 ESC/EAS guidelines for the management of dyslipidemias (Mach et al 2020) and elevated levels of LDL-C (≥ 70 mg/dL) despite being on a maximally tolerated high-intensity (HI) statin dose (+/- Ezetimibe). Currently, BPA is recommended ahead of injectables by German HTA body (GBA). A head-to-head trial is proposed to provide robust scientific data on the superiority of Inclisiran vs. BPA and to support the early use of Inclisiran.
Detailed Description
During the screening period study eligibility will be assessed and the participants' individual LDL-C target according to guideline (Mach et al., 2020) will be determined. Among other criteria, at screening, a participant must be on a stable maximally tolerated dose of a HI statin with either atorvastatin ≥40 mg once a day (QD) or rosuvastatin ≥20 mg QD (+/- Ezetimibe \[10mg\]) for ≥ 4 weeks with which, however, a target LDL-C of \< 70 mg/dL is not reached. During the open-label treatment period, all participants, who fulfill the inclusion/exclusion criteria, will be randomized at V1 (Day 1) in a 1:1 open-label fashion to either Inclisiran sodium 300 mg s.c. (administered at Day 1 and Day 90) or to BPA tablets 180 mg p.o. (given once daily). Participants will be required to maintain their background lipid-lowering treatment (maximally tolerated statin dose +/- Ezetimibe) unchanged for the duration of the study. The end of treatment (EOT) is reached at day 150. A Safety-Follow-up call will be conducted 30 days after EOT visit (Day 180). The overall study duration is approximately 190 days but can vary depending on individual screening and the visit windows allowed for the treatment period and EOS visit.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Fasting LDL-C ≥ 70 mg/dL at screening
- •Participants must be on a stable (≥ 4 weeks) and well-tolerated lipid-lowering regimen (with or without Ezetimibe \[10mg\]) that must include a high-intensity statin therapy with either atorvastatin ≥40 mg QD or rosuvastatin ≥20 mg QD in a maximally tolerated or maximally approved dose at screening
- •Participants categorized as very high or high CV risk, as defined below:
- •Very high risk participants with at least one of the following:
- •Documented ASCVD: ACS: Unstable angina or myocardial infarction, Stable angina, Coronary revascularization, Unequivocally documented ASCVD upon prior imaging, Stroke and Transient Ischaemic Attack (TIA), Peripheral artery disease (PAD)
- •Diabetes mellitus (DM) with target organ damage (defined as microalbuminuria, retinopathy, or neuropathy), or at least ≥ 3 major risk factors, or early onset of Type 1 DM of long duration (\< 20 years)
- •A calculated SCORE2 ≥ 7.5 % for age \< 50 years; SCORE2 ≥ 10 % for age 50-69 years; SCORE2-OP ≥ 15 % for age ≥ 70 years to estimate 10-year risk of fatal and non-fatal CVD
- •Pre-existing diagnosis of heterozygous familial hyper-cholesterolemia (HeFH) with ASCVD or with another major risk factor OR
- •High risk participants with at least one of the following:
- •Markedly elevated single risk factors, in particular total cholesterol \> 310 mg/dL, LDL-C \> 190 mg/dL, or blood pressure ≥ 180/110 mmHg
Exclusion Criteria
- •Acute coronary syndrome, ischemic stroke, peripheral arterial revascularization procedure or amputation due to atherosclerotic disease \< 4 months prior to screening visit or V
- •Planned or expected cardiac, cerebrovascular or peripheral artery surgery or coronary re-vascularization within 6 months after screening visit.
- •Heart failure NYHA class IV at screening or V
- •Participants on more than one other lipid-lowering drug on top of statin at screening visit.
- •Previous treatment with a mAb directed towards PCSK9 (e.g., evolocumab, alirocumab) or planned use after screening visit.
- •Previous treatment prior to screening with BPA within 90 days
- •Previous exposure to Inclisiran or any other non-mAb PCSK9-targeted therapy, either as an investigational or marketed drug.
Arms & Interventions
Inclisiran
Inclisiran treatment on top of background treatment (high intensity statin with/without ezetimibe)
Intervention: Inclisiran sodium
Bempedoic acid (BPA)
BPA treatment on top of background treatment (high intensity statin with/without ezetimibe)
Intervention: BPA
Outcomes
Primary Outcomes
Percent change from baseline in LDL-C levels
Time Frame: Baseline, Day 150
To demonstrate superiority of Inclisiran compared to BPA, in combination with standard of care (maximally tolerated HI statin dose +/- Ezetimibe) in reducing relative LDL-C levels at Day 150.
Secondary Outcomes
- Number of participants by individual responsiveness(Day 150)
- Percent change from baseline in LDL-C levels in patients with Ezetimibe(Baseline, Day 150)
- Percent change from baseline in LDL-C levels in patients without Ezetimibe(Baseline, Day 150)
- Absolute change from Baseline in LDL-C(Day 150)
- Percent change from Baseline in LDL-C levels(Between Day 90 and Day 150)
- Mean change from baseline in MMAS-8 over time(From Baseline up to Day 150)
- Mean change from Baseline in TSQM over time(From Baseline up to Day 150)
- Mean change from Baseline in SF-BPI over time(From Baseline up to Day 150)
- Proportion of participants with clinically significant change from Baseline in SF-BPI(At day 150)
- Percent change from Baseline in LDL-C levels(Baseline, from Day 30 up to Day 150)