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

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma GmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

21 Jun 2024 → 2 Jan 2026

Decision date (initial)

2024-05-28

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Novartis Pharma GmbH (ORG-100000596)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

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 objectives 9

1. To demonstrate superiority of Inclisiran compared to BPA, in patients on maximally tolerated HI statin dose without Ezetimibe in relative reduction of LDL-C levels at Day 150.
2. To demonstrate superiority of Inclisiran compared to BPA, in patients on maximally tolerated HI statin dose with Ezetimibe in reducing relative LDL-C levels at Day 150.
3. Explore the effect of Inclisiran compared to BPA on the individual responsiveness of participants.
4. To assess efficacy of Inclisiran compared to BPA in reducing LDL-C (absolute reduction).
5. To assess efficacy of Inclisiran compared to BPA in reducing LDL-C [time-adjusted percent change] starting Day 30 and up to Day 150.
6. To assess efficacy of Inclisiran compared to BPA in reducing LDL-C [time-adjusted percent change] between Day 90 and Day 150.
7. Assess adherence to lipid-lowering therapy over time in participants receiving Inclisiran compared to BPA on top of maximally tolerated HI statins (+/- Ezetimibe) using the Morisky 8-Item Medication Adherence Scale (MMAS-8).
8. Assess effect of Inclisiran compared to BPA regarding treatment satisfaction using the Treatment Satisfaction Questionnaire for Medication (TSQM v. II).
9. To assess the effect of Inclisiran compared to BPA regarding pain-related quality of life using the Short Form Brief Pain Inventory (SF-BPI).

Conditions and MedDRA coding

Hypercholesterolemia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Fasting LDL-C ≥ 70 mg/dL at screening
2. 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
3. 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 • Pre-existing diagnosis of HeFH without other major risk factors • DM without target organ damage (defined as microalbuminuria, retinopathy, or neuropathy), with DM duration ≥ 10 years or other additional risk factors • Moderate chronic kidney disease (eGFR 30-59 mL/min/1.73m2) • A calculated SCORE2 2.5 to < 7.5 % for age < 50 years; SCORE2 5 to < 10 % for age 50-69 years; SCORE2-OP 7.5 to < 15 % for age ≥ 70 years to estimate 10-year risk of fatal and non-fatal CVD as defined by the cardiovascular risk categories in the 2019 ESC/EAS guideline (Mach et al 2020), and updated SCORE2 and SCORE2-OP (Hageman et al 2021, de Vries et al 2021, Visseren et al 2021). Further details for documented ASCVD will be provided in the protocol
4. Fasting triglyceride < 400 mg/dL at screening

Exclusion criteria 7

1. Acute coronary syndrome, ischemic stroke, peripheral arterial revascularization procedure or amputation due to atherosclerotic disease < 4 months prior to screening visit or V1
2. Planned or expected cardiac, cerebrovascular or peripheral artery surgery or coronary re-vascularization within 6 months after screening visit
3. Heart failure NYHA class IV at screening or V1
4. Participants on more than one other lipid-lowering drug on top of statin at screening visit
5. Previous treatment with a mAb directed towards PCSK9 (e.g., evolocumab, alirocumab) or planned use after screening visit
6. Previous treatment prior to screening visit with BPA within 90 days
7. Previous exposure to Inclisiran or any other non-mAb PCSK9-targeted therapy, either as an investigational or marketed drug

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percent change from baseline in LDL-C levels at day 150

Secondary endpoints 9

1. Percent change from baseline in LDL-C levels at day 150
2. Individual responsiveness of participants defined through on treatment LDL-C levels of < 55 mg/dL (very high-risk subjects) and < 70 mg/dL (high risk subjects) at Day 150
3. Absolute change from Baseline in LDL-C at day 150
4. Percent change from baseline in LDL-C levels between Day 30 up to Day 150
5. Percent change from baseline in LDL-C levels between Day 90 and Day 150
6. Mean change from BL in MMAS-8 over time
7. Mean change from BL in TSQM over time
8. Mean change from BL in SF-BPI over time
9. Proportion of participants with clinically significant change from BL [MCID of 2 points] in SF-BPI at Day 150

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma GmbH

Sponsor organisation

Novartis Pharma GmbH

Address

Sophie-Germain-Strasse 10

City

Nuremberg

Postcode

90443

Country

Germany

Scientific contact point

Organisation

Novartis Pharma GmbH

Contact name

Medizinischer Infoservice (MCC)

Public contact point

Organisation

Novartis Pharma GmbH

Contact name

Medizinischer Infoservice (MCC)

Third parties 3

Locations

1 EU/EEA country · 62 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 28 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications