A randomized, double-blind, placebo-controlled multicenter study to evaluate the effect of inclisiran on preventing major adverse cardiovascular events in high-risk primary prevention patients (VICTORION-1 PREVENT)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

4 Sep 2023 → ongoing

Decision date (initial)

2023-08-21

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy, Pharmacogenomic

To demonstrate the superiority of inclisiran compared to placebo in reducing the risk of 4P-MACE (composite of CV death, non-fatal MI, non-fatal ischemic stroke, and urgent coronary revascularization)

Secondary objectives 6

1. To demonstrate the superiority of inclisiran compared to placebo in reducing the risk of 3PMACE (composite of CV death, non-fatal MI, and non-fatal ischemic stroke).
2. To demonstrate the superiority of inclisiran compared to placebo in reducing the rate of total 4P-MACE (composite of CV death, non-fatal MI, non-fatal ischemic stroke, and urgent coronary revascularization)
3. To demonstrate the superiority of inclisiran compared to placebo in reducing the rate of total 3P-MACE (composite of CV death, non-fatal MI, and non-fatal ischemic stroke).
4. To demonstrate the superiority of inclisiran compared to placebo in reducing the risk of CV death.
5. To demonstrate the superiority of inclisiran compared to placebo in reducing the risk of all cause mortality.
6. To evaluate the safety and tolerability of inclisiran compared to placebo.

Conditions and MedDRA coding

Primary prevention of atherosclerotic cardiovascular disease (ASCVD)

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

Yes

IPD plan description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Written informed consent must be obtained before any assessment is performed
2. Male or female ≥40 but <80 years of age
3. At an increased risk for a first MACE (i.e., no prior major ASCVD event), defined as any one of the following: a. Evidence of atherosclerotic coronary artery disease (CAD) on computer tomography (CT) or invasive coronary angiogram defined as a coronary artery stenosis ≥20% but <50% in the left main coronary artery or stenosis ≥20% but <70% in any major epicardial coronary artery, or b. Coronary artery calcium (CAC) score obtained by CT-scan ≥100 Agatston units -determined at anytime before screening, or c. High 10-year ASCVD risk ≥20%, or d. Intermediate 10-year ASCVD risk 7.5% - <20% with at least 2 risk enhancing factors.
4. If on a background lipid lowering therapy (LLT), the dose should be stable for at least 4 weeks prior to the screening visit and the participant should be willing to remain on this background therapy for the entire duration of the study.
5. LDL-C ≥70 mg/dL (≥1.81 mmol/L) but <190 mg/dL (<4.91 mmol/L) at the screening visit.

Exclusion criteria 8

1. History of major ASCVD event defined as any one of the following: a. Acute coronary syndrome (ACS) in the 12 months prior to randomization, or b. Prior myocardial infarction at any time prior to randomization, or c. Prior ischemic stroke at any time prior to randomization, or d. Symptomatic peripheral artery disease (PAD) as evidenced by either intermittent claudication, previous revascularization, or amputation due to atherosclerotic disease at any time prior to randomization.
2. History of, or planned, ischemia-driven revascularization in a coronary or extracoronary arterial bed prior to randomization
3. Absence of coronary atherosclerosis on a CT angiogram or an invasive coronary angiogram in the 2 years prior to randomization
4. Coronary artery calcium (CAC) score of 0 obtained in the 2 years prior to randomization
5. Active liver disease or hepatic dysfunction
6. Previous, current, or planned treatment with a monoclonal antibody (mAb) directed toward proprotein convertase subtilisin/kexin type 9 (PCSK9) (e.g., evolocumab, alirocumab)
7. Pregnant or nursing (lactating) women
8. Women of childbearing potential unless they are using effective methods of contraception while taking study treatment which includes for 6 months after last study drug administration.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Time to the first occurrence of 4P-MACE

Secondary endpoints 7

1. Time to the first occurrence of 3P-MACE.
2. Times to the occurrences of CV death, nonfatal MI, non-fatal ischemic stroke, and urgent coronary revascularization (first and recurrent).
3. Times to the occurrences of CV death, nonfatal MI, and non-fatal ischemic stroke (first and recurrent).
4. Time to CV death.
5. Time to all-cause mortality.
6. Number of participants with SAEs.
7. Number of participants with AEs leading to study treatment discontinuation.

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel Town

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 34

Locations

20 EU/EEA countries · 414 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 211 files

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

Application history

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