Evaluation of efficacy and safety of early in hospital initiation of inclisiran treatment in patients with acute coronary syndromes

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 Mar 2026 → ongoing

Decision date (initial)

2026-02-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Novartis Pharma AG

External identifiers

EU CT number

2025-521670-34-00

WHO UTN

U1111-1322-7672

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy, Diagnosis, Dose response

To demonstrate the superiority of inclisiran treatment compared to placebo, when initiated before/at discharge, in combination with SoC (statin therapy +/- LLT or non-statin treatment in case of documented statin intolerance) on LDL-C reduction at Day 150

Secondary objectives 5

1. To assess the proportion of participants reaching pre-specified LDL-C targets (<70 mg/dL, <55 mg/dL, <100 mg/dL, ≥50% reduction from baseline) on inclisiran treatment compared to placebo, on top of SoC at Day 150
2. To assess the mean change (averaged over all post-baseline visits), and the change by visit, from baseline in LDL-C for participants receiving inclisiran treatment compared to placebo, on top of SoC
3. To assess the change of PCSK9 from baseline to Day 150 in participants on inclisiran treatment compared to placebo, on top of SoC
4. To assess the change in plasma lipoproteins and triglycerides from baseline to Day 150 in participants on inclisiran treatment compared to placebo, on top of SoC
5. To assess overall safety and tolerability of inclisiran

Conditions and MedDRA coding

Acute coronary syndrome (ST-elevation myocardial infarction [STEMI] or non-ST-elevation myocardial infarction [NSTEMI]) of recent onset.

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Signed informed consent must be obtained prior to participation in the study.
2. Males and females, ≥18 years of age at the time of providing written informed consent.
3. Ability to understand the study's requirements and provide informed consent and comply with all required study procedures.
4. Hospitalization for an ACS event (STEMI or NSTEMI).
5. Receiving treatment for the qualifying ACS event, according to clinical judgement, by means of medical treatment alone or percutaneous coronary revascularization.
6. Had a successful PCI (with or without stent) for the qualifying event, if PCI is required.
7. LDL-C value at the Screening visit measured by the local lab of: • LDL-C ≥70 mg/dL in participant previously treated with high-intensity statin (atorvastatin ≥40 mg/day or rosuvastatin ≥20 mg/day) or equivalent as per national guidelines and local regulation for at least 4 weeks before screening or • LDL-C ≥100 mg/dL in participant previously treated with low/moderate-intensity statin for at least 4 weeks before screening or • LDL-C ≥125 mg/dL in participant previously not treated with statins for at least 4 weeks before screening, or who never received statins (including statin intolerant participants).
8. The participant must have a Baseline fasting LDL-C ≥70 mg/dL (local lab assessment) to be eligible for randomization.
9. Randomization within 7 days (≤ 7 days) following hospital admission for the qualifying ACS event and before/at discharge.

Exclusion criteria 11

1. Participant who is clinically unstable during hospitalization for the qualifying ACS event, defined by any of the following events within 24 hours prior to randomization: • Hemodynamic instability: hypotension, defined as sustained systolic blood pressure of <90 mmHg due to cardiac failure with associated symptoms requiring inotropes • Arrhythmic events: Ventricular storm (e.g., torsade, ventricular tachycardia, ventricular flutter) • Cardiogenic shock or mechanical complication of myocardial infarction • New York Heart Association (NYHA) class IV heart failure • Left ventricular ejection fraction <20% at randomization (after all treatment procedures, based on the latest assessment of the LVEF using invasive or non-invasive assessment modalities) • Uncontrolled severe hypertension: systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg prior to randomization despite antihypertensive therapy.
2. Participant who has undergone or is scheduled to undergo CABG for treatment of the qualifying ACS event.
3. Active liver disease defined as: (i) any known current infectious, neoplastic, or metabolic pathology of the liver or (ii) ALT elevation >3x ULN, or AST elevation >3x ULN, or total bilirubin elevation >2x ULN (except participant with Gilbert’s syndrome) at the Screening visit, in the context of an ACS, and assessed as related to the index event and/or treatment procedures (such as PCI). Eligibility will be based on Investigator’s judgement for participant who will be randomized.
4. Renal insufficiency (eGFR <30 mL/min/1.73m2) at the Screening visit.
5. Fasting triglycerides value >400 mg/dL (4.52 mmol/L; assessed by local labs) at randomization visit.
6. Participant, who based on the Investigator's judgement, could reach the LDL-C target value of <55 mg/dL after 4 weeks on statin treatment only.
7. Secondary hypercholesterolemia (based on medical history).
8. Homozygous familial hypercholesterolemia (based on medical history).
9. Participant on apheresis at Screening visit.
10. Ongoing or medical history of myopathy at the Screening visit.
11. CK values ≥5x ULN at Screening visit and confirmed by repeat test during Screening (local lab), in the context of an ACS, and assessed as related to the index event and/or treatment procedures (such as PCI) eligibility will be based on Investigator’s judgement for participant who will be randomized (who will be switched to or initiated on the protocol-specified dose of high-intensity statin of atorvastatin ≥40 mg QD or rosuvastatin ≥20 mg QD). Unless a more stringent CK value threshold is mandated by a local regulatory authority (e.g., ≥3x ULN in Korea according to MFDS internal guideline).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percent change in LDL-C from baseline to Day 150

Secondary endpoints 5

1. • Participants achieving LDL-C <70 mg/dL (yes, no) at Day 150 • Participants achieving LDL-C <55 mg/dL (yes, no) at Day 150 • Participants achieving LDL-C <100 mg/dL (yes, no) (among the subset of participants with LDL-C ≥100 mg/dL at baseline) at Day 150 • Participants achieving ≥50% reduction from baseline in LDL-C (yes, no) at Day 150
2. • Percent change from baseline to mean LDL-C over the double-blind treatment period (averaged over all post-baseline visits) • Absolute change from baseline to mean LDL-C over the double-blind treatment period (averaged over all post-baseline visits) • Percent change in LDL-C from baseline to Day 30 and Day 90 • Absolute change in LDL-C from baseline to Day 30, Day 90 and Day 150
3. Percent change and absolute change in PCSK9 from baseline to Day 30, Day 90 and Day 150
4. Percent change and absolute change from baseline in: apoB, VLDL, non-HDLC, HDL-C, total cholesterol and triglycerides at Day 150
5. Number and percentage of participants experiencing treatment emergent AEs or SAEs

Investigational products

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

Test 1

Placebo 1

Auxiliary 8

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel

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 9

Locations

5 EU/EEA countries · 36 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 31 files

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

Application history

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