Acute Coronary Syndrome
Conditions
Keywords
KJX839, Acute Coronary Syndrome, ACS, NSTEMI, STEMI, Inclisiran, LDL-C, Hyperlipidemia
Brief summary
The purpose of this trial is to learn about the effects of inclisiran in people with serious heart conditions (acute coronary syndromes), when this treatment is started early after hospital admission. To do this, researchers will test the effects of inclisiran compared to placebo, when given with standard treatment.
Detailed description
This is a multicenter, prospective, randomized, double-blind, placebo-controlled, two arms, parallel groups clinical trial in participants experiencing an ACS (STEMI or NSTEMI) of recent onset. The study drug treatment (inclisiran/placebo) will be initiated at randomization (Day 1) and before discharge. The study consists of: 1. Screening visit within 7 days (≤ 7 days) from hospital admission. Screening visit might happen at hospital admission day or any time after hospital admission and before randomization (Day 1). 2. Randomization/Baseline visit (Day 1) within 7 days (≤ 7 days) from hospital admission and before or at day of discharge. The discharge can happen any time after randomization and first study drug administration (Day 1). 3. Double-blinded treatment period (150 days). 4. Scheduled safety calls in between visits during the double-blind treatment period (they do not replace on-site visits) 5. Safety Follow-up call (30 days after EOS visit) Screening and randomization visits must happen during the in-hospital phase, within 7 days (≤ 7 days), and before discharge. The Screening period, of no more than 6 days after the date of hospital admission, will be used to determine if patients qualify to enter the double-blind treatment phase of the study. Screening and Randomization/Day 1 visits cannot occur on the same day. The overall study duration is 150 days.
Interventions
DRUGPlacebo
The participants will receive placebo subcutaneous at randomization (Day 1, Baseline visit) and Day 90
DRUGInclisiran
The participants will receive Inclisiran sodium 300 mg subcutaneous at randomization (Day 1, Baseline visit) and Day 90
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Participant eligible for inclusion in this study must meet all the following criteria: At Screening: 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 study's requirements and provide informed consent and comply with all required study procedures. 4. Hospitalization for a 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 a PCI was required. 7. LDL-C values measured by the local lab either at the Screening visit or results from local lab tests performed prior to ICF signature, strictly as part of the routine clinical practice in this emergency ACS setting and not older than 2 days 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 ≥80 mg/dL in participant previously treated with low/moderate-intensity statin for at least 4 weeks before screening or * LDL-C ≥100 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). At Randomization: 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
Participant meeting any of the following criteria is not eligible for inclusion in this study. Only for Japan: For
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent change in LDL-C | From baseline to Day 150 | To demonstrate the superiority of inclisiran treatment compared to placebo, when initiated before/at discharge, in combination with standard of care (SoC) (statin therapy +/- LLT (Lipid Lowering Therapy) or non-statin treatment in case of documented statin intolerance) on LDL-C reduction at Day 150 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Participants achieving LDL-C <70 mg/dL (yes, no) | At Day 90 and Day 150 | To assess the proportion of participants reaching pre-specified LDL-C target (\<70 mg/dL) on inclisiran treatment compared to placebo, on top of SoC |
| Participants achieving LDL-C <55 mg/dL (yes, no) | At Day 90 and Day 150 | To assess the proportion of participants reaching pre-specified LDL-C target (\<55 mg/dL) on inclisiran treatment compared to placebo, on top of SoC |
| Participants achieving LDL-C <100 mg/dL (yes, no) (among the subset of participants with LDL-C ≥100 mg/dL at baseline) | At Day 90 and Day 150 | To assess the proportion of participants reaching pre-specified LDL-C target (\<100 mg/dL) on inclisiran treatment compared to placebo, on top of SoC |
| Participants achieving ≥50% reduction from baseline in LDL-C (yes, no) | At Day 90 and Day 150 | To assess the proportion of participants reaching pre-specified LDL-C target (≥50% reduction from baseline) on inclisiran treatment compared to placebo, on top of SoC |
| Percent change from baseline to mean LDL-C over the double-blind treatment period (averaged over all post-baseline visits) | From baseline to Day 30, Day 90 and Day 150 | 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 |
| Absolute change from baseline to mean LDL-C over the double-blind treatment period (averaged over all post-baseline visits) | From baseline to Day 30, Day 90 and Day 150 | 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 |
| Percent change in LDL-C | From baseline to Day 30 and Day 90 | 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 |
| Absolute change in LDL-C | From baseline to Day 30, Day 90 and Day 150 | 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 |
| Percent change and absolute change in PCSK9 | From baseline to Day 30, Day 90 and Day 150 | To assess the change of PCSK9 from baseline to Day 150 in participants on inclisiran treatment compared to placebo, on top of SoC |
| Percent change and absolute change from baseline in: apoB, VLDL, non-HDLC, HDL-C, total cholesterol and triglycerides | At Day 150 | 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 |
Countries
Argentina, Australia, Canada, China, France, Germany, Hong Kong, Hungary, India, Japan, Poland, South Korea, Spain, Switzerland
Contacts
CONTACTNovartis Pharmaceuticals
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Outcome results
None listed