Aterosklerotik Kardiyovasküler Hastalığı Olan Hastalarda Inclisiran ile Bempedoik Asidin LDL-Kolesterol Düşürücü Etkisini Karşılaştıran Çalışma

Sade dilde özet

Bu Faz 4 (Phase 4), açık etiketli, randomize çalışma, kardiyovasküler olay riski yüksek ve çok yüksek olan 400 yetişkinde inclisiran (PCSK9 inhibitörü, siRNA) ile bempedoik asidin (BPA, ACL inhibitörü küçük molekül) etkililiğini doğrudan karşılaştırmaktadır. Katılımcılar, tolere edebildikleri en yüksek dozda yüksek yoğunluklu statin (ve gerekirse ezetimib) kullanmasına rağmen LDL kolesterolü ≥70 mg/dL olan kişilerdir; risk sınıflandırması 2019 ESC/EAS dislipidemi kılavuzlarına göre yapılmıştır. Çalışmanın gerekçesi, Almanya'da bempedoik asidin enjeksiyonluk seçeneklerden önce önerilmesi nedeniyle iki tedaviyi doğrudan karşılaştıran bilimsel veri üretme ihtiyacıdır.

Yukarıdaki özet, resmî kaydın sade dile aktarılmış halidir. Orijinal İngilizce başlık referans için gösterilir.

Deney bilgileri

Faz

Faz 4 (Phase 4)

Durum

Tamamlandı

Sponsor

Novartis Pharmaceuticals

Müdahale

Inclisiran sodium (PCSK9 inhibitor, siRNA), BPA (small molecule, ACL inhibitor)

Başlangıç

21.06.2024

Tahmini bitiş

02.01.2026

Ülkeler

Germany

İlgili genler

Merkezler

• Mannheim, Germany
• Stuttgart, Germany
• Lichtenfels, Germany
• Muehldorf Am Inn, Germany
• Regensburg, Germany
• Sulzbach-Rosenberg, Germany
• Frankfurt am Main, Germany
• Frankfurt am Main, Germany
• Frankfurt am Main, Germany
• Offenbach, Germany
• Göttingen, Germany
• Cologne, Germany
• Essen, Germany
• Löhne, Germany
• Kaiserslautern, Germany
• Saint Ingbert, Germany
• Dresden, Germany
• Dresden, Germany
• Leipzig, Germany
• Jena, Germany
• Aachen, Germany
• Bad Homburg, Germany
• Bad Krozingen, Germany
• Bad Oeynhausen, Germany
• Bamberg, Germany
• Berlin, Germany
• Berlin, Germany
• Berlin, Germany
• Bochum, Germany
• Bochum, Germany
• Bremen, Germany
• Dessau, Germany
• Dresden, Germany
• Erfurt, Germany
• Essen, Germany
• Essen, Germany
• Falkensee, Germany
• Gladbeck, Germany
• Hamburg, Germany
• Hamburg, Germany

+15

Uygunluk kriterleri

Kriterler ClinicalTrials.gov kaydından orijinal İngilizce haliyle alınmıştır. Uygunluk kararını yalnızca deneyi yürüten ekip verebilir.

Inclusion Criteria:

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 factor
     * 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:

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 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.