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Dual PCSK9 Inhibition With Inclisiran and Alirocumab in Secondary Prevention (PCSK9-DUO)

28 maggio 2026 aggiornato da: University Medical Centre Ljubljana

PCSK9-DUO Trial: Dual PCSK9 Inhibition With Inclisiran and Alirocumab in Patients With High Cardiovascular Risk in Secondary Prevention

This study will evaluate the effectiveness and safety of combining two different types of PCSK9 inhibitors, inclisiran and alirocumab, in patients with high cardiovascular risk who are unable to tolerate statins.

Lowering low-density lipoprotein cholesterol (LDL-C) is essential to reduce the risk of cardiovascular events. While PCSK9 inhibitors are effective, many patients treated with a single agent do not reach recommended LDL-C targets, especially those who cannot take statins.

Inclisiran and alirocumab reduce LDL-C through different mechanisms. Inclisiran decreases the production of PCSK9 in the liver, while alirocumab binds circulating PCSK9 in the blood. Combining these therapies may lead to a greater reduction in LDL-C levels.

In this randomized, open-label clinical trial, approximately 60 patients in secondary prevention will be assigned to one of three groups: inclisiran alone, alirocumab alone, or a combination of both treatments. Patients will be followed for 9 months with regular clinical and laboratory assessments.

The main goal of the study is to determine whether combination therapy leads to greater LDL-C reduction compared to each treatment alone. Secondary objectives include assessing the proportion of patients achieving target LDL-C levels and evaluating treatment safety and tolerability.

Panoramica dello studio

Stato

Reclutamento

Condizioni

Intervento / Trattamento

Descrizione dettagliata

Atherosclerotic cardiovascular disease remains a leading cause of morbidity and mortality, with elevated low-density lipoprotein cholesterol (LDL-C) being a major modifiable risk factor. Despite the availability of effective lipid-lowering therapies, a substantial proportion of high-risk patients fail to achieve recommended LDL-C targets, particularly those with statin intolerance.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a key role in regulating LDL receptor degradation and plasma LDL-C levels. Pharmacological inhibition of PCSK9 has emerged as an effective strategy to reduce LDL-C. Two distinct therapeutic approaches are currently available: monoclonal antibodies (such as alirocumab), which neutralize circulating PCSK9, and small interfering RNA therapies (such as inclisiran), which reduce hepatic production of PCSK9.

Although both approaches have demonstrated efficacy, real-world data suggest that monotherapy may not be sufficient for many high-risk patients. The combination of these two mechanisms may provide additive or synergistic effects, leading to more profound LDL-C reduction.

This study is designed as a prospective, randomized, open-label, monocentric clinical trial. Approximately 60 adult patients in secondary prevention with statin intolerance and elevated LDL-C (2.5-5.0 mmol/L) will be enrolled. Participants will be randomized in a 1:1:1 ratio to receive inclisiran, alirocumab, or a combination of both therapies.

Inclisiran will be administered subcutaneously at baseline and at 3 months. Alirocumab will be administered subcutaneously at a dose of 300 mg every 4 weeks in a supervised clinical setting. Patients will be followed for 9 months, with study visits at baseline, 1 month, 3 months, 6 months, and 9 months.

The primary endpoint is the percentage change in LDL-C from baseline at 3 and 9 months. Secondary endpoints include the proportion of patients achieving guideline-recommended LDL-C targets, changes in other lipid parameters, and safety outcomes including adverse events and treatment tolerability.

This study aims to provide proof-of-concept evidence on the effectiveness and safety of dual PCSK9 inhibition using complementary mechanisms, with potential implications for improving lipid management in high-risk, statin-intolerant patients.

Tipo di studio

Interventistico

Iscrizione (Stimato)

60

Fase

  • Fase 4

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Contatto studio

Backup dei contatti dello studio

Luoghi di studio

  • Slovenia
      • Ljubljana, Slovenia, 1000
        • Reclutamento
        • University Medical Centre Ljubljana
        • Contatto:
        • Contatto:
        • Investigatore principale:
          • Jan Kafol, MD
        • Sub-investigatore:
          • Zlatko Fras, MD, PhD
        • Sub-investigatore:
          • Borut Jug, MD, PhD
        • Sub-investigatore:
          • Marko Novakovic, MD, PhD

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

  • Adulto
  • Adulto più anziano

Accetta volontari sani

No

Descrizione

Inclusion Criteria:

  • Adults aged ≥18 years
  • Established atherosclerotic cardiovascular disease (secondary prevention), defined as prior cardiovascular events or imaging-confirmed atherosclerosis (e.g., coronary artery disease on angiography or CT, carotid plaque on ultrasound, or peripheral arterial disease).
  • Eligible for PCSK9 inhibitor therapy according to national clinical criteria
  • Fasting LDL cholesterol ≥2.5 mmol/L and ≤5.0 mmol/L at screening
  • Documented statin intolerance or contraindication to statin therapy
  • On stable background lipid-lowering therapy (including ezetimibe if applicable) for at least 4 weeks prior to enrollment
  • Able and willing to provide written informed consent

Exclusion Criteria:

  • Eligibility for PCSK9 inhibitor therapy solely based on elevated lipoprotein(a) >1000 mg/L with LDL-C below inclusion threshold
  • Prior use of any PCSK9 inhibitor (alirocumab, evolocumab or inclisiran) before enrollment
  • Planned initiation or modification of lipid-lowering therapy during the study period
  • Known homozygous familial hypercholesterolemia
  • Active liver disease or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3× upper limit of normal
  • Severe renal impairment (eGFR <30 mL/min/1.73 m²)
  • Active malignancy or life expectancy <1 year
  • Pregnancy, breastfeeding, or women of childbearing potential not using effective contraception
  • Known hypersensitivity to inclisiran, alirocumab, or any of their excipients
  • Participation in another interventional clinical trial within 30 days prior to enrollment
  • Any condition that, in the opinion of the investigator, would interfere with study participation or interpretation of results

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: Inclisiran
Participants receive inclisiran 284 mg administered subcutaneously at baseline and at 3 months. Patients will be followed for 9 months with scheduled clinical and laboratory assessments.
Droga: Inclisiran
Participants receive inclisiran 284 mg administered subcutaneously at baseline (Day 0) and at Month 3.
Sperimentale: Alirocumab
Participants receive alirocumab 300 mg administered subcutaneously every four weeks in a supervised clinical setting for 9 months. Patients will be followed with regular clinical and laboratory assessments.
Droga: Alirocumab
Participants receive alirocumab 300 mg administered subcutaneously every four weeks in a supervised clinical setting for 9 months.
Sperimentale: Inclisiran Plus Alirocumab
Participants receive inclisiran 284 mg administered subcutaneously at baseline and at 3 months, in combination with alirocumab 300 mg administered subcutaneously every four weeks in a supervised clinical setting for 9 months. Patients will be followed with scheduled clinical and laboratory assessments.
Droga: Inclisiran
Participants receive inclisiran 284 mg administered subcutaneously at baseline (Day 0) and at Month 3.
Droga: Alirocumab
Participants receive alirocumab 300 mg administered subcutaneously every four weeks in a supervised clinical setting for 9 months.

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Percent Change in LDL-C From Baseline
Lasso di tempo: 3 months and 9 months
Percent change in low-density lipoprotein cholesterol (LDL-C) from baseline at 3 months and 9 months, comparing inclisiran, alirocumab, and combination therapy.
3 months and 9 months

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Trajectory of Percent Change in LDL-C From Baseline
Lasso di tempo: 1, 3, 6, and 9 months
Percent change in LDL-C from baseline at each scheduled follow-up visit to assess early response and durability of treatment effect.
1, 3, 6, and 9 months
Proportion of Participants Achieving LDL-C <1.4 mmol/L
Lasso di tempo: 1, 3, 6, and 9 months
Proportion of participants achieving LDL-C below 1.4 mmol/L at each scheduled follow-up visit.
1, 3, 6, and 9 months
Change in Apolipoprotein B From Baseline
Lasso di tempo: 1, 3, 6, and 9 months
Absolute and percent change in apolipoprotein B from baseline.
1, 3, 6, and 9 months
Change in Non-HDL Cholesterol From Baseline
Lasso di tempo: 1, 3, 6, and 9 months
Absolute and percent change in non-HDL cholesterol from baseline.
1, 3, 6, and 9 months
Change in Lipoprotein(a) From Baseline
Lasso di tempo: 1, 3, 6, and 9 months
Absolute and percent change in lipoprotein(a) from baseline.
1, 3, 6, and 9 months
Incidence of Adverse Events
Lasso di tempo: Up to 9 months
Number and proportion of participants experiencing any adverse event during the study.
Up to 9 months
Treatment Discontinuation Due to Adverse Events
Lasso di tempo: Up to 9 months
Proportion of participants who discontinue assigned study treatment because of adverse events.
Up to 9 months
Change in Circulating PCSK9 Concentration From Baseline
Lasso di tempo: 1, 3, 6, and 9 months
Absolute and percent change in circulating PCSK9 concentration to assess pharmacodynamic effects of treatment.
1, 3, 6, and 9 months
Change From Baseline in LDL-C Concentration
Lasso di tempo: 1, 3, 6, and 9 months
Absolute change in LDL-C concentration compared with baseline at each scheduled follow-up visit.
1, 3, 6, and 9 months
Change From Baseline in Total Cholesterol, HDL Cholesterol, and Triglyceride Concentrations
Lasso di tempo: 1, 3, 6, and 9 months
Change in serum total cholesterol, HDL cholesterol, and triglyceride concentrations compared with baseline values.
1, 3, 6, and 9 months

Altre misure di risultato

Misura del risultato
Misura Descrizione
Lasso di tempo
Incidence of Injection-Site Reactions
Lasso di tempo: Up to 9 months
Number and proportion of participants experiencing injection-site reactions.
Up to 9 months
Treatment Adherence
Lasso di tempo: Up to 9 months
Adherence to assigned therapy assessed by documented administration of inclisiran and alirocumab.
Up to 9 months
Major Adverse Cardiovascular Events
Lasso di tempo: Up to 9 months
Exploratory assessment of cardiovascular death, myocardial infarction, stroke, urgent coronary revascularization, or hospitalization for unstable angina.
Up to 9 months

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

University Medical Centre Ljubljana

Investigatori

  • Cattedra di studio: Zlatko Fras, MD, PhD, University Medical Centre Ljubljana
  • Investigatore principale: Jan Kafol, MD, University Medical Centre Ljubljana

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Effettivo)

18 maggio 2026

Completamento primario (Stimato)

1 maggio 2027

Completamento dello studio (Stimato)

1 giugno 2027

Date di iscrizione allo studio

Primo inviato

5 maggio 2026

Primo inviato che soddisfa i criteri di controllo qualità

5 maggio 2026

Primo Inserito (Effettivo)

12 maggio 2026

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

2 giugno 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

28 maggio 2026

Ultimo verificato

1 maggio 2026

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • UKC-PCSK9-DUO

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

SÌ

Descrizione del piano IPD

De-identified individual participant data (IPD) underlying the results reported in this study will be made available upon reasonable request to qualified researchers. Data sharing will be subject to approval by the study investigators and institutional policies, and will require a data use agreement to ensure appropriate use and protection of participant confidentiality.

Periodo di condivisione IPD

Individual participant data and supporting documents will be available beginning 6 months following publication of the primary results and ending 5 years after publication.

Criteri di accesso alla condivisione IPD

De-identified individual participant data, study protocol, statistical analysis plan, and informed consent form will be made available to qualified researchers who provide a methodologically sound research proposal. Data access will be subject to approval by the study investigators and the sponsoring institution. A data use agreement will be required to ensure appropriate use of the data and protection of participant confidentiality. Requests for access should be directed to the principal investigator.

Tipo di informazioni di supporto alla condivisione IPD

  • STUDIO_PROTOCOLLO
  • LINFA
  • ICF

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

No

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

prodotto fabbricato ed esportato dagli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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