Influence of Pelacarsen on Patients After Myocardial Infarction With High Lp(a) Values (PEMILA)

NCT04993664 | Withdrawn DMC

• 1 other identifier: PEMILA
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of study is to examine the relationship between lipid subfractions, inflammation and structural-functional properties of the arterial wall in patients after myocardial infarction with high lipoprotein (a) (Lp (a)) levels, to study genetic polymorphisms that determine lipid subfractions concentration on the functional and morphological properties of the arterial vascular wall in patients after myocardial infarction with high Lp (a) levels, to study the effect of pelacarsen on lipid subfractions, inflammation and structural-functional properties of arterial wall in patients after myocardial infarction with high Lp (a) levels and to study the influence of NOS-3 gene expression on the functional and morphological properties of the arterial vascular wall in the same patients. Impaired blood fat metabolism and chronic inflammation represent possible causes of atherosclerosis. Lp (a) is an independent risk factor for cardiovascular disease and a prognostic predictor in patients after myocardial infarction. Despite recommended screening for elevated Lp (a), there is no specific drug treatment approved to reduce cardiovascular risk through lowering Lp (a). Besides subtilisin-kexin convertase type 9 (PCSK9) inhibitors, antisense oligonucleotides (ASOs) are currently only therapeutic agents that significantly reduce serum Lp (a) concentration. Pelacarsen by using an ASO directed against the messenger ribonucleic acid (mRNA) of apolipoprotein (a), reduces the production of apolipoprotein (a) in the liver and thus, the level of Lp (a). However, there are no data on the relationship between Lp (a) values and polymorphisms for Lp (a), indicators of inflammation and impaired arterial function, and response to treatment with pelacarsen in patients after myocardial infarction with extremely high Lp (a) levels.

Conditions

Acute Coronary Syndrome; Lipoproteinemia; Inflammation; Genetic Polymorphisms

Keywords

Coronary heart disease; Acute coronary syndrome; Lipoprotein (a); Genetics; Secondary prevention; Endothelium; Inflammation; Genetic polymorphisms; NO synthetase; Dyslipidemia

Outcome Measures

Primary Outcomes (3)

• Ultrasound functional and morphological properties of the arterial wall and Lp (a) concentration

  Functional and morphological characteristics of arterial wall will correlate to Lp (a) concentrations.

  Baseline

• Concentration of Lp (a) and SNP in the LPA gene

  The serum concentration of Lp (a) will correlate with single nucleotide polymorphisms (SNP) in the LPA gene.

  Baseline

• The effect of pelacarsen on functional and morphological properties of arterial wall after 6 months

  Pelacarsen will improve functional and morphological properties of arterial wall. The investigators expect the improvements will be in correlation with the decrease of Lp (a) concentration.

  Baseline

Study Arms (2)

Pelacarsen group (TQJ230)

EXPERIMENTAL

The first group will receive 80 mg of pelacarsen every month subcutaneously for 6 months.

Drug: Pelacarsen (TQJ230)

Placebo group

PLACEBO COMPARATOR

The first group will receive 80 mg of placebo every month subcutaneously for 6 months.

Drug: Placebo

Interventions

Pelacarsen (TQJ230) DRUG

The first group will receive pelacarsen. Blood samples from all patients will be drawn for laboratory measurements and genetics determination. Ultrasound measurement of endothelium-dependent dilatation of the brachial artery and beta stiffness of carotid arteries will be measured.

Pelacarsen group (TQJ230)

Placebo DRUG

The second group will receive placebo. Blood samples from all patients will be drawn for laboratory measurements and genetics determination. Ultrasound measurement of endothelium-dependent dilatation of the brachial artery and beta stiffness of carotid arteries will be measured.

Placebo group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• concentration Lp (a) above 700 mg / L,
• optimally treated risk factors for cardiovascular events according to currently valid guidelines,
• history of myocardial infarction having occurred in the period 3 months to 10 years prior to the screening visit and / or
• history of ischemic stroke having occurred in the period 3 months to 10 years prior to the screening visit and / or
• clinically significant symptomatic peripheral artery disease.

You may not qualify if:

• uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg and / or diastolic blood pressure ≥ 100 mmHg),
• heart failure New York Heart Association (NYHA) class IV,
• history of malignancy of any organ system,
• history of hemorrhagic stroke or other major bleeding,
• platelet count \<140,000 per mm3,
• active liver disease or hepatic dysfunction (elevated transaminases above 3 times the norm, elevated bilirubin above 2 times the norm, elevated creatinine kinase above 3 times the norm),
• significant kidney disease (oGFR \<30 ml / min),
• pregnant or nursing women,
• life expectancy less than 5 years,
• unwillingness to participate or lack of availability for follow-up.

Sponsors & Collaborators

• University Medical Centre Ljubljana: lead

Study Sites (1)

University Medical Centre Ljubljana-Department of Vascular diseases and dept. of Cardiology

Ljubljana, 1000, Slovenia

Location

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MeSH Terms

Conditions

Acute Coronary Syndrome; Inflammation; Coronary Disease; Dyslipidemias

Interventions

pelacarsen

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Miran Šebeštjen, prof., PhD

  University Medical Centre Ljubljana (Slovenia)

  STUDY CHAIR

• Sabina Ugovšek, MD

  University Medical Centre Ljubljana (Slovenia)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, principal investigator

Study Record Dates

• First Submitted: July 30, 2021
• First Posted: August 6, 2021
• Study Start: October 1, 2021
• Primary Completion: June 30, 2022
• Study Completion: October 1, 2022
• Last Updated: January 3, 2022

Record last verified: 2021-12

Locations

SL (1)