Adverse events and inefficacy of PCSK9 Inhibition with evolocumab or alirocumab in hypercholesTeraemic pAtients. (AKITA)

Study identification

• PURI:
  https://redirect.ema.europa.eu/resource/33788
• EU PAS number:
  EUPAS33787
• Study ID:
  33788
• Official title and acronym:
  Adverse events and inefficacy of PCSK9 Inhibition with evolocumab or alirocumab in hypercholesTeraemic pAtients. (AKITA)
• DARWIN EU® study:
  No
• Study countries:
  Netherlands
• Study description:
  Rationale: Patients with elevated plasma levels of Low Density Lipoprotein-cholesterol (LDLC) are at increased risk for cardiovascular disease. Monoclonal antibodies against proprotein convertase subtilisin/kexin type 9 (PCSK9) have been shown to result in LDL-C lowering and CVD risk reduction. This relatively new class of drugs has not been widely studied in daily clinic, and anecdotal evidence has suggested that a small proportion of patients do either not respond to this medication or suffer from side effects.Objective: To describe the characteristics of patients with either low PCSK9 inhibitor therapy efficacy or adverse effects, based on the interpretation of the treating physician.Study design: Multi-center case-control studyStudy population: 20 subjects in whom PCSK9 inhibitor therapy has been shown to result less than 30 percent reduction in LDL-C as assessed by the referring physician, and 20 subjects in whom PCSK9 inhibitor therapy was discontinued due to adverse effects will be compared with 40 controls in whom PCSK9 inhibitor therapy is considered to be successful.Main study parameters/endpoints: This is a descriptive study in which we will assess differences in clinical parameters (e.g., patient anthropometrics between patients and controls, and identify possible (novel) mutations in the PCSK9 gene possibly interfering with PCSK9 inhibitor therapy, variants in other lipid metabolism or PCSK9 related genes, assess gene expression, (semi)quantification of proteins (PCSK9 protein, other proteins involved in lipid metabolism, proteomics), PCSK9 antibody concentrations, antidrug antibodies, and (semi-) quantification of metabolites (e.g. lipids/fatty acids).
• Study status:
  Planned

Research institutions and networks

Institutions

Amsterdam UMC

Erasmus Medical Centre Rotterdam

Rotterdam Erasmus UMC

Study timelines

Date when funding contract was signed

Planned: 15/10/2018

Study start date

Planned: 15/10/2018

Date of final study report

Planned: 31/12/2020

Sources of funding

Other

More details on funding

NWO

Regulatory

• Was the study required by a regulatory body?:
  No
• Is the study required by a Risk Management Plan (RMP)?:
  Not applicable