New therapies for the treatment of Fabry disease are being developed and approved. One main focus of our clinical research is to monitor the therapeutic effect of these new drugs after their approval. To this end, we conduct non-interventional observational studies in a so-called "real-world design", as this type of study best reflects the course of the disease in patients in everyday clinical practice.

German observational multicenter study of patients with Fabry disease under enzyme replacement therapy with pegunigalsidase-alfa (GoPEG)

Description

A prospective Germany-wide multicenter observational study

Investigational sites

Fabry disease center Münster, University Hospital Münster (principal investigator)

Fabry disease center Würzburg, University Hospital Würzburg

Fabry disease center Berlin - Charité - Universitätsmedizin Berlin, Campus Mitte (CCM)

Fabry disease center Cologne, University Hospital Cologne

Fabry disease center Hamburg, University Hospital Hamburg

Fabry disease center Hannover, University Hospital Hannover

Fabry disease center Mainz, University Medical Center Mainz

Internal medicine practice, Müllheim

Background and rationale

Pegunigalsidase-alfa, a recently approved PEGylated, covalently cross-linked form of α-galactosidase A developed as an enzyme replacement therapy (ERT) for Fabry disease (FD), has been designed to increase plasma half-life and decrease immunogenicity, thereby potentially improving efficacy compared to available ERT products. The rationale of the current project is that disease progression in patients with Fabry disease underpegunigalsidase-alfa can be stabilized comparable to patients on current ERT, leading to validation of phase 3 clinical trials and translation of these previous results to a nationwide study in Germany.

Study objectives

Pegunigalsidase-alfa could represent an advance in ERT for FD due to its unique pharmacokinetics and apparently low immunogenicity. The aim of the study is to document long-term data on treatment with pegunigalsidase-alfa under "real-life" conditions. 60 patients with FD (treatment-naive or pre-treated with agalsidase-alfa or agalsidase-beta) will be recruited in 8 German Fabry centers. The treatment duration will be 2 years. All patients will be followed up by the Fabry expert centers listed above.

Course of the study

The European guidelines and recommendations for the treatment of patients with FD recommend a consistent examination of affected patients every 12 months (Biegstraaten et al. 2015). As treatment with pegunigalsidase-alfa is a recently approved therapy option and the current literature is scarce, the examination interval should be shortened once from 12 to six months in the first year of treatment. For this reason, five visits of the included patients to the participating centers will be documented during the study period:

Visit 1: T-1= retrospective evaluation of the patient’s disease state (including cerebral MRI investigation, and measurements of α-Gal A-activity and lyso-Gb3) at -6 months,

Visit 2: T0= baseline (including cerebral MRI investigation), therapy initiation/switch

Visit 3: T1 = 6 months follow-up,

Visit 4: T2 = 12 months follow-up,

Visit 5: T3 = 24 months follow-up (including cerebral MRI investigation)

Echocardiographic analyses will be performed by a cardiological core center. MRI analyses will be performed by a core neuroimaging working group. Compact discs of the echocardiographic imaging and MRI data from all participating centers will be collected.

To analyze the potentially reduced immunogenicity of pegunigalsidase-alfa full spectrum of biochemical analysis will be performed including ELISA-based determination of antibody titers and antibody-enzyme complexes and antibody-mediated ERT inhibition assays and titrations.

Funding

A full funding of this study is provided by Chiesi GmbH, Germany.