A Multi-Country Observational Study of Safety and Effectiveness of Elfabrio® in Fabry Patients (MODERN)

A multi-centre, multi-country, observational, non-interventional, retrospective and prospective (hybrid) study among Fabry disease participants treated with pegunigalsidase alfa (Elfabrio®) in routine clinical care.

Study Overview

• Status: Recruiting
• Conditions: Fabry Disease
• Intervention / Treatment: Drug: Pegunigalsidase-alfa

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Medical Information Chiesi; Phone Number: (888) 661-9260; Email: us.medical@chiesi.com

Study Locations

• Slovenia
  • Slovenj Gradec, Slovenia, 2380
    • Recruiting
    • General Hospital Slovenj Gradec
    • Contact: Bojan Vujkovac; Phone Number: 386 (0)28823708; Email: bojan.vujkovac@guest.arnes.si
• United Kingdom
  • London, United Kingdom, NW3 2QG
    • Recruiting
    • The Royal Free Hospital
    • Contact: Derralynn Hughes, MD; Phone Number: 22496 +442074726588; Email: derralynnhughes@nhs.net
  • Birmingham
    • Edgbaston, Birmingham, United Kingdom, B152TH
      • Recruiting
      • University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital
      • Contact: Tarekegn G Hiwot, MD; Phone Number: +441213716983; Email: tarekegn.hiwot@uhb.nhs.uk
  • Greater Manchester
    • Salford, Greater Manchester, United Kingdom, M6 8HD
      • Recruiting
      • Salford Royal
      • Contact: Ana Jovanovic, MD; Phone Number: +441612064365; Email: ana.jovanovic@nca.nhs.uk
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Recruiting
      • University of Alabama at Birmingham
      • Contact: Eric Wallace, MD; Phone Number: +1 205-975-2935; Email: elwallace@uabmc.edu
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University School of Medicine
      • Contact: William Wilcox, MD; Phone Number: 404-778-8518; Email: william.wilcox@emory.edu
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern University - Feinberg School of Medicine - Ann & Robert H. Lurie Children's Hospital of Chicago
      • Contact: Carlos Prada, MD; Phone Number: +1 312-227-3724; Email: cprada@luriechildrens.org
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa Hospitals and Clinics
      • Contact: John Bernat; Phone Number: 319-356-2007
  • Michigan
    • Grand Rapids, Michigan, United States, 49525
      • Recruiting
      • Infusion Associates
      • Contact: Michael Mawby, MD
  • Virginia
    • Fairfax, Virginia, United States, 22030
      • Recruiting
      • Lysosomal & Rare Disorder Research & Treatment Center (LRDRTC)
      • Contact: Ozlem Goker-Alpan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The eligible population for this study includes participants who have a genetically confirmed diagnosis of Fabry disease and are being treated or plan to initiate treatment with pegunigalsidase alfa (Elfabrio®). Participants will be required to meet inclusion, not meet exclusion criteria and sign informed consent to be enrolled in the study.

Description

Inclusion Criteria:

• Male or female aged > 18 years of age at the time of consent.
• Genetically confirmed diagnosis of Fabry disease.
• Either taking or planning to take pegunigalsidase alfa as treatment for Fabry disease.
• No contraindications for cardiac magnetic resonance imaging (cMRI)
• Informed consent form (ICF) signed and dated indicating the individual has been informed of and agreed to all pertinent aspects of the study and is willing to comply with all study requirements, including completion of electronic patient reported outcomes (ePROs).
• Cardiac Cohort:
• Evidence of Fabry disease (FD)-related heart disease including one or more of the following:
• Left ventricular hypertrophy (LVH) measured by left ventricular mass index (LVMI) (g/m2) elevation above age/sex specific reference ranges.
• Posterior septum wall thickness (e.g., >=13mm) not explained by other factors (e.g., hypertension)
• Low native T1 mapping on cMRI.
• Typical Fabry-like scar on cMRI
• Participants can receive cardiac magnetic resonance imaging (cMRI) with gadolinium enhancement as part of their SoC.
• Estimated glomerular filtration rate (eGFR) >45 mL/min/1.73 m2, assessed within the prior 6 months.
• Naïve Cohort:
• Most recent eGFR>45 mL/min/1.73 m2, assessed within prior 6 months.
• Male participants should have abnormal elevation in plasma lysoGb3 as assessed within 6 months prior to enrolment.
• Long-Term Cohort:
• Participants previously enrolled in the open label study CLI-06657AA1-04 (Previously PB-102-F60) (using pegunigalsidase alfa at a dose of 1mg/kg every 2 weeks) who have initiated or plan to initiate commercial pegunigalsidase alfa (Elfabrio®).

Exclusion Criteria:

• Contraindication to magnetic resonance imaging (MRI) including known history of hypersensitivity to gadolinium contrast agent that is not managed by the use of premedication.
• Pregnant at the time of enrolment.
• Presence of any medical, emotional, behavioural, or psychological condition that, in the judgment of the physician, could interfere with the ability to participate in the study.
• Active participation in any interventional study for Fabry disease
• Treatment regimen at the time of enrolment in the study is different from the approved 1mg/kg every two weeks (note if regimen subsequently changes during the prospective part of the study, the participants can remain in the study)
• Prior participation in a pegunigalsidase alfa trial using a dose of 2 mg/kg administered every 4 weeks.
• Cardiac Cohort:
• History of acute myocardial infarction or congestive heart failure with reduced left ventricular (LV) ejection fraction of less than 35%.
• Cerebral vascular accident (CVA) in the prior 6 months.
• Chronic liver cirrhosis.
• FD-unrelated heart disease (e.g., scarring due to myocardial infarction, symptomatic occlusive coronary artery disease, moderate valvular heart disease not thought to be Fabry related).
• The participant is or has been treated with any investigational drug for Fabry disease within 6 months of study start or investigational gene therapy for Fabry disease at any time point in the past.
• Severe cardiac fibrosis defined as more than 3 segments that each have >50% fibrosis upon late gadolinium enhancement cMRI at any prior cMRI.
• Naïve Cohort:
• Prior exposure to a FD therapy (Replagal®, Fabrazyme®, and Galafold®) at any time point.
• Severe cardiac fibrosis defined as more than 3 segments that each have >50% fibrosis upon late gadolinium enhancement cMRI on any prior cMRI

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cardiac Cohort; Patients with Fabry-related cardiac disease	Drug: Pegunigalsidase-alfa; Administered via intravenous (IV) infusion under conditions of routine clinical care; Other Names: Elfabrio®
Naïve Cohort; Patients naïve to prior Fabry disease treatment	Drug: Pegunigalsidase-alfa; Administered via intravenous (IV) infusion under conditions of routine clinical care; Other Names: Elfabrio®
Long-Term Cohort; Patients previously participating in the pegunigalsidase alfa open label extension study and transitioning to routine care	Drug: Pegunigalsidase-alfa; Administered via intravenous (IV) infusion under conditions of routine clinical care; Other Names: Elfabrio®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Estimated Glomerular Filtration Rate (eGFR)	eGFR, calculated using the Chronic Kidney Disease - Epidemiology Collaboration (eGFRCKD-EPI) equation from study baseline and from pegunigalsidase alfa treatment start to end of follow-up and to pre-specified time points (annually).	4 years
Plasma Globotriaosylsphingosine (LysoGb3) Concentration	Levels of the Fabry disease biomarker plasma globotriaosylsphingosine (lyso-Gb3) over time, and change from study baseline and from pegunigalsidase alfa treatment start to end of follow-up.	4 years
Left Ventricular Mass Index (LVMI; g/m2)	Change in LVMI over time as assessed by cardiac MRI. Based on LVM indexed by height and/or body surface area.	4 years
High Sensitivity Troponin (hs-cTnT)	Change in levels of hs-cTnT over time	4 years
Safety Assessments	The endpoints will include occurrence of SAEs, infusion-related reactions (IRRs), drug-related adverse events, and proportion of participants with ADAs over time.	4 years

Collaborators and Investigators

• Sponsor: Chiesi Farmaceutici S.p.A.

Study record dates

Study Major Dates

• Study Start (Actual): November 6, 2024
• Primary Completion (Estimated): November 1, 2029
• Study Completion (Estimated): November 1, 2029

Study Registration Dates

• First Submitted: September 23, 2024
• First Submitted That Met QC Criteria: October 25, 2024
• First Posted (Actual): October 29, 2024

Study Record Updates

• Last Update Posted (Estimated): November 14, 2025
• Last Update Submitted That Met QC Criteria: November 13, 2025
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Lipid Metabolism Disorders; Genetic Diseases, X-Linked; Lysosomal Storage Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases, Nervous System; Cerebral Small Vessel Diseases; Sphingolipidoses; Lipidoses; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Fabry Disease
• Other Study ID Numbers: CLI-06657AA1-10

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No