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NCT Number: NCT06328608

A Study to Learn About the Safety and Effects of the Study Drug PRX-102 in Children and Adolescents With Fabry Disease

A Study to Learn About the Safety and Effects of the Study Drug PRX-102 in Children and Adolescents with Fabry Disease.

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Key information

Conditions

Fabry Disease Brain Diseases Brain Diseases, Metabolic Brain Diseases, Metabolic, Inborn Cardiovascular Diseases Central Nervous System Diseases Cerebral Small Vessel Diseases Cerebrovascular Disorders Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Genetic Diseases, X-Linked Lipid Metabolism Disorders Lipid Metabolism, Inborn Errors Lipidoses Lysosomal Storage Diseases Lysosomal Storage Diseases, Nervous System Metabolic Diseases Metabolism, Inborn Errors Nervous System Diseases Nutritional and Metabolic Diseases Sphingolipidoses Vascular Diseases

Age range

2 year–17 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

UK für Kinder- und Jugendheilkunde der PMU Salzburg, Salzburg, Austria

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About this study

This study aims to learn how safe pegunigalsidase alfa (PRX-102 for short) is and how it works at treating Fabry disease in children and adolescents.

PRX-102 is an enzyme replacement therapy (ERT), meaning it acts like a natural enzyme. PRX-102 is given through a needle placed in a vein (intravenous infusion) every two weeks.

The main questions this study aims to answer are:

  • Which is the safest and most effective dose to be given to children and adolescents.
  • Which effects PRX-102 has on signs and symptoms of Fabry disease (e.g. renal and cardiac function, pain, gastrointestinal symptoms)

20 to 22 boys and girls with Fabry disease between the ages of 2 and 17 will be part of this study. There will be three age cohorts, with children aged 2 to 7 years included (enrolled) in Cohort A, children aged 8 to 12 years in Cohort B, and adolescents aged 13 to less than 18 years in Cohort C.

The study is divided into three parts, or "stages":

  • A dose-finding stage (Stage I). In this stage, researchers will determine the dose for children.
  • A confirmatory stage (Stage II). In this part, researchers will learn about the safety and efficacy of PRX-102.
  • and an optional extension stage (Stage III) will continue until the study drug becomes commercially available or the Sponsor chooses to end this study.

PRX-102 will be given at the study visits, which will occur at least every two weeks. Tests for verifying the study drug's safety and efficacy and determining the dose will also be conducted at different time points throughout the study (not all tests will be done at all visits). These tests may include a review of any health problems and medications the participants have had or taken since the last visit; a physical examination; ECG; ultrasound of the heart; questionnaires that evaluate the nature and severity of Fabry disease symptoms, quality of life and pain; a collection of blood and urine samples for standard safety tests, to analyse the severity of Fabry disease and to see how the drug is behaving and how long it remains active in the body (this involves taking multiple blood samples over several days with the first sample taken just before the start of the PRX-102 infusion and the last one taken just before the start of the next PRX-102 at the next visit).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Participants with the provision of informed consent from their legal guardians
  • Boys and girls aged 2 to 7 years (Cohort A), 8 to 12 years (Cohort B), or 13 to <18 years (Cohort C).
  • Confirmed diagnosis of Fabry disease
  • Presence of at least one of the following characteristic features of Fabry disease: neuropathic pain, cornea verticillata, and/or clustered angiokeratoma.
  • History of Fabry pain: Fabry crises OR chronic pain.
  • Clinical condition that, in the investigator's opinion, requires ERT treatment.

Exclusion criteria

All Subjects:

  • Estimated glomerular filtration rate (eGFR) at screening < 80 mL/min/1.73 m2.
  • History of type I hypersensitivity reactions (anaphylactic or anaphylactoid life-threatening reaction) to other ERT treatment for Fabry disease or any component of the study drug.
  • Initiation of treatment with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB) or a dose change in ongoing treatment in the four weeks before screening.
  • Urine protein to creatinine ratio (UPCR) > 0.5 g/g (0.5 mg/mg or 500 mg/g) if not treated with an ACE inhibitor or ARB.
  • Currently taking another investigational drug for any condition.
  • History of acute kidney injury in the 12 months before screening, including specific kidney diseases (e.g., acute interstitial nephritis, acute glomerular and vasculitic renal diseases); non-specific conditions (e.g., ischaemia, toxic injury); or extrarenal pathology (e.g., prerenal azotaemia, acute postrenal obstructive nephropathy).
  • History of renal dialysis or kidney transplantation.
  • History of or current malignancy requiring treatment.
  • Severe cardiomyopathy or significant unstable cardiac disease within six months before screening.
  • A positive test for Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) within three months before screening.
  • Presence of any medical, emotional, behavioural, or psychological condition that, in the Investigator's judgement, could interfere with the subject's compliance with the requirements of the study.

Additional Exclusion Criteria for Subjects Enrolled in Stage I:

  • Female
  • Non-classic form of Fabry disease
  • Receipt of treatment for Fabry disease within six months before screening
  • Positive for anti-PRX-102 antibodies at screening

Additional Exclusion Criteria for Subjects in Stage II (i.e., non-treatment naïve males or females):

  • Unwilling to discontinue current ERT treatment for Fabry disease before baseline.
  • Females: Pregnant or lactating, or of childbearing potential with a fertile male partner and unwilling to use a highly reliable method of contraception from the informed consent signature until 30 days after the last infusion.

Treatment and study plan

PRX-102 1 mg/kg every two weeks

Drug

Drug: PRX-102 1 mg/kg every two weeks

Other names: pegunigalsidase alfa, Recombinant human alpha galactosidase-A

Primary outcomes

  1. Incidence of Treatment Emergent Adverse Events (TEAEs)

    Time frame: 12 Months

  2. Incidence of Infusion Related Reactions (IRRs)

    Time frame: 12 Months

  3. Incidence of Injection site reactions (ISRs)

    Time frame: 12 Months

  4. Change in Tanner stage

    Time frame: Baseline and 12 Months

    Tanner Staging of Sexual Development will be used to assess sexual development (i.e. breast development (B1 to B5) and pubic hair development (Ph-1 to Ph-5) in females and pubic hair and genetical development (G1-G5) in males.

  5. Change from baseline of 12-lead ECG quantitative parameters: Mean Heart Rate

    Time frame: Baseline and 12 Months

  6. Change from baseline of 12-lead ECG quantitative parameters: PR Interval

    Time frame: Baseline and 12 Months

  7. Change from baseline of 12-lead ECG quantitative parameters: QRS Duration

    Time frame: Baseline and 12 Months

  8. Change from baseline of 12-lead ECG quantitative parameters: QT Interval

    Time frame: Baseline and 12 Months

  9. Change from baseline of 12-lead ECG quantitative parameters: QTc Interval

    Time frame: Baseline and 12 Months

  10. Change from baseline of 12-lead ECG quantitative parameters: ST Segment

    Time frame: Baseline and 12 Months

  11. Incidence of treatment-emergent Anti-Drug Antibodies (ADAs)

    Time frame: Baseline and 12 Months

  12. Incidence of premedication use at each visit and change of infusion premedications from baseline

    Time frame: Baseline and 12 Months

  13. Pharmacokinetics: Time to maximum plasma concentration (tmax)

    Time frame: Stage I - Baseline, week 2, week 4, week 12, week 26 and week 52; Stage II -Baseline, week 12, week 26 and week 52]

  14. Pharmacokinetic : Area under the plasma concentration-time curve from time 0 to time t (AUC0 t)

    Time frame: Stage I - Baseline, week 2, week 4, week 12, week 26 and week 52; Stage II -Baseline, week 12, week 26 and week 52]

  15. Pharmacokinetics: Area under the curve from time 0 to 2 weeks (AUC0-2wk)

    Time frame: Stage I - Baseline, week 2, week 4, week 12, week 26 and week 52; Stage II -Baseline, week 12, week 26 and week 52]

  16. Pharmacokinetics: Area under the curve from time 0 to infinity (AUC0-∞)

    Time frame: Stage I - Baseline, week 2, week 4, week 12, week 26 and week 52; Stage II -Baseline, week 12, week 26 and week 52]

  17. Pharmacokinetics: Terminal half-life (t1/2)

    Time frame: Baseline, week 2, week 4, week 12, week 26 and week 52]

  18. Pharmacokinetics: Area under the curve over a dosing interval (AUCτ)

    Time frame: Baseline, week 2, week 4, week 12, week 26 and week 52; Stage II -Baseline, week 12, week 26 and week 52]

  19. Pharmacokinetics: Observed drug concentration at the end of the dosing interval (Cτ)

    Time frame: Stage I - Baseline, week 2, week 4, week 12, week 26 and week 52; Stage II -Baseline, week 12, week 26 and week 52]

  20. Pharmacokinetics: Clearance (Cl)

    Time frame: Stage I - Baseline, week 2, week 4, week 12, week 26 and week 52; Stage II -Baseline, week 12, week 26 and week 52]

  21. Pharmacokinetics: Volume of distribution (Vz)

    Time frame: Stage I - Baseline, week 2, week 4, week 12, week 26 and week 52; Stage II -Baseline, week 12, week 26 and week 52]

  22. Change in eGFR

    Time frame: Baseline and 12 Months

  23. Change in annualized eGFR slope

    Time frame: Baseline and 12 Months

  24. Change in urine albumin levels

    Time frame: Baseline and 12 Months

  25. Change in urine protein levels

    Time frame: Baseline and 12 Months

  26. Change from baseline in LVMi as assessed by echocardiogram

    Time frame: Baseline and 12 Months

    Echocardiogram parameters include left ventricular mass index (LVMi)

  27. Change from baseline in LVMi as assessed by echocardiogram

    Time frame: Baseline and 12 Months

    Echocardiogram parameters include ejection fraction

  28. Change from baseline in LVMi as assessed by echocardiogram

    Time frame: Baseline and 12 Months

    Echocardiogram parameters include, fractional shortening

  29. Change from baseline in LVMi as assessed by echocardiogram

    Time frame: Baseline and 12 Months

    Echocardiogram parameters include left ventricular mass

  30. Change from baseline in LVMi as assessed by echocardiogram

    Time frame: Baseline and 12 Months

    Echocardiogram parameters include valve abnormalities and thickness.

  31. Incidence of any cardiac arrythmias as assessed by Holter ECG

    Time frame: Baseline and 12 Months

  32. Change in plasma levels of cardiac biomarkers

    Time frame: Baseline and 12 Months

    High-sensitivity cardiac troponin T (hs-cTnT) and N- terminal pro brain natriuretic peptide (NT-Pro BNP) will be assessed.

  33. Change in plasma level of Gb3 concentration (nM)

    Time frame: Baseline and 12 Months

  34. Change in plasma level of lyso-Gb3 (nM)

    Time frame: Baseline and 12 Months

  35. Change in urine level of lyso-Gb3 (nM)

    Time frame: Baseline and 12 Months

  36. Incidence of change from baseline in the number of different pain medications

    Time frame: Baseline and 12 Months

  37. Incidence of Fabry Clinical Events

    Time frame: 12 Months

    FCEs are classified into four categories: renal, cardiac, cerebrovascular and death due to non-cardiac reasons

  38. Change from baseline of Mainz Severity Score Index (MSSI) scores

    Time frame: Baseline and 12 Months

    Domains (general, neurological, cardiovascular, renal dysfunction)

  39. Change from baseline of PedsQL-GI (or GSRS for subjects who reaches 18 yrs of age) scores

    Time frame: Baseline and 12 Months

  40. Change from baseline of FPHPQ scores

    Time frame: Baseline and 12 Months

  41. Change from baseline of PedsQL-PPQ (or BPI-SF for subjects who reaches 18 yrs of age) scores

    Time frame: Baseline and 12 Months

  42. Change from baseline of EQ-5D-Y (or EQ-5D-5L for subjects who reaches 18 yrs of age) scores

    Time frame: Baseline and 12 Months

Study contacts

Contact information is provided by the study sponsor or research team.

Chiesi Clinical Trial

CONTACT

[email protected]

+3905212791

Sponsors and collaborators

Lead sponsor

Chiesi Farmaceutici S.p.A.

Industry

Collaborators

  • ICON plc

Registry information

Official study title

Multi-centre, Open-label Trial to Assess the saFety, Pharmacodynamics, Efficacy and Pharmacokinetics of pegunigaLsidase Alfa in Patients From 2 Years to Less Than 18 Years of Age With Confirmed FabrY Disease

Acronym: FLY

Important dates

Study start
2025
Primary completion
2028
Study completion
2031
First posted
Mar 25, 2024
Registry last updated
Mar 19, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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