FLY: A Study to Learn About the Safety and Effects of the Study Drug PRX‑102 in Children and Adolescents with Fabry Disease (FLY)
About the Condition
Fabry disease is a genetic disorder (a disease passed on by parents) where the body does not correctly make a special protein (or enzyme). This enzyme is needed to break down a special kind of fat called globotriaosylceramide (Gb3 for short). If this enzyme is missing or not working right, Gb3 builds up in the body’s cells and tissues, leading to organ damage and other serious health problems. Symptoms of Fabry disease appear at a young age and get worse over time. There are only a few options available to treat Fabry disease in younger age groups (for example, children and teenagers), so there is an important need to develop and study medicines in these groups.
Trial Details
FLY is a Phase 2/3 study that will be conducted in children and adolescents with Fabry disease, to learn more about an investigational new medicine called pegunigalsidase alfa (or “PRX-102”, an enzyme replacement therapy - ERT), designed to prevent or reduce the development of health problems caused by Fabry disease.
A Phase 2/3 study means that the drug is studied in a larger number of patients, to see if the drug is effective in treating the disease or symptoms of the disease (also called efficacy), as well to confirm its safety.
The main goal of the FLY study is to find out how well the medicine PRX-102 works and if it is safe for children and teens. Right now, PRX-102 is only approved for adults with Fabry disease, based on earlier studies that showed it is safe and works well. The main questions this study aims to answer are:
- What is the safest and most effective dose for children and teenagers?
- How does PRX-102 affect the main symptoms of Fabry disease after one year of treatment (e.g. stabilisation of renal and cardiac function, pain, gastrointestinal symptoms)?
- Are there any unwanted effects (known as adverse effects) after one year of treatment with PRX-102 (e.g. number of infusion reactions, injection reactions, changes in growth and development)?
Trial Design
The FLY study is divided into three age groups (cohorts):
- Cohort A: Age 2 to 7 years old
- Cohort B: Age 8-12 years old
- Cohort C: Age 13-17 years old
The FLY study is divided into three parts, or “stages”:
- A dose-finding stage (Stage I) that will include only the first 9 patients (3 for each age group). In this stage, researchers will determine the dose for children. Only boys will be included in Stage I.
- A confirmatory stage (Stage II). In this part, researchers will learn about the safety and efficacy of PRX-102. Boys and girls can be included in Stage II.
- An optional extension stage (Stage III). This stage will allow for continued study of the selected dose until PRX-102 is approved and available for sale by prescription in the younger population(s) in the participant’s area.
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 be conducted at different time points throughout the study.
- 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.
Trial Participant Requirements
Key Inclusion and Exclusion Criteria
Participants Must:
- be between 2 and 17 years of age
- be diagnosed with Fabry disease;
- have manifestations of the disease, specifically Fabry pain symptoms. (in the opinion of the doctor in charge of the study) need treatment with ERT.
- If currently receiving enzyme replacement, be willing to switch to PRX-102
- have no history of severe reaction to enzyme replacements for Fabry Disease
- be otherwise healthy except for Fabry Disease
- 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.
- 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.