PRX-102 for Fabry Disease

(FLY Trial)

Recruiting at 13 trial locations

Overseen By Chiesi Clinical Trial

Age: < 18

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Chiesi Farmaceutici S.p.A.

Must be taking: ERT treatment

Must not be taking: ACE inhibitors, ARBs, Investigational drugs

Disqualifiers: Acute kidney injury, Dialysis, Malignancy, Cardiomyopathy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

22 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety and effects of a new treatment called PRX-102 (also known as Elfabrio or pegunigalsidase alfa) for children and teens with Fabry disease. Fabry disease is a rare genetic disorder that can cause pain, skin issues, and eye problems. Participants receive PRX-102 every two weeks to assess its effectiveness and safety. The trial suits young individuals with a confirmed Fabry diagnosis who experience symptoms like neuropathic pain or skin issues known as angiokeratomas. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

If you are currently receiving ERT treatment for Fabry disease, you must be willing to stop it before starting the trial. The protocol does not specify about other medications, but you should discuss your current medications with the study team.

Is there any evidence suggesting that PRX-102 is likely to be safe for children and adolescents with Fabry Disease?

Research has shown that pegunigalsidase alfa, also known as PRX-102, is generally safe for people with Fabry disease. In past studies, patients used this treatment safely over extended periods. For example, one study followed patients for six years and found it safe for adults with Fabry disease. Another study demonstrated that patients who switched from a different treatment to PRX-102 tolerated it well after one year.

The treatment has already received approval in the EU and the US for adults with Fabry disease, indicating it meets safety standards for adults. While the current study focuses on children and teenagers, existing evidence from adult studies provides some reassurance about its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Fabry Disease?

Unlike the standard treatments for Fabry disease, which often involve enzyme replacement therapies like agalsidase beta or agalsidase alfa, PRX-102 is unique because it uses a novel enzyme called pegunigalsidase alfa. This enzyme is designed to have a longer half-life, meaning it stays active in the body for a longer period, potentially reducing the frequency of infusions needed. Additionally, PRX-102 is engineered to have enhanced stability and activity, which might improve its effectiveness in breaking down the fatty substances that build up in the bodies of people with Fabry disease. Researchers are excited about PRX-102 because these features could lead to improved outcomes and convenience for patients.

What evidence suggests that PRX-102 might be an effective treatment for Fabry Disease?

Research has shown that PRX-102, also known as pegunigalsidase alfa, yields promising results for treating Fabry disease. A long-term study found it safe and effective over six years in adults with this condition. Elfabrio, a version of PRX-102, has already received approval for treating adults with Fabry disease, supporting its effectiveness. Studies have demonstrated that it helps manage symptoms and is generally well-tolerated. This treatment is an enzyme replacement therapy, replacing missing or deficient enzymes in people with Fabry disease, which can improve symptoms and quality of life. Participants in this trial will receive PRX-102 in a single treatment arm, administered every two weeks. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

This trial is for boys and girls aged 2-18 with Fabry disease who need enzyme replacement therapy (ERT). They must have symptoms like neuropathic pain, cornea verticillata, or angiokeratoma. Legal guardians must consent to their participation.

Inclusion Criteria

Participants with the provision of informed consent from their legal guardians

I have experienced Fabry-related pain, either as crises or chronic.

I am a child or teenager between 2 and 17 years old.

Exclusion Criteria

I am not pregnant, breastfeeding, and if able to have children, I agree to use reliable birth control.

I have been treated for Fabry disease within the last 6 months.

Estimated glomerular filtration rate (eGFR) at screening < 80 mL/min/1.73 m2

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-finding stage (Stage I)

Researchers determine the dose for children

12 months

Visits every two weeks

Confirmatory stage (Stage II)

Researchers learn about the safety and efficacy of PRX-102

12 months

Visits every two weeks

Optional extension stage (Stage III)

Continues until the study drug becomes commercially available or the Sponsor chooses to end the study

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• PRX-102

Trial Overview The study tests PRX-102 at a dose of 1 mg/kg every two weeks to understand its safety and effects in treating children and adolescents with Fabry disease.

How Is the Trial Designed?

Group I: Single Arm - Pegunigalsidase alfa (PRX-102) Experimental Treatment 1 Intervention

For Cohort C, PXR-102 administered every two weeks at 1.0 mg/kg is believed to be the minimum effective dose. For Cohorts A and B, the starting dose will be 1.0 mg/kg every two weeks but it may be adjusted on the outcomes of Stage I, with the support of the Data Safety Monitoring Board.

PRX-102 is already approved in European Union, United States for the following indications:

Approved in European Union as Elfabrio for:

• Fabry disease

Approved in United States as Elfabrio for:

• Fabry disease

Who Is Running the Clinical Trial?

Chiesi Farmaceutici S.p.A.

Lead Sponsor

Trials

206

Recruited

315,000+

Founded

1935

Headquarters

Parma, Italy

Known For

Respiratory diseases

Top Products

NEXThaler, Trimbow, Curosurf, Holoclar

ICON plc

Industry Sponsor

Trials

88

Recruited

28,900+

Dr. Steve Cutler

ICON plc

Chief Executive Officer since 2017

PhD from the University of Sydney, MBA from the University of Birmingham

Dr. Greg Licholai

ICON plc

Chief Medical Officer since 2023

Degrees from Harvard Business School, Yale School of Medicine, Columbia University, and Boston College

Published Research Related to This Trial

In a study involving 77 adults with Fabry disease, pegunigalsidase alfa was found to be non-inferior to agalsidase beta in terms of kidney function, as measured by the annualized eGFR slope over 2 years.

Pegunigalsidase alfa demonstrated a better safety profile, with significantly lower rates of treatment-related adverse events and infusion-related reactions compared to agalsidase beta.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Head-to-head trial of pegunigalsidase alfa versus agalsidase beta in patients with Fabry disease and deteriorating renal function: results from the 2-year randomised phase III BALANCE study. Wallace, EL., Goker-Alpan, O., Wilcox, WR., et al.[2023]

PRX-102, a novel enzyme replacement therapy for Fabry disease, shows significantly improved stability and prolonged activity compared to existing therapies, retaining 30% activity in plasma after 1 hour and over 80% activity after 10 days under lysosomal-like conditions.

In animal studies, PRX-102 demonstrated a 10-fold increase in half-life compared to approved drugs and effectively reduced Gb3 levels in various tissues of Fabry mice, indicating its potential as a more effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of a chemically modified plant cell culture expressed human α-Galactosidase-A enzyme for treatment of Fabry disease. Kizhner, T., Azulay, Y., Hainrichson, M., et al.[2023]

In a phase 3 study involving 20 adults with Fabry disease, pegunigalsidase alfa was well-tolerated, with 97% of treatment-emergent adverse events being mild or moderate, indicating a favorable safety profile.

After switching to pegunigalsidase alfa, the decline in kidney function (measured by eGFR) significantly slowed, with a mean eGFR slope of -1.19 mL/min/1.73 m2/year compared to -5.90 mL/min/1.73 m2/year before the switch, suggesting improved efficacy in preserving kidney function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of pegunigalsidase alfa in patients with Fabry disease who were previously treated with agalsidase alfa: results from BRIDGE, a phase 3 open-label study. Linhart, A., Dostálová, G., Nicholls, K., et al.[2023]

In a long-term study of 15 adults with Fabry disease, pegunigalsidase alfa, a new enzyme replacement therapy, demonstrated favorable safety with most side effects being mild to moderate, and no severe infusion reactions reported.

Patients showed significant reductions in plasma lyso-Gb3 levels over 60 months, indicating effective treatment, and maintained stable kidney and cardiac function, suggesting long-term benefits of this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of pegunigalsidase alfa: A multicenter 6-year study in adult patients with Fabry disease. Hughes, D., Gonzalez, D., Maegawa, G., et al.[2023]

Pegunigalsidase alfa, an enzyme replacement therapy for Fabry disease, demonstrated a significantly extended plasma half-life of 53 to 121 hours, which may enhance its efficacy and reduce immunogenicity compared to existing treatments.

In a study involving 16 symptomatic adults over one year, treatment led to an 84% reduction in kidney globotriaosylceramide (Gb3) inclusions, with most adverse events being mild or moderate, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegunigalsidase alfa, a novel PEGylated enzyme replacement therapy for Fabry disease, provides sustained plasma concentrations and favorable pharmacodynamics: A 1-year Phase 1/2 clinical trial. Schiffmann, R., Goker-Alpan, O., Holida, M., et al.[2022]

In a study of 49 patients with Fabry disease, the novel PEGylated enzyme pegunigalsidase-alfa (PRX-102) showed significantly lower affinity for anti-drug antibodies (ADAs) compared to traditional treatments agalsidase-alfa and -beta, suggesting it may be less affected by these antibodies.

The research indicates that patients with pre-existing ADAs may experience a 30% reduction in inhibitory effects when switching to PRX-102, potentially making it a more effective treatment option for those affected by Fabry disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-existing anti-drug antibodies in Fabry disease show less affinity for pegunigalsidase alfa. Lenders, M., Pollmann, S., Terlinden, M., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10589982/

Safety and efficacy of pegunigalsidase alfa in patients with ... Effectiveness of agalsidase alfa enzyme replacement in Fabry disease: cardiac outcomes after 10 years' treatment. Orphanet J Rare Dis. 2015 ...

2. chiesirarediseases.com chiesirarediseases.com/media/20241028-chiesi-global-rare-diseases-announces-publication-of-results-from-phase-3-bright-study-of-elfabrio-pegunigalsidase-al

Data published in Journal of Inherited Metabolic Disease Results show that 2 mg/kg pegunigalsidase alfa administered every four weeks is generally well-tolerated in stable adult ERT-experienced patients with Fabry ...

3. hcp.elfabrio.com hcp.elfabrio.com/

Elfabrio® (pegunigalsidase alfa-iwxj) | Overview for ... Elfabrio is an enzyme replacement therapy (ERT) approved for the treatment of adults with confirmed Fabry disease.

4. ir.protalix.com ir.protalix.com/news-releases/news-release-details/chiesi-global-rare-diseases-and-protalix-biotherapeutics-3

Chiesi Global Rare Diseases and ... Elfabrio® (pegunigalsidase alfa-iwxj) is indicated for the treatment of adults with confirmed Fabry disease. Important Safety Information ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S109836002300984X

Long-term safety and efficacy of pegunigalsidase alfa Article. Long-term safety and efficacy of pegunigalsidase alfa: A multicenter 6-year study in adult patients with Fabry disease.