Pegunigalsidase Alfa for Fabry Disease

(Bright51 Trial)

Not currently recruiting at 17 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Chiesi Farmaceutici S.p.A.

Disqualifiers: Medical, emotional, behavioral, psychological, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 1

Duration: 364 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety and effectiveness of a treatment called pegunigalsidase alfa for individuals with Fabry disease. Fabry disease is a rare condition that can lead to pain, kidney problems, and heart issues. The trial administers the treatment through an IV every four weeks. Individuals who completed a previous related study may be suitable candidates for this trial. Participants must agree to use effective birth control methods if they or their partners can have children. As a Phase 3 trial, this study represents the final step before FDA approval, providing participants an opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that pegunigalsidase alfa is likely to be safe for humans?

Research has shown that pegunigalsidase alfa is generally safe for patients. In one study, patients who used this treatment every four weeks did not encounter any new safety issues over more than two years. Another study found that pegunigalsidase alfa significantly improved patients' health and was well tolerated, even for those who had never received enzyme replacement therapy before. Additionally, nearly 91% of patients completed a 24-month treatment with pegunigalsidase alfa, indicating it is manageable for many. Overall, these studies suggest that the treatment is relatively safe for people with Fabry disease. ^{1 2 3 4 5}

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

Unlike traditional treatments for Fabry Disease, such as enzyme replacement therapies like agalsidase beta and agalsidase alfa, pegunigalsidase alfa is a unique option. Researchers are excited about it because it is a novel, pegylated enzyme replacement therapy. This pegylation process potentially enhances the stability and circulatory half-life of the enzyme, which might improve its effectiveness and reduce the frequency of infusions needed. Additionally, its design aims to provide more consistent and sustained enzyme activity, which could lead to better management of the disease symptoms.

What evidence suggests that pegunigalsidase alfa might be an effective treatment for Fabry disease?

Research has shown that pegunigalsidase alfa, the treatment under study in this trial, may help treat Fabry disease. In one study, 45% of patients experienced improved kidney function after 12 months of treatment, as measured by eGFR, a test that assesses kidney performance. Another study found that this treatment slowed the decline of kidney function, similar to other enzyme replacement therapies (ERTs), and maintained stable results over time. Additionally, no new safety issues emerged after two years of treatment. These findings suggest that pegunigalsidase alfa could be a safe and effective option for people with Fabry disease. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

This trial is for adult Fabry disease patients who completed the PB-102-F50 study. Participants must agree to use effective contraception if they or their partners can have children, and sign an informed consent. Those with conditions that could affect study compliance are excluded.

Inclusion Criteria

Completion of study PB-102-F50

The patient signs informed consent

I agree to use effective birth control during and for 2 weeks after the treatment.

Exclusion Criteria

Presence of any medical, emotional, behavioral, or psychological condition that, in the judgment of the Investigator, would interfere with patient compliance with the requirements of the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 2 mg/kg pegunigalsidase alfa administered intravenously every 4 weeks

364 weeks

1 visit every 4 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants continue receiving treatment until pegunigalsidase alfa is commercially available or at the discretion of the Sponsor

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• pegunigalsidase alfa

Trial Overview The trial tests the long-term safety and effectiveness of a drug called pegunigalsidase alfa, given intravenously at a dose of 2 mg/kg every four weeks to adults with Fabry disease who previously finished another related trial.

How Is the Trial Designed?

Group I: Experimental open label Experimental Treatment 1 Intervention

Pegunigalsidase alfa

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

Protalix

Lead Sponsor

Trials

19

Recruited

490+

Published Research Related to This Trial

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]

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]

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 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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37865771/

Safety and efficacy of pegunigalsidase alfa in patients with ... Conclusion: Pegunigalsidase alfa may offer a safe and effective treatment option for patients with FD, including those previously treated with ...

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

Long-term safety and efficacy of pegunigalsidase alfa Treatment with pegunigalsidase alfa was also associated with reduction of eGFR decline comparable to that seen with other ERTs and stable outcomes in other ...

3. jmg.bmj.com jmg.bmj.com/content/61/6/520

results from the 2-year randomised phase III BALANCE study Forty-eight (90.6%) patients receiving pegunigalsidase alfa and 24 (96.0%) receiving agalsidase beta completed 24 months of treatment. Three patients on ...

4. ojrd.biomedcentral.com ojrd.biomedcentral.com/articles/10.1186/s13023-023-02937-6

Safety and efficacy of pegunigalsidase alfa in patients with ... After 12 months of pegunigalsidase alfa treatment, 9 patients (45%) experienced a positive change in eGFR slope sufficient to move into a ...

5. gimopen.org gimopen.org/article/S2949-7744(23)00016-X/fulltext

Long-term safety and efficacy of pegunigalsidase alfa ... Conclusion. Patients treated with pegunigalsidase alfa 2.0 mg/kg every 4 weeks showed no new safety concerns during ≥2 years of treatment. Additional analyses ...