Pegunigalsidase Alfa for Fabry Disease

No longer recruiting at 32 trial locations

Age: 18 - 65

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: 6

Duration: Until pegunigalsidase alfa is commercially available or at the discretion of the Sponsor

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests pegunigalsidase alfa, a treatment for Fabry disease, to assess its long-term safety and effectiveness. Fabry disease is a rare genetic condition that causes pain, kidney problems, and heart issues due to a buildup of certain fats in the body. The treatment is administered as an IV drip every other week. This trial is ideal for those who have participated in related studies and are willing to continue with the treatment plan. Participants should have completed one of the specified previous studies and agree to use birth control if they can have children. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance 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 well tolerated by patients. In one study, 90.6% of patients completed 24 months of treatment without any new safety concerns. Another study found that patients using pegunigalsidase alfa for over two years did not experience major safety issues.

Additionally, pegunigalsidase alfa has positively impacted health outcomes for patients who have not previously received enzyme replacement therapy. This suggests that the treatment is generally safe for humans. However, as with any treatment, it is important to be aware of possible side effects and discuss them with a healthcare professional. ^{1 2 3 4 5}

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

Pegunigalsidase alfa is unique because it is a modified enzyme replacement therapy for Fabry disease. Unlike current treatments such as agalsidase beta and agalsidase alfa, pegunigalsidase alfa is designed to have an extended half-life, potentially allowing for less frequent dosing. This longer duration in the body could improve the convenience and quality of life for patients, which is why researchers are excited about its potential. Additionally, the modified structure of pegunigalsidase alfa may enhance its stability and efficacy in breaking down the accumulated fatty substances in cells that are characteristic of Fabry disease.

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

Research has shown that pegunigalsidase alfa, the investigational treatment in this trial, might be a safe and effective option for Fabry disease. Studies indicate that patients taking this medication experienced a slower decline in kidney function, measured by eGFR, similar to other enzyme replacement therapies (ERTs). Specifically, after 12 months, about 45% of patients showed improvements in kidney function. Another study found that 90.6% of patients completed 24 months of treatment, indicating good tolerance. Overall, these findings suggest that pegunigalsidase alfa could be a promising option for managing Fabry disease. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

This trial is for adult patients with Fabry Disease who completed previous studies (PB-102-F20, PB-102-F03, or PB-102-F30) and consent to participate. They must use effective contraception if they can have children. Those with conditions affecting study compliance are excluded.

Inclusion Criteria

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

You have already taken part in studies PB-102-F20, PB-102-F03, or PB-102-F30.

The patient signs informed consent

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 1 mg/kg pegunigalsidase alfa intravenously every 2 weeks

Until pegunigalsidase alfa is commercially available or at the discretion of the Sponsor

Bi-weekly visits for infusions

Follow-up

Participants are monitored for safety and effectiveness after treatment

7 years

Every 6 months for assessments

Open-label extension

Participants continue receiving treatment to evaluate long-term safety and efficacy

7 years

What Are the Treatments Tested in This Trial?

Interventions

• pegunigalsidase alfa

Trial Overview The trial tests the long-term safety and effectiveness of pegunigalsidase alfa at a dose of 1 mg/kg given intravenously every two weeks to adults with Fabry Disease who participated in earlier related trials.

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 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]

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]

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]

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 ...