Pegunigalsidase Alfa for Fabry Disease

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

97 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug pegunigalsidase alfa for Fabry disease?

Research shows that pegunigalsidase alfa, a new enzyme replacement therapy, helps maintain kidney function and reduces harmful substances in the body for people with Fabry disease. It also has a longer-lasting effect in the bloodstream and causes fewer immune reactions compared to similar treatments. ^{1 2 3 4 5}

Is pegunigalsidase alfa safe for humans?

Pegunigalsidase alfa has been studied for safety in people with Fabry disease, and most side effects were mild or moderate. In a long-term study, one person had a serious side effect, but overall, the treatment was generally well-tolerated. ^{1 2 3 4 5}

How is the drug pegunigalsidase alfa different from other treatments for Fabry disease?

Pegunigalsidase alfa is unique because it is a PEGylated form of enzyme replacement therapy, which means it has a longer half-life in the body and is less likely to cause immune reactions compared to other treatments. This can lead to more stable and effective management of Fabry disease symptoms. ^{1 2 3 4 5}

What is the purpose of this trial?

The objective of CLI-06657AA1-04 (formerly PB-102-F60) is to evaluate the long-term safety, tolerability, and efficacy parameters of 1 mg/kg pegunigalsidase alfa administered intravenously every other week in adult Fabry patients who have successfully completed studies PB-102-F03, PB-102-F20 or PB-102-F30.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

References

1. England 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. [2023]

2. England 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. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of pegunigalsidase alfa: A multicenter 6-year study in adult patients with Fabry disease. [2023]

4. United States 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. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Pre-existing anti-drug antibodies in Fabry disease show less affinity for pegunigalsidase alfa. [2022]