Safety, Efficacy, & PK of PRX-102 in Patients With Fabry Disease Administered Intravenously Every 4 Weeks

NCT ID: NCT03180840

Last Updated: 2023-09-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-07-10
• Study Completion Date: 2020-08-01

Brief Summary

This open-label switchover study will assess the safety, efficacy, and pharmacokinetics of pegunigalsidase alfa (PRX-102) 2 mg/kg administered every 4 weeks for 52 weeks in Fabry patients previously treated with ERT: agalsidase alfa or agalsidase beta for at least 3 years. Safety and efficacy exploratory endpoints will be evaluated throughout the study period and pharmacokinetics will be obtained on Day 1 and Week 52.

Detailed Description

This is an open-label switchover study to assess the safety, efficacy, and pharmacokinetics of pegunigalsidase alfa treatment of 2 mg/kg every 4 weeks in patients previously treated with enzyme-replacement therapy (ERT): agalsidase alfa or agalsidase beta, for at least 3 years and on a stable dose (>80% labelled dose/kg) for at least the last 6 months. Following screening, patients will be enrolled and switched from their current ERT to receive intravenous (IV) infusions of pegunigalsidase alfa 2 mg/kg every 4 weeks for 52 weeks (total of 14 infusions). At the time of enrollment, premedication, if used for the agalsidase alfa or agalsidase beta infusions before enrollment, will be continued using the same premedication regimen during the first infusion with pegunigalsidase alfa and then will be gradually tapered down at the Investigator's discretion during the next infusions based on protocol-specified criteria. First infusions of pegunigalsidase alfa will be administered under controlled conditions at the investigation site. Based on the protocol-specified criteria, patients will be able to receive their pegunigalsidase alfa infusions at a home care setup once the Investigator and Sponsor Medical Monitor agree that it is safe to do so. Safety and efficacy exploratory endpoints will be assessed throughout the 52-week study. In the case of clear clinical deterioration, the treatment may be changed to 1.0 mg/kg every 2 weeks at the Investigator's discretion and discussion with the Medical Monitor.

Conditions

Fabry Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pegunigalsidase alfa

Pegunigalsidase alfa 2 mg/kg intravenous infusion every 4 weeks

Group Type: EXPERIMENTAL

Pegunigalsidase alfa

Intervention Type: BIOLOGICAL

Pegunigalsidase alfa 2 mg/kg every 4 weeks

Interventions

Pegunigalsidase alfa

Pegunigalsidase alfa 2 mg/kg every 4 weeks

Intervention Type: BIOLOGICAL

Other Intervention Names

PRX-102; Recombinant human alpha galactosidase-A

Eligibility Criteria

Inclusion Criteria

1. Age: 18-60 years

2. A documented diagnosis of Fabry disease

3. Males: plasma and/or leucocyte alpha galactosidase activity (by activity assay) less than lower limit of normal according to the laboratory reference ranges and one or more of the characteristic features of Fabry disease

1. Neuropathic pain

2. Cornea verticillata

3. Clustered angiokeratoma

4. Females: historical genetic test results consistent with Fabry mutations, or in the case of novel mutations a first-degree male relative with Fabry disease, and one or more of the characteristic features of Fabry disease

1. Neuropathic pain

2. Cornea verticillata

3. Clustered angiokeratoma

5. Treatment with agalsidase alfa or agalsidase beta for at least 3 years and on a stable dose (>80% labelled dose/kg) for at least last 6 months

6. eGFR ≥ 30 mL/min/1.73m^2 by CKD-EPI equation at screening visit

7. Availability of at least 3 historical serum creatinine evaluations since starting agalsidase alfa or agalsidase beta treatment and not more than 2 years old

8. Female patients and male patients whose co-partners are of child-bearing potential agree to use a medically accepted, highly effective method of contraception. These include combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable), intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomised partner, or sexual abstinence

9. Patients whose clinical condition, in the opinion of the Investigator, is suitable for treatment with ERT every 4 weeks.

Exclusion Criteria

The presence of any of the following excludes a subject from study enrollment:

1. History of anaphylaxis or Type 1 hypersensitivity reaction to agalsidase alfa or agalsidase beta

2. History of renal dialysis or transplantation

3. Linear negative slope of eGFR of ≥ 2 mL/min/1.73m^2/year based on at least 4 serum creatinine values over approximately 2 years (including the value obtained at the screening visit)

4. History of acute kidney injury in the 12 months prior to screening, including specific kidney diseases (e.g., acute interstitial nephritis, acute glomerular and vasculitic renal diseases); non-specific conditions (e.g., ischemia, toxic injury); as well as extrarenal pathology (e.g., prerenal azotemia and acute post renal obstructive nephropathy)

5. Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy initiated or dose changed in the 4 weeks prior to screening

6. Urine protein to creatinine ratio (UPCR) at screening > 0.5 g/g or mg/mg or 500 mg/g and not treated with an ACE inhibitor or ARB

7. Females who are pregnant, planning to become pregnant during the study, or are breast feeding

8. Cardiovascular event (myocardial infarction, unstable angina) in the 6-month period before screening

9. Cerebrovascular event (stroke, transient ischemic attack) in the 6-month period before screening

10. Presence of any medical, emotional, behavioral, or psychological condition that, in the judgment of the Investigator and/or Medical Director, would interfere with the patient's compliance with the requirements of the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chiesi Farmaceutici S.p.A.

INDUSTRY

Sponsor Role: collaborator

Protalix

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

UAB Medicine

Birmingham, Alabama, United States

Emory University School of Medicine

Atlanta, Georgia, United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Infusion Associates

Grand Rapids, Michigan, United States

Institute of Metabolic Disease

Dallas, Texas, United States

University of Utah Hospital & Clinics

Salt Lake City, Utah, United States

O & O Alpan

Fairfax, Virginia, United States

UZ Antwerpen

Edegem, , Belgium

Fakultní poliklinika Všeobecné fakultní nemocnice v Praze

Prague, , Czechia

Rigshospitalet

Copenhagen, , Denmark

Azienda Ospedaliera Universitaria "Federico II"

Napoli, , Italy

Helse Bergen HF Haukeland Universitetssykehus

Bergen, , Norway

Addenbrooke's Hospital

Cambridge, , United Kingdom

The Royal Free Hospital

London, , United Kingdom

Countries

United States; Belgium; Czechia; Denmark; Italy; Norway; United Kingdom

References

Azimpour K, Dorling P, Koulinska I, Kunduri S, Lan Z, Poritz J, Tremblay G, Raad-Faherty A. Health State Utility Values in Fabry Disease: Insights from the Pegunigalsidase Alfa Clinical Trials. Adv Ther. 2025 Mar;42(3):1421-1434. doi: 10.1007/s12325-024-03095-2. Epub 2025 Jan 23.

Reference Type: DERIVED

PMID: 39847314 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

PB-102-F50

Identifier Type: -

Identifier Source: org_study_id