Study of the Safety and Efficacy of PRX-102 Compared to Agalsidase Beta on Renal Function (BALANCE)

• ClinicalTrials.gov Identifier: NCT02795676
• Recruitment Status: Completed
• First Posted: June 10, 2016
• Last Update Posted: October 13, 2022
• Sponsor: Protalix
• Information provided by (Responsible Party): Protalix

Study Description

Brief Summary:

This is a randomized, double blind, active control study of PRX-102 (pegunigalsidase alfa) in Fabry disease patients with impaired renal function. Patients treated for approximately 1 year with agalsidase beta and on a stable dose for at least 6 months will be screened and then randomized to continue treatment with 1mg/kg agalsidase beta or to treatment with 1 mg/kg of PRX-102. The identity of the enzyme will be blinded to the patient and the investigator. Patients will receive intravenous infusions every two weeks. Patients will be randomized in a 2:1 ratio of PRX-102 to agalsidase beta. Randomization will be stratified by urinary protein to creatinine ratio (UPCR) of < or ≥ 1 g/g by spot urine sample. No more than 50% of the patients will be female.

Condition or disease	Intervention/treatment	Phase
Fabry Disease	Biological: PRX-102 (pegunigalsidase alfa); Biological: agalsidase beta	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 78 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double Blind, Active Control Study of the Safety and Efficacy of PRX-102 Compared to Agalsidase Beta on Renal Function in Patients With Fabry Disease Previously Treated With Agalsidase Beta
• Actual Study Start Date: June 2016
• Actual Primary Completion Date: October 2021
• Actual Study Completion Date: July 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: PRX-102 (pegunigalsidase alfa); PRX-102 infusion every 2 weeks	Biological: PRX-102 (pegunigalsidase alfa); PRX-102 1 mg/kg every 2 weeks; Other Names: pegunigalsidase alfa; Recombinant human alpha galactosidase-A
Active Comparator: agalsidase beta; agalsidase beta infusion every 2 weeks	Biological: agalsidase beta; agalsidase beta 1 mg/kg every 2 weeks; Other Name: Fabrazyme

Outcome Measures

Primary Outcome Measures :

1. eGFR Slope [ Time Frame: Every month for 2 years ]
   eGFR Slope

Secondary Outcome Measures :

1. Left Ventricular Mass Index (g/m2) by MRI [ Time Frame: Every 12 months for 2 years ]
2. Plasma Lyso-Gb3 [ Time Frame: 1.5 month, every 3 months for 1 year and then every 6 months up to 24 months ]
3. Plasma Gb3 [ Time Frame: 1.5 month, every 3 months for 1 year and then every 6 months up to 24 months ]
4. Urine Lyso-GB3 [ Time Frame: 1.5 month, every 3 months for 1 year and then every 6 months up to 24 months ]
5. Protein/creatinine ratio [ Time Frame: Every 3 months for 2 years ]
6. Frequency of pain medication use [ Time Frame: Every 2 weeks for 2 years ]
7. Exercise tolerance (Stress Test) [ Time Frame: Every year for 2 years ]
8. Short Form Brief Pain Inventory (BPI) [ Time Frame: Every 6 months for 2 years ]
9. Mainz Severity Score Index (MSSI) [ Time Frame: Every 6 months for 2 years ]
10. Quality of life EQ-5D-5L [ Time Frame: Every 6 months for 2 years ]

Other Outcome Measures:

1. PRX-102 pharmacokinetics [ Time Frame: Day 1, 6 months, 12 months and 24 months ]
   PRX-102 pharmacokinetics parameters
2. Anti-drug IgG antibodies [ Time Frame: Every 2 weeks for 1 month, then every month for the first 6 months and every 3 month up to 24 months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Symptomatic adult Fabry disease patients, age 18-60 years

  1. Males: Plasma and/or leucocyte alpha galactosidase activity (by activity assay) less than 30% mean normal levels and one or more of the characteristic features of Fabry disease

     i. neuropathic pain

     ii. cornea verticillata

     iii. clustered angiokeratoma

  2. Females:

     a. historical genetic test results consistent with Fabry pathogenic mutation and one or more of the described characteristic features of Fabry disease:

     i. neuropathic pain

     ii. cornea verticillata

     iii. clustered angiokeratoma

     b. or in the case of novel mutations a first degree male family member with Fabry disease with the same mutation, and one or more of the characteristic features of Fabry disease

     i. neuropathic pain

     ii. cornea verticillata

     iii. clustered angiokeratoma

• Screening eGFR by CKD-EPI equation 40 to 120 mL/min/1.73 m²
• Linear negative slope of eGFR based on at least 3 serum creatinine values over approximately 1 year (range of 9 to 18 months, including the value obtained at the screening visit) of ≥ 2 mL/min/1.73 m²/year
• Treatment with a dose of 1 mg/kg agalsidase beta per infusion every 2 weeks for at least one year and at least 80% of 13 (10.4) mg/kg total dose over the last 6 months.
• Female patients and male patients whose co-partners are of child-bearing potential agree to use a medically accepted method of contraception, not including the rhythm method.

Exclusion Criteria:

• History of anaphylaxis or Type 1 hypersensitivity reaction to agalsidase beta
• Known non-pathogenic Fabry mutations
• History of renal dialysis or transplantation
• 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 postrenal obstructive nephropathy)
• Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy initiated or dose changed in the 4 weeks prior to screening
• Patient with a screening eGFR value between 91-120 mL/min/1.73 m², having an historical eGFR value higher than 120 mL/min/1.73 m² (during 9 to 18 months before screening)
• Urine protein to creatinine ratio (UPCR) > 0.5 g/g and not treated with an ACE inhibitor or ARB
• Cardiovascular event (myocardial infarction, unstable angina) in the 6 month period before randomization
• Congestive heart failure NYHA Class IV
• Cerebrovascular event (stroke, transient ischemic attack) in the 6 month period before randomization
• Known history of hypersensitivity to Gadolinium contrast agent that is not managed by the use of pre-medication
• Female subjects who are pregnant, planning to become pregnant during the study, or are breastfeeding
• 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

Contacts and Locations

Locations

United States, Alabama

UAB Medicine

Birmingham, Alabama, United States, 35233

United States, Arizona

Phoenix Children's Hospital

Phoenix, Arizona, United States, 85016

United States, California

University of California Irvine Center

Orange, California, United States, 92868

University of California San Diego

San Diego, California, United States, 92093

United States, Georgia

Emory University School of Medicine

Atlanta, Georgia, United States, 30322

United States, Iowa

University of Iowa Hosptials and Clinics

Iowa City, Iowa, United States, 52242

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

United States, Michigan

Infusion Associates

Grand Rapids, Michigan, United States, 49525

United States, Ohio

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States, 45229

United States, Pennsylvania

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States, 15224

United States, Texas

Institute of Metabolic Disease, Baylor Healthcare

Dallas, Texas, United States, 75226

Renal Disease Research Institute, LLC - Dallas

Dallas, Texas, United States, 75235

United States, Utah

Eccles Primary Children's Outpatient Services Building

Salt Lake City, Utah, United States, 84132

United States, Virginia

O+O Alpan LLC

Fairfax, Virginia, United States, 22030

United States, Wisconsin

Medical College of Wisconsin

Milwaukee, Wisconsin, United States, 53226-3596

Czechia

Vseobecna fakultni nemocnice v Praze

Prague, Czech Republic, Czechia, 12808

Finland

Turku University Central Hospital

Turku, Finland, 20520

France

Hôpital Raymond Poincaré

Paris, France, 92380

Hungary

Semmelweis Egyetem

Budapest, Hungary, 1083

Italy

Azienda Ospedaliera Universitaria "Federico II"

Napoli, Italy

Netherlands

Academisch Medisch Centrum

Amsterdam, Netherlands, 1105 AZ

Norway

Haukeland University Hospital Klinisk Forskningspost

Bergen, Norway, 5021

Slovenia

General Hospital Slovenj Gradec

Slovenj Gradec, Slovenia, 2380

Spain

Hospital de Dia Quiron Zaragoza

Zaragoza, Spain, 50012

Switzerland

Klinik und Poliklinik für Innere Medizin UniversitätsSpital Zürich

Zürich, Switzerland

United Kingdom

Institute of Metabolism and Systems Research

Edgbaston, Birmingham, United Kingdom

Addenbrooke's Hospital

Cambridge, United Kingdom, CB2 0QQ

The Royal Free Hospital

London, United Kingdom, NW3 2QG

Salford Royal NHS Foundation Trust

Salford, United Kingdom, M6 8HD

Sponsors and Collaborators

Protalix

Investigators

• Study Director: Raul Chertkoff, MD; Protalix Ltd.

More Information

• Responsible Party: Protalix
• ClinicalTrials.gov Identifier: NCT02795676
• Other Study ID Numbers: PB-102-F20
• First Posted: June 10, 2016
• Last Update Posted: October 13, 2022
• Last Verified: October 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Keywords provided by Protalix:

Glomerular filtration rate; Proteinuria; PRX-102; pegunigalsidase alfa; Fabry Disease

Additional relevant MeSH terms:

Fabry Disease; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Lysosomal Storage Diseases; Metabolic Diseases; Lipid Metabolism Disorders; Sphingolipidoses; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors