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History of Changes for Study: NCT03180840
Study of the Safety, Efficacy, & PK of Pegunigalsidase Alfa (PRX-102) 2 mg/kg IV Administered Every 4 Weeks in Fabry Disease Patients (BRIGHT)
Latest version (submitted September 20, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 June 7, 2017 None (earliest Version on record)
2 January 12, 2018 Recruitment Status, Contacts/Locations, Study Status, Outcome Measures and Oversight
3 March 18, 2019 Recruitment Status, Study Status and Contacts/Locations
4 March 28, 2019 Recruitment Status, Contacts/Locations, Study Status and Study Description
5 September 25, 2019 Recruitment Status, Study Status, Contacts/Locations and Study Design
6 January 20, 2022 Recruitment Status, Study Status and Contacts/Locations
7 March 29, 2022 Study Status and Outcome Measures
8 September 20, 2022
Quality Control Review has not concluded Returned: October 18, 2022
Study Status, Outcome Measures, Contacts/Locations, Study Identification, Document Section, Results, IPDSharing and Eligibility
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Study NCT03180840
Submitted Date:  June 7, 2017 (v1)

Open or close this module Study Identification
Unique Protocol ID: PB-102-F50
Brief Title: Study of the Safety, Efficacy, & PK of Pegunigalsidase Alfa (PRX-102) 2 mg/kg IV Administered Every 4 Weeks in Fabry Disease Patients (BRIGHT)
Official Title: Phase 3, Open-Label, Switch Over Study to Assess Safety, Efficacy & PK of Pegunigalsidase Alfa 2 mg/kg Administered Every 4 Weeks for 52 Weeks in Fabry Disease Patients Currently Treated With Enzyme Replacement Therapy: Fabrazyme® (Agalsidase Beta) or Replagal™ (Agalsidase Alfa)
Secondary IDs:
Open or close this module Study Status
Record Verification: June 2017
Overall Status: Not yet recruiting
Study Start: December 2017
Primary Completion: August 2019 [Anticipated]
Study Completion: December 2019 [Anticipated]
First Submitted: May 29, 2017
First Submitted that
Met QC Criteria:
June 7, 2017
First Posted: June 8, 2017 [Actual]
Last Update Submitted that
Met QC Criteria:
June 7, 2017
Last Update Posted: June 8, 2017 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Protalix
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
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 (approximately 15 patients on each 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.
Open or close this module Conditions
Conditions: Fabry Disease
Keywords: Enzyme-Replacement Therapy
pegunigalsidase alfa
Fabry Disease
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 3
Interventional Study Model: Single Group Assignment
Switch over study in patients previously receiving either agalsidase alfa or agalsidase beta and switched to pegunigalsidase alfa (PRX-102) for the treatment of Fabry disease.
Number of Arms: 1
Masking: None (Open Label)
Allocation: N/A
Enrollment: 30 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Pegunigalsidase alfa
Pegunigalsidase alfa 2 mg/kg intravenous infusion every 4 weeks
Biological: Pegunigalsidase alfa
Pegunigalsidase alfa 2 mg/kg every 4 weeks
Other Names:
  • PRX-102
  • Recombinant human alpha galactosidase-A
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Number of participants with treatment-related adverse events as assessed by CTCAE v4.03
[ Time Frame: Throughout the 52-week study ]

Secondary Outcome Measures:
1. estimated Glomerular Filtration Rate (eGFR)
[ Time Frame: Baseline and end-of-study (52 weeks) ]

Change in baseline eGFR
2. Frequency of pain medication use
[ Time Frame: Screening and Day 1 ]

Concomitant use of analgesics
3. Left Ventricular Mass Index
[ Time Frame: Baseline and End-of-Study (52 weeks) ]

LVMI measured in g/m2 by echocardiogram
4. Plasma Lyso-Gb3
[ Time Frame: Baseline, and 12, 24, 40, and 52 weeks ]

Biomarker of disease
5. Plasma Gb3
[ Time Frame: Baseline, and 12, 24, 40, and 52 weeks ]

Biomarker of disease
6. Urine Lyso-Gb3
[ Time Frame: Baseline, and 12, 24, 40, and 52 weeks ]

Biomarker of disease
7. Protein/creatinine ratio
[ Time Frame: Baseline, and 12, 24, 40, and 52 weeks ]

Biomarker of renal function
8. Cardiac function assessment
[ Time Frame: Day 1 and week 52 ]

Exercise tolerance (stress test)
9. Short-form Brief Pain Inventory (BPI)
[ Time Frame: Day 1 and weeks 24 and 52 ]

Visual analog scale to measure pain
10. Mainz Severity Score Index (MSSI)
[ Time Frame: Day 1 and week 52 ]

Monitoring of clinical improvement with treatment
11. Quality-of-Life EQ-5D-5L
[ Time Frame: Day 1 and 24 and 52 weeks ]

Self-evaluation describing current patient health
12. Blood samples analyzed for pegunigalsidase alfa concentrations
[ Time Frame: Day 1 and after the final infusion on Week 52 ]

Pharmacokinetic parameters are derived from blood concentrations of pegunigalsidase alfa
13. Anti-drug IgG antibodies
[ Time Frame: Screening and Baseline, and 12, 24, 40, and 52 weeks ]

To assess and characterize the formation of antibodies to pegunigalsidase alfa
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age: 60 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Key inclusion criteria:

Eligible subjects must fulfill the following 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/1.73 m2 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.

Key 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/1.73 m2 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.
Open or close this module Contacts/Locations
Central Contact Person: Raul Chertkoff, MD
Telephone: +972-4-9028100 Ext. 109
Email: raul@protalix.com
Central Contact Backup: Mali Szlaifer, MS
Email: malis@protalix.com
Study Officials: Raul Chertkoff, MD
Study Director
Protalix Inc.
Locations: United States, Alabama
University of Alabama, Department of Medicine
Birmingham, Alabama, United States, 35294
Contact:Contact: Eric L Wallace, MD 205-975-9676 ericlwallace@uab.edu
Contact:Principal Investigator: Eric L Wallace, MD
United States, Georgia
Emory University School of Medicine
Atlanta, Georgia, United States, 30322
Contact:Contact: William Wilcox, MD 404-727-5624 william.wilcox@emory.edu
Contact:Principal Investigator: William Wilcox, MD
United States, Iowa
University of Iowa Hosptals and Clinics, Division of Medical Genetics
Iowa City, Iowa, United States, 52242
Contact:Contact: Myrl Holida, MD 319-356-2007 myrl-holida@uiowa.edu
Contact:Principal Investigator: Myrl Holida, MD
United States, Michigan
Infusion Associates
Grand Rapids, Michigan, United States, 49525
Contact:Contact: Kahn Nedd, MD 616-954-0600 khannedd@yahoo.com
Contact:Principal Investigator: Kahn Nedd, MD
United States, Texas
Institute of Metabolic Disease, Baylor Research Institute
Dallas, Texas, United States, 75226
Contact:Contact: Raphael Schiffmann, MD, MHSc 214-820-4533 raphael.schiffmann@baylorhealth.edu
Contact:Principal Investigator: Raphael Schiffmann, MD, MHSc
United States, Utah
University of Utah Hospital and Clinics
Salt Lake City, Utah, United States, 84132
Contact:Contact: Nicola Longo, MD, PhD 801-587-3605 nicola.longo@hsc.utah.edu
Contact:Principal Investigator: Nicola Longo, MD, PhD
Canada, Nova Scotia
Capital Health
Halifax, Nova Scotia, Canada, B3H 1V8
Contact:Contact: Michael L West, MD +9024734023 mlwest@dal.ca
Contact:Principal Investigator: Michael L West, MD
Turkey
Department and Laboratory of Pediatric Metabolic Disorders
Ankara, Turkey
Contact:Contact: Fatih Ezgu, MD 90 5326853697 Ext. 6107 fezgu@hotmail.com
Contact:Principal Investigator: Fatih Ezgu, MD
United Kingdom
Addenbrooke's Hospital
Cambridge, United Kingdom, CB2 0QQ
Contact:Contact: Patrick Deegan, MD +441223245151 patrick.deegan@addenbrookes.nhs.uk
Contact:Principal Investigator: Patrick Deegan, MD
University College London Hospitals
London, United Kingdom, NW1 2PG
Contact:Contact: Robin Lachmann, MD +442078298778 robin.lachmann@uclh.nhs.uk
Contact:Principal Investigator: Robin Lachmann, MD
The Royal Free Hospital
London, United Kingdom, NW3 2QG
Contact:Contact: Derralynn Hughes, MD 4402077940500 Ext. 22496 rmgvdah@ucl.ac.uk
Contact:Principal Investigator: Derralynn Hughes, MD
Salford Royal NHS Foundation Trust
Salford, United Kingdom, M6 8HD
Contact:Contact: Ana Jovanovic, MD +441612064365 ana.jovanovic@srft.nhs.uk
Contact:Principal Investigator: Ana Jovanovic, MD
Open or close this module IPDSharing
Plan to Share IPD: Undecided
Open or close this module References
Citations:
Links:
Available IPD/Information:

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