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Study of the Safety, Efficacy, & PK of Pegunigalsidase Alfa (PRX-102) 2 mg/kg IV Administered Every 4 Weeks in Fabry Disease Patients (BRIGHT)

This study is not yet open for participant recruitment.
Verified June 2017 by Protalix
Sponsor:
ClinicalTrials.gov Identifier:
NCT03180840
First Posted: June 8, 2017
Last Update Posted: June 8, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Protalix
  Purpose
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.

Condition Intervention Phase
Fabry Disease Biological: Pegunigalsidase alfa Phase 3

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Intervention Model Description:
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.
Masking: None (Open Label)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Protalix:

Primary Outcome Measures:
  • Number of participants with treatment-related adverse events as assessed by CTCAE v4.03 [ Time Frame: Throughout the 52-week study ]

Secondary Outcome Measures:
  • estimated Glomerular Filtration Rate (eGFR) [ Time Frame: Baseline and end-of-study (52 weeks) ]
    Change in baseline eGFR

  • Frequency of pain medication use [ Time Frame: Screening and Day 1 ]
    Concomitant use of analgesics

  • Left Ventricular Mass Index [ Time Frame: Baseline and End-of-Study (52 weeks) ]
    LVMI measured in g/m2 by echocardiogram

  • Plasma Lyso-Gb3 [ Time Frame: Baseline, and 12, 24, 40, and 52 weeks ]
    Biomarker of disease

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

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

  • Protein/creatinine ratio [ Time Frame: Baseline, and 12, 24, 40, and 52 weeks ]
    Biomarker of renal function

  • Cardiac function assessment [ Time Frame: Day 1 and week 52 ]
    Exercise tolerance (stress test)

  • Short-form Brief Pain Inventory (BPI) [ Time Frame: Day 1 and weeks 24 and 52 ]
    Visual analog scale to measure pain

  • Mainz Severity Score Index (MSSI) [ Time Frame: Day 1 and week 52 ]
    Monitoring of clinical improvement with treatment

  • Quality-of-Life EQ-5D-5L [ Time Frame: Day 1 and 24 and 52 weeks ]
    Self-evaluation describing current patient health

  • 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

  • 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


Estimated Enrollment: 30
Anticipated Study Start Date: December 2017
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: August 2019 (Final data collection date for primary outcome measure)
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

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.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03180840


Contacts
Contact: Raul Chertkoff, MD +972-4-9028100 ext 109 raul@protalix.com
Contact: Mali Szlaifer, MS malis@protalix.com

Locations
United States, Alabama
University of Alabama, Department of Medicine Not yet recruiting
Birmingham, Alabama, United States, 35294
Contact: Eric L Wallace, MD    205-975-9676    ericlwallace@uab.edu   
Principal Investigator: Eric L Wallace, MD         
United States, Georgia
Emory University School of Medicine Not yet recruiting
Atlanta, Georgia, United States, 30322
Contact: William Wilcox, MD    404-727-5624    william.wilcox@emory.edu   
Principal Investigator: William Wilcox, MD         
United States, Iowa
University of Iowa Hosptals and Clinics, Division of Medical Genetics Not yet recruiting
Iowa City, Iowa, United States, 52242
Contact: Myrl Holida, MD    319-356-2007    myrl-holida@uiowa.edu   
Principal Investigator: Myrl Holida, MD         
United States, Michigan
Infusion Associates Not yet recruiting
Grand Rapids, Michigan, United States, 49525
Contact: Kahn Nedd, MD    616-954-0600    khannedd@yahoo.com   
Principal Investigator: Kahn Nedd, MD         
United States, Texas
Institute of Metabolic Disease, Baylor Research Institute Not yet recruiting
Dallas, Texas, United States, 75226
Contact: Raphael Schiffmann, MD, MHSc    214-820-4533    raphael.schiffmann@baylorhealth.edu   
Principal Investigator: Raphael Schiffmann, MD, MHSc         
United States, Utah
University of Utah Hospital and Clinics Not yet recruiting
Salt Lake City, Utah, United States, 84132
Contact: Nicola Longo, MD, PhD    801-587-3605    nicola.longo@hsc.utah.edu   
Principal Investigator: Nicola Longo, MD, PhD         
Canada, Nova Scotia
Capital Health Not yet recruiting
Halifax, Nova Scotia, Canada, B3H 1V8
Contact: Michael L West, MD    +9024734023    mlwest@dal.ca   
Principal Investigator: Michael L West, MD         
Turkey
Department and Laboratory of Pediatric Metabolic Disorders Not yet recruiting
Ankara, Turkey
Contact: Fatih Ezgu, MD    90 5326853697 ext 6107    fezgu@hotmail.com   
Principal Investigator: Fatih Ezgu, MD         
United Kingdom
Addenbrooke's Hospital Not yet recruiting
Cambridge, United Kingdom, CB2 0QQ
Contact: Patrick Deegan, MD    +441223245151    patrick.deegan@addenbrookes.nhs.uk   
Principal Investigator: Patrick Deegan, MD         
University College London Hospitals Not yet recruiting
London, United Kingdom, NW1 2PG
Contact: Robin Lachmann, MD    +442078298778    robin.lachmann@uclh.nhs.uk   
Principal Investigator: Robin Lachmann, MD         
The Royal Free Hospital Not yet recruiting
London, United Kingdom, NW3 2QG
Contact: Derralynn Hughes, MD    4402077940500 ext 22496    rmgvdah@ucl.ac.uk   
Principal Investigator: Derralynn Hughes, MD         
Salford Royal NHS Foundation Trust Not yet recruiting
Salford, United Kingdom, M6 8HD
Contact: Ana Jovanovic, MD    +441612064365    ana.jovanovic@srft.nhs.uk   
Principal Investigator: Ana Jovanovic, MD         
Sponsors and Collaborators
Protalix
Investigators
Study Director: Raul Chertkoff, MD Protalix Inc.
  More Information

Responsible Party: Protalix
ClinicalTrials.gov Identifier: NCT03180840     History of Changes
Other Study ID Numbers: PB-102-F50
First Submitted: May 29, 2017
First Posted: June 8, 2017
Last Update Posted: June 8, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Protalix:
Enzyme-Replacement Therapy
pegunigalsidase alfa
Fabry Disease

Additional relevant MeSH terms:
Fabry Disease
Sphingolipidoses
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
Metabolism, Inborn Errors
Lipidoses
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders