We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03180840
Recruitment Status : Completed
First Posted : June 8, 2017
Results First Posted : January 5, 2023
Last Update Posted : January 5, 2023
Sponsor:
Information provided by (Responsible Party):
Protalix

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.

Condition or disease Intervention/treatment Phase
Fabry Disease Biological: Pegunigalsidase alfa Phase 3

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: N/A
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 (PRX-102) 2mg/kg IV Every 4 Weeks for 52 Weeks in Fabry Disease Patients Currently Treated With Enzyme Replacement Therapy Fabrazyme® or Replagal™
Actual Study Start Date : July 10, 2017
Actual Primary Completion Date : August 1, 2020
Actual Study Completion Date : August 1, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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




Primary Outcome Measures :
  1. Number of Participants With Treatment-related Adverse Events (TEAE) as Assessed by CTCAE v4.03 [ Time Frame: Month 12 ]
    Results represent the number of treatment-emergent adverse events (TEAE) that were considered possibly, probably, or definitely related to treatment.


Other Outcome Measures:
  1. Estimated Glomerular Filtration Rate (eGFR) [ Time Frame: Baseline and Month 12 (week 52) ]
    eGFR was calculated based on the serum creatinine values that were assessed at Day 1, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 according to the CKD-EPI formula, baseline and Month 12 (week 52) reported. The change in eGFR from baseline measurement at Day 1 prior to first PRX-102 infusion to last measurement at Month 12 was summarized using descriptive statistics. The change was calculated for each subject and the reported value is the mean (Standard Error) of these changes.

  2. Plasma Lyso-Gb3 [ Time Frame: Baseline and month 12 (Week 52) ]

    Globotriaosylsphingosine (Lyso-Gb3) is Fabry disease specific biomarker that can assess treatment outcome, for which was measured at Baseline, weeks 12, 24, 40 and 52. The mean Plasma Lyso-Gb3 concentrations at baseline and Month 12 (week 52) and the mean change from Baseline reported.

    The change from baseline to month 12 was calculated for each subject and the reported values is the mean (Standard Error) of these changes.


  3. Quality of Life by EQ-VAS [ Time Frame: Baseline and 12 months (week 52) ]
    The EQ-VAS, of the EQ-5D-5L questionnaire, records the subject's self-rated health on a vertical, visual analogue scale where the endpoints are labelled 'Best imaginable health state' (Score 100) and 'Worst imaginable health state' (Score 0). The change from baseline to month 12 was calculated for each subject and the reported value is the mean (Standard Error) of these changes.

  4. Pharmacokinetics - Cmax [ Time Frame: Day 1, Month 9 or 11, and Month 12 ]
    Pharmacokinetic (PK) parameters were derived from the plasma concentration versus time profiles. Cmax is the maximal plasma concentration of a drug after administration. Results reported represent the values following a single dosing of the study drug.

  5. Pharmacokinetics - AUC [ Time Frame: Day 1, Month 9 or 11, and Month 12. ]
    PK parameters were derived from the plasma concentration versus time profiles. AUC is the area under the plasma concentration curve from 0 hour to infinity. Results reported represent the values following a single dosing of the study drug.

  6. Pharmacokinetics - Terminal Half Life [ Time Frame: Day 1, Month 9 or 11, and Month 12. ]
    PK parameters were derived from the plasma concentration versus time profiles. t1/2 = half life. Results reported represent the values following a single dosing of the study drug.



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.


Layout table for eligibility information
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/1.73m^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.

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/1.73m^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.

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


Locations
Layout table for location information
United States, Alabama
UAB Medicine
Birmingham, Alabama, United States, 35294
United States, Georgia
Emory University School of Medicine
Atlanta, Georgia, United States, 30322
United States, Iowa
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States, 52242
United States, Michigan
Infusion Associates
Grand Rapids, Michigan, United States, 49525
United States, Texas
Institute of Metabolic Disease
Dallas, Texas, United States, 75226
United States, Utah
University of Utah Hospital & Clinics
Salt Lake City, Utah, United States, 84132
United States, Virginia
O & O Alpan
Fairfax, Virginia, United States, 22030
Belgium
UZ Antwerpen
Edegem, Belgium, 2650
Czechia
Fakultní poliklinika Všeobecné fakultní nemocnice v Praze
Praha 2, Czechia, 120 00
Denmark
Rigshospitalet
Copenhagen, Denmark, 2100
Italy
Azienda Ospedaliera Universitaria "Federico II"
Napoli, Italy
Norway
Helse Bergen HF Haukeland Universitetssykehus
Bergen, Norway, 5021
United Kingdom
Addenbrooke's Hospital
Cambridge, United Kingdom, CB2 0QQ
The Royal Free Hospital
London, United Kingdom, NW3 2QG
Sponsors and Collaborators
Protalix
Investigators
Layout table for investigator information
Study Director: Sari Alon Sr. Director Regulatory Affairs
  Study Documents (Full-Text)

Documents provided by Protalix:
Study Protocol  [PDF] July 25, 2018
Statistical Analysis Plan  [PDF] November 25, 2020

Layout table for additonal information
Responsible Party: Protalix
ClinicalTrials.gov Identifier: NCT03180840    
Other Study ID Numbers: PB-102-F50
First Posted: June 8, 2017    Key Record Dates
Results First Posted: January 5, 2023
Last Update Posted: January 5, 2023
Last Verified: December 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
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:
Layout table for 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