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

Sponsor
Protalix (Industry)
Overall Status
Completed
CT.gov ID
NCT03180840
Collaborator
(none)
30
Enrollment
21
Locations
1
Arm
34.1
Actual Duration (Months)
1.4
Patients Per Site
0
Patients Per Site Per Month

Study Details

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.

Condition or Disease Intervention/Treatment Phase
  • 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.

Study Design

Study Type:
Interventional
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.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)
Actual Study Start Date :
Sep 27, 2017
Actual Primary Completion Date :
Jul 2, 2020
Actual Study Completion Date :
Aug 1, 2020

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of participants with treatment-related adverse events as assessed by CTCAE v4.03 [Throughout the 52-week study]

    Secondary Outcome Measures

    1. estimated Glomerular Filtration Rate (eGFR) [Baseline and every 4 weeks throughout week 52]

      Change in eGFR

    2. Frequency of pain medication use [All visits until week 52]

      Concomitant use of analgesics

    3. Left Ventricular Mass Index [Baseline, week 24 and week 52]

      LVMI measured in g/m2 by echocardiogram

    4. Plasma Lyso-Gb3 [Baseline, and 12, 24, 40, and 52 weeks]

      Biomarker of disease

    5. Plasma Gb3 [Baseline, and 12, 24, 40, and 52 weeks]

      Biomarker of disease

    6. Urine Lyso-Gb3 [Baseline, and 12, 24, 40, and 52 weeks]

      Biomarker of disease

    7. Protein/creatinine ratio [Baseline, and 12, 24, 40, and 52 weeks]

      Biomarker of renal function

    8. Cardiac function assessment [Day 1 and week 52]

      Exercise tolerance (stress test)

    9. Short-form Brief Pain Inventory (BPI) [Day 1 and weeks 24 and 52]

      Visual analog scale to measure pain

    10. Mainz Severity Score Index (MSSI) [Day 1 and week 52]

      Monitoring of clinical improvement with treatment

    11. Quality-of-Life EQ-5D-5L [Day 1 and 24 and 52 weeks]

      Self-evaluation describing current patient health

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 60 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    4. Neuropathic pain

    5. Cornea verticillata

    6. Clustered angiokeratoma

    7. 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

    8. Neuropathic pain

    9. Cornea verticillata

    10. Clustered angiokeratoma

    11. 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

    12. eGFR ≥ 30 mL/min/1.73 m2 by CKD-EPI equation at screening visit

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

    14. 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

    15. 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

    Locations

    Site City State Country Postal Code
    1 UAB Medicine Birmingham Alabama United States 35294
    2 Emory University School of Medicine Atlanta Georgia United States 30322
    3 University of Iowa Hospitals and Clinics Iowa City Iowa United States 52242
    4 Infusion Associates Grand Rapids Michigan United States 49525
    5 Cincinnati Children's Hospital Medical Center Cincinnati Ohio United States 45229
    6 Institute of Metabolic Disease Dallas Texas United States 75226
    7 University of Utah Hospital & Clinics Salt Lake City Utah United States 84132
    8 O & O Alpan Fairfax Virginia United States 22030
    9 UZ Antwerpen Edegem Belgium 2650
    10 Capital District Health Authority Halifax Nova Scotia Canada B3H 1V8
    11 Fakultní poliklinika Všeobecné fakultní nemocnice v Praze Praha 2 Czechia 120 00
    12 Rigshospitalet Copenhagen Denmark 2100
    13 Azienda Ospedaliera Universitaria "Federico II" Napoli Italy
    14 Academisch Medisch Centrum Amsterdam Netherlands 1105
    15 Helse Bergen HF Haukeland Universitetssykehus Bergen Norway 5021
    16 Hospital Quirón Floresta Zaragoza Spain 50012
    17 Genetic Counselling Center of Taipei Veterans General Hospital Taipei Taiwan 11217
    18 Gazi Universitesi Tip Fakultesi Cocuk Sagligi ve Hastaliklari Anabilim Dali Ankara Turkey 06560
    19 Addenbrooke's Hospital Cambridge United Kingdom CB2 0QQ
    20 University of Birmingham, Institute of Metabolism and Systems Research Edgbaston United Kingdom B15 2TQ
    21 The Royal Free Hospital London United Kingdom NW3 2QG

    Sponsors and Collaborators

    • Protalix

    Investigators

    • Study Director: Raul Chertkoff, MD, Protalix Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Protalix
    ClinicalTrials.gov Identifier:
    NCT03180840
    Other Study ID Numbers:
    • PB-102-F50
    First Posted:
    Jun 8, 2017
    Last Update Posted:
    Apr 7, 2022
    Last Verified:
    Mar 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    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

    Study Results

    No Results Posted as of Apr 7, 2022