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

• ClinicalTrials.gov Identifier: NCT03180840
• Recruitment Status: Active, not recruiting
• First Posted: June 8, 2017
• Last Update Posted: September 26, 2019
• Sponsor: Protalix
• Information provided by (Responsible Party): Protalix

Tracking Information

• First Submitted Date: May 29, 2017
• First Posted Date: June 8, 2017
• Last Update Posted Date: September 26, 2019
• Actual Study Start Date: September 27, 2017
• Estimated Primary Completion Date: July 2020 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: June 7, 2017): Number of participants with treatment-related adverse events as assessed by CTCAE v4.03 [ Time Frame: Throughout the 52-week study ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 12, 2018)

• estimated Glomerular Filtration Rate (eGFR) [ Time Frame: Baseline and every 4 weeks throughout week 52 ]
  Change in eGFR
• Frequency of pain medication use [ Time Frame: Screening and Day 1 ]
  Concomitant use of analgesics
• Left Ventricular Mass Index [ Time Frame: Baseline, week 24 and week 52 ]
  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

Original Secondary Outcome Measures (submitted: June 7, 2017)

• 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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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)
• 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 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 Type: Interventional
• Study Phase: Phase 3

Study Design

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

• Condition: Fabry Disease

Intervention

Biological: Pegunigalsidase alfa

Pegunigalsidase alfa 2 mg/kg every 4 weeks

Other Names:

• PRX-102
• Recombinant human alpha galactosidase-A

Study Arms

Experimental: Pegunigalsidase alfa

Pegunigalsidase alfa 2 mg/kg intravenous infusion every 4 weeks

Intervention: Biological: Pegunigalsidase alfa

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: June 7, 2017): 30
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2020
• Estimated Primary Completion Date: July 2020 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 60 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Canada, Czechia, Denmark, Italy, Netherlands, Norway, Spain, Taiwan, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT03180840
• Other Study ID Numbers: PB-102-F50
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Responsible Party: Protalix
• Study Sponsor: Protalix
• Collaborators: Not Provided

Investigators

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

• PRS Account: Protalix
• Verification Date: September 2019