Safety and Efficacy of PRX 102 in Patients With Fabry Disease Currently Treated With REPLAGAL® (Agalsidase Alfa)

• ClinicalTrials.gov Identifier: NCT03018730
• Recruitment Status: Active, not recruiting
• First Posted: January 12, 2017
• Last Update Posted: October 1, 2019
• Sponsor: Protalix
• Information provided by (Responsible Party): Protalix

Tracking Information

• First Submitted Date: January 9, 2017
• First Posted Date: January 12, 2017
• Last Update Posted Date: October 1, 2019
• Actual Study Start Date: February 23, 2017
• Estimated Primary Completion Date: January 2020 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: January 12, 2018): Number of participants with treatment-related adverse events as assessed by CTCAE v4.03 [ Time Frame: Throughout the 12 months study ]
• Original Primary Outcome Measures (submitted: January 10, 2017): Treatment-emergent anti-PRX-102 antibodies [ Time Frame: 12 months ]
• Change History: Complete list of historical versions of study NCT03018730 on ClinicalTrials.gov Archive Site

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

• Mean annualised change in eGFR [ Time Frame: Every 4 weeks for 12 months ]
  Mean annualised change in eGFR
• Left Ventricular Mass Index (g/m2) preferably by MRI [ Time Frame: Every 6 months for 12 months ]
  Left Ventricular Mass Index (g/m2) preferably by MRI (ECG can be used as an alternative)
• Plasma Lyso-Gb3 [ Time Frame: Every 3 months for 12 months ]
• Plasma Gb3 [ Time Frame: Every 3 months for 12 months ]
• Urine Lyso-Gb3 [ Time Frame: Every 3 months for 12 months ]
• Protein/Creatinine ratio [ Time Frame: Every 3 months for 12 months ]
  Protein/Creatinine ratio spot urine test
• Frequency of pain medication use [ Time Frame: Every 2 weeks for 12 months ]
• Exercise tolerance (Stress Test) [ Time Frame: Every 6 months for 12 months ]
• Short Form Brief Pain Inventory (BPI) [ Time Frame: Every 3 months for 12 months ]
• Mainz Severity Score Index (MSSI) [ Time Frame: Every 6 months for 12 months ]
• Quality of life EQ-5D-5L [ Time Frame: Every 6 months for 12 months ]

Original Secondary Outcome Measures (submitted: January 10, 2017)

• Mean annualised change in eGFR [ Time Frame: Every 2 weeks for 12 months ]
  Mean annualised change in eGFR
• Left Ventricular Mass Index (g/m2) preferably by MRI [ Time Frame: Every 6 months for 12 months ]
  Left Ventricular Mass Index (g/m2) preferably by MRI (ECG can be used as an alternative)
• Plasma Lyso-Gb3 [ Time Frame: Every 3 months for 12 months ]
• Plasma Gb3 [ Time Frame: Every 3 months for 12 months ]
• Urine Lyso-Gb3 [ Time Frame: Every 3 months for 12 months ]
• Protein/Creatinine ratio [ Time Frame: Every 3 months for 12 months ]
  Protein/Creatinine ratio spot urine test
• Frequency of pain medication use [ Time Frame: Every 2 weeks for 12 months ]
• Exercise tolerance (Stress Test) [ Time Frame: Every 6 months for 12 months ]
• Short Form Brief Pain Inventory (BPI) [ Time Frame: Every 3 months for 12 months ]
• Mainz Severity Score Index (MSSI) [ Time Frame: Every 6 months for 12 months ]
• Quality of life EQ-5D-5L [ Time Frame: Every 6 months for 12 months ]

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

Descriptive Information

• Brief Title: Safety and Efficacy of PRX 102 in Patients With Fabry Disease Currently Treated With REPLAGAL® (Agalsidase Alfa)
• Official Title: An Open Label Study of the Safety and Efficacy of PRX 102 in Patients With Fabry Disease Currently Treated With REPLAGAL® (Agalsidase Alfa)
• Brief Summary: This is an open label switch over study to assess the safety and efficacy of PRX-102 (pegunigalsidase alfa). Patients treated with agalsidase alfa for at least 2 years and on a stable dose (>80% labelled dose/kg) for at least 6 months. Patients will be screened and evaluated over 3 months while continuing on agalsidase alfa. Following the screening period, the patient will be enrolled and switched from their agalsidase alfa treatment to receive intravenous (IV) infusions of PRX-102 1 mg/kg every two weeks for 12 months. No more than 25% of treated patients will be female.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Fabry Disease

Intervention

Biological: PRX-102 (pegunigalsidase alfa)

PRX-102 1 mg/kg every 2 weeks

Other Names:

• pegunigalsidase alfa
• Recombinant human alpha galactosidase-A

Study Arms

Experimental: PRX-102

PRX-102 infusion every 2 weeks

Intervention: Biological: PRX-102 (pegunigalsidase alfa)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: January 10, 2017): 22
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 2020
• Estimated Primary Completion Date: January 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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 laboratory range and one or more of the characteristic features of Fabry disease i. Neuropathic pain ii. Cornea verticillata iii. 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 i. Neuropathic pain ii. Cornea verticillata iii. Clustered angiokeratoma
5. Treatment with agalsidase alfa for at least 2 years and on a stable dose (>80% labelled dose/kg) for at least 6 months
6. eGFR ≥ 40 ml/min/1.73 m2 by CKD-EPI equation
7. Availability of at least 2 historical serum creatinine evaluations since starting agalsidase alfa treatment and not more than 2 years
8. Female patients and male patients whose co-partners are of child-bearing potential agree to use a medically acceptable method of contraception, not including the rhythm method

Exclusion Criteria:

1. History of anaphylaxis or Type 1 hypersensitivity reaction to agalsidase alfa
2. History of renal dialysis or transplantation
3. 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 postrenal obstructive nephropathy)
4. Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy initiated or dose changed in the 4 weeks prior to screening
5. Urine protein to creatinine ratio (UPCR) > 0.5 g/g and not treated with an ACE inhibitor or ARB
6. Known history of hypersensitivity to Gadolinium contrast agent
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. Congestive heart failure NYHA Class IV
10. Cerebrovascular event (stroke, transient ischemic attack) in the 6 month period before screening
11. 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: Australia, Canada, Czechia, Germany, Netherlands, Norway, Slovenia, Spain, United Kingdom
• Removed Location Countries: Czech Republic

Administrative Information

• NCT Number: NCT03018730
• Other Study ID Numbers: PB-102-F30
• Has Data Monitoring Committee: No

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: No

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

Investigators

• Study Director: Raul Chertkoff, MD; Protalix Ltd

• PRS Account: Protalix
• Verification Date: September 2019