Safety and Efficacy study assessing PRX 102 in Patients with Fabry Disease currently treated with REPLAGAL® (Agalsidase alfa)

• Register: EUCTR
• Last refreshed on: 5 April 2021
• Main ID: EUCTR2016-001318-11-DE
• Date of registration: 10/01/2017
• Prospective Registration: Yes
• Primary sponsor: Protalix Ltd.
• Public title: Safety and Efficacy study assessing PRX 102 in Patients with Fabry Disease currently treated with REPLAGAL® (Agalsidase alfa)
• Scientific title: An Open Label Study of the Safety and Efficacy of PRX 102 in Patients with Fabry Disease Currently Treated With REPLAGAL® (Agalsidase alfa)
• Date of first enrolment: 15/12/2017
• Target sample size: 22
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-001318-11
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Canada, Czech Republic, Germany, Netherlands, Norway, Slovenia, Spain, United Kingdom

Contacts

• Name: Raul Chertkoff
• Affiliation: Protalix Ltd.

• Name: Raul Chertkoff
• Affiliation: Protalix Ltd.

Key inclusion & exclusion 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
9. Subject signed an ICF before the start of protocol related activities.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 22
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. History of anaphylaxis or Type 1 hypersensitivity reaction to agalsidase alfa
2. Hypersensitivity to the active substance or to any of the excipients
(listed in section 7.2 )
3. History of renal dialysis or transplantation
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 postrenal 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) > 0.5 g/g and not treated with an ACE inhibitor or ARB
7. Known history of hypersensitivity to Gadolinium contrast agent that is not managed by the use of premedication
8. Females who are pregnant, planning to become pregnant during the study, or are breast feeding
9. Cardiovascular event (myocardial infarction, unstable angina) in the 6 month period before screening
10. Congestive heart failure NYHA Class IV
11. Cerebrovascular event (stroke, transient ischemic attack) in the 6 month period before screening
12. 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



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Body processes [G] - Genetic Phenomena [G05]

Fabry disease (a-galactosidase A deficiency)
MedDRA version: 20.0 Level: PT Classification code 10016016 Term: Fabry's disease System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Product Name: Pegunigalsidase alfa
Product Code: PRX-102
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Pegunigalsidase alpha
CAS Number: 1333358-30-7
Current Sponsor code: PRX-102
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: As per protocol

Primary end point(s): SAFETY ENDPOINTS:
Change from baseline in:
• Clinical laboratory tests
• Physical examination
• Assessment of the injection site
• Electrocardiogram
• Treatment-emergent adverse events
• Ability to taper off infusion premedication throughout the first 2 months of the study
• Requirement for use of premedication overall to manage infusion reactions
• Treatment-emergent anti-PRX-102 antibodies

EFFICACY ENDPOINTS:
• Mean annualised change in estimated glomerular filtration rate (eGFRCKD-EPI)
• Left Ventricular Mass Index (g/m2) preferably by MRI (echocardiogram can be used as an alternative)
• Plasma Lyso-Gb3
• Plasma Gb3
• Urine Lyso-Gb3
• Protein/Creatinine ratio spot urine test
• Frequency of pain medication use
• Exercise tolerance (Stress Test)
• Short Form Brief Pain Inventory (BPI)
• Mainz Severity Score Index (MSSI)
• Quality of life EQ-5D-5L

Main Objective: To evaluate the safety and efficacy of PRX-102 in patients with Fabry disease currently treated with agalsidase alfa

Secondary Objective: N/A

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: N/A

Secondary end point(s): N/A

Secondary ID(s)

NCT03018730

2016-001318-11-GB

PB-102-F30

Source(s) of Monetary Support

Protalix Ltd.

Ethics review

Status: Approved
Approval date: 15/12/2017
Contact: