Clinical trial NCT03018730: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Fabry Disease
Keywords: Fabry disease
Enzyme-Replacement Therapy
pegunigalsidase alfa
PRX-102
alpha galactosidase-A
Lead sponsor: Protalix
Sponsor class: INDUSTRY
Collaborators: name: Chiesi Farmaceutici S.p.A.
First posted: 2017-01-12
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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: Dosage and administration details:

pegunigalsidase alfa individual dose for each patient was prepared according to the patient's weight. Pegunigalsidase alfa administrated at 1 mg/kg, intravenously over 3 hours, every 2 weeks. After the first 2 months of treatment with pegunigalsidase alfa, infusion time may be reduced gradually to 1.5 hours pending patient tolerability.

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 that was not managed by the use of premedication;
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 Monitor would interfere with the patient's compliance with the requirements of the study

Primary outcomes:
measure: Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.03
timeFrame: 12 months
Secondary outcomes:
Other outcomes:
measure: eGFR
timeFrame: Baseline and Month 12 (week 52)
measure: Mean Annualised Change in eGFR (Slope)
timeFrame: Pre-switch, Post-switch
measure: Plasma Lyso-Gb3
timeFrame: Baseline and month 12 (week 52)
measure: Number of Participants According to Protein/Creatinine Ratio (UPCR)
timeFrame: 12 months
measure: Left Ventricular Mass Index (g/m^2) by MRI
timeFrame: 12 months
measure: Quality of Life EQ VAS
timeFrame: 12 months
Locations:
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Halifax
country: Canada
facility: Capital Health
state: Nova Scotia
city: Prague
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum
city: Bergen
country: Norway
facility: Helse Bergen HF Haukeland Universitetssykehus
city: Slovenj Gradec
country: Slovenia
facility: General Hospital Slovenj Gradec
city: Edgbaston
country: United Kingdom
facility: Queen Elizabeth Hospital, Department of Neurology,
state: Birmingham
city: London
country: United Kingdom
facility: The Royal Free Hospital
city: Salford
country: United Kingdom
facility: Salford Royal NHS Foundation Trust
Study officials:
References: