Fabry Disease
Conditions
Interventions
This will be an open-label, dose ranging study to evaluate the safety, tolerability, pharmacokinetics and exploratory efficacy parameters of PRX-102 in adult Fabry patients (>18 years of age). Subjec
Drug
Biological/vaccine
Sponsors
Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da USP
INC Research
Eligibility
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: Symptomatic adult Fabry patients (?18 yrs; Males: plasma and/or leucocyte alpha galactosidase activity (by activity assay) less than lower limit of normal (LLN in plasma=3.2 nmol/hr/ml, LLN in leucocytes=32 nmol/hr/mg/protein); Females: historical genetic test results consistent with Fabry mutations; Globotriaosylceramide (Gb3) concentration in urine > 1.5 times upper normal limit; Patients who have never received enzyme replacement therapy (ERT) in the past, or patients who have not received ERT in the past 6 months and have a negative anti PRX-102 antibody test; Chronic kidney disease - stages 1 or 2 (CKD1 or 2) (Appendix 7) with proteinuria > 200 mg/g protein-to-creatinine ratio or equivalent, measured in a Spot urine sample, demonstrated in at least one of 2 separate samples (1 sample at screening visit and the other from historical data); The patient signs informed consent; 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
Exclusion criteria: Participation in any trial of an investigational drug within 30 days prior to study screening; Chronic kidney disease stages 3-5 (CKD 3-5) (Appendix 7); History of dialysis or renal transplantation; Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy initiated or dose changed in the 4 weeks prior to screening ; Severe myocardial fibrosis by MRI (?2 late-enhancement [LE] positive left ventricular segments) (Weidemann et al. 2009); History of clinical stroke; Pregnant or nursing; Presence of HIV and/or HBsAg and/or Hepatitis C infections; Known allergies to ERT; Known allergy to Gadolinium based contrast agents; 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate the safety and tolerability: Safety will be assessed by the frequency, severity, and duration of treatment-emergent AEs (adverse events), including clinically significant laboratory abnormalities, ECG changes from baseline, physical examination findings and assessment of the injection site after administration of the study drug; Anti-PRX-102 antibodies will be assessed before dosing at: baseline, every month, at last infusion, and 1 and 3 months after last infusion. To evaluate pharmacokinetics: The following PK parameters will be derived from the plasma concentration versus time profiles to determine the profile of the study drug: Cmax, t1/2, Tmax, AUC0-t, and AUC0-?. Samples will be taken at first and last infusions at the following time points: pre-infusion (baseline); 1 hour after the beginning of the infusion; at the end of the infusion; 1, 4, 8, 24, 48±3, 72±3, 96±3 hours and 2 weeks ± 3 days post-infusion (last blood sample will be drawn just before the second infusion of the patient and just before the first infusion of the extension study). To evaluate the exploratory efficacy parameters of PRX-102 in adult Fabry patients: Exploratory efficacy parameters will be evaluated as a preliminary analysis of endpoints that may be appropriate for late stage clinical studies. The variables are as follows: Gb3 concentrations in plasma and urine sediment at baseline and at every infusion during the study; Globotriaosylsphingosine (Lyso-Gb3) concentration in plasma at baseline and at every infusion during the study; Assessment of gastrointestinal symptoms at baseline and at last infusion (Appendix 8); Kidney functions (eGFR and proteinuria) at baseline and at last infusion; Short Form Brief Pain Inventory (BPI) at baseline and at last infusion (Appendix 9).The following additional procedures will be performed only at baseline in this protocol as a reference point for evaluation as an exploratory efficacy endpoint parameter in an extension protocol. These p | — |
Countries
Australia, Brazil, Israel, Paraguay, Russian Federation, Serbia, Spain, United Kingdom, United States
Contacts
Public ContactINC Research
INC Research
Outcome results
None listed