Study to evaluate the safety, tolerability and efficacy parameters of the drug PRX-102 administered by intravenous infusion every 2 weeks for 12 weeks, to adult patients with Fabry disease

• Register: REBEC
• Last refreshed on: 29 May 2023
• Main ID: RBR-97trz9
• Date of registration: 21/12/2015
• Prospective Registration: No
• Primary sponsor: Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da USP
• Public title: Study to evaluate the safety, tolerability and efficacy parameters of the drug PRX-102 administered by intravenous infusion every 2 weeks for 12 weeks, to adult patients with Fabry disease
• Scientific title: A Phase 1/2, Open Label, Dose Ranging Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Exploratory Efficacy Parameters of PRX-102 Administered by Intravenous Infusion Every 2 Weeks for 12 Weeks to Adult Fabry Patients
• Date of first enrolment: 02/12/2013
• Recruitment status: Withdrawn
• URL: http://ensaiosclinicos.gov.br/rg/RBR-97trz9
• Study type: Intervention
• Study design: Safety and efficacy clinical trial, open label, single-group, phase 1/2.
• Phase: 1-2

Countries of recruitment

Australia, Brazil, Israel, Paraguay, Russian Federation, Serbia, Spain, United Kingdom, United States

Contacts

• Name: INC Research
• Affiliation: INC Research

• Name: INC Research
• Affiliation: INC Research

Key inclusion & exclusion 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: 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


Age minimum: 18Y
Age maximum:
Gender: -

Health Condition(s) or Problem(s) studied

C10.228.140.163.100.435.825.200

Fabry Disease

Intervention(s)

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). Subjects will receive intravenous infusions of PRX-102 every 2 weeks for 12 weeks, totaling 7 infusions.
Subjects will be enrolled into one of three PRX-102 dosing groups (6 patients per group). The first patient will be given the lowest dose (0.2 mg/kg) for at least 4 infusions and, only if well tolerated, the second patient in the first Treatment Group will be given at least 4 infusions. The last 4 patients in the first Treatment Group will be infused only if the entire series of 7 infusions have been well-tolerated in the first patient and the 4 infusions have been well-tolerated in the second patient. Only after all 6 patients of the first Treatment Group have tolerated all 7 infusions each the next Treatment Group of 6 patients will be given the next dose of 1 mg/kg. Only after all 6 patients of the second Treatment Group have tolerated all 7 infusions each, the last Treatment Group of 6 patients will be given the next dose of 2 mg/kg. Upon completion of the 12-week treatment period, subjects will have the option to enrol in an open-label extension study.
All infusions will be given during hospitalization, with observation period post- infusion to complete at least 24 hours of hospitalization.
If, in the 2nd and 3rd Treatment Groups, the first 4 infusions will be well tolerated, and hospitalization will be a significant burden for the patient, outpatient setup at a selected medical center with adequate emergency treatment facilities to provide cardiopulmonary resuscitation if needed, including access to intubation and qualified personnel, could be considered

Biological/vaccine

Drug

E02.095

Primary Outcome(s)

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 parameters are not expected to show significant response during the 12 weeks of dosing in this study and will not be repeated at the last infusion. Kidney biopsy for Gb3 concentration (Appendix 5). Skin punch biopsy for Gb3 concentration (Appendix 5).MRI of the heart and brain. Mainz Severity Score Index (MSSI) (Appendix 6). Cardiac function assessment (echocardiography and stress test)

Source(s) of Monetary Support

Protalix Ltd

Secondary Sponsor(s)

INC Research