Dose-ranging Study of PRX-102 in Adult Fabry Disease Patients

Study Overview
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Brief Summary
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This is the first human treatment with PRX-102, an enzyme being developed as a long-term enzyme replacement therapy in patients with a confirmed diagnosis of Fabry disease (alpha galactosidase deficiency). The safety, tolerability, and exploratory efficacy will be evaluated in this study of increasing doses. Patients will be treated with infusions every two weeks for 12 months.

Detailed Description
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Under the PB-102-F01 study protocol, patients will be enrolled into one of three PRX-102 dosing groups (0.2 mg/kg, 1.0 mg/kg, 2.0 mg/kg) and receive PRX-102 as an intravenous infusion every 2 weeks for 12 weeks (3 months). Patients who finish the PB-102-F01 study will be enrolled in the PB-102-F02 extension study and receive the same dose they had received in the PB-102-F01 study for an additional 38 weeks (9 months).

Official Title
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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 Months to Adult Fabry Patients

Conditions
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Fabry Disease

Intervention / Treatment
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* Drug: PRX-102


Participation Criteria
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Eligibility Criteria
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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 alpha galactosidase antibody test eGFR ≥ 60 mL/min/1.73m2 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 0.2 mg/kg<br>PRX-102 0.2 mg/kg every 2 weeks | Drug: PRX-102<br> <br> * Other names: plant cell expressed recombinant human alpha-galactosidase-A;|
| Experimental: 1 mg/kg<br>PRX-102 1 mg/kg every 2 weeks | Drug: PRX-102<br> <br> * Other names: plant cell expressed recombinant human alpha-galactosidase-A;|
| Experimental: 2 mg/kg<br>PRX-102 2 mg/kg every 2 weeks | Drug: PRX-102<br> <br> * Other names: plant cell expressed recombinant human alpha-galactosidase-A;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Reportings of adverse events reported by the patient and from monitoring with clinical laboratory, physical examination and ECG. Results represent the number of AEs that were considered possibly, probably, or definitely related to treatment. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fabry disease, Alpha galactosidase deficiency, Metabolic storage disease