Pharmacokinetics, Pharmacodynamics, and Safety of Moss-aGalactosidase A in Patients With Fabry Disease

Study Overview
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Brief Summary
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Six patients with Fabry disease will be recruited. Patients will receive a single dose of 0.2 mg/kg recombinant human alpha-galactosidase A produced in moss (moss-aGal) as intravenous infusion. Patients will be hospitalized during the infusion and for at least 24 hours after the end of the infusion. Treatment will be administered sequentially: if a patient shows no safety concerns on the treatment day, treatment of the next patient will commence on the following day.

Official Title
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An Open-Label, Multi-Center Study to Evaluate the Pharmacokinetics, Pharmacodynamics, and Safety of Moss-aGal in Patients With Fabry Disease

Conditions
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Fabry Disease

Intervention / Treatment
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* Drug: Moss-aGal (recombinant human alpha-galactosidase A produced in moss)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with Fabry disease evidenced by a deficient α-galactosidase A (α-Gal A) activity or an α-Gal A gene mutation (the latter is mandatory in women); Treatment naïve Fabry patients or Fabry patients who paused any enzyme replacement therapy for Fabry disease due to personal reasons for 3 months before study entry; Female and male patients between 18 and <=65 years; At least one of the clinical manifestations of Fabry disease including neuropathic pain, angiokeratoma, cornea verticillata, cardiomyopathy, hypo- or anhydrosis, abdominal pain, diarrhea, serum creatinine >1.0 mg/dL, or proteinuria >300 mg/24 hours; Lyso-Gb3 concentrations in plasma above upper limit of normal; Male patients with a female partner of child-bearing potential agree to use a medically acceptable method of contraception (e.g. condoms, sexual abstinence, vasectomy), not including the rhythm method for 30 days after administration of the study medication; Female patients of childbearing potential must apply a highly effective method of birth control (failure rate less than 1% per year when used consistently and correctly [e.g. implants, injectables, combined oral contraceptives, some intrauterine contraceptive devices, sexual abstinence, or a vasectomized partner]). The birth control method must have been applied for at least one monthly cycle prior to the first administration of study medication and 30 days after administration of the study medication. Patient is willing and able (in the opinion of the investigator) to understand and comply with the procedures and evaluations of the study; Patient must be willing and legally able to give written informed consent. Exclusion Criteria: Treatment with any enzyme replacement therapy for Fabry disease within 3 months before study entry; Fabry patients who paused any enzyme replacement therapy for Fabry disease due to intolerability; Patient is positive for anti-alpha-Gal A immunoglobulin G (IgG) at Screening; Participation in any other clinical study with a medical device or investigational medicinal product concurrently or within 3 months before study start; Patient is currently on dialysis, is expected to begin dialysis during the study, has received a kidney transplant, or is on the renal transplant waiting list; Patient is unable to comply with the protocol (e.g. clinical relevant medical condition making implementation of the protocol difficult, unstable social situation, or otherwise unlikely to complete the study) or is, in the opinion of the investigator, otherwise unsuited for the study; Known human immunodeficiency virus, hepatitis B surface antigen and/or hepatitis C infection; Known allergies or intolerabilities to enzyme replacement therapy; Hypersensitivity (like anaphylactic reaction) to the active substance or to any excipients of moss-aGal; Co-administration of moss-aGal with chloroquine, amiodarone, benoquin or gentamicin; Breast-feeding and pregnant women; Patients with liver impairment; Women with signs of cardiac fibrosis detectable by echocardiography; Other, not Fabry disease-related severe illnesses; Malignancies within the past 5 years; Liver transaminases >=3 times above the upper Limit of normal; Alcohol and/or drug abuse; Weight >100 kg; Employees of the sponsor or patients who are employees or relatives of the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Moss-aGal<br>Single administration of 0.2 mg/kg recombinant human alpha-galactosidase A produced in moss (moss-aGal) as intravenous infusion | Drug: Moss-aGal (recombinant human alpha-galactosidase A produced in moss)<br>* Single i.v. Infusion of 0.2 mg/kg moss-aGal over 60 minutes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-inf | Area under the serum concentration curve extrapolated to infinity | PK sampling for 24 h after moss-aGal administration | 
| Number of patients with drug-related adverse events |  | Adverse event monitoring for 28 days after moss-aGal administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gb3 concentration in plasma | Globotriaosylceramide concentration in plasma | Monitoring up to Day 28 after moss-aGal administration | 
| Gb3 concentration in morning urine | Globotriaosylceramide concentration in morning urine | Monitoring up to Day 28 after moss-aGal administration | 
| Lyso-Gb3 concentration in plasma | Globotriaosylsphingosine concentration in plasma | Monitoring up to Day 28 after moss-aGal administration |