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

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

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.

Study Overview

• Status: Completed
• Conditions: Fabry Disease
• Intervention / Treatment: Drug: Moss-aGal (recombinant human alpha-galactosidase A produced in moss)

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Bochum, Germany, 44791
    • Ruhruniversität Bochum, Klinik für Kinder- und Jugendmedizin im St. Josef-Hospital im Katholischen Klinikum Bochum
  • Mainz, Germany, 55131
    • Universitätsmedizin Mainz, Zentrum für Kinder- und Jugendmedizin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Moss-aGal; 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); Single i.v. Infusion of 0.2 mg/kg moss-aGal over 60 minutes

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Greenovation Biotech GmbH
• Collaborators: FGK Clinical Research GmbH

Publications and helpful links

General Publications

• Shen JS, Busch A, Day TS, Meng XL, Yu CI, Dabrowska-Schlepp P, Fode B, Niederkruger H, Forni S, Chen S, Schiffmann R, Frischmuth T, Schaaf A. Mannose receptor-mediated delivery of moss-made alpha-galactosidase A efficiently corrects enzyme deficiency in Fabry mice. J Inherit Metab Dis. 2016 Mar;39(2):293-303. doi: 10.1007/s10545-015-9886-9. Epub 2015 Aug 27.

Study record dates

Study Major Dates

• Study Start: November 1, 2016
• Primary Completion (Actual): October 9, 2017
• Study Completion (Actual): October 9, 2017

Study Registration Dates

• First Submitted: December 14, 2016
• First Submitted That Met QC Criteria: December 14, 2016
• First Posted (Estimate): December 19, 2016

Study Record Updates

• Last Update Posted (Actual): December 13, 2017
• Last Update Submitted That Met QC Criteria: December 12, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Cerebral Small Vessel Diseases; Lipidoses; Lipid Metabolism, Inborn Errors; Fabry Disease
• Other Study ID Numbers: CT-GR-MaGal-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No