|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Medical condition in easily understood language
|Inherited metabolic disorder
|Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
|E.1.2 Medical condition or disease under investigation
|System Organ Class
|10010331 - Congenital, familial and genetic disorders
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|The primary objective of this study is to assess the long-term safety of FLT190 in subjects with Fabry disease.
|Secondary objectives of the trial
|• To investigate the durability of endogenous production of αGLA enzyme.
• To investigate the clearance of Gb3 and LysoGb3 in plasma and urine.
• To investigate the clearance of cellular Gb3 inclusions in skin and renal biopsies.
• To describe the immune responses to the αGLA transgene product.
• To assess viral shedding in various body fluids, where applicable.
|Trial contains a sub-study
|Principal inclusion criteria
|(i) Subjects who have previously received FLT190 (including those who may have required recommencement/initiation of ERT/PCT).
(ii) Subjects able to give full informed consent and able to comply with all requirements of the study including long-term follow-up for 60 months (5 years) post-treatment.
|Principal exclusion criteria
|Subjects who do not meet the inclusion criteria will be excluded
|E.5 End points
|Primary end point(s)
|• The primary safety endpoint will be assessed by the reporting of adverse event (AE) according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
• Other safety endpoints will be reviewed including:
- Laboratory parameter abnormalities
- Vital signs, physical examination, liver ultrasound, and electrocardiogram (ECG) abnormalities
|Timepoint(s) of evaluation of this end point
|Assessments will run throughout the study
|Secondary end point(s)
|- Production of αGLA enzyme will be summarised over time and durability investigated. Change from baseline in plasma αGLA activity will be summarised and plotted for each subject and overall.
- Change from baseline in Gb3 and LysoGb3 in plasma and urine will be summarised and plotted for each subject and overall.
- Change from baseline in cellular Gb3 inclusions in skin and renal biopsies will be summarised and plotted. A detailed description of the variables that will be studied is provided in the Biopsy Analysis Plan.
- Change from baseline in αGLA antibody levels will be summarised and plotted. Where applicable, descriptive statistics (number of observations, mean, standard deviation, minimum, median, and maximum values) will be calculated for other immune response laboratory tests at applicable visits.
- Clearance of vector genomes in blood (plasma), saliva, urine, stool, and semen will be assessed, and levels summarised until no further shedding is seen in a minimum of three consecutive samples. This may occur in the preceding treatment study and, in this case, will not be followed-up further within this protocol. The time to clearance (from FLT190 administration until the third consecutive clear sample) will be summarised and may be plotted.
|Timepoint(s) of evaluation of this end point
|Assessments will run throughout the study.
Clearance of vector genomes in blood (plasma), saliva, urine, stool, and semen will be assessed, and levels summarised until no further shedding is seen in a minimum of three consecutive samples.
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
|Number of treatment arms in the trial
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|Number of sites anticipated in Member State concerned
|The trial involves multiple Member States
|Number of sites anticipated in the EEA
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial years
|In all countries concerned by the trial months