Fabry Disease
Conditions
Keywords
a-Galactosidase A, aGal, r-haGAL, Fabry, GL-3, Fabrazyme
Brief summary
People with Fabry disease have an alteration in their genetic material (DNA) which causes a deficiency of the a-galactosidase A enzyme. This enzyme helps to break down and remove certain types of fatty substances called glycolipids. These glycolipids are normally present within the body in most cells. In people with Fabry disease, glycolipids build up in various tissues such as the liver, kidney, skin, and blood vessels because a-galactosidase A is not present, or is present in small quantities. The build up of glycolipid levels (also referred to as globotriaosylceramide or GL-3) in these tissues is thought to cause the clinical symptoms that are common to Fabry disease. Symptoms commonly appear during childhood with pain in the hands and feet. This study explored the safety, efficacy and pharmacokinetics of Fabrazyme in pediatric patients aged between 7 and 15 years.
Interventions
BIOLOGICALFabrazyme (agalsidase beta)
1 mg/kg every 2 weeks
Sponsors
Genzyme, a Sanofi Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
7 Years to 15 Years
Healthy volunteers
No
Inclusion criteria
* Patient or legal guardian must provide written informed consent * Patients must have a clinical diagnosis of Fabry disease and active Fabry disease (clinical signs and symptoms) * Patients must be at least 7 years of age but no older than 15 years of age at time of enrollment * Patients must be Tanner Stage ≤ III * Female patients must have a negative pregnancy test prior to each infusion and use a medically accepted form of contraception throughout the study
Exclusion criteria
* Patient has a clinically significant organic disease (with the exception of symptoms relating to Fabry disease) that in the opinion of the investigator would preclude participation in the trial * Patient has participated in a study employing investigational drug within 30 days of the start of this study * Patient has received prior treatment with enzyme replacement therapy * Patient is unable to comply with the clinical protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Globotriaosylceramide (GL-3) Clearance in Capillary Endothelium in the Skin | Baseline, Week 24 and Week 48 | Skin biopsies were taken at Baseline, Week 24 and Week 48 and analyzed for cellular GL-3 accumulation (inclusions) by light microscopy. Each biopsy was evaluated by pathologists for the total number of vessels with GL-3 accumulation on an inclusion severity score of 0 (none/trace), 1 (mild), 2 (moderate), and 3 (severe). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma GL-3 | Baseline, Week 24 and Week 48 | Plasma GL-3 values at Baseline, Week 24, and Week 48. Normal plasma GL-3 level is ≤ 7.03 µg/mL. |
Countries
France, Poland, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fabrazyme 1.0 mg/kg of Fabrazyme given to the patients every 2 weeks. | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Fabrazyme |
|---|---|
| Age, Continuous | 12.1 years STANDARD_DEVIATION 2.52 |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 16 / 16 |
| serious Total, serious adverse events | 1 / 16 |
Outcome results
Primary
Globotriaosylceramide (GL-3) Clearance in Capillary Endothelium in the Skin
Skin biopsies were taken at Baseline, Week 24 and Week 48 and analyzed for cellular GL-3 accumulation (inclusions) by light microscopy. Each biopsy was evaluated by pathologists for the total number of vessels with GL-3 accumulation on an inclusion severity score of 0 (none/trace), 1 (mild), 2 (moderate), and 3 (severe).
Time frame: Baseline, Week 24 and Week 48
Population: Intent to Treat (ITT) population - male patients only. 14 patients had skin biopsies performed at Baseline and Week 24 but only 5 patients had skin biopsies performed at Week 48.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fabrazyme | Globotriaosylceramide (GL-3) Clearance in Capillary Endothelium in the Skin | None/Trace (0) Score at Baseline | 2 patients |
| Fabrazyme | Globotriaosylceramide (GL-3) Clearance in Capillary Endothelium in the Skin | None/Trace (0) Score at Week 24 | 14 patients |
| Fabrazyme | Globotriaosylceramide (GL-3) Clearance in Capillary Endothelium in the Skin | None/Trace (0) Score at Week 48 | 5 patients |
| Fabrazyme | Globotriaosylceramide (GL-3) Clearance in Capillary Endothelium in the Skin | Mild (1) Score at Baseline | 0 patients |
| Fabrazyme | Globotriaosylceramide (GL-3) Clearance in Capillary Endothelium in the Skin | Mild (1) Score at Week 24 | 0 patients |
| Fabrazyme | Globotriaosylceramide (GL-3) Clearance in Capillary Endothelium in the Skin | Mild (1) Score at Week 48 | 0 patients |
| Fabrazyme | Globotriaosylceramide (GL-3) Clearance in Capillary Endothelium in the Skin | Moderate (2) Score at Baseline | 11 patients |
| Fabrazyme | Globotriaosylceramide (GL-3) Clearance in Capillary Endothelium in the Skin | Moderate (2) Score at Week 24 | 0 patients |
| Fabrazyme | Globotriaosylceramide (GL-3) Clearance in Capillary Endothelium in the Skin | Moderate (2) Score at Week 48 | 0 patients |
| Fabrazyme | Globotriaosylceramide (GL-3) Clearance in Capillary Endothelium in the Skin | Severe (3) Score at Baseline | 1 patients |
| Fabrazyme | Globotriaosylceramide (GL-3) Clearance in Capillary Endothelium in the Skin | Severe (3) Score at Week 24 | 0 patients |
| Fabrazyme | Globotriaosylceramide (GL-3) Clearance in Capillary Endothelium in the Skin | Severe (3) Score at Week 48 | 0 patients |
Secondary
Plasma GL-3
Plasma GL-3 values at Baseline, Week 24, and Week 48. Normal plasma GL-3 level is ≤ 7.03 µg/mL.
Time frame: Baseline, Week 24 and Week 48
Population: ITT population. 16 male patients had plasma GL-3 values at Baseline and Week 24, while 15 male patients had plasma GL-3 values at Week 48. 2 female patients had plasma GL-3 values at Baseline, Week 24 and Week 48.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fabrazyme | Plasma GL-3 | Male Patients at Baseline | 15.4 µg/mL | Standard Deviation 4.1 |
| Fabrazyme | Plasma GL-3 | Female Patients at Baseline | 4.9 µg/mL | Standard Deviation 0.64 |
| Fabrazyme | Plasma GL-3 | Overall at Baseline | 14.1 µg/mL | Standard Deviation 5.25 |
| Fabrazyme | Plasma GL-3 | Males at Week 24 | 5.5 µg/mL | Standard Deviation 0.95 |
| Fabrazyme | Plasma GL-3 | Females at Week 24 | 3.6 µg/mL | Standard Deviation 0.57 |
| Fabrazyme | Plasma GL-3 | Overall at Week 24 | 5.2 µg/mL | Standard Deviation 1.1 |
| Fabrazyme | Plasma GL-3 | Males at Week 48 | 5.0 µg/mL | Standard Deviation 1 |
| Fabrazyme | Plasma GL-3 | Females at Week 48 | 4.4 µg/mL | Standard Deviation 1.27 |
| Fabrazyme | Plasma GL-3 | Overall at Week 48 | 4.9 µg/mL | Standard Deviation 1.01 |