Fabry Disease
Conditions
Keywords
agalsidase alfa, Replagal, Enzyme Replacement Therapy
Brief summary
The purpose of this study is to assess the safety of Replagal in children with Fabry disease who who have not previously been treated with enzyme replacement therapy (ERT).
Detailed description
In 2008, a change in the agalsidase alfa drug substance manufacturing process was made. There are no changes to the drug product formulation, manufacturing site, manufacturing process, or container closure. An agalsidase alfa bioreactor manufacturing process (agalAF1) utilizing animal component-free media replaced the previous roller bottle (RB) process. This study will evaluate the safety of Replagal AF, manufactured using the new bioreactor process at a dose of 0.2 mg/kg infused IV over 40 minutes, every other week (EOW) in children with Fabry disease who are 7 years to less than 18 years of age and who are naive to ERT.
Interventions
BIOLOGICALReplagal (agalsidase alfa)
0.2 mg/kg administered over 40 minutes every other week (EOW)
Sponsors
Shire
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
7 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
Patients must meet all of the following criteria to be enrolled in this study. 1. All patients must be diagnosed with Fabry disease by the following criteria: * Male Patients: The patient is a hemizygous male with Fabry disease as confirmed by a deficiency of alfa-galactosidase A activity measured in serum, leukocytes, or fibroblasts or has a confirmed mutation of the alfa-galactosidase-A gene. * Female Patients: The patient is a heterozygous female with Fabry disease as confirmed by a mutation of the alfa-galactosidase A gene. Note: If the diagnosis of Fabry disease is previously documented in the patient's medical record, screening tests do not need to be repeated. 2. The patient is 7 to \<18 years of age 3. The patient is ERT-naïve 4. Adequate general health (as determined by the Investigators) to undergo the specified phlebotomy regimen and protocol-related procedures and no safety or medical contraindications for participation 5. The minor child must assent to participate in the protocol and the parent(s) or legally authorized representative(s) must have voluntarily signed an Institutional Review Board/Independent Ethics Committee (IRB/IEC) approved informed consent form after all relevant aspects of the study have been explained and discussed with the child and the child's parent(s) or legally authorized representative(s)
Exclusion criteria
Patients who meet any of the following criteria will be excluded from the study. 1. Patient and/or the patient's parent(s) or legally authorized representative(s) are unable to understand the nature, scope, and possible consequences of the study 2. Patient is unable to comply with the protocol, eg, uncooperative with protocol schedule, refusal to agree to all of the study procedures, inability to return for evaluations, or is otherwise unlikely to complete the study, as determined by the Investigator or the medical monitor. 3. Otherwise unsuitable for the study, in the opinion of the Investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Heart Rate Variability Parameter pNN50 | Baseline to week 55 | — |
| Number of Treatment Emergent Adverse Event (TEAE) | Baseline to week 55 | — |
| Development of IgG Anti-Agalsidase Alfa Antibody | Baseline to Week 55 | Reflects development of Anti-Agalsidase antibodies post baseline |
| Change From Baseline in Heart Rate Variability Parameter SDNN | Baseline to week 55 | — |
| Change From Baseline in Heart Rate Variability Parameter rMSSD | Baseline to week 55 | — |
| Number of Serious Adverse Event (SAE) | Baseline to week 55 | — |
Secondary
| Measure | Time frame |
|---|---|
| Change From Baseline in LVMI | Baseline to week 55 |
| Change From Baseline in Plasma Gb3 | Baseline to week 55 |
| Change From Baseline in Urine Gb3 | Baseline to week 55 |
| Change From Baseline in MFS | Baseline to week 55 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Replagal (0.2 mg/kg) 0.2 mg/kg Replagal (agalsidase alfa) administered over 40 minutes EOW | 14 |
| Total | 14 |
Baseline characteristics
| Characteristic | Replagal (0.2 mg/kg) |
|---|---|
| Age, Continuous | 12.16 Years STANDARD_DEVIATION 2.992 |
| Age, Customized <=18 years | 14 Participants |
| Heart rate variability parameter pNN50 | 32.79 msec STANDARD_DEVIATION 19.997 |
| Heart rate variability parameter rMSSD | 75.92 msec STANDARD_DEVIATION 45.747 |
| Heart rate variability parameter SDNN | 103.46 msec STANDARD_DEVIATION 32.928 |
| Left Ventricular Mass Index (LVMI) | 35.37 (g/m^2.7) STANDARD_DEVIATION 10.129 |
| Midwall Fractional Shortening (MFS) | 18.63 (%) STANDARD_DEVIATION 2.891 |
| Plasma Gb3 | 14.79 (nmol/mL) STANDARD_DEVIATION 12.228 |
| Region of Enrollment UNITED STATES | 14 Participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 5 Participants |
| Urine Gb3 | 1775.08 (nmol/g creatinine) STANDARD_DEVIATION 3691.087 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 14 / 14 |
| serious Total, serious adverse events | 0 / 14 |
Outcome results
Primary
Change From Baseline in Heart Rate Variability Parameter pNN50
Time frame: Baseline to week 55
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Replagal (0.2 mg/kg) | Change From Baseline in Heart Rate Variability Parameter pNN50 | -4.13 msec | Standard Deviation 20.166 |
Primary
Change From Baseline in Heart Rate Variability Parameter rMSSD
Time frame: Baseline to week 55
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Replagal (0.2 mg/kg) | Change From Baseline in Heart Rate Variability Parameter rMSSD | 1.46 msec | Standard Deviation 53.502 |
Primary
Change From Baseline in Heart Rate Variability Parameter SDNN
Time frame: Baseline to week 55
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Replagal (0.2 mg/kg) | Change From Baseline in Heart Rate Variability Parameter SDNN | 10.46 msec | Standard Deviation 24.223 |
Primary
Development of IgG Anti-Agalsidase Alfa Antibody
Reflects development of Anti-Agalsidase antibodies post baseline
Time frame: Baseline to Week 55
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Replagal (0.2 mg/kg) | Development of IgG Anti-Agalsidase Alfa Antibody | 1 participants |
Primary
Number of Serious Adverse Event (SAE)
Time frame: Baseline to week 55
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Replagal (0.2 mg/kg) | Number of Serious Adverse Event (SAE) | 0 events |
Primary
Number of Treatment Emergent Adverse Event (TEAE)
Time frame: Baseline to week 55
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Replagal (0.2 mg/kg) | Number of Treatment Emergent Adverse Event (TEAE) | 166 events |
Secondary
Change From Baseline in LVMI
Time frame: Baseline to week 55
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Replagal (0.2 mg/kg) | Change From Baseline in LVMI | 0.16 (g/m^2.7) | Standard Deviation 6.059 |
Secondary
Change From Baseline in MFS
Time frame: Baseline to week 55
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Replagal (0.2 mg/kg) | Change From Baseline in MFS | -0.62 (%) | Standard Deviation 3.596 |
Secondary
Change From Baseline in Plasma Gb3
Time frame: Baseline to week 55
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Replagal (0.2 mg/kg) | Change From Baseline in Plasma Gb3 | -5.71 (nmol/mL) | Standard Deviation 8.799 |
Secondary
Change From Baseline in Urine Gb3
Time frame: Baseline to week 55
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Replagal (0.2 mg/kg) | Change From Baseline in Urine Gb3 | -1403.25 (nmol/g creatinine) | Standard Deviation 3636.711 |