Chronic Kidney Disease, Stage IV (Severe), Fabry Disease
Conditions
Keywords
Fabry Disease patients with Severe Renal Disease
Brief summary
This study was designed to determine appropriate treatment with Fabrazyme at a biweekly dose of either 1 mg/kg or 3 mg/kg in a population of patients with severe renal disease burden.
Interventions
BIOLOGICALFabrazyme (agalsidase beta)
1.0 mg/kg every 2 weeks
Sponsors
CRL/Medinet
Genzyme, a Sanofi Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* provided written informed consent prior to any study-related procedures being performed. * be ≥16 years old. * have a current diagnosis of Fabry disease (defined as abnormal α-galactosidase (α GAL) enzyme levels or Fabry genotype). * have one of the following clinical conditions present at enrollment: serum creatinine level greater than 3.0 mg/dL (an average of two values at least one week apart), or be currently on dialysis, or be status post kidney transplant by greater than 3 months. * have the ability to comply with the requirements of the protocol * have a negative pregnancy test, if a female patient of childbearing potential. In addition, all female patients of childbearing potential must use a medically accepted method of contraception throughout the study.
Exclusion criteria
* if they did not meet the specific inclusion criteria. * if they had participated in a study employing an investigational drug within 30 days of the start of their participation in this trial. * had previously received enzyme replacement therapy (ERT) for their Fabry disease. * had diabetic nephropathy. * were pregnant or lactating. * were unwilling to comply with the requirements of the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Clinically Significant Progression of Cardiac Disease, Cerebrovascular Disease, and/or Death Among Fabry Patients With Severe Kidney Disease | 7 months | The trial was terminated early due to inadequate study design. During the study period of 7 months, only 1 patient had a clinical event, a stroke, in the Fabrazyme 1 mg/kg treatment arm. The time to event was determined from first dose of Fabrazyme to the date of event. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Globotriaosylceramide (GL-3) | Evaluated at Baseline, Month 3, and Final Visit | This outcome measure evaluated the mean plasma GL-3 values for all patients to see if it decreased while on Fabrazyme. Normal plasma GL-3 level is defined as ≤ 7.03 µg/mL. |
Countries
United States
Participant flow
Pre-assignment details
Because the study was ended early only 20 patients from 9 sites were randomized into this study using a 1:1 randomization scheme to receive biweekly infusions of either 1 mg/kg (11 patients) or 3 mg/kg (9 patients) of Fabrazyme.
Participants by arm
| Arm | Count |
|---|---|
| Fabrazyme 1mg/kg Every 2 Weeks Fabrazyme 1.0 mg/kg every 2 weeks | 11 |
| Fabrazyme 3mg/kg Every 2 Weeks Fabrazyme 3.0 mg/kg every 2 weeks | 9 |
| Total | 20 |
Baseline characteristics
| Characteristic | Total | Fabrazyme 3mg/kg Every 2 Weeks | Fabrazyme 1mg/kg Every 2 Weeks |
|---|---|---|---|
| Age, Continuous | 49.2 years STANDARD_DEVIATION 7.04 | 48.9 years STANDARD_DEVIATION 7.55 | 49.4 years STANDARD_DEVIATION 6.96 |
| Age, Customized < 40 Years | 2 Years | 1 Years | 1 Years |
| Age, Customized ≥ 40 Years | 18 Years | 8 Years | 10 Years |
| Race/Ethnicity, Customized Black | 5 Number of Participants | 2 Number of Participants | 3 Number of Participants |
| Race/Ethnicity, Customized Caucasian | 14 Number of Participants | 7 Number of Participants | 7 Number of Participants |
| Race/Ethnicity, Customized Hispanic | 1 Number of Participants | 0 Number of Participants | 1 Number of Participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 17 Participants | 7 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 10 / 11 | 9 / 9 | 19 / 20 |
| serious Total, serious adverse events | 4 / 11 | 1 / 9 | 5 / 20 |
Outcome results
Primary
Time to Clinically Significant Progression of Cardiac Disease, Cerebrovascular Disease, and/or Death Among Fabry Patients With Severe Kidney Disease
The trial was terminated early due to inadequate study design. During the study period of 7 months, only 1 patient had a clinical event, a stroke, in the Fabrazyme 1 mg/kg treatment arm. The time to event was determined from first dose of Fabrazyme to the date of event.
Time frame: 7 months
Population: Intent-to-Treat (ITT) Population-consisted of all 20 patients enrolled in the trial. The original sample size was 120 patients. Due to early termination, only 20 patients were enrolled in this trial. No imputation of data was performed. During the 7 months study period, only 1 patient had a clinical event in the Fabrazyme 1 mg/kg treatment arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fabrazyme 1mg/kg Every 2 Weeks | Time to Clinically Significant Progression of Cardiac Disease, Cerebrovascular Disease, and/or Death Among Fabry Patients With Severe Kidney Disease | 35 Days |
Secondary
Plasma Globotriaosylceramide (GL-3)
This outcome measure evaluated the mean plasma GL-3 values for all patients to see if it decreased while on Fabrazyme. Normal plasma GL-3 level is defined as ≤ 7.03 µg/mL.
Time frame: Evaluated at Baseline, Month 3, and Final Visit
Population: Fabrazyme 1mg/kg every 2 weeks: ITT population - 11 patients at baseline, 7 patients at Month 3, and 9 patients at Final Visit had Plasma GL-3 values.~Fabrazyme 3mg/kg every 2 weeks: ITT population - 9 patients at baseline, 2 patients at Month 3, and 7 patients at Final Visit had Plasma GL-3 values
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fabrazyme 1mg/kg Every 2 Weeks | Plasma Globotriaosylceramide (GL-3) | Plasma GL-3 at Baseline | 8.7 µg/mL | Standard Deviation 3.33 |
| Fabrazyme 1mg/kg Every 2 Weeks | Plasma Globotriaosylceramide (GL-3) | Plasma GL-3 at Month 3 | 5.1 µg/mL | Standard Deviation 2.05 |
| Fabrazyme 1mg/kg Every 2 Weeks | Plasma Globotriaosylceramide (GL-3) | Plasma GL-3 at Final Visit | 5.1 µg/mL | Standard Deviation 1.53 |
| Fabrazyme 3mg/kg Every 2 Weeks | Plasma Globotriaosylceramide (GL-3) | Plasma GL-3 at Baseline | 8.3 µg/mL | Standard Deviation 3.92 |
| Fabrazyme 3mg/kg Every 2 Weeks | Plasma Globotriaosylceramide (GL-3) | Plasma GL-3 at Month 3 | 5.6 µg/mL | Standard Deviation 0.28 |
| Fabrazyme 3mg/kg Every 2 Weeks | Plasma Globotriaosylceramide (GL-3) | Plasma GL-3 at Final Visit | 4.9 µg/mL | Standard Deviation 1.74 |