Pompe Disease
Conditions
Brief summary
The objective of this study was to evaluate the efficacy and safety of treatment with 4000 litre (L) alglucosidase alfa (Lumizyme®) in Pompe participants.
Interventions
4000 L alglucosidase alfa administered by IV infusion at the same dose and dose regimen used for the patient's routine treatment prior to the study for 52 weeks.
Sponsors
Genzyme, a Sanofi Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to No maximum
Healthy volunteers
No
Inclusion criteria
A participant might meet all of the following criteria to be eligible for this study. 1. The participant and/or their parent/legal guardian was willing and able to provide signed informed consent. 2. The participant might be at least 1 year of age at the time of informed consent. 3. The participant had a diagnosis of Pompe disease and might have received treatment with 160 L alglucosidase alfa prior to screening. 4. The participant, if female and of childbearing potential, might have a negative pregnancy test (urine beta-human chorionic gonadotropin) at baseline. Note: all female participants of childbearing potential and sexually mature males might agree to use a medically accepted method of contraception throughout the study.
Exclusion criteria
A participant who met any of the following criteria were to be excluded from this study. 1. The participant had within the past 3 months received or was currently receiving any investigational product other than 160 L alglucosidase alfa or was currently participating in another clinical treatment study. 2. The participant, in the opinion of the Investigator, was clinically unstable and would not be expected to survive to completion of the 52-week treatment period. 3. The participant and/or their parent/legal guardian, in the opinion of the Investigator, was unable to adhere to the requirements of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Were Clinically Stable or Improved at Week 52 | Week 52 | Clinical stability was defined as absence of death due to disease progression or new dependency on invasive ventilation and; decline in cardiac status, motor function, and pulmonary function from baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Invasive Ventilator-Free Survival Rate at Week 52 | Week 52 | Percentage of participants, who were invasive ventilator-free at week 52, are reported. Invasive ventilation was defined as mechanical ventilatory support applied with the use of an endotracheal tube or tracheostomy. Invasive ventilator-free survival rate was calculated by Kaplan-Meier estimate. |
| Change From Baseline on Left Ventricular Mass Z-Score (LVM-Z) at Week 52 | Baseline, Week 52 | Z-Scores indicate the number of standard deviations (SD) from the mean in a normal distribution. A negative change from baseline indicates an increase in LVM-Z score. The normal range is -2 to 2 and greater than 2 may indicate left ventricular hypertrophy. |
| Survival Rate at Week 52 | Week 52 | Percentage of participants who were alive at Week 52, were reported. Survival rate was calculated by Kaplan-Meier estimate. |
| Change From Baseline in Forced Vital Capacity (FVC) at Week 52- At Supine Position | Baseline, Week 52 | Percent predicted FVC values are reported. FVC is the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in litres. Predicted forced vital capacity is based on a formula using sex, age and height of a person, and is an estimate of healthy lung capacity. Percent of predicted FVC = (observed value)/(predicted value) \* 100%. |
| Change From Baseline in Forced Vital Capacity (FVC) at Week 52- At Sitting Position | Baseline, Week 52 | Percent predicted FVC values are reported. FVC is the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in litres. Predicted forced vital capacity is based on a formula using sex, age and height of a person, and is an estimate of healthy lung capacity. Percent of predicted FVC = (observed value)/(predicted value) \* 100%. |
| Change From Baseline on Gross Motor Function Measure-88 (GMFM-88) at Week 52 | Baseline, Week 52 | GMFM-88 (88-item measure to detect gross motor function) consists of 5 components, each measured on a 4-point Likert scale.The score for each dimension was expressed as a percentage of the maximum score for that dimension.Total score ranges from 0% to 100%, where higher scores indicate better motor functions. |
Countries
United States
Participant flow
Pre-assignment details
The study was conducted in the United States. A total of 113 participants were treated between 9 March 2012 and 4 June 2014.
Participants by arm
| Arm | Count |
|---|---|
| Alglucosidase Alfa Alglucosidase alfa (4000 L scale) IV infusion administered for 52 weeks as per physician's routine practice. | 113 |
| Total | 113 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 2 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Study Terminated by Sponsor | 8 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Alglucosidase Alfa |
|---|---|
| Age, Continuous | 4.8 years STANDARD_DEVIATION 3.73 |
| Sex: Female, Male Female | 53 Participants |
| Sex: Female, Male Male | 60 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 113 / 113 |
| serious Total, serious adverse events | 73 / 113 |
Outcome results
Primary
Percentage of Participants Who Were Clinically Stable or Improved at Week 52
Clinical stability was defined as absence of death due to disease progression or new dependency on invasive ventilation and; decline in cardiac status, motor function, and pulmonary function from baseline.
Time frame: Week 52
Population: Full analysis population. Number of participants analyzed = participants with available data at Week 52 for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alglucosidase Alfa | Percentage of Participants Who Were Clinically Stable or Improved at Week 52 | 83.7 percentage of participants |
Secondary
Change From Baseline in Forced Vital Capacity (FVC) at Week 52- At Sitting Position
Percent predicted FVC values are reported. FVC is the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in litres. Predicted forced vital capacity is based on a formula using sex, age and height of a person, and is an estimate of healthy lung capacity. Percent of predicted FVC = (observed value)/(predicted value) \* 100%.
Time frame: Baseline, Week 52
Population: Full analysis population. Number of participants analysed = participants with baseline and Week 52 FVC data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alglucosidase Alfa | Change From Baseline in Forced Vital Capacity (FVC) at Week 52- At Sitting Position | 2.3 percent predicted FVC | Standard Deviation 11.8 |
Secondary
Change From Baseline in Forced Vital Capacity (FVC) at Week 52- At Supine Position
Percent predicted FVC values are reported. FVC is the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in litres. Predicted forced vital capacity is based on a formula using sex, age and height of a person, and is an estimate of healthy lung capacity. Percent of predicted FVC = (observed value)/(predicted value) \* 100%.
Time frame: Baseline, Week 52
Population: Full analysis population. Number of participants analysed = participants with baseline and Week 52 FVC data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alglucosidase Alfa | Change From Baseline in Forced Vital Capacity (FVC) at Week 52- At Supine Position | 3.2 percent predicted FVC | Standard Deviation 11.07 |
Secondary
Change From Baseline on Gross Motor Function Measure-88 (GMFM-88) at Week 52
GMFM-88 (88-item measure to detect gross motor function) consists of 5 components, each measured on a 4-point Likert scale.The score for each dimension was expressed as a percentage of the maximum score for that dimension.Total score ranges from 0% to 100%, where higher scores indicate better motor functions.
Time frame: Baseline, Week 52
Population: Full analysis population. Number of participants analysed = participants with baseline and Week 52 GMFM-88 data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alglucosidase Alfa | Change From Baseline on Gross Motor Function Measure-88 (GMFM-88) at Week 52 | 3.7 percentage of total score | Standard Deviation 17.46 |
Secondary
Change From Baseline on Left Ventricular Mass Z-Score (LVM-Z) at Week 52
Z-Scores indicate the number of standard deviations (SD) from the mean in a normal distribution. A negative change from baseline indicates an increase in LVM-Z score. The normal range is -2 to 2 and greater than 2 may indicate left ventricular hypertrophy.
Time frame: Baseline, Week 52
Population: Full analysis population. Number of participants analyzed = participants with available data at Week 52 for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alglucosidase Alfa | Change From Baseline on Left Ventricular Mass Z-Score (LVM-Z) at Week 52 | -0.5 Z score | Standard Deviation 1.71 |
Secondary
Invasive Ventilator-Free Survival Rate at Week 52
Percentage of participants, who were invasive ventilator-free at week 52, are reported. Invasive ventilation was defined as mechanical ventilatory support applied with the use of an endotracheal tube or tracheostomy. Invasive ventilator-free survival rate was calculated by Kaplan-Meier estimate.
Time frame: Week 52
Population: Full analysis population. Number of participants analyzed = participants with available data at Week 52 for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alglucosidase Alfa | Invasive Ventilator-Free Survival Rate at Week 52 | 92.4 percentage of participants |
Secondary
Survival Rate at Week 52
Percentage of participants who were alive at Week 52, were reported. Survival rate was calculated by Kaplan-Meier estimate.
Time frame: Week 52
Population: Full analysis population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alglucosidase Alfa | Survival Rate at Week 52 | 98.1 percentage of participants |