Pompe Disease (Late-Onset), Glycogen Storage Disease Type II (GSD-II), Glycogenesis Type II, Acid Maltase Deficiency (AMD)
Conditions
Brief summary
Pompe disease (also known as glycogen storage disease Type II) is caused by a deficiency of a critical enzyme in the body called acid alpha-glucosidase (GAA). Normally, GAA is used by the body's cells to break down glycogen (a stored form of sugar) within specialized structures called lysosomes. In patients with Pompe disease, an excessive amount of glycogen accumulates and is stored in various tissues, especially heart and skeletal muscle, which prevents their normal function. The objective of this extension study is to assess the long-term safety and efficacy of alglucosidase alfa treatment in patients with Late-Onset Pompe Disease who were previously treated under the placebo-controlled, double-blind study AGLU02704 (NCT00158600).
Interventions
BIOLOGICALalglucosidase alfa
IV infusion of 20 mg/kg; every other week (qow)
Sponsors
Genzyme, a Sanofi Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
8 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient must have completed protocol AGLU02704 (NCT00158600) * Patient must provide signed, informed consent prior to performing any study-related procedures * Patient (and patient's legal guardian if patient is under 18 years of age) must have the ability to comply with the clinical protocol * A female patient of childbearing potential must have a negative pregnancy test at Baseline. (note: all female patients of childbearing potential and sexually mature males must use a medically accepted method of contraception throughout the study.)
Exclusion criteria
* The patient has a medical condition, serious intercurrent illness, or other extenuating circumstance that, in the opinion of the Investigator, would preclude treatment with alglucosidase alfa.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline (Week 0) in the Percent Predicted Forced Vital Capacity (FVC) at Week 104 For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600) | Week 0, Week 104 | Forced vital capacity (FVC) is a standard pulmonary function test used to quantify respiratory muscle weakness. FVC is the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. 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 frames are stated from the start of the double-blind study AGLU02704 (NCT00158600). Change is calculated as the value minus the baseline value. |
| Summary of Participants Reporting Treatment-Emergent Adverse Events For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600) | Week 0 to 2.5 years | The numbers of participants who experienced Adverse Events (AEs), Serious Adverse Events (SAEs), treatment-related AEs, and Infusion Associated Reactions (IARs). Summary is based on treatment-emergent AEs (TEAEs), defined as AEs that occurred following the initiation of study treatment with alglucosidase alfa. Participants with long-term exposure to alglucosidase alfa (those from the Alglucosidase Alfa/Alglucosidase Alfa treatment group) are included. Time frames are stated from the start of the double-blind study AGLU02704 (NCT00158600). |
| Baseline Values (Week 0) of Functional Endurance as Measured by Six-Minute Walk Test (6MWT) For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600) | Week 0 | Six-Minute Walk Test (6MWT) measures the distance walked (in meters) in 6 minutes. A longer distance indicates greater endurance. Time frames are stated from the start of the double-blind study AGLU02704 (NCT00158600). |
| Change From Baseline (Week 0) in the Six-Minute Walk Test (6MWT) at Week 104 For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600) | Week 0, Week 104 | Six-Minute Walk Test (6MWT) measures the distance walked (in meters) in 6 minutes. A longer distance indicates greater endurance. Time frames are stated from the start of the double-blind study AGLU02704 (NCT00158600). Change is calculated as the value minus the baseline value. |
| Baseline Values (Week 0) for Percent Predicted Forced Vital Capacity (FVC) For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600) | Week 0 | Forced vital capacity (FVC) is a standard pulmonary function test used to quantify respiratory muscle weakness. FVC is the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. 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 frames are stated from the start of the double-blind study AGLU02704 (NCT00158600). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline (Week 0) for Percent Predicted Proximal Muscle Strength of the Lower Limbs as Measured by Quantitative Muscle Testing (QMT) at Week 104 For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600) | Week 0, Week 104 | Quantitative muscle testing (QMT) is a standardized system to measure muscle force production during maximal voluntary isometric contraction. QMT data were collected directly from sensors into laptop computers. Predicted normal values for QMT are based on a formula using sex, age and body mass index of a person, and are an estimate of healthy muscle force. Percent of predicted QMT = (observed value)/(predicted value) \* 100%. The QMT Leg Score is the average of the bilateral means for percent predicted knee flexors and extensors. A value of 100% indicates 'normal' muscle strength. |
| Baseline Values (Week 0) for Quality of Life Related to Physical Component Score (PCS) as Measured by the Medical Outcomes Study (MOS) Short Form-36 Health Survey For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600) | Week 0 | The Medical Outcomes Study Short Form (MOS SF)-36 questionnaire consists of 36 items grouped into 8 domains designed to assess generic health-related quality of life in healthy and ill adult populations. Physical Component Score reports the four domains of physical functioning, role-physical, bodily pain, and general health and are standardized as Z-scores (scale of 0-100). Higher scores are associated with better quality of life. Time frames are stated from the start of the double-blind study AGLU02704 (NCT00158600). |
| Change From Baseline in Quality of Life Related to Physical Component Score (PCS) as Measured by the Medical Outcomes Study (MOS) Short Form-36 Health Survey For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600) | Week 0 , Week 104 | The Medical Outcomes Study Short Form (MOS SF)-36 questionnaire consists of 36 items grouped into 8 domains designed to assess generic health-related quality of life in healthy and ill adult populations. Physical Component Score reports the four domains of physical functioning, role-physical, bodily pain, and general health and is standardized as Z-scores (scale of 0-100). Higher scores are associated with better quality of life. Change is calculated as the value minus the baseline value. Time frames are stated from the start of the double-blind study AGLU02704 (NCT00158600). |
| Baseline Values (Week 0) for Percent Predicted Proximal Muscle Strength of the Lower Limbs as Measured by Quantitative Muscle Testing (QMT) For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600) | Week 0 | Quantitative muscle testing (QMT) is a standardized system to measure muscle force production during maximal voluntary isometric contraction. QMT data were collected directly from sensors into laptop computers. Predicted normal values for QMT are based on a formula using sex, age and body mass index of a person, and are an estimate of healthy muscle force. Percent of predicted QMT = (observed value)/(predicted value) \* 100%. The QMT Leg Score is the average of the bilateral means for percent predicted knee flexors and extensors. A value of 100% indicates 'normal' muscle strength. |
Countries
Australia, Canada, France, Netherlands, United States
Participant flow
Pre-assignment details
81 of the 90 participants enrolled in the double-blind placebo controlled AGLU02704 (NCT00158600) study continued on to the open-label extension study AGLU03206.
Participants by arm
| Arm | Count |
|---|---|
| Alglucosidase Alfa/Alglucosidase Alfa Participants who received alglucosidase alfa during the double-blind study AGLU02704 (NCT00158600) and, if they completed the double blind study, continued alglucosidase alfa in the extension study. Both study experiences on alglucosidase alfa are represented within AGLU03206. | 60 |
| Placebo/Alglucosidase Alfa Participants who received placebo during the double-blind study AGLU02704 (NCT00158600), completed the double-blind study, and started alglucosidase alfa in the extension study. Only participants' experience on alglucosidase alfa in the extension study is represented. | 26 |
| Total | 86 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-blind Study AGLU02704 | Adverse Event | 2 | 1 |
| Double-blind Study AGLU02704 | Death | 1 | 0 |
| Double-blind Study AGLU02704 | Unable to commit time to study | 0 | 1 |
| Double-blind Study AGLU02704 | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | Alglucosidase Alfa/Alglucosidase Alfa | Placebo/Alglucosidase Alfa | Total |
|---|---|---|---|
| Age, Continuous | 45.3 years STANDARD_DEVIATION 12.37 | 46.8 years STANDARD_DEVIATION 8.62 | 45.73 years STANDARD_DEVIATION 11.34 |
| Race/Ethnicity, Customized Asian | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Black or African American | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Hispanic | 1 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 1 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized White | 57 participants | 24 participants | 81 participants |
| Sex: Female, Male Female | 26 Participants | 15 Participants | 41 Participants |
| Sex: Female, Male Male | 34 Participants | 11 Participants | 45 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 | 60 / 60 | 25 / 26 | 85 / 86 |
| serious Total, serious adverse events | 15 / 60 | 2 / 26 | 17 / 86 |
Outcome results
Primary
Baseline Values (Week 0) for Percent Predicted Forced Vital Capacity (FVC) For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)
Forced vital capacity (FVC) is a standard pulmonary function test used to quantify respiratory muscle weakness. FVC is the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. 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 frames are stated from the start of the double-blind study AGLU02704 (NCT00158600).
Time frame: Week 0
Population: Intent-to-treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alglucosidase Alfa/Alglucosidase Alfa | Baseline Values (Week 0) for Percent Predicted Forced Vital Capacity (FVC) For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600) | 55.4 percent of predicted FVC | Standard Deviation 14.44 |
Primary
Baseline Values (Week 0) of Functional Endurance as Measured by Six-Minute Walk Test (6MWT) For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)
Six-Minute Walk Test (6MWT) measures the distance walked (in meters) in 6 minutes. A longer distance indicates greater endurance. Time frames are stated from the start of the double-blind study AGLU02704 (NCT00158600).
Time frame: Week 0
Population: Intent-to-treat population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alglucosidase Alfa/Alglucosidase Alfa | Baseline Values (Week 0) of Functional Endurance as Measured by Six-Minute Walk Test (6MWT) For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600) | 332.2 meters | Standard Deviation 126.69 |
Primary
Change From Baseline (Week 0) in the Percent Predicted Forced Vital Capacity (FVC) at Week 104 For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)
Forced vital capacity (FVC) is a standard pulmonary function test used to quantify respiratory muscle weakness. FVC is the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. 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 frames are stated from the start of the double-blind study AGLU02704 (NCT00158600). Change is calculated as the value minus the baseline value.
Time frame: Week 0, Week 104
Population: Intent-to-treat population of participants who had both baseline (Week 0) and Week 104 data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alglucosidase Alfa/Alglucosidase Alfa | Change From Baseline (Week 0) in the Percent Predicted Forced Vital Capacity (FVC) at Week 104 For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600) | 0.8 percent of predicted FVC | Standard Deviation 6.68 |
Primary
Change From Baseline (Week 0) in the Six-Minute Walk Test (6MWT) at Week 104 For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)
Six-Minute Walk Test (6MWT) measures the distance walked (in meters) in 6 minutes. A longer distance indicates greater endurance. Time frames are stated from the start of the double-blind study AGLU02704 (NCT00158600). Change is calculated as the value minus the baseline value.
Time frame: Week 0, Week 104
Population: Intent-to-treat population of participants who had both baseline (Week 0) and Week 104 data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alglucosidase Alfa/Alglucosidase Alfa | Change From Baseline (Week 0) in the Six-Minute Walk Test (6MWT) at Week 104 For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600) | 21.3 meters | Standard Deviation 78.02 |
Primary
Summary of Participants Reporting Treatment-Emergent Adverse Events For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)
The numbers of participants who experienced Adverse Events (AEs), Serious Adverse Events (SAEs), treatment-related AEs, and Infusion Associated Reactions (IARs). Summary is based on treatment-emergent AEs (TEAEs), defined as AEs that occurred following the initiation of study treatment with alglucosidase alfa. Participants with long-term exposure to alglucosidase alfa (those from the Alglucosidase Alfa/Alglucosidase Alfa treatment group) are included. Time frames are stated from the start of the double-blind study AGLU02704 (NCT00158600).
Time frame: Week 0 to 2.5 years
Population: The safety population includes all participants randomized to alglucosidase alfa treatment in AGLU02704 (NCT00158600) who received at least one infusion of alglucosidase alfa.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alglucosidase Alfa/Alglucosidase Alfa | Summary of Participants Reporting Treatment-Emergent Adverse Events For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600) | Participants with any AEs | 60 participants |
| Alglucosidase Alfa/Alglucosidase Alfa | Summary of Participants Reporting Treatment-Emergent Adverse Events For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600) | Participants with Treatment-Related AEs | 37 participants |
| Alglucosidase Alfa/Alglucosidase Alfa | Summary of Participants Reporting Treatment-Emergent Adverse Events For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600) | Participants with Infusion-Associated Reactions | 21 participants |
| Alglucosidase Alfa/Alglucosidase Alfa | Summary of Participants Reporting Treatment-Emergent Adverse Events For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600) | Participants with Serious AEs | 15 participants |
| Alglucosidase Alfa/Alglucosidase Alfa | Summary of Participants Reporting Treatment-Emergent Adverse Events For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600) | Participants with Severe AEs | 16 participants |
| Alglucosidase Alfa/Alglucosidase Alfa | Summary of Participants Reporting Treatment-Emergent Adverse Events For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600) | Participants- Discontinued Due to AEs (incl death) | 3 participants |
| Alglucosidase Alfa/Alglucosidase Alfa | Summary of Participants Reporting Treatment-Emergent Adverse Events For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600) | Participants Who Died | 1 participants |
Secondary
Baseline Values (Week 0) for Percent Predicted Proximal Muscle Strength of the Lower Limbs as Measured by Quantitative Muscle Testing (QMT) For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)
Quantitative muscle testing (QMT) is a standardized system to measure muscle force production during maximal voluntary isometric contraction. QMT data were collected directly from sensors into laptop computers. Predicted normal values for QMT are based on a formula using sex, age and body mass index of a person, and are an estimate of healthy muscle force. Percent of predicted QMT = (observed value)/(predicted value) \* 100%. The QMT Leg Score is the average of the bilateral means for percent predicted knee flexors and extensors. A value of 100% indicates 'normal' muscle strength.
Time frame: Week 0
Population: Intent-to-treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alglucosidase Alfa/Alglucosidase Alfa | Baseline Values (Week 0) for Percent Predicted Proximal Muscle Strength of the Lower Limbs as Measured by Quantitative Muscle Testing (QMT) For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600) | 37.7 percent of predicted QMT | Standard Deviation 18.88 |
Secondary
Baseline Values (Week 0) for Quality of Life Related to Physical Component Score (PCS) as Measured by the Medical Outcomes Study (MOS) Short Form-36 Health Survey For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)
The Medical Outcomes Study Short Form (MOS SF)-36 questionnaire consists of 36 items grouped into 8 domains designed to assess generic health-related quality of life in healthy and ill adult populations. Physical Component Score reports the four domains of physical functioning, role-physical, bodily pain, and general health and are standardized as Z-scores (scale of 0-100). Higher scores are associated with better quality of life. Time frames are stated from the start of the double-blind study AGLU02704 (NCT00158600).
Time frame: Week 0
Population: Intent-to-treat population of participants with valid baseline (Week 0) PCS surveys.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alglucosidase Alfa/Alglucosidase Alfa | Baseline Values (Week 0) for Quality of Life Related to Physical Component Score (PCS) as Measured by the Medical Outcomes Study (MOS) Short Form-36 Health Survey For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600) | 34.33 units on a scale | Standard Deviation 8.934 |
Secondary
Change From Baseline in Quality of Life Related to Physical Component Score (PCS) as Measured by the Medical Outcomes Study (MOS) Short Form-36 Health Survey For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)
The Medical Outcomes Study Short Form (MOS SF)-36 questionnaire consists of 36 items grouped into 8 domains designed to assess generic health-related quality of life in healthy and ill adult populations. Physical Component Score reports the four domains of physical functioning, role-physical, bodily pain, and general health and is standardized as Z-scores (scale of 0-100). Higher scores are associated with better quality of life. Change is calculated as the value minus the baseline value. Time frames are stated from the start of the double-blind study AGLU02704 (NCT00158600).
Time frame: Week 0 , Week 104
Population: Intent-to-treat population of participants who had valid baseline (Week 0) and Week 104 data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alglucosidase Alfa/Alglucosidase Alfa | Change From Baseline in Quality of Life Related to Physical Component Score (PCS) as Measured by the Medical Outcomes Study (MOS) Short Form-36 Health Survey For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600) | 0.64 units on a scale | Standard Deviation 7.618 |
Secondary
Change From Baseline (Week 0) for Percent Predicted Proximal Muscle Strength of the Lower Limbs as Measured by Quantitative Muscle Testing (QMT) at Week 104 For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)
Quantitative muscle testing (QMT) is a standardized system to measure muscle force production during maximal voluntary isometric contraction. QMT data were collected directly from sensors into laptop computers. Predicted normal values for QMT are based on a formula using sex, age and body mass index of a person, and are an estimate of healthy muscle force. Percent of predicted QMT = (observed value)/(predicted value) \* 100%. The QMT Leg Score is the average of the bilateral means for percent predicted knee flexors and extensors. A value of 100% indicates 'normal' muscle strength.
Time frame: Week 0, Week 104
Population: Intent-to-treat population of participants who had both baseline (Week 0) and Week 104 data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alglucosidase Alfa/Alglucosidase Alfa | Change From Baseline (Week 0) for Percent Predicted Proximal Muscle Strength of the Lower Limbs as Measured by Quantitative Muscle Testing (QMT) at Week 104 For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600) | 2.1 percent of predicted QMT | Standard Deviation 11.06 |