Pompe Disease, Glycogen Storage Disease Type II (GSD-II), Glycogenesis 2 Acid Maltase Deficiency
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 exploratory study is to evaluate the safety and efficacy of alternative dosing regimens of alglucosidase alfa in patients with Pompe disease who have not demonstrated an optimal response to the standard dosing regimen of 20 mg/kg every other week after a minimum of 6 months treatment immediately prior to study entry.
Interventions
BIOLOGICALalglucosidase alfa
intravenous infusion
Sponsors
Genzyme, a Sanofi Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Months to No maximum
Healthy volunteers
No
Inclusion criteria
* The patient or patient's legal guardian must provide signed, informed consent prior to performing any study-related procedures; * The patient must have a clinical diagnosis of Pompe disease as defined by documented GAA deficiency in skin fibroblasts or blood; * The patient must have been compliant with the standard dosing regimen of alglucosidase alfa (20 mg/kg every other week) for a minimum of 6 months immediately prior to study entry * The patient must have clinical decline or sub-optimal improvement in at least one of the following parameters as compared to their condition prior to the beginning alglucosidase alfa treatment: 1. Cardiac: Left Ventricular Mass (LVM) Z-score ≥6 or LVM index ≥150 g/m2 after a minimum of 6 months of regular treatment with alglucosidase alfa; OR 2. Respiratory: New development of respiratory failure requiring the use of ventilatory assistance (invasive or non-invasive) after a minimum of 6 months of regular treatment with alglucosidase alfa. Ventilatory assistance must have been required for at least 4 weeks prior to study enrollment; OR 3. Motor Skills: * For patients ≤ 2 years of age at study entry, failure to acquire at least 2 new gross motor milestones after a minimum of 6 months of regular treatment with alglucosidase alfa; OR * For patients \> 2 years of age at study entry, worsening of proximal upper extremity muscle weakness as determined by the Investigator through loss of functional use of the upper extremities after a minimum of 6 months of regular treatment with alglucosidase alfa, OR * For patients \> 8 years of age at study entry, worsening of proximal upper extremity muscle weakness as determined by the Investigator through longitudinal assessments of manual muscle testing after a minimum of 6 months of regular treatment with alglucosidase alfa, OR * For patients previously ambulatory, progression to use of an assistive device for ambulation due to worsening of proximal lower extremity muscle weakness after a minimum of 6 months of regular treatment with alglucosidase alfa.
Exclusion criteria
* For patients \< 18 years of age, negative Cross-Reactive Immunologic Material (CRIM) assay result (added in protocol amendment #2); * Any medical condition which, in the opinion of the Investigator, could interfere with treatment or evaluation of safety and/or efficacy of alglucosidase alfa; * The patient is not currently receiving alglucosidase alfa; * The patient has major congenital abnormality; * The patient has used any investigational product (other than alglucosidase alfa in those regions where the product is not commercially available) within 30 days prior to study enrollment; * The patient is pregnant or lactating.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants' Efficacy Response During the Treatment Period as Compared to Baseline for Participants With Respiratory Decline on Standard Treatment | Baseline, Week 52 | Participants were enrolled based on clinical decline or sub-optimal clinical response in cardiac, respiratory and/or motor function parameters pre-study while on standard treatment. Each participant was evaluated at Week 52 for change from baseline in the criteria that declined; respiratory decline as measured by change in ventilator use is summarized in this outcome. Ventilator use might have improved (less use of ventilator support), had no change, or worsened (more use of ventilator support). Each participant served as his or her own control. |
| Participants' Efficacy Response During the Treatment Period as Compared to Baseline for Participants With Motor Function Decline on Standard Treatment | Baseline, Week 52 | Participants were enrolled based on clinical decline or sub-optimal clinical response in cardiac, respiratory and/or motor function parameters pre-study while on standard treatment. Each participant was evaluated at Week 52 for change from baseline in the criteria that declined; motor function decline primarily based on Gross Motor Function Measure 66 and Pompe Pediatric Evaluation of Disability Inventory results is summarized. Participants could gain motor function (improve), had no change (declined stopped), or continued loss (worsened). Each participant served as his or her own control. |
| Summary of Participants Reporting Treatment-Emergent Adverse Events During the Treatment Period | Day 1 up to Week 52 | Overall safety summary of participants experiencing 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Left Ventricular Mass Index (LVMI) at Week 52 | Baseline, Week 52 | Cardiac pathophysiology was assessed by a central cardiologist using left ventricular mass index (LVMI) measured by echocardiogram at Baseline and after 12 months of treatment (Week 52). Left Ventricular Mass is adjusted to the participant's body surface area in the calculation of LVMI. |
| Change From Baseline in Ventilator Use at Last Assessment (Approximately Week 52) | Baseline, approximately Week 52 | The change from baseline in ventilator use at the last assessment is summarized as improved (less use of ventilator support), no change, worsened (increased use of ventilator support), and did not use ventilator support. |
| Change From Baseline in Body Strength Measured by the Manual Muscle Testing (MMT) Total Score at Week 52 | Baseline, Week 52 | Body strength is measured by the MMT score on a scale of 0-10 with higher scores representing greater body strength. |
| Baseline Values of Raw Scores for Gross Motor Function Measure 66 (GMFM-66) Results | Day 0 | The Gross Motor Function Measure 66 contains sixty-six questions with a total raw score range of 0 - 198. Raw scores are derived from the following dimensions: Lying and rolling = 12; Sitting = 45; Crawling and kneeling = 30; Standing = 39; Walking, running and jumping = 72. Higher scores indicate better gross motor functions. |
| Baseline Values for Left Ventricular Mass (LVM) Z-Scores | Day 0 | Z-Scores indicate the number of standard deviations (SD) from the mean in a normal distribution. Negative values indicate a smaller than mean LVM and values higher than 0 indicate a larger LVM than the mean. The normal range is -2 to 2 and greater than 2 may indicate left ventricular hypertrophy. The Z-scores for all parameters are calculated with reference to the normative data from the Children's Hospital, Boston, MA (Colan, 1992, J Am Coll Cardiol) based on the reference population with matched body surface area (BSA). Z-scores for LVM were provided by the central cardiologist. |
| Baseline Values in Mobility as Measured by the Pompe Pediatric Evaluation of Disability Inventory (Pompe PEDI) | Day 0 | The Pompe PEDI is a disease specific version of the PEDI that was developed to assess functional capabilities and performance in children with Pompe disease from 2 months through adolescence. Baseline results for the mobility domain are reported. Scaled scores are used as an evaluative measure of change in performance over time with acquisition of new skills or new levels of independence. The range of scores is from 0-100 with scores near 0 reflecting low capability and scores near 100 reflecting high capability. |
| Change From Baseline in Mobility as Measured by the Pompe Pediatric Evaluation of Disability Inventory (Pompe PEDI) at Week 52 | Baseline, Week 52 | The Pompe PEDI is a disease specific version of the PEDI that was developed to assess functional capabilities and performance in children with Pompe disease from 2 months through adolescence. Change from baseline results for the mobility domain are reported. Scaled scores are used as an evaluative measure of change in performance over time with acquisition of new skills or new levels of independence. The range of scores is from 0-100 with scores near 0 reflecting low capability and scores near 100 reflecting high capability. |
| Baseline Values for Normative Physical Component Summary of Medical Outcomes Study Short Form Health Survey (SF-36) | Day 0 | Health related quality of life is measured using the Physical Component Summary (PCS) score of the Medical Outcomes Study (MOS) Short Form Health Survey (SF-36) for participants ≥14 years of age. SF-36 normative-based scoring has a mean of 50 and a standard deviation of 10. Higher scores represent better quality of life. |
| Change From Baseline in Normative Physical Component Summary of Medical Outcomes Study Short Form Health Survey (SF-36) at Week 52 | Baseline, Week 52 | Health related quality of life is measured using the Physical Component Summary (PCS) score of the Medical Outcomes Study (MOS) Short Form Health Survey (SF-36) for participants ≥14 years of age. SF-36 normative-based scoring has a mean of 50 and a standard deviation of 10. Higher scores represent better quality of life. |
| Change From Baseline in Raw Scores for Gross Motor Function Measure 66 (GMFM-66) Results at Week 52 | Baseline, Week 52 | The Gross Motor Function Measure 66 contains sixty-six questions with a total raw score range of 0 - 198. Raw scores are derived from the following dimensions: Lying and rolling = 12; Sitting = 45; Crawling and kneeling = 30; Standing = 39; Walking, running and jumping = 72. Higher scores indicate better gross motor functions. |
| Change From Baseline in Left Ventricular Mass (LVM) Z-Score 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 a decrease and positive change from baseline an increase in LVM Z-score. The normal range is -2 to 2 and greater than 2 may indicate left ventricular hypertrophy. The Z-scores for all parameters are calculated with reference to the normative data from the Children's Hospital, Boston, MA (Colan, 1992, J Am Coll Cardiol) based on the reference population with matched body surface area (BSA). Z-scores for LVM were provided by the central cardiologist. |
| Baseline Values for Left Ventricular Mass Index (LVMI) | Day 0 | Cardiac pathophysiology was assessed by a central cardiologist using left ventricular mass index (LVMI) measured by echocardiogram at Baseline. Left Ventricular Mass is adjusted to the participant's body surface area in the calculation of LVMI. |
Countries
Australia, Canada, United States
Participant flow
Pre-assignment details
Fourteen participants were screened and enrolled; however, one withdrew before receiving any study infusions due to the burden of weekly trips to the medical center.
Participants by arm
| Arm | Count |
|---|---|
| Alglucosidase Alfa 20 mg/kg Every Week Participants were treated with alglucosidase alfa 20 mg/kg every week for 52 weeks. This was the 'frequent dose' arm. | 6 |
| Alglucosidase Alfa 40 mg/kg Every Other Week Participants were treated with alglucosidase alfa 40 mg/kg every other week for 52 weeks. This was the 'high dose' arm. | 7 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Treatment Period | Adverse Event | 1 | 0 |
| Treatment Period | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Alglucosidase Alfa 20 mg/kg Every Week | Alglucosidase Alfa 40 mg/kg Every Other Week | Total |
|---|---|---|---|
| Age, Continuous | 23.3 years STANDARD_DEVIATION 27.75 | 16.8 years STANDARD_DEVIATION 15.56 | 19.8 years STANDARD_DEVIATION 21.29 |
| Age, Customized >= 18 and <=65 years | 2 participants | 2 participants | 4 participants |
| Age, Customized <18 years | 4 participants | 5 participants | 9 participants |
| Age, Customized >65 years | 0 participants | 0 participants | 0 participants |
| Cross-Reactive Immunologic Material (CRIM) Assay Result Negative | 1 participants | 0 participants | 1 participants |
| Cross-Reactive Immunologic Material (CRIM) Assay Result Positive | 0 participants | 3 participants | 3 participants |
| Cross-Reactive Immunologic Material (CRIM) Assay Result Unknown | 5 participants | 4 participants | 9 participants |
| Life-stage of Disease Onset Infantile-onset Pompe Disease | 4 participants | 5 participants | 9 participants |
| Life-stage of Disease Onset Late-onset Pompe Disease | 2 participants | 2 participants | 4 participants |
| Parameter in Clinical Decline Cardiac | 0 participants | 0 participants | 0 participants |
| Parameter in Clinical Decline Motor Skills | 5 participants | 6 participants | 11 participants |
| Parameter in Clinical Decline Respiratory | 1 participants | 1 participants | 2 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 6 Participants | 12 Participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 5 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 6 | 7 / 7 | 1 / 1 | 1 / 2 |
| serious Total, serious adverse events | 2 / 6 | 1 / 7 | 1 / 1 | 0 / 2 |
Outcome results
Primary
Participants' Efficacy Response During the Treatment Period as Compared to Baseline for Participants With Motor Function Decline on Standard Treatment
Participants were enrolled based on clinical decline or sub-optimal clinical response in cardiac, respiratory and/or motor function parameters pre-study while on standard treatment. Each participant was evaluated at Week 52 for change from baseline in the criteria that declined; motor function decline primarily based on Gross Motor Function Measure 66 and Pompe Pediatric Evaluation of Disability Inventory results is summarized. Participants could gain motor function (improve), had no change (declined stopped), or continued loss (worsened). Each participant served as his or her own control.
Time frame: Baseline, Week 52
Population: All participants who enrolled due to decline in motor function while on standard treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alglucosidase Alfa 20 mg/kg Every Week | Participants' Efficacy Response During the Treatment Period as Compared to Baseline for Participants With Motor Function Decline on Standard Treatment | Gained gross or fine motor skills | 2 participants |
| Alglucosidase Alfa 20 mg/kg Every Week | Participants' Efficacy Response During the Treatment Period as Compared to Baseline for Participants With Motor Function Decline on Standard Treatment | No change | 1 participants |
| Alglucosidase Alfa 20 mg/kg Every Week | Participants' Efficacy Response During the Treatment Period as Compared to Baseline for Participants With Motor Function Decline on Standard Treatment | Continued motor loss | 1 participants |
| Alglucosidase Alfa 20 mg/kg Every Week | Participants' Efficacy Response During the Treatment Period as Compared to Baseline for Participants With Motor Function Decline on Standard Treatment | Not evaluated | 1 participants |
| Alglucosidase Alfa 40 mg/kg Every Other Week | Participants' Efficacy Response During the Treatment Period as Compared to Baseline for Participants With Motor Function Decline on Standard Treatment | Not evaluated | 0 participants |
| Alglucosidase Alfa 40 mg/kg Every Other Week | Participants' Efficacy Response During the Treatment Period as Compared to Baseline for Participants With Motor Function Decline on Standard Treatment | Gained gross or fine motor skills | 4 participants |
| Alglucosidase Alfa 40 mg/kg Every Other Week | Participants' Efficacy Response During the Treatment Period as Compared to Baseline for Participants With Motor Function Decline on Standard Treatment | Continued motor loss | 0 participants |
| Alglucosidase Alfa 40 mg/kg Every Other Week | Participants' Efficacy Response During the Treatment Period as Compared to Baseline for Participants With Motor Function Decline on Standard Treatment | No change | 2 participants |
Primary
Participants' Efficacy Response During the Treatment Period as Compared to Baseline for Participants With Respiratory Decline on Standard Treatment
Participants were enrolled based on clinical decline or sub-optimal clinical response in cardiac, respiratory and/or motor function parameters pre-study while on standard treatment. Each participant was evaluated at Week 52 for change from baseline in the criteria that declined; respiratory decline as measured by change in ventilator use is summarized in this outcome. Ventilator use might have improved (less use of ventilator support), had no change, or worsened (more use of ventilator support). Each participant served as his or her own control.
Time frame: Baseline, Week 52
Population: All participants who enrolled due to decline in respiratory function while on standard treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alglucosidase Alfa 20 mg/kg Every Week | Participants' Efficacy Response During the Treatment Period as Compared to Baseline for Participants With Respiratory Decline on Standard Treatment | Improved | 0 participants |
| Alglucosidase Alfa 20 mg/kg Every Week | Participants' Efficacy Response During the Treatment Period as Compared to Baseline for Participants With Respiratory Decline on Standard Treatment | No change (on invasive ventilator for 24 hrs) | 0 participants |
| Alglucosidase Alfa 20 mg/kg Every Week | Participants' Efficacy Response During the Treatment Period as Compared to Baseline for Participants With Respiratory Decline on Standard Treatment | Worsened | 0 participants |
| Alglucosidase Alfa 20 mg/kg Every Week | Participants' Efficacy Response During the Treatment Period as Compared to Baseline for Participants With Respiratory Decline on Standard Treatment | Not evaluated | 1 participants |
| Alglucosidase Alfa 40 mg/kg Every Other Week | Participants' Efficacy Response During the Treatment Period as Compared to Baseline for Participants With Respiratory Decline on Standard Treatment | Not evaluated | 0 participants |
| Alglucosidase Alfa 40 mg/kg Every Other Week | Participants' Efficacy Response During the Treatment Period as Compared to Baseline for Participants With Respiratory Decline on Standard Treatment | Improved | 0 participants |
| Alglucosidase Alfa 40 mg/kg Every Other Week | Participants' Efficacy Response During the Treatment Period as Compared to Baseline for Participants With Respiratory Decline on Standard Treatment | Worsened | 0 participants |
| Alglucosidase Alfa 40 mg/kg Every Other Week | Participants' Efficacy Response During the Treatment Period as Compared to Baseline for Participants With Respiratory Decline on Standard Treatment | No change (on invasive ventilator for 24 hrs) | 1 participants |
Primary
Summary of Participants Reporting Treatment-Emergent Adverse Events During the Treatment Period
Overall safety summary of participants experiencing 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.
Time frame: Day 1 up to Week 52
Population: Safety population comprised of all participants who received intervention.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alglucosidase Alfa 20 mg/kg Every Week | Summary of Participants Reporting Treatment-Emergent Adverse Events During the Treatment Period | Participants with AEs | 6 participants |
| Alglucosidase Alfa 20 mg/kg Every Week | Summary of Participants Reporting Treatment-Emergent Adverse Events During the Treatment Period | Related AEs | 0 participants |
| Alglucosidase Alfa 20 mg/kg Every Week | Summary of Participants Reporting Treatment-Emergent Adverse Events During the Treatment Period | Not related AEs | 6 participants |
| Alglucosidase Alfa 20 mg/kg Every Week | Summary of Participants Reporting Treatment-Emergent Adverse Events During the Treatment Period | Mild AEs | 6 participants |
| Alglucosidase Alfa 20 mg/kg Every Week | Summary of Participants Reporting Treatment-Emergent Adverse Events During the Treatment Period | Moderate AEs | 3 participants |
| Alglucosidase Alfa 20 mg/kg Every Week | Summary of Participants Reporting Treatment-Emergent Adverse Events During the Treatment Period | Severe AEs | 2 participants |
| Alglucosidase Alfa 20 mg/kg Every Week | Summary of Participants Reporting Treatment-Emergent Adverse Events During the Treatment Period | AEs leading to discontinuation from study | 1 participants |
| Alglucosidase Alfa 20 mg/kg Every Week | Summary of Participants Reporting Treatment-Emergent Adverse Events During the Treatment Period | Deaths | 1 participants |
| Alglucosidase Alfa 20 mg/kg Every Week | Summary of Participants Reporting Treatment-Emergent Adverse Events During the Treatment Period | Infusion Associated Reactions | 0 participants |
| Alglucosidase Alfa 20 mg/kg Every Week | Summary of Participants Reporting Treatment-Emergent Adverse Events During the Treatment Period | Serious AEs | 2 participants |
| Alglucosidase Alfa 40 mg/kg Every Other Week | Summary of Participants Reporting Treatment-Emergent Adverse Events During the Treatment Period | Deaths | 0 participants |
| Alglucosidase Alfa 40 mg/kg Every Other Week | Summary of Participants Reporting Treatment-Emergent Adverse Events During the Treatment Period | Participants with AEs | 7 participants |
| Alglucosidase Alfa 40 mg/kg Every Other Week | Summary of Participants Reporting Treatment-Emergent Adverse Events During the Treatment Period | Severe AEs | 0 participants |
| Alglucosidase Alfa 40 mg/kg Every Other Week | Summary of Participants Reporting Treatment-Emergent Adverse Events During the Treatment Period | Related AEs | 2 participants |
| Alglucosidase Alfa 40 mg/kg Every Other Week | Summary of Participants Reporting Treatment-Emergent Adverse Events During the Treatment Period | Serious AEs | 1 participants |
| Alglucosidase Alfa 40 mg/kg Every Other Week | Summary of Participants Reporting Treatment-Emergent Adverse Events During the Treatment Period | Not related AEs | 7 participants |
| Alglucosidase Alfa 40 mg/kg Every Other Week | Summary of Participants Reporting Treatment-Emergent Adverse Events During the Treatment Period | AEs leading to discontinuation from study | 0 participants |
| Alglucosidase Alfa 40 mg/kg Every Other Week | Summary of Participants Reporting Treatment-Emergent Adverse Events During the Treatment Period | Mild AEs | 6 participants |
| Alglucosidase Alfa 40 mg/kg Every Other Week | Summary of Participants Reporting Treatment-Emergent Adverse Events During the Treatment Period | Infusion Associated Reactions | 2 participants |
| Alglucosidase Alfa 40 mg/kg Every Other Week | Summary of Participants Reporting Treatment-Emergent Adverse Events During the Treatment Period | Moderate AEs | 2 participants |
Secondary
Baseline Values for Left Ventricular Mass Index (LVMI)
Cardiac pathophysiology was assessed by a central cardiologist using left ventricular mass index (LVMI) measured by echocardiogram at Baseline. Left Ventricular Mass is adjusted to the participant's body surface area in the calculation of LVMI.
Time frame: Day 0
Population: Full analysis population of participants with LVMI data
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Alglucosidase Alfa 20 mg/kg Every Week | Baseline Values for Left Ventricular Mass Index (LVMI) | 62.1 g/m^2 |
| Alglucosidase Alfa 40 mg/kg Every Other Week | Baseline Values for Left Ventricular Mass Index (LVMI) | 56.5 g/m^2 |
Secondary
Baseline Values for Left Ventricular Mass (LVM) Z-Scores
Z-Scores indicate the number of standard deviations (SD) from the mean in a normal distribution. Negative values indicate a smaller than mean LVM and values higher than 0 indicate a larger LVM than the mean. The normal range is -2 to 2 and greater than 2 may indicate left ventricular hypertrophy. The Z-scores for all parameters are calculated with reference to the normative data from the Children's Hospital, Boston, MA (Colan, 1992, J Am Coll Cardiol) based on the reference population with matched body surface area (BSA). Z-scores for LVM were provided by the central cardiologist.
Time frame: Day 0
Population: Full analysis population of participants with LVM data
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Alglucosidase Alfa 20 mg/kg Every Week | Baseline Values for Left Ventricular Mass (LVM) Z-Scores | 0.3 Z-score |
| Alglucosidase Alfa 40 mg/kg Every Other Week | Baseline Values for Left Ventricular Mass (LVM) Z-Scores | -0.3 Z-score |
Secondary
Baseline Values for Normative Physical Component Summary of Medical Outcomes Study Short Form Health Survey (SF-36)
Health related quality of life is measured using the Physical Component Summary (PCS) score of the Medical Outcomes Study (MOS) Short Form Health Survey (SF-36) for participants ≥14 years of age. SF-36 normative-based scoring has a mean of 50 and a standard deviation of 10. Higher scores represent better quality of life.
Time frame: Day 0
Population: Full analysis population of participants \>= 14 years old.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alglucosidase Alfa 20 mg/kg Every Week | Baseline Values for Normative Physical Component Summary of Medical Outcomes Study Short Form Health Survey (SF-36) | 31.3 units on a scale | Standard Deviation 2.84 |
| Alglucosidase Alfa 40 mg/kg Every Other Week | Baseline Values for Normative Physical Component Summary of Medical Outcomes Study Short Form Health Survey (SF-36) | 36.0 units on a scale | Standard Deviation 9.33 |
Secondary
Baseline Values in Mobility as Measured by the Pompe Pediatric Evaluation of Disability Inventory (Pompe PEDI)
The Pompe PEDI is a disease specific version of the PEDI that was developed to assess functional capabilities and performance in children with Pompe disease from 2 months through adolescence. Baseline results for the mobility domain are reported. Scaled scores are used as an evaluative measure of change in performance over time with acquisition of new skills or new levels of independence. The range of scores is from 0-100 with scores near 0 reflecting low capability and scores near 100 reflecting high capability.
Time frame: Day 0
Population: Full analysis population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alglucosidase Alfa 20 mg/kg Every Week | Baseline Values in Mobility as Measured by the Pompe Pediatric Evaluation of Disability Inventory (Pompe PEDI) | 38.3 units on a scale | Standard Deviation 20.94 |
| Alglucosidase Alfa 40 mg/kg Every Other Week | Baseline Values in Mobility as Measured by the Pompe Pediatric Evaluation of Disability Inventory (Pompe PEDI) | 46.8 units on a scale | Standard Deviation 21.26 |
Secondary
Baseline Values of Raw Scores for Gross Motor Function Measure 66 (GMFM-66) Results
The Gross Motor Function Measure 66 contains sixty-six questions with a total raw score range of 0 - 198. Raw scores are derived from the following dimensions: Lying and rolling = 12; Sitting = 45; Crawling and kneeling = 30; Standing = 39; Walking, running and jumping = 72. Higher scores indicate better gross motor functions.
Time frame: Day 0
Population: Full analysis population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alglucosidase Alfa 20 mg/kg Every Week | Baseline Values of Raw Scores for Gross Motor Function Measure 66 (GMFM-66) Results | 65.0 units on a scale | Standard Deviation 60.52 |
| Alglucosidase Alfa 40 mg/kg Every Other Week | Baseline Values of Raw Scores for Gross Motor Function Measure 66 (GMFM-66) Results | 82.8 units on a scale | Standard Deviation 84 |
Secondary
Change From Baseline in Body Strength Measured by the Manual Muscle Testing (MMT) Total Score at Week 52
Body strength is measured by the MMT score on a scale of 0-10 with higher scores representing greater body strength.
Time frame: Baseline, Week 52
Population: Full analysis population of participants \>= 8 years old. Due to the age restriction and small study population, the number of participants analyzed is too small for results to be meaningful.
Secondary
Change From Baseline in Left Ventricular Mass Index (LVMI) at Week 52
Cardiac pathophysiology was assessed by a central cardiologist using left ventricular mass index (LVMI) measured by echocardiogram at Baseline and after 12 months of treatment (Week 52). Left Ventricular Mass is adjusted to the participant's body surface area in the calculation of LVMI.
Time frame: Baseline, Week 52
Population: Full analysis population of participants with LVMI data at both timepoints
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Alglucosidase Alfa 20 mg/kg Every Week | Change From Baseline in Left Ventricular Mass Index (LVMI) at Week 52 | 12.5 g/m^2 | Full Range 14.44 |
| Alglucosidase Alfa 40 mg/kg Every Other Week | Change From Baseline in Left Ventricular Mass Index (LVMI) at Week 52 | 4.0 g/m^2 | Full Range 5.95 |
Secondary
Change From Baseline in Left Ventricular Mass (LVM) Z-Score 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 a decrease and positive change from baseline an increase in LVM Z-score. The normal range is -2 to 2 and greater than 2 may indicate left ventricular hypertrophy. The Z-scores for all parameters are calculated with reference to the normative data from the Children's Hospital, Boston, MA (Colan, 1992, J Am Coll Cardiol) based on the reference population with matched body surface area (BSA). Z-scores for LVM were provided by the central cardiologist.
Time frame: Baseline, Week 52
Population: Full analysis population of participants with LVM data at both timepoints
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Alglucosidase Alfa 20 mg/kg Every Week | Change From Baseline in Left Ventricular Mass (LVM) Z-Score at Week 52 | 0.3 Z-score | Full Range 1.04 |
| Alglucosidase Alfa 40 mg/kg Every Other Week | Change From Baseline in Left Ventricular Mass (LVM) Z-Score at Week 52 | 0.4 Z-score | Full Range 0.33 |
Secondary
Change From Baseline in Mobility as Measured by the Pompe Pediatric Evaluation of Disability Inventory (Pompe PEDI) at Week 52
The Pompe PEDI is a disease specific version of the PEDI that was developed to assess functional capabilities and performance in children with Pompe disease from 2 months through adolescence. Change from baseline results for the mobility domain are reported. Scaled scores are used as an evaluative measure of change in performance over time with acquisition of new skills or new levels of independence. The range of scores is from 0-100 with scores near 0 reflecting low capability and scores near 100 reflecting high capability.
Time frame: Baseline, Week 52
Population: Full analysis population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alglucosidase Alfa 20 mg/kg Every Week | Change From Baseline in Mobility as Measured by the Pompe Pediatric Evaluation of Disability Inventory (Pompe PEDI) at Week 52 | 0.6 units on a scale | Standard Deviation 4.28 |
| Alglucosidase Alfa 40 mg/kg Every Other Week | Change From Baseline in Mobility as Measured by the Pompe Pediatric Evaluation of Disability Inventory (Pompe PEDI) at Week 52 | 3.5 units on a scale | Standard Deviation 3.84 |
Secondary
Change From Baseline in Normative Physical Component Summary of Medical Outcomes Study Short Form Health Survey (SF-36) at Week 52
Health related quality of life is measured using the Physical Component Summary (PCS) score of the Medical Outcomes Study (MOS) Short Form Health Survey (SF-36) for participants ≥14 years of age. SF-36 normative-based scoring has a mean of 50 and a standard deviation of 10. Higher scores represent better quality of life.
Time frame: Baseline, Week 52
Population: Full analysis population of participants \>= 14 years old.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alglucosidase Alfa 20 mg/kg Every Week | Change From Baseline in Normative Physical Component Summary of Medical Outcomes Study Short Form Health Survey (SF-36) at Week 52 | 2.5 units on a scale | — |
| Alglucosidase Alfa 40 mg/kg Every Other Week | Change From Baseline in Normative Physical Component Summary of Medical Outcomes Study Short Form Health Survey (SF-36) at Week 52 | 4.4 units on a scale | Standard Deviation 11.24 |
Secondary
Change From Baseline in Raw Scores for Gross Motor Function Measure 66 (GMFM-66) Results at Week 52
The Gross Motor Function Measure 66 contains sixty-six questions with a total raw score range of 0 - 198. Raw scores are derived from the following dimensions: Lying and rolling = 12; Sitting = 45; Crawling and kneeling = 30; Standing = 39; Walking, running and jumping = 72. Higher scores indicate better gross motor functions.
Time frame: Baseline, Week 52
Population: Full analysis population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alglucosidase Alfa 20 mg/kg Every Week | Change From Baseline in Raw Scores for Gross Motor Function Measure 66 (GMFM-66) Results at Week 52 | 6.0 units on a scale | Standard Deviation 8.49 |
| Alglucosidase Alfa 40 mg/kg Every Other Week | Change From Baseline in Raw Scores for Gross Motor Function Measure 66 (GMFM-66) Results at Week 52 | 6.7 units on a scale | Standard Deviation 6.12 |
Secondary
Change From Baseline in Ventilator Use at Last Assessment (Approximately Week 52)
The change from baseline in ventilator use at the last assessment is summarized as improved (less use of ventilator support), no change, worsened (increased use of ventilator support), and did not use ventilator support.
Time frame: Baseline, approximately Week 52
Population: Full analysis population. The participant in the worsened category died after week 52.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alglucosidase Alfa 20 mg/kg Every Week | Change From Baseline in Ventilator Use at Last Assessment (Approximately Week 52) | Did not use ventilator | 3 participants |
| Alglucosidase Alfa 20 mg/kg Every Week | Change From Baseline in Ventilator Use at Last Assessment (Approximately Week 52) | Worsened | 1 participants |
| Alglucosidase Alfa 20 mg/kg Every Week | Change From Baseline in Ventilator Use at Last Assessment (Approximately Week 52) | Improved | 0 participants |
| Alglucosidase Alfa 20 mg/kg Every Week | Change From Baseline in Ventilator Use at Last Assessment (Approximately Week 52) | No change | 2 participants |
| Alglucosidase Alfa 40 mg/kg Every Other Week | Change From Baseline in Ventilator Use at Last Assessment (Approximately Week 52) | Did not use ventilator | 4 participants |
| Alglucosidase Alfa 40 mg/kg Every Other Week | Change From Baseline in Ventilator Use at Last Assessment (Approximately Week 52) | No change | 3 participants |
| Alglucosidase Alfa 40 mg/kg Every Other Week | Change From Baseline in Ventilator Use at Last Assessment (Approximately Week 52) | Worsened | 0 participants |
| Alglucosidase Alfa 40 mg/kg Every Other Week | Change From Baseline in Ventilator Use at Last Assessment (Approximately Week 52) | Improved | 0 participants |