Pompe Disease (Infantile-Onset), Glycogen Storage Disease Type II (GSD II), Glycogenosis 2, Acid Maltase Deficiency
Conditions
Brief summary
A study to demonstrate comparable safety, efficacy, and pharmacokinetics (PK) of alglucosidase alfa manufactured at the 160 litre (L) and 4000 L scales in participants who had been diagnosed with infantile-onset Pompe disease. Participants were treated with alglucosidase alfa 160 L scale product in the United States (US) and 4000 L scale product in the regions outside the US.
Interventions
BIOLOGICALalglucosidase alfa
Intravenous (IV) infusion of alglucosidase alfa (4000 L material) 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
No minimum to 12 Months
Healthy volunteers
No
Inclusion criteria
* The participant's parent/legal guardian was willing and able to provide signed informed consent. * The participant might be less than or equal to 12 months of age. * The participant might have documented GAA enzyme deficiency from blood, skin, or muscle tissue. * The participant might be naïve to treatment with alglucosidase alfa.
Exclusion criteria
* The participant was cross-reactive immunologic material negative. * The participant required invasive ventilator support at the time of enrollment. * The participant had decompensated clinical heart failure. * The participant had a major congenital abnormality, excluding cardiac hypertrophy. * The participant had a clinically significant organ disease (excluding the signs and symptoms of Pompe disease). * The participant was currently receiving any investigational product. * The participant was participating in another clinical study. * The participant and/or the patient's parent/legal guardian was unable to adhere to the requirements of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Cardiac Function at Week 52 | Baseline, Week 52 | Cardiac function was measured by the left ventricular mass Z-score (LVM-Z). 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 indicates an increase in LVM Z-score. The normal range is -2 to 2 and greater than 2 may indicate left ventricular hypertrophy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Estimated Probability of Survival | Up to Week 52 | — |
| Number of Participants With Invasive Ventilator-Free Survival | Up to Week 52 | Invasive ventilator-free survival was defined as the time during which the participant is alive and not invasively ventilated. Number of Participants with invasive ventilator-free survival were reported. |
| Change From Baseline in Motor Development Status at Week 52 | Baseline, Week 52 | Motor development status was assessed by the Gross Motor Function Measure - 88 Scale (GMFM-88) total percent scores. GMFM-88 is an 88-item measure to detect gross motor function. It consists of 5 categories: lying and rolling; sitting; crawling and kneeling; standing; walking, running and jumping. Each item was scored on a 4-point Likert scale (0 = cannot do; 1 = initiates \[\<10% of the task\]; 2 = partially completes \[10% to \<100% of the task\]; 3 = task completion). 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
Germany, Taiwan, United States
Participant flow
Recruitment details
The study was conducted between 21 August 2012 and 1 December 2014.
Pre-assignment details
A total of 5 participants were screened and 4 participants were treated.
Participants by arm
| Arm | Count |
|---|---|
| Alglucosidase Alfa 4000 L Material (Non-US Participants) Alglucosidase alfa (4000 L material) 20 mg/kg IV infusion QOW for 52 weeks. | 1 |
| Alglucosidase Alfa 160 L Material (US Participants) Alglucosidase alfa (160 L material) 20 mg/kg IV infusion QOW for 52 weeks. | 3 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Study terminated by sponsor | 1 | 0 |
Baseline characteristics
| Characteristic | Alglucosidase Alfa 4000 L Material (Non-US Participants) | Alglucosidase Alfa 160 L Material (US Participants) | Total |
|---|---|---|---|
| Age, Continuous | 0.3 years | 0.5 years STANDARD_DEVIATION 0.28 | 0.4 years STANDARD_DEVIATION 0.14 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 1 | 3 / 3 |
| serious Total, serious adverse events | 0 / 1 | 3 / 3 |
Outcome results
Primary
Change From Baseline in Cardiac Function at Week 52
Cardiac function was measured by the left ventricular mass Z-score (LVM-Z). 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 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 defined as all participants who receive at least 1 infusion of alglucosidase alfa. For this endpoint no participants were analyzed in 'Algucosidase Alfa 4000 L material' arm at Baseline and Week 52. One participant from 'Algucosidase Alfa 160 L Material' arm was discontinued from study at Week 31 due to physician's decision
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alglucosidase Alfa 160 L Material (US Participants) | Change From Baseline in Cardiac Function at Week 52 | -5.06 Z-score | Standard Deviation 1.103 |
Secondary
Change From Baseline in Motor Development Status at Week 52
Motor development status was assessed by the Gross Motor Function Measure - 88 Scale (GMFM-88) total percent scores. GMFM-88 is an 88-item measure to detect gross motor function. It consists of 5 categories: lying and rolling; sitting; crawling and kneeling; standing; walking, running and jumping. Each item was scored on a 4-point Likert scale (0 = cannot do; 1 = initiates \[\<10% of the task\]; 2 = partially completes \[10% to \<100% of the task\]; 3 = task completion). 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. For this endpoint no participants were analyzed in 'Algucosidase Alfa 4000 L material' arm at Baseline and Week 52. One participant from 'Algucosidase Alfa 160 L Material' arm was discontinued from study at Week 31 due to physician's decision.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alglucosidase Alfa 160 L Material (US Participants) | Change From Baseline in Motor Development Status at Week 52 | 48.65 percentage of maximum total score | Standard Deviation 17.183 |
Secondary
Number of Participants With Invasive Ventilator-Free Survival
Invasive ventilator-free survival was defined as the time during which the participant is alive and not invasively ventilated. Number of Participants with invasive ventilator-free survival were reported.
Time frame: Up to Week 52
Population: Full analysis population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alglucosidase Alfa 4000 L Material (Non-US Participants) | Number of Participants With Invasive Ventilator-Free Survival | 1 participants |
| Alglucosidase Alfa 160 L Material (US Participants) | Number of Participants With Invasive Ventilator-Free Survival | 2 participants |
Secondary
Percentage of Participants With Estimated Probability of Survival
Time frame: Up to Week 52
Population: Full analysis population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alglucosidase Alfa 4000 L Material (Non-US Participants) | Percentage of Participants With Estimated Probability of Survival | 100 percentage of participants |
| Alglucosidase Alfa 160 L Material (US Participants) | Percentage of Participants With Estimated Probability of Survival | 100 percentage of participants |