E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pompe disease (acid alpha-glucosidase deficiency) |
|
E.1.1.1 | Medical condition in easily understood language |
People with Pompe disease have low levels of an enzyme called acid alpha-glucosidase. This enzyme helps the body control levels of glycogen (a type of carbohydrate). |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036143 |
E.1.2 | Term | Pompe's disease |
E.1.2 | System Organ Class | 100000004850 |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to demonstrate the noninferiority of alglucosidase alfa produced at the 4000 L scale to the 160 L scale product in terms of the change from baseline of the left ventricular mass Z-score (LVM-Z) after 52 weeks of treatment. Patients will be treated with alglucosidase alfa from the 160 L scale in the US and from the 4000 L scale in Europe and in countries outside the US. |
|
E.2.2 | Secondary objectives of the trial |
Secondary objectives of this study are to: •compare alglucosidase alfa produced at the 4000 L scale to the 160 L scale relating to the estimated probabilities of survival to Week 52; •compare alglucosidase alfa produced at the 4000 L scale to the 160 L scale relating to the estimated probabilities of invasive ventilator-free survival to Week 52; •compare the survival and invasive ventilator-free survival of the 160 L and 4000 L treatment arms to an untreated historical cohort at 12 months of age; •assess motor development and performance in treated patients; •compare the safety profile of alglucosidase alfa produced at the 160 L and 4000 L scales. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. The patient’s parent(s)/legal guardian(s) is willing and able to provide signed informed consent. 2. The patient must be less than or equal to 12 months of age at the time of the first study infusion. 3. The patient must have a documented GAA enzyme deficiency from blood, skin, or muscle tissue. 4. The patient must be naïve to treatment with alglucosidase alfa. |
|
E.4 | Principal exclusion criteria |
1. The patient is cross-reactive immunologic material (CRIM) negative. 2. The patient requires invasive ventilatory support at the time of enrollment. 3. The patient has decompensated clinical heart failure. 4. The patient has a major congenital abnormality, excluding cardiac hypertrophy. 5. The patient has a clinically significant organ disease (excluding the signs and symptoms of Pompe disease). 6. The patient is currently receiving any investigational product. 7. The patient is currently participating in another clinical study. 8. The patient and/or the patient’s parent(s)/legal guardian(s) is unable to adhere to the requirements of the study. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this study is change from baseline in cardiac function as measured by the left ventricular mass Z-score (LVM-Z) assessed at the end of the 52-week treatment period. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
The secondary endpoints of this study are: •estimated probability of survival to Week 52; •estimated probability of invasive ventilator-free survival to Week 52; •change in motor development status from baseline to Week 52 as assessed by the Gross Motor Function Measure – 88 Scale (GMFM-88) total percent scores. •Number of Treatment-emergent Serious Adverse Events (SAEs) and Adverse Events (AEs) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Alglucosidase alfa manufactured at the 160L scale (in US only). |
|
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Germany |
India |
Russian Federation |
Taiwan |
Turkey |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The end of the study is defined as the date the last active patient completes the last required study visit. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |