E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pompe disease (acid alpha-glucosidase deficiency) |
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E.1.1.1 | Medical condition in easily understood language |
Treatment of enzyme deficiency in glycogen storage disease type II (Pompe disease)
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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 | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10053185 |
E.1.2 | Term | Glycogen storage disease type II |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036143 |
E.1.2 | Term | Pompe's disease |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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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 |
To evaluate the safety profile of avalglucosidase alfa in patients with infantile-onset Pompe disease (IOPD) previously treated with alglucosidase alfa. |
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E.2.2 | Secondary objectives of the trial |
To characterize the pharmacokinetic profile of avalglucosidase alfa and to evaluate the preliminary efficacy of avalglucosidase alfa in comparison to alglucosidase alfa. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- The patient has confirmed acid alpha-glucosidase (GAA) enzyme deficiency from any tissue source. -The patient who has reached legal age of majority as defined by local regulation, or the patient's legal guardian(s) must provide signed informed consent prior to performing any study-related procedures. If the patient is legally minor per local regulations, assent shall be obtained from patients, if applicable. -The patient (and patient’s legal guardian if patient is legally minor as defined by local regulation) must have the ability to comply with the clinical protocol. -The patient is <18 years old. -The patient, if female and of childbearing potential, must have a negative serum pregnancy test (beta-human chorionic gonadotropin) and must not be breastfeeding at screening/baseline. -The patient has cardiomyopathy at the time of diagnosis: ie, left ventricular mass index (LVMI) equivalent to mean age specific LVMI plus 2 standard deviations. -The patient has been receiving a stable dose of alglucosidase alfa regularly for a minimum of 6 months immediately prior to study entry. -For participants in Stage 1: The patient has documented evidence of clinical decline in at least 1 of the following parameters related to Pompe Disease and NOT related to intercurrent illness as assessed by the Investigator: respiratory function, motor skills, and/or cardiac parameters. - For participants in Stage 2: The patient has documented evidence of suboptimal clinical response in at least 1 of the following parameters related to Pompe Disease and NOT related to intercurrent illness as assessed by the Investigator: respiratory function, motor skills, and/or new onset of ptosis. |
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E.4 | Principal exclusion criteria |
-The patient has high antibody titer to alglucosidase alfa. -The patient has a high risk for a severe allergic reaction to Avalglucosidase Alfa (NeoGAA). -The patient requires any prohibited concomitant medications (e.g., immune modulatory treatment) for the duration of the study. -The patient has previously participated in any ACT14132 study cohort. - Female patient of childbearing potential not protected by highly effective contraceptive method of birth control and/or who is unwilling or unable to be tested for pregnancy |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Number of participants with adverse events - Number of participants with immunogenicity response |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Assessment of pharmacokinetic parameter: maximum concentration (Cmax) - Assessment of pharmacokinetic parameter: area under curve (AUC) - Change from baseline in Gross Motor Function Measure-88 Test - Change from revised Gross Motor Function Classification System score - Change from baseline in Pompe specific Pediatric Evaluation of Disability Inventory (Pompe PEDI), Functional Skills Scale: Mobility Domain Test score - Change from baseline in Quick Motor Function Test scores - Change from baseline in Left Ventricular Mass Index - Change from baseline in Left Ventricular Mass Index Z score - Change from baseline in Eyelid position measurements - Change from baseline in Creatine kinase value |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
Stage1: ascending dose cohort study design - Stage 2: randomised parallel group study design |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
France |
Germany |
Japan |
Taiwan |
United Kingdom |
United States |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |