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 | 20.0 |
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.1.2 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.1.3 | 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 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 or beta-blockers) 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) |
1 / Assessment of pharmacokinetic parameter: maximum plasma concentration (Cmax)
Assessment of pharmacokinetic parameter: time to achieve maximum plasma concentration (tmax)
2 / Assessment of pharmacokinetic parameter: area under curve (AUC0 to last)
Assessment of pharmacokinetic parameter: terminal half-life (t1/2z)
3 / Change from baseline in Gross Motor Function Measure-88 Test
4 / Change from revised Gross Motor Function Classification System score
5 / Change from baseline in Pompe specific Pediatric Evaluation of Disability Inventory (Pompe PEDI), Functional Skills Scale: Mobility Domain Test score (normative standard score)
6 / Change from baseline for Pompe PEDI Functional Skills Scale: Mobility Domain Test score (scaled score)
7 / Change from baseline in Quick Motor Function Test scores
8 / Change from baseline in Left Ventricular Mass Index
9 / Change from baseline in Left Ventricular Mass Index Z score
10 / Change from baseline in Eyelid position measurements
Interpalpebral fissure distance (IPFD)
11 / Change from baseline in Eyelid position measurements: Margin reflex distance-1 (MRD-1)
12 / Change from baseline in Eyelid position measurements: Margin pupil distance (MPD)
13/ Change from baseline in Creatine kinase value
14 / Number of participants with adverse events
15 / Number of participants with immunogenicity response |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1 / to 13 / : Baseline to 25 weeks
14 / and 15 / : Up to 7 years |
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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 |
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 | 5 |
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 |
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.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 7 |
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 |