E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Pompe disease is an enzyme deficiency which results in buildup of glycogen, primarily in muscle cells, that leads to a progressive loss of muscle function.
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036143 |
E.1.2 | Term | Pompe's disease |
E.1.2 | System Organ Class | 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 of single ascending oral doses of AT2220 administered 1 hour before administration of alglucosidase alfa in patients with Pompe disease • To evaluate the effect of single ascending oral doses of AT2220 administered 1 hour before administration of a single intravenous infusion of alglucosidase alfa on the plasma pharmacokinetics of recombinant human acid alpha-glucosidase (rhGAA) in patients with Pompe disease |
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E.2.2 | Secondary objectives of the trial |
• To assess acid alpha glucosidase (GAA) enzyme activity and protein levels in skeletal muscle at Day 3 or Day 7 following a single intravenous infusion with alglucosidase alfa alone and after pre-administration of single ascending oral doses of AT2220 • To evaluate the concentration of AT2220 in skeletal muscle at Day 3 or Day 7 after pre-administration of single ascending oral doses of AT2220. Subjects will be assigned to either Day 3 or Day 7 for both treatment periods. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female, diagnosed with Pompe disease and between 18 and 65 years of age, inclusive 2. Subject has been on a stable regimen and dose of alglucosidase alfa for at least 3 months before screening (stable regimen defined as currently receiving alglucosidase alfa every 2 weeks and stable dose defined as not varying by more than ± 10%) 3. Subject has an estimated glomerular filtration rate (eGFR) ≥ 50 mL/min at Screening; eGFR to be estimated using the 4-parameter Modification of Diet in Renal Disease (MDRD) equation: eGFR (mL/min/1.73 m^2) = 175 x (Scr)^(-1.154) x (Age)^(-0.203) x (0.742 if female) x (1.212 if African-American) 4. Male and female subjects of childbearing potential agree to use medically accepted methods of contraception during the study and for 30 days after study drug administration 5. Subject is willing and able to provide written informed consent and is able to comply with all study procedures |
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E.4 | Principal exclusion criteria |
1. Subject has had a documented transient ischemic attack, stroke, unstable angina or myocardial infarction within the 3 months before Screening 2. Subject has clinically significant unstable cardiac disease (e.g., cardiac disease requiring active management, such as symptomatic arrhythmia, unstable angina or NYHA class III or IV congestive heart failure) 3. Subject requiring invasive mechanical ventilation or is confined to a wheelchair 4. Subject has a history of allergy or sensitivity to study drug (including excipients) or other iminosugars (e.g., miglustat, miglitol) 5. Subject is pregnant or breastfeeding 6. Subject tests positive for hepatitis B surface antigen or hepatitis C antibody 7. Subject has received any investigational/experimental drug or device within 30 days of Screening 8. Subject has any concurrent illness or condition that may preclude the subject from fulfilling the protocol requirements or suggests to the investigator that the potential subject may have an unacceptable risk by participating in this study |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Safety, including AEs (including infusion-associated reactions), clinical laboratory tests (hematology, urinalysis, serum chemistry including creatine kinase, LDH, alkaline phosphatase, ALT and AST), Urine glucose Hex4, 12-lead ECGs, physical examinations, vital signs, and muscle strength tests • Plasma acid alpha glucosidase Cmax and AUC (estimated) for enzyme activity after an alglucosidase alfa intravenous infusion alone and after pre-administration of single ascending oral doses of AT2220; total protein concentration will also be evaluated for each infusion |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Tests described in E.5.1 will be performed throughout the study |
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E.5.2 | Secondary end point(s) |
• Acid alpha glucosidase levels in muscle at Day 3 or Day 7after a single intravenous administration of alglucosidase alfa alone and in combination with single ascending oral doses of AT2220 by measuring acid alpha glucosidase enzyme activity and protein levels • The concentration of AT2220 in skeletal muscle tissue homogenate at Day 3 or Day 7 after pre-administration of single ascending oral doses of AT2220 in Treatment Period 2. • Acid alpha glucosidase levels in muscle at Day 3 or Day 7after a single intravenous administration of alglucosidase alfa alone and in combination with single ascending oral doses of AT2220 by measuring acid alpha glucosidase enzyme activity and protein levels. The concentration of AT2220 in skeletal muscle tissue homogenate at Day 3 or Day 7 after pre-administration of single ascending oral doses of AT2220 in Treatment Period 2. |
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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 | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
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) | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
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 |
Canada |
France |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 30 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 30 |