Acid Maltase Deficiency, Glycogen Storage Disease Type II (GSD II), Pompe Disease
Conditions
Brief summary
Primary Objective: To evaluate the safety and tolerability of neoGAA in treatment naïve and alglucosidase alfa treated late-onset Pompe disease patients. Secondary Objective: To evaluate the pharmacokinetics, pharmacodynamics of neoGAA in treatment naïve and alglucosidase alfa treated late-onset Pompe disease patients. To evaluate the effect of neoGAA on exploratory efficacy endpoints in treatment naïve and alglucosidase alfa treated late-onset Pompe disease patients.
Detailed description
Screening: within 90 days Period of treatment: 24 weeks (including 13 bi-weekly infusions) Post treatment evaluation visit: 2 weeks after last neoGAA infusion (at Week 27) End of study visit: 4 weeks after last neoGAA infusion (at Week 29) Total duration: approximately 41 weeks
Interventions
DRUGGZ402666
Pharmaceutical form:lyophilized powder reconstituted for infusion Route of administration: intravenous
Sponsors
Genzyme, a Sanofi Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
: For both Group 1 and Group 2: * Male or female patients with confirmed acid α-glucosidase (GAA) enzyme deficiency from any tissue source and/or confirmed GAA gene mutation and without known cardiac hypertrophy. * Patient willing and able to provide signed informed consent * Patient is able to ambulate 50 meters (approximately 160 feet) without stopping and without an assistive device. Use of assistive device for community ambulation is appropriate. * Patient has a forced vital capacity (FVC) in upright position of ≥50% predicted. * The patient, if female and of childbearing potential, must have a negative pregnancy test \[urine beta-human chorionic gonadotropin (β-hCG)\] at baseline. Group 2 patients only: \- The patient has been previously treated with alglucosidase alfa for at least 9 months.
Exclusion criteria
For both Group 1 and Group 2: * Patient is wheelchair dependent. * Patient requires invasive-ventilation (non-invasive ventilation is allowed). * Patient is participating in another clinical study using investigational treatment. * Patient, in the opinion of the Investigator, is unable to adhere to the requirements of the study. * Patient has clinically significant organic disease (with the exception of symptoms relating to Pompe disease), including clinically significant cardiovascular, hepatic, pulmonary, neurologic, or renal disease, or other medical condition, serious intercurrent illness, or extenuating circumstance that, in the opinion of the Investigator, precludes participation in the study or potentially decreases survival. * Patient cannot submit to MRI examination because of a formal contraindication such as a pacemaker, implanted ferromagnetic metals, anxiety disorder, etc. Group 1 only: \- Patient has had previous treatment with alglucosidase alfa or any other enzyme replacement therapy (ERT) for Pompe disease. Group 2 only: \- Patient has a high risk for a severe allergic reaction to neoGAA (i.e. previous moderate to severe anaphylactic reaction to alglucosidase alfa and/or patient has immunoglobulin (Ig) E antibodies to alglucosidase alfa, and/or a history of sustained high immunoglobulin G (IgG) antibody titers to alglucosidase alfa that in the opinion of the investigator suggest a high risk for an allergic reaction to neoGAA). The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Adverse events | screening/baseline to Week 25 |
| Laboratory assessments including hematology, biochemistry and urinalysis | screening/baseline to Week 25 |
| Vital signs | screening/baseline to Week 25 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC | Week 1, Week 13, Week 25 | — |
| t1/2 | Week 1, Week 13, Week 25 | — |
| Skeletal muscle glycogen content | screening/baseline, Week 27 | — |
| Electrocardiogram | screening/baseline, Week 1, Week 13, Week 25 | — |
| Urinary Hex4 | screening/baseline to Week 25 | — |
| Functional assessments including 6 Minute Walk Test (6MWT) | screening/baseline, Week 13, Week 25 | Functional Assessment includes - pulmonary function testing (PFT) endpoints, Gait, Stair, Gower's Maneuver, Chair (GSGC), Gross Motor Function Measure-88 (GMFM-88), Quick Motor Function Test (QMFT), hand-held dynamometer testing, Pediatric Quality of Life Inventory Multidimensional Fatigue Scale (PedsQL) |
| Quality of life assessments | screening/baseline, Week 13, Week 25 | — |
| Skeletal muscle magnetic resonance images for qualitative and quantitative muscle degenerative assessments. | screening/baseline, Week 27 | — |
| Immunogenicity assessments | screening/baseline to Week 29 | — |
| Cmax | Week 1, Week 13, Week 25 | — |
Countries
Belgium, Denmark, France, Germany, Netherlands, United Kingdom, United States
Outcome results
None listed