A Study to Assess Safety and Efficacy of Avalglucosidase Alfa Administered Every Other Week in Pediatric Patients With Infantile-onset Pompe Disease Previously Treated With Alglucosidase Alfa (Mini-COMET)
Glycogen Storage Disease Type II-Pompe's Disease
About this trial
This is an interventional treatment trial for Glycogen Storage Disease Type II-Pompe's Disease
Eligibility Criteria
Inclusion criteria:
- The participants has confirmed acid alpha-glucosidase (GAA) enzyme deficiency from any tissue source.
- The participants who has reached legal age of majority as defined by local regulation, or the participant's legal guardian(s) must provide signed informed consent prior to performing any study-related procedures. If the participant is legally minor per local regulations, assent shall be obtained from participants, if applicable.
- The participants (and participant's legal guardian if participant is legally minor as defined by local regulation) must have the ability to comply with the clinical protocol.
- The participants is less than 18 years old.
- The participants, if female and of childbearing potential, must have a negative serum pregnancy test (beta-human chorionic gonadotropin) and must not breastfeeding at screening/Baseline.
- The participant has cardiomyopathy at the time of diagnosis: i.e., left ventricular mass index (LVMI) equivalent to mean age specific LVMI plus 2 standard deviations.
- The participant 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 participant 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 participant 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.
Exclusion criteria:
- The participant has high antibody titer to alglucosidase alfa.
- The participant has a high risk for a severe allergic reaction to neoGAA (avalglucosidase alfa).
- The participant requires any prohibited concomitant medications (e.g., immune modulatory treatment) for the duration of the study.
- The participant has previously participated in any ACT14132 study cohort.
- Female participant of childbearing potential not protected by highly effective contraceptive method of birth control and/or who is unwilling or unable to tested for pregnancy.
The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Sites / Locations
- Investigational Site Number 8400002
- Investigational Site Number 8400001
- Investigational Site Number 8400005
- Investigational Site Number 2500003
- Investigational Site Number 2500001
- Investigational Site Number 3920001
- Investigational Site Number 3920002
- Investigational Site Number 1580001
- Investigational Site Number 8260001
- Investigational Site Number 8260002
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Experimental
Experimental
Experimental
Cohort 1: Avalglucosidase Alfa 20 mg/kg
Cohort 2: Avalglucosidase Alfa 40 mg/kg
Cohort 3a: Avalglucosidase Alfa 40 mg//kg
Cohort 3b: Alglucosidase Alfa in PAP
Avalglucosidase alfa, 20 mg/kg intravenous (IV) infusion every other week (qow) for 25 weeks in the Primary Analysis Period (PAP), followed by same treatment from Week 26 up to Week 371 in extension treatment period (ETP).
Avalglucosidase alfa 40 mg/kg IV infusion qow for 25 weeks in the PAP, followed by same treatment from Week 26 up to Week 371 in ETP.
After determination of the highest tolerated avalglucosidase alfa dose in Cohort 1 and Cohort 2 (after at least 5 participants in each Cohort 1 and Cohort 2 had received the 7th dose of avalglucosidase alfa or completed Week 13 with a minimum of 6 infusions), participants received avalglucosidase alfa 40 mg/kg (the highest tolerated dose) IV infusion qow for 25 weeks in PAP, followed by same treatment from Week 26 up to Week 371 in ETP.
After determination of the highest tolerated avalglucosidase alfa dose in Cohort 1 and Cohort 2 (after at least 5 participants in each Cohort 1 and Cohort 2 had received the 7th dose of avalglucosidase alfa or completed Week 13 with a minimum of 6 infusions), participants received alglucosidase alfa at their current stable dose (defined as dose [between 20 mg/kg qow and 40 mg/kg weekly as per physician] administered regularly for a minimum of 6 months immediately prior to entry in this study) IV infusion for 25 weeks in PAP. After PAP, participants received avalglucosidase alfa 40mg/kg IV infusion qow from Week 26 up to Week 371 in ETP.