Trial on Safety and Efficacy of Velmanase Alfa Treatment in Pediatric Patients With Alpha-Mannosidosis

The Primary endpoints of the study include:

• Safety and tolerability of velmanase alfa as per Adverse events (AEs, including IRR), vital signs, laboratory parameters (hematology, biochemistry and urinanalysis)
• Detection of anti-velmanase alfa antibodies and neutralizing/inhibitory antibodies

The Secondary endpoints include changes from baseline to 24 months for the following parameters. Efficacy outcomes:

• Serum oligosaccharides
• Functional capacity: Peabody Developmental Motor Scale - 2nd edition (PDMS-2) scores, Mullen's Scale of Early Learning (MSEL) scores, Bruininks-Oseretsky Test Of Motor Proficiency-2nd Edition (BOT-2), when applicable by age (from 4 years) or upon the judgment of the physician
• Endurance: 3-Minute Stair Climb Test (3MSCT) and 6-Minute Walk Test (6MWT) in pediatric patients from 4 years of age, or when applicable according to the judgment of the physician, 2-Minute Walk Test (2MWT) in pediatric patients below 4 years of age, or when applicable according to the judgment of the physician
• Hearing evaluation: Otoacoustic Emissions (OAE) testing, Automatic Auditory Brainstem Response (A-ABR) audiometry
• Immunological profile, when applicable upon the judgment of the physician:
• CSF biomarkers: Tau protein (Tau), Neurofilament Protein Light (NFL), Glial Fibrillary Acidic Protein (GFAp), Oligosaccharides
• Assessment of quality of life via Questionnaire to parents
• Assessment of mannose-rich oligosaccharides in brain tissue, MRI
• Pharmacokinetic parameters

Inclusion criteria

• Patient's custodial parent(s) must provide signed ICF prior to the involvement of the patient in any trial-related activities
• The subject's custodial parent(s) must have the ability to comply with the protocol
• The subject must have a confirmed diagnosis of alpha-mannosidosis as defined by alpha-mannosidase activity in leukocytes or fibroblasts < 10% of normal activity (historical data)
• The subject must have an age at the time of screening < 6 years.

Exclusion criteria

• The subject's diagnosis cannot be confirmed by alpha-mannosidase activity < 10% of normal activity
• Presence of known chromosomal abnormality and syndromes affecting psychomotor development, other than alpha-mannosidosis
• History of BMT
• Presence of known clinically significant cardiovascular, hepatic, pulmonary, or renal disease or other medical conditions that, in the opinion of the Investigator, would preclude participation in the trial
• Any other medical condition or serious intercurrent illness, or extenuating circumstance that, in the opinion of the Investigator, would preclude participation in the trial
• Planned major surgery that, in the opinion of the Investigator, would preclude participation in the trial
• Participation in other interventional trials testing the IMP within the last 3 months.