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

• Register: ClinicalTrials.gov
• Last refreshed on: 1 November 2021
• Main ID: NCT02998879
• Date of registration: 25/11/2016
• Prospective Registration: Yes
• Primary sponsor: Chiesi Farmaceutici S.p.A.
• Public title: Trial on Safety and Efficacy of Velmanase Alfa Treatment in Pediatric Patients With Alpha-Mannosidosis rhLaman-08
• Scientific title: A 24-month Multicenter, Open-label Phase II Trial Investigating the Safety and Efficacy of Repeated Velmanase Alfa (Recombinant Human Alpha-mannosidase) Treatment in Pediatric Patients Below 6 Years of Age With Alpha-Mannosidosis
• Date of first enrolment: December 2016
• Target sample size: 5
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02998879
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Austria, Denmark, France, Germany, Italy

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Patient's custodial parent(s) must provide signed ICF prior to the involvement of the
patient in any trial-related activities

2. The subject's custodial parent(s) must have the ability to comply with the protocol

3. 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)

4. The subject must have an age at the time of screening < 6 years.

Exclusion Criteria:

1. The subject's diagnosis cannot be confirmed by alpha-mannosidase activity < 10% of
normal activity

2. Presence of known chromosomal abnormality and syndromes affecting psychomotor
development, other than alpha-mannosidosis

3. History of BMT

4. 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

5. Any other medical condition or serious intercurrent illness, or extenuating
circumstance that, in the opinion of the Investigator, would preclude participation in
the trial

6. Planned major surgery that, in the opinion of the Investigator, would preclude
participation in the trial

7. Participation in other interventional trials testing the IMP within the last 3 months.



Age minimum: N/A
Age maximum: 6 Years
Gender: All

Health Condition(s) or Problem(s) studied

Alpha-Mannosidosis

Intervention(s)

Drug: Velmanase Alfa (e.g. Lamazym)

Primary Outcome(s)

Safety and tolerability of velmanase alfa as per clinical laboratory parameters as per blood biochemistry [Time Frame: From baseline throughout study completion, at least of 2 years]

Safety and tolerability of velmanase alfa as per clinical laboratory parameters as per hematology [Time Frame: From baseline throughout study completion, at least of 2 years]

Detection of anti-velmanase alfa-IgG antibodies (ADA) and neutralizing/inhibitory antibodies [Time Frame: From baseline throughout study completion, at least of 2 years]

Safety and tolerability of velmanase alfa as per Adverse events [Time Frame: From baseline throughout study completion, at least of 2 years]

Safety and tolerability of velmanase alfa as per clinical laboratory parameters as per urinalysis [Time Frame: From baseline throughout study completion, at least of 2 years]

Safety and tolerability of velmanase alfa as per vital signs [Time Frame: From baseline throughout study completion, at least of 2 years]

Secondary Outcome(s)

Functional capacity: Bruininks-Oseretsky test of Motor Proficiency (BOT-2) when applicable by age (from 4 years) or upon the judgment of the physician [Time Frame: From baseline throughout study completion, at least for 2 years]

Pharmacokinetic parameters to determine AUCinf (Area Under Curve From Time Zero To Infinity) [Time Frame: At first dose (visit 1) and after 6 months (visit 26)]

Magnetic Resonance Imaging (MRI) in white matter, gray matter and in centrum semi ovale, and diffusion-MRI of the brain, [Time Frame: From baseline throughout study completion, at least for 2 years]

Endurance: 3-Minute Stair Climb Test (3MSCT) in pediatric patients from 4 years of age, or when applicable according to the judgment of the physician [Time Frame: From baseline throughout study completion, at least for 2 years]

Functional capacity: The Peabody Developmental Motor Scale test (PDMS-2) [Time Frame: From baseline throughout study completion, at least for 2 years]

Immunological profile when applicable upon the judgement of the physician (Serum IgG, IgA, IgM; in vitro synthesis of IgG; in vitro proliferative response and Immunophenotype) [Time Frame: From baseline throughout study completion, at least for 2 years]

Pharmacokinetic parameters to determine Rac (Obs) Observed Accumulation Ratio [Time Frame: At first dose (visit 1) and after 6 months (visit 26)]

Assessment of quality of life via Questionnaire [Time Frame: From baseline throughout study completion, at least for 2 years]

Functional capacity: Mullen Scales of Early Learning (MSEL) [Time Frame: From baseline throughout study completion, at least for 2 years]

Assessment of mannose-rich oligosaccharides in brain tissue, as measured by Magnetic Resonance Spectroscopy (MRS) [Time Frame: From baseline throughout study completion, at least for 2 years]

Endurance: 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 [Time Frame: From baseline throughout study completion, at least for 2 years]

Hearing evaluation: Otoacoustic Emissions (OAE) testing [Time Frame: From baseline throughout study completion, at least for 2 years]

Pharmacokinetic parameters to determine Area Under Curve (AUC24) [Time Frame: At first dose (visit 1) and after 6 months (visit 26)]

Pharmacokinetic parameters to determine AUClast (Area Under Curve After The Last Count) [Time Frame: At first dose (visit 1) and after 6 months (visit 26)]

Pharmacokinetic parameters to determine Cmax (Peak Concentration) [Time Frame: At first dose (visit 1) and after 6 months (visit 26)]

Pharmacokinetic parameters to determine Ctrough (Trough Plasma Concentration) [Time Frame: At first dose (visit 1) and after 6 months (visit 26)]

Pharmacokinetic parameters to determine t1/2 (Elimination Half-Life) [Time Frame: At first dose (visit 1) and after 6 months (visit 26)]

Pharmacokinetic parameters to determine tmax (Time To Peak Concentration) [Time Frame: At first dose (visit 1) and after 6 months (visit 26)]

CSF biomarkers: Tau protein (Tau) § Neurofilament Protein Light (NFL) § Glial Fibrillary Acidic Protein (GFAp) § Oligosaccharides [Time Frame: From baseline throughout study completion, at least for 2 years]

Evaluation of levels of Serum oligosaccharides [Time Frame: From baseline throughout study completion, at least for 2 years]

Pharmacokinetic parameters to determine CL (Clearance) [Time Frame: At first dose (visit 1) and after 6 months (visit 26)]

Hearing evaluation: Automatic Auditory Brainstem Response (A-ABR) audiometry [Time Frame: From baseline throughout study completion, at least for 2 years]

Secondary ID(s)

2016-001988-36

CCD-LMZYMAA1-08

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Cromsource