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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02998879
Other study ID # CCD-LMZYMAA1-08
Secondary ID 2016-001988-36
Status Completed
Phase Phase 2
First received
Last updated
Start date December 2016
Est. completion date July 2020

Study information

Verified date October 2021
Source Chiesi Farmaceutici S.p.A.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The main objectives of the study are to evaluate safety and efficacy of repeated treatment with recombinant human alfa-mannosidase of patients with alfa-mannosidosis aged less than 6 years


Description:

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


Recruitment information / eligibility

Status Completed
Enrollment 5
Est. completion date July 2020
Est. primary completion date July 2020
Accepts healthy volunteers No
Gender All
Age group N/A to 6 Years
Eligibility 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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Velmanase Alfa (e.g. Lamazym)
iv infusion treatment

Locations

Country Name City State
n/a

Sponsors (2)

Lead Sponsor Collaborator
Chiesi Farmaceutici S.p.A. Cromsource

Countries where clinical trial is conducted

Austria,  Denmark,  France,  Germany,  Italy, 

Outcome

Type Measure Description Time frame Safety issue
Primary Safety and tolerability of velmanase alfa as per Adverse events Safety and tolerability assessed as per AEs including infusion-related reactions [IRRs] From baseline throughout study completion, at least of 2 years
Primary Safety and tolerability of velmanase alfa as per vital signs From baseline throughout study completion, at least of 2 years
Primary Safety and tolerability of velmanase alfa as per clinical laboratory parameters as per hematology From baseline throughout study completion, at least of 2 years
Primary Safety and tolerability of velmanase alfa as per clinical laboratory parameters as per blood biochemistry From baseline throughout study completion, at least of 2 years
Primary Safety and tolerability of velmanase alfa as per clinical laboratory parameters as per urinalysis From baseline throughout study completion, at least of 2 years
Primary Detection of anti-velmanase alfa-IgG antibodies (ADA) and neutralizing/inhibitory antibodies Serum samples for anti-velmanase alfa-IgG antibody (ADA) testing will be obtained From baseline throughout study completion, at least of 2 years
Secondary Evaluation of levels of Serum oligosaccharides Assessment of change from baseline in levels of Serum oligosaccharides From baseline throughout study completion, at least for 2 years
Secondary Functional capacity: The Peabody Developmental Motor Scale test (PDMS-2) Serum samples for anti-velmanase alfa-IgG antibody (ADA) testing will be obtained From baseline throughout study completion, at least for 2 years
Secondary Functional capacity: Bruininks-Oseretsky test of Motor Proficiency (BOT-2) when applicable by age (from 4 years) or upon the judgment of the physician From baseline throughout study completion, at least for 2 years
Secondary Functional capacity: Mullen Scales of Early Learning (MSEL) From baseline throughout study completion, at least for 2 years
Secondary 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 From baseline throughout study completion, at least for 2 years
Secondary 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 From baseline throughout study completion, at least for 2 years
Secondary Hearing evaluation: Otoacoustic Emissions (OAE) testing From baseline throughout study completion, at least for 2 years
Secondary Hearing evaluation: Automatic Auditory Brainstem Response (A-ABR) audiometry From baseline throughout study completion, at least for 2 years
Secondary 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) From baseline throughout study completion, at least for 2 years
Secondary CSF biomarkers: Tau protein (Tau) § Neurofilament Protein Light (NFL) § Glial Fibrillary Acidic Protein (GFAp) § Oligosaccharides From baseline throughout study completion, at least for 2 years
Secondary Assessment of quality of life via Questionnaire From baseline throughout study completion, at least for 2 years
Secondary Assessment of mannose-rich oligosaccharides in brain tissue, as measured by Magnetic Resonance Spectroscopy (MRS) From baseline throughout study completion, at least for 2 years
Secondary Magnetic Resonance Imaging (MRI) in white matter, gray matter and in centrum semi ovale, and diffusion-MRI of the brain, From baseline throughout study completion, at least for 2 years
Secondary Pharmacokinetic parameters to determine Cmax (Peak Concentration) At first dose (visit 1) and after 6 months (visit 26)
Secondary Pharmacokinetic parameters to determine Ctrough (Trough Plasma Concentration) At first dose (visit 1) and after 6 months (visit 26)
Secondary Pharmacokinetic parameters to determine Area Under Curve (AUC24) At first dose (visit 1) and after 6 months (visit 26)
Secondary Pharmacokinetic parameters to determine AUClast (Area Under Curve After The Last Count) At first dose (visit 1) and after 6 months (visit 26)
Secondary Pharmacokinetic parameters to determine AUCinf (Area Under Curve From Time Zero To Infinity) At first dose (visit 1) and after 6 months (visit 26)
Secondary Pharmacokinetic parameters to determine tmax (Time To Peak Concentration) At first dose (visit 1) and after 6 months (visit 26)
Secondary Pharmacokinetic parameters to determine CL (Clearance) At first dose (visit 1) and after 6 months (visit 26)
Secondary Pharmacokinetic parameters to determine t1/2 (Elimination Half-Life) At first dose (visit 1) and after 6 months (visit 26)
Secondary Pharmacokinetic parameters to determine Rac (Obs) Observed Accumulation Ratio At first dose (visit 1) and after 6 months (visit 26)
See also
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Not yet recruiting NCT06184503 - Analysis of Velmanase Alfa (Lamzede®)'s Effects in the Body of Children With Alpha-Mannosidosis Under the Age 3
Completed NCT01908725 - Lamazym Aftercare Study Phase 3
Completed NCT02141503 - Clinical Biomarkers in Alpha-mannosidosis
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Completed NCT01681940 - Long-term Efficacy and Safety of Lamazym for the Treatment of Patients With Alpha-Mannosidosis Phase 2
Withdrawn NCT04031066 - Interventional Study to Assess Efficacy and Safety of Velmanase Alfa in Patients With Alpha Mannosidosis Phase 3
Recruiting NCT03333200 - Longitudinal Study of Neurodegenerative Disorders
Completed NCT02478840 - Evaluation of Long-term Efficacy of Treatment With Lamazym Phase 3
Completed NCT01908712 - Lamazym Aftercare Study FR Designed to Provide Treatment for French Patients Phase 3
Completed NCT01681953 - A Placebo-Controlled Phase 3 Trial of Repeated Lamazym Treatment of Subjects With Alpha-Mannosidosis Phase 3
Terminated NCT01372228 - Phase I/II Pilot Study of Mixed Chimerism to Treat Inherited Metabolic Disorders Phase 1/Phase 2
Available NCT04959240 - Expanded Access to Velmanase Alfa