The overall objective is to evaluate the long-term efficacy of Lamazym i.v. treatment in patients with alpha-Mannosidosis previously enrolled in Lamazym trials and currently receiving the treatment according to the AfterCare Program.
The primary objective of the trial is to evaluate the impact of the long-term treatment with Lamazym upon the level of biomarker oligosaccharides in serum and upon the endurance as measured by the change from baseline in the number of steps climbed in 3 minutes (3MSCT). As secondary objectives, the long term efficacy of Lamazym will be investigated upon endurance as measured by the change from baseline in the number of meters walked in six minutes (6MWT), upon pulmonary function, motor proficiency by BOT-2 and hearing capability by audiometry. In addition, cognitive development will be assessed by Leiter-R test. CNS involvement will be evaluated with MRI/MRS (for patients who previously participated in rhLAMAN-02 trial), CSF biomarkers (Tau, NFL, GFAp) and CSF biomarkers oligosaccharides. Clearance of oligosaccharides in urine will be measured. Long-term safety and Pharmaco-Kinetic (PK) profile after long-term treatment as measured by rhLAMAN levels in plasma will be assessed as well. Quality of life will be assessed by questionnaires (CHAQ and EQ-5D-5L).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
recombinant human alpha-mannosidase
Center for Metabolic Diseases, Department of Clinical Genetics, Juliane Marie Centre, Copenhagen University Hospital, Blegdamsvej 9
Copenhagen, Denmark
Change from baseline in reduction of oligosaccharides in serum
Primary Endpoint evaluation as change
Time frame: Baseline evaluation prior to first dose compared to evaluation after one, two or four years of treatment
Change from baseline in 3 Minutes Stair Climb Test (3MSCT)
Primary Endpoint evaluation as change
Time frame: Baseline evaluation prior to first dose compared to evaluation after one, two or four years of treatment
6 Minute Walk Test (6MWT)
Endpoint evaluation as change
Time frame: Baseline evaluation prior to first dose compared to evaluation after one, two or four years of treatment
Pulmonary function: Forced Vital Capacity (FVC)
Endpoint evaluation as change
Time frame: Baseline evaluation prior to first dose compared to evaluation after one, two or four years of treatment
Pulmonary function: Forced Expiratory Volume during first second (FEV1)
Endpoint evaluation as change
Time frame: Baseline evaluation prior to first dose compared to evaluation after one, two or four years of treatment
Pulmonary function: Peak Expiratory Flow Rate (PEF)
Endpoint evaluation as change
Time frame: Baseline evaluation prior to first dose compared to evaluation after one, two or four years of treatment
Functional capacity according to Bruininks-Oseretsky test of Motor Proficiency (BOT-2)
Endpoint evaluation as change
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Time frame: Baseline evaluation prior to first dose compared to evaluation after one, two or four years of treatment
Pure Tone Audiometry (PTA)
Endpoint evaluation as change
Time frame: Baseline evaluation prior to first dose compared to evaluation after one, two or four years of treatment
Equivalence age measured by Leiter International Performance Scale-Revised (Leiter-R)
Endpoint evaluation as change
Time frame: Baseline evaluation prior to first dose compared to evaluation after one, two or four years of treatment
Assessment of mannose-rich oligosaccharides in brain tissue as measured by Magnetic Resonance Spectroscopy (MRS) visual score (for patients who previously participated in rhLAMAN-02)
Endpoint evaluation as change
Time frame: Baseline evaluation prior to first dose compared to evaluation after one, two or four years of treatment
Assessment of mannose-rich oligosaccharides in brain tissue as measured by Magnetic Resonance Imaging (MRI) diffusion coefficient (for patients who previously participated in rhLAMAN-02)
Endpoint evaluation as change
Time frame: Baseline evaluation prior to first dose compared to evaluation after one, two or four years of treatment
Cerebrospinal fluid biomarkers: Oligosaccharides in Cerebrospinal Fluid (CSF)
Endpoint evaluation as change
Time frame: Baseline evaluation prior to first dose compared to evaluation after one, two or four years of treatment
Cerebrospinal fluid neuro-degeneration biomarkers: Tau Protein (Tau) in Cerebrospinal Fluid (CSF)
Endpoint evaluation as change
Time frame: Baseline evaluation prior to first dose compared to evaluation after one, two or four years of treatment
Cerebrospinal fluid neuro-degeneration biomarkers: Neurofilament Protein Light (NFL) in Cerebrospinal Fluid (CSF)
Endpoint evaluation as change
Time frame: Baseline evaluation prior to first dose compared to evaluation after one, two or four years of treatment
Cerebrospinal fluid neuro-degeneration biomarkers: Glial Fibrillary Acidic protein (GFAp) in Cerebrospinal Fluid (CSF)
Endpoint evaluation as change
Time frame: Baseline evaluation prior to first dose compared to evaluation after one, two or four years of treatment
Drug exposure by Pharmaco Kinetic (PK) sampling profile on plasma
Evaluation of steady state Pharmaco Kinetics
Time frame: 1 week
Measurement of in vivo biological activity of Lamazym in blood before and after Infusion of Lamazym
Comparing with Anti Body (AB) and PK measurements. Measuring unit is mU/mL
Time frame: 1 week
Oligosaccharides in urine
Evaluation of steady state
Time frame: 1 week