Dose Finding Study of Recombinant Human Alpha-mannosidase for the Treatment of Patients With Alpha-mannosidosis

Study Overview
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Brief Summary
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This is a single-center, open-label, multiple-dose study of the efficacy and long-term safety of Lamazym for the treatment of patients with alpha-mannosidosis.

Official Title
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A Single Center, Randomized, Open-label, Multiple-dose Study of the Efficacy and Long-term Safety of rhLAMAN (Recombinant Human Alpha-mannosidase or Lamazym) for the Treatment of Patients With Alpha-mannosidosis.

Conditions
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Alpha Mannosidosis

Intervention / Treatment
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* Drug: Lamazym


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient must have a confirmed diagnosis of alpha-Mannosidosis as defined by alpha-mannosidase activity < 10% of normal activity in blood leukocytes The patient must have an age at the time of screening ≥ 5 year and ≤ 21 years The patient must have physical ability to perform 6-minutes walk test (6MWT), 3 minute-stair climb test (3MSCT) and pulmonary lung function test (spirometry, body plethysmography). The patient must have the ability to mentally cooperate in the cognitive and motor function tests The patient must have the ability to hear and follow a request. Hearing aids can be worn. Patient or patient's legally authorized guardian(s) must provide signed, informed consent prior to performing any study-related activities (trial-related activities are any procedures that would not have been performed during normal management of the subject) The patient and his/her guardian(s) must have the ability to comply with the protocol Exclusion Criteria: The patient cannot walk without support. Presence of known chromosomal abnormality and syndromes affecting psychomotor development, other than alpha-Mannosidosis History of bone marrow transplantation 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 Presence of an ECHO with abnormalities within half a year 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 Pregnancy Psychosis within the last 3 months

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Lamazym 25<br>25 U/kg | Drug: Lamazym<br>* ERT, infusion weekly<br>* Other names: rhLAMAN;|
| Active Comparator: Lamazym 50<br>50 U/kg | Drug: Lamazym<br>* ERT, infusion weekly<br>* Other names: rhLAMAN;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of Oligosaccharides in urine | Efficacy endpoint evaluation as change from baseline | 3 months (interim evaluation) + 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of Oligosaccharides in serum | Efficacy endpoint evaluation as change from baseline | 3 months (interim evaluation) + 6 months | 
| Reduction of Oligosaccharides in CSF | Efficacy endpoint evaluation as change from baseline | 3 months (interim evaluation) + 6 months | 
| The distance walked in 6 minutes | Efficacy endpoint evaluation as change from baseline | 3 months (interim evaluation) + 6 months | 
| The number of steps climbed in 3 minutes | Efficacy endpoint evaluation as change from baseline | 3 months (interim evaluation) + 6 months | 
| Pulmonary Function | Efficacy endpoint evaluation as change from baseline | 3 months (interim evaluation) + 6 months | 
| Adverse events | Safety endpoint assessed weekly throughout the trial | 1 week | 
| Development of clinically significant changes in vital signs and change in physical examination | Safety endpoint assessed weekly throughout the trial | 1 week | 
| Development of clinically significant changes in the clinical laboratory parameters (hematology, biochemistry and urinalysis) | Safety endpoint assessed every 4th week throughout the trial | 4 weeks | 
| Development of rhLAMAN antibodies and neutralizing/inhibitory antibodies | Safety endpoint assessed every other week throughout the trial | 2 weeks |