A Placebo-Controlled Phase 3 Trial of Repeated Lamazym Treatment of Subjects With Alpha-Mannosidosis

Study Overview
=================
Brief Summary
-----------------
The overall objective of this trial is to evaluate the efficacy and safety of repeated Lamazym i.v. treatment, compared with placebo, in subjects 5-35 years of age with alpha-Mannosidosis

Official Title
-----------------
A Multi-Center, Double-Blind, Randomized, Placebo-Controlled, Parallel Group Trial, Investigating the Efficacy and Safety of Repeated Lamazym Treatment of Subjects With Alpha-Mannosidosis.

Conditions
-----------------
Alpha-Mannosidosis

Intervention / Treatment
-----------------
* Drug: Lamazym
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject or subjects legally authorized guardian(s) must provide signed, informed consent prior to performing any trial-related activities The subject and his/her guardian(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 < 10% of normal activity (historical data) The subject must have an age at the time of screening ≥ 5 years and ≤ 35 years The subject must have the ability to physically and mentally cooperate in the tests The subject must have an ECHO without abnormalities that, in the opinion of the Investigator, would preclude participation in the trial Exclusion Criteria: The subjects diagnosis cannot be confirmed by alpha-Mannosidase activity < 10% of normal activity The subject cannot walk without support 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 Pregnancy: Pregnant woman is excluded. Before start of the treatment the investigators will for women of childbearing potential perform a pregnancy test and decide whether or not there is a need for contraception Psychosis; any psychotic disease, also in remission, is an exclusion criteria Planned major surgery that, in the opinion of the Investigator, would preclude participation in the trial Participation in other interventional trials testing IMP (including Lamazym) within the last 3 months Adult patients who, in the opinion of the Investigator, would be unable to give consent, and who does not have any legal protection or guardianship Total IgE >800 IU/ml Known allergy to the IMP or any excipients (Sodium-Phosphate, Glycine, Mannitol)

Ages Eligible for Study
-----------------
Minimum Age: 5 Years
Maximum Age: 35 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Lamazym<br>1 mg Lamazym/kg body weight | Drug: Lamazym<br>* ERT, i.v. infusions weekly<br>* Other names: recombinant human alpha-mannosidase;|
| Placebo Comparator: Placebo<br>Placebo is formulated as an isotonic phosphate buffer with glycine and mannitol | Drug: Placebo<br>* Infusions weekly<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of oligosaccharides in serum | Primary efficacy endpoint evaluated as change from baseline in the active group versus the placebo group | Baseline evaluation prior to first dose, midterm evaluation after 26 weeks, and end evaluation after 52 weeks | 
| The number of steps climbed in 3 minutes (3-minute stair climb test) | Primary efficacy endpoint evaluated as change from baseline in the active group versus the placebo group | Baseline evaluation prior to first dose, midterm evaluation after 26 weeks, and end evaluation after 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forced Vital Capacity | Secondary efficacy endpoint evaluated as change from baseline in the active group versus the placebo group | Baseline evaluation prior to first dose, midterm evaluation after 26 weeks, and end evaluation after 52 weeks | 
| The distance walked in 6 minutes (6-minute walk test) | Secondary efficacy endpoint evaluated as change from baseline in the active group versus the placebo group | Baseline evaluation prior to first dose, midterm evaluation after 26 weeks, and end evaluation after 52 weeks | 
| 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 endpoints assessed weekly throughout the trial | 1 week | 
| Clinical laboratory parameters (hematology, biochemistry and urinalysis) | Safety endpoints assessed weekly throughout the trial | 1 week | 
| Development of Lamazym antibodies and neutralizing/inhibitory antibodies | Safety endpoints assessed weekly throughout the trial | 1 week |