Alpha-Mannosidosis
Conditions
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
Interventions
DRUGLamazym
ERT, i.v. infusions weekly
DRUGPlacebo
Infusions weekly
Sponsors
European Commission
Zymenex A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
5 Years to 35 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The number of steps climbed in 3 minutes (3-minute stair climb test) | Baseline evaluation prior to first dose, midterm evaluation after 26 weeks, and end evaluation after 52 weeks | Primary efficacy endpoint evaluated as change from baseline in the active group versus the placebo group |
| Reduction of oligosaccharides in serum | Baseline evaluation prior to first dose, midterm evaluation after 26 weeks, and end evaluation after 52 weeks | Primary efficacy endpoint evaluated as change from baseline in the active group versus the placebo group |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The distance walked in 6 minutes (6-minute walk test) | Baseline evaluation prior to first dose, midterm evaluation after 26 weeks, and end evaluation after 52 weeks | Secondary efficacy endpoint evaluated as change from baseline in the active group versus the placebo group |
| Adverse Events | 1 week | Safety endpoint assessed weekly throughout the trial |
| Clinical laboratory parameters (hematology, biochemistry and urinalysis) | 1 week | Safety endpoints assessed weekly throughout the trial |
| Development of Lamazym antibodies and neutralizing/inhibitory antibodies | 1 week | Safety endpoints assessed weekly throughout the trial |
| Development of clinically significant changes in vital signs and change in physical examination | 1 week | Safety endpoints assessed weekly throughout the trial |
| Forced Vital Capacity | Baseline evaluation prior to first dose, midterm evaluation after 26 weeks, and end evaluation after 52 weeks | Secondary efficacy endpoint evaluated as change from baseline in the active group versus the placebo group |
Other
| Measure | Time frame | Description |
|---|---|---|
| Quantitative determination of rhLAMAN in plasma | 10 min, 60 min, 2 hours, 24 hours, 3 days, 7 days | Pharmacokinetic (PK) assessments. Blood samples are drawn pre-treatment and at various times post-treatment (see time frame above) |
Countries
Denmark, France, Germany, Poland, United Kingdom
Outcome results
None listed