Clinical trial NCT01285700: Dose Finding Study of Recombinant Human Alpha-mannosidase for the Treatment of Patients With Alpha-mannosidosis
Official title: 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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Alpha Mannosidosis
Lead sponsor: Zymenex A/S
Sponsor class: INDUSTRY
Collaborators: name: European Commission
First posted: 2011-01-28
Enrollment: 10
Sex: ALL
Minimum age (years): 5
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. The patient must have a confirmed diagnosis of alpha-Mannosidosis as defined by alpha-mannosidase activity \< 10% of normal activity in blood leukocytes
2. The patient must have an age at the time of screening ≥ 5 year and ≤ 21 years
3. 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).
4. The patient must have the ability to mentally cooperate in the cognitive and motor function tests
5. The patient must have the ability to hear and follow a request. Hearing aids can be worn.
6. 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)
7. The patient and his/her guardian(s) must have the ability to comply with the protocol

Exclusion Criteria:

1. The patient cannot walk without support.
2. Presence of known chromosomal abnormality and syndromes affecting psychomotor development, other than alpha-Mannosidosis
3. History of bone marrow transplantation
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. Presence of an ECHO with abnormalities within half a year that, in the opinion of the Investigator, would preclude participation in the trial
6. Any other medical condition or serious intercurrent illness, or extenuating circumstance that, in the opinion of the investigator, would preclude participation in the trial
7. Pregnancy
8. Psychosis within the last 3 months

Primary outcomes:
measure: Reduction of Oligosaccharides in urine
timeFrame: 3 months (interim evaluation) + 6 months
Secondary outcomes:
measure: Reduction of Oligosaccharides in serum
timeFrame: 3 months (interim evaluation) + 6 months
measure: Reduction of Oligosaccharides in CSF
timeFrame: 3 months (interim evaluation) + 6 months
measure: The distance walked in 6 minutes
timeFrame: 3 months (interim evaluation) + 6 months
measure: The number of steps climbed in 3 minutes
timeFrame: 3 months (interim evaluation) + 6 months
measure: Pulmonary Function
timeFrame: 3 months (interim evaluation) + 6 months
measure: Adverse events
timeFrame: 1 week
measure: Development of clinically significant changes in vital signs and change in physical examination
timeFrame: 1 week
measure: Development of clinically significant changes in the clinical laboratory parameters (hematology, biochemistry and urinalysis)
timeFrame: 4 weeks
measure: Development of rhLAMAN antibodies and neutralizing/inhibitory antibodies
timeFrame: 2 weeks
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Department of Clinical Genetics, Juliane Marie Centre, Copenhagen University Hospital, Blegdamsvej 9
Study officials:
affiliation: Department of Clinical Genetics, Juliane Marie Centre, Region Hovedstaden, Copenhagen University hospital, Denmark
name: Allan M. Lund, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Zymenex A/S
name: Jens Fogh
role: STUDY_CHAIR
References: