Safety Study of Recombinant Human Alpha-mannosidase for the Treatment of Patients With Alpha-mannosidosis
Primary Purpose
Alpha Mannosidosis
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Lamazym
Sponsored by
About this trial
This is an interventional treatment trial for Alpha Mannosidosis
Eligibility Criteria
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 ≤ 20 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Lamazym 6.25
Lamazym 12.5
Lamazym 25
Lamazym 50
Lamazym 100
Arm Description
Outcomes
Primary Outcome Measures
To evaluate the safety profile of rhLAMAN (Lamazym)
Secondary Outcome Measures
To determine the PK profile of rhLAMAN (Lamazym) in patients with alpha-mannosidosis as measured by rhLAMAN levels in plasma
To collect baseline measurements that are to be used for efficacy evaluation in the following trial (rhLAMAN-03)
Full Information
NCT ID
NCT01268358
First Posted
December 29, 2010
Last Updated
July 30, 2020
Sponsor
Zymenex A/S
Collaborators
European Commission
1. Study Identification
Unique Protocol Identification Number
NCT01268358
Brief Title
Safety Study of Recombinant Human Alpha-mannosidase for the Treatment of Patients With Alpha-mannosidosis
Official Title
A Single Center, Open-label, Dose Escalation Study of the Safety and Pharmacokinetics of rhLAMAN (Recombinant Human Alpha-mannosidase or Lamazym) for the Treatment of Patients With Alpha-mannosidosis.
Study Type
Interventional
2. Study Status
Record Verification Date
July 2020
Overall Recruitment Status
Completed
Study Start Date
October 2010 (undefined)
Primary Completion Date
January 2011 (Actual)
Study Completion Date
January 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Zymenex A/S
Collaborators
European Commission
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a single-center, open-label, dose escalation study of patients with alpha-mannosidosis. 10 patients will be enrolled in this study receiving intravenous infusions of Lamazym. In order to avoid development of delayed hypersensitivity all patients will continue weekly treatment at the designated dose until the Safety Committee approves transfer to the rhLAMAN-03 protocol.
It is the hypothesis that Lamazym is safe to use.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alpha Mannosidosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Lamazym 6.25
Arm Type
Experimental
Arm Title
Lamazym 12.5
Arm Type
Experimental
Arm Title
Lamazym 25
Arm Type
Experimental
Arm Title
Lamazym 50
Arm Type
Experimental
Arm Title
Lamazym 100
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Lamazym
Other Intervention Name(s)
rhLAMAN
Intervention Description
Lamazym, ERT, infusion weekly
Primary Outcome Measure Information:
Title
To evaluate the safety profile of rhLAMAN (Lamazym)
Time Frame
1-5 weeks
Secondary Outcome Measure Information:
Title
To determine the PK profile of rhLAMAN (Lamazym) in patients with alpha-mannosidosis as measured by rhLAMAN levels in plasma
Time Frame
1 dosis
Title
To collect baseline measurements that are to be used for efficacy evaluation in the following trial (rhLAMAN-03)
Time Frame
1 week
10. Eligibility
Sex
All
Minimum Age & Unit of Time
5 Years
Maximum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 ≤ 20 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Allan M. Lund, MD
Organizational Affiliation
Department of Clinical Genetics, Juliane Marie Centre, Region Hovedstaden, Copenhagen University hospital, Denmark
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jens Fogh
Organizational Affiliation
Zymenex A/S
Official's Role
Study Chair
12. IPD Sharing Statement
Citations:
PubMed Identifier
26016802
Citation
Borgwardt L, Thuesen AM, Olsen KJ, Fogh J, Dali CI, Lund AM. Cognitive profile and activities of daily living: 35 patients with alpha-mannosidosis. J Inherit Metab Dis. 2015 Nov;38(6):1119-27. doi: 10.1007/s10545-015-9862-4. Epub 2015 May 28.
Results Reference
background
PubMed Identifier
23494656
Citation
Borgwardt L, Dali CI, Fogh J, Mansson JE, Olsen KJ, Beck HC, Nielsen KG, Nielsen LH, Olsen SO, Riise Stensland HM, Nilssen O, Wibrand F, Thuesen AM, Pearl T, Haugsted U, Saftig P, Blanz J, Jones SA, Tylki-Szymanska A, Guffon-Fouiloux N, Beck M, Lund AM. Enzyme replacement therapy for alpha-mannosidosis: 12 months follow-up of a single centre, randomised, multiple dose study. J Inherit Metab Dis. 2013 Nov;36(6):1015-24. doi: 10.1007/s10545-013-9595-1. Epub 2013 Mar 14.
Results Reference
result
PubMed Identifier
26048034
Citation
Borgwardt L, Stensland HM, Olsen KJ, Wibrand F, Klenow HB, Beck M, Amraoui Y, Arash L, Fogh J, Nilssen O, Dali CI, Lund AM. Alpha-mannosidosis: correlation between phenotype, genotype and mutant MAN2B1 subcellular localisation. Orphanet J Rare Dis. 2015 Jun 6;10:70. doi: 10.1186/s13023-015-0286-x.
Results Reference
result
Links:
URL
https://www.clinicaltrialsregister.eu/ctr-search/search?query=2010-022084-36
Description
Study Record on EU Clinical Trials Register including results
Learn more about this trial
Safety Study of Recombinant Human Alpha-mannosidase for the Treatment of Patients With Alpha-mannosidosis
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