Clinical trial NCT01268358: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Alpha Mannosidosis
Lead sponsor: Chiesi Farmaceutici S.p.A.
Sponsor class: INDUSTRY
Collaborators: name: European Commission
First posted: 2010-12-30
Enrollment: 10
Sex: ALL
Minimum age (years): 5
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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 ≤ 20 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: To evaluate the safety profile of rhLAMAN (Lamazym)
timeFrame: 1-5 weeks
Secondary outcomes:
measure: To determine the PK profile of rhLAMAN (Lamazym) in patients with alpha-mannosidosis as measured by rhLAMAN levels in plasma
timeFrame: 1 dosis
measure: To collect baseline measurements that are to be used for efficacy evaluation in the following trial (rhLAMAN-03)
timeFrame: 1 week
Other outcomes:
Locations:
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:
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.
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.
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.