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Work Package 4

Clinical trial Phase I

Objectives:
The Phase I trial is the first study of the experimental drug (rhLAMAN). The study will collect information on the tolerability, pharmacokinetics and adverse effects of rhLAMAN for the treatment of patients with alpha-Mannosidosis.

Description of the Work:
A phase I clinical trial, with 10 alpha-Mannosidosis patients, in a dose escalation trial, will take place at Copenhagen University Hospital. The Principal Investigator will be Dr. Allan Meldgaard Lund. An independent Data Monitoring Committee will evaluate safety of the trial.

Procedure:
Two patients will be allocated in each cohort. The patients participating in the clinical trials must have a confirmed diagnosis of alpha-Mannosidosis as defined by deficiency of alpha-Mannosidase activity and confirmed pathogenic mutation in the MAN2B1 gene. In addition the patients must have the ability and mental capacity to perform the endurance test (6-minute walk test). To avoid the potential development of delayed hypersensitivity to the product treatment on the initial dose must continue until all dose levels have been evaluated. Dosing will be administered weekly, as clinical trials within closely linked clinical disorders such as the mucopolysaccharidoses have shown, that weekly dosing is superior to dosing every other week (EOW).
Efficacy on functional capacity in the trials will be assessed by

  1. change in endurance (6-minute walk test)
  2. improved lung function (absolute FVC) and
  3. reduction of oligosaccharides in urine and serum.
Before the Data Monitoring Committee has finished evaluating the highest dose (100 units/kg) and given permission to continue with the phase II trial, a second dosing of 100 units/kg will have taken place. The Integrated Clinical Trial Report will evaluate all safety data obtained in the dose escalation study

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