Packages

Work Package 5

Clinical trial Phase IIa and IIb

Involves Partners ZYMX, CUH, DTI, Larix and Unilabs

Objectives:
The aim of this WP is to demonstrate the safety and pharmacokinetics of rhLAMAN and to find the minimum effective dose for an effective treatment of alpha-Mannosidosis patients including their neuropathology.

Description of the Work:

Phase IIa:
Immediately after the safety evaluation of the highest dose in clinical trial phase I, the same 10 patients (see WP 4) will be randomized to treatment with 25 and 50 Units/kg (5 Patients each dose) at Copenhagen University Hospital. The doses are based on the efficient doses seen in the preclinical mouse studies and body surface correlated to humans. Dosing will be given weekly over a period of 6 months. Efficacy on functional capacity in the trials will be assessed by i) change in endurance (6-minute walk test), ii) improved lung function (absolute FVC) and iii) reduction of oligosaccharides in urine and serum. The minimum effective dose will then be used for clincial trial phase IIb.

Phase IIb:
In the Phase IIb trial all 10 patients will continue treatment on the minimum effective dose detected in phase IIa. Dosing will be given weekly over a period of 6 months. Efficacy on functional capacity in the trials will be assessed by i) change in endurance (6-minute walk test), ii) improved lung function (absolute FVC) and iii) reduction of oligosaccharides in urine and serum.