evaluation of long-term efficacy of treatment with lamazym

Conditions: Alpha-Mannosidosis

Summary: the overall objective is to evaluate the long-term efficacy of lamazym i.v. treatment in patients with alpha-mannosidosis previously enrolled in lamazym trials and currently receiving the treatment according to the aftercare program.

the primary objective of the trial is to evaluate the impact of the long-term treatment with lamazym upon the level of biomarker oligosaccharides in serum and upon the endurance as measured by the change from baseline in the number of steps climbed in 3 minutes (3msct). as secondary objectives, the long term efficacy of lamazym will be investigated upon endurance as measured by the change from baseline in the number of meters walked in six minutes (6mwt), upon pulmonary function, motor proficiency by bot-2 and hearing capability by audiometry. in addition, cognitive development will be assessed by leiter-r test. cns involvement will be evaluated with mri/mrs (for patients who previously participated in rhlaman-02 trial), csf biomarkers (tau, nfl, gfap) and csf biomarkers oligosaccharides. clearance of oligosaccharides in urine will be measured. long-term safety and pharmaco-kinetic (pk) profile after long-term treatment as measured by rhlaman levels in plasma will be assessed as well. quality of life will be assessed by questionnaires (chaq and eq-5d-5l).

Eligibility criteria:
inclusion criteria: 1. the subject must have participated in the phase 1 trial (eudract number: 2010-022084-36), phase 2a trial (eudract number: 2010-022085-26), phase 2b trial (eudract number: 2011-004355-40) or phase 3 trial (eudract number: 2012-000979-17) 2. the subject must still be receiving weekly intravenous infusions of lamazym according to the aftercare program 3. the subject or subjects legally authorized guardian(s) must provide signed, informed consent prior to performing any trial-related activities 4. the subject and his/her guardian(s) must have the ability to comply with the protocol exclusion criteria: 1. history of bone marrow transplantation 2. 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. subjects unable to perform the motor tests independently from support are permitted to participate in the trial and will be evaluated for the remnant non motor endpoints 3. any other medical condition or serious intercurrent illness, or extenuating circumstance that, in the opinion of the investigator, would preclude participation in the trial 4. pregnant and/or lactating women cannot participate in the trial. concerning women of child bearing potential (wocbp), the investigators will decide whether or not there is a need for contraception. this assessment will be done through interviews with the patient and parents. 5. participation in other interventional trials testing imp, including rhlaman-07 (eudract number: 2013-000336-97) and rhlaman-09 (eudract number: 2013-000321-31) trials with lamazym 6. pause of the imp for 2 consecutive weeks during the last month. subjects are allowed to be re-screened