RT Journal Article
T1 Efficacy and safety of Velmanase alfa in the treatment of patients with alpha-mannosidosis: results from the core and extension phase analysis of a phase III multicentre, double-blind, randomised, placebo-controlled trial.
A1 Borgwardt, Line
A1 Guffon, Nathalie
A1 Amraoui, Yasmina
A1 Dali, Christine I
A1 De Meirleir, Linda
A1 Gil-Campos, Mercedes
A1 Heron, Bénédicte
A1 Geraci, Silvia
A1 Ardigo, Diego
A1 Cattaneo, Federica
A1 Fogh, Jens
A1 Van den Hout, J M Hannerieke
A1 Beck, Michael
A1 Jones, Simon A
A1 Tylki-Szymanska, Anna
A1 Haugsted, Ulla
A1 Lund, Allan M
K1 Adolescent
K1 Adult
K1 Child
K1 Child, preschool
K1 Double-blind method
K1 Enzyme replacement therapy
AB This phase III, double-blind, randomised, placebo-controlled trial (and extension phase) was designed to assess the efficacy and safety of velmanase alfa (VA) in alpha-mannosidosis (AM) patients. Twenty-five patients were randomised to weekly 1 mg/kg VA or placebo for 52 weeks. At study conclusion, placebo patients switched to VA; 23 patients continued receiving VA in compassionate-use/follow-on studies and were evaluated in the extension phase [last observation (LO)]. Co-primary endpoints were changes in serum oligosaccharide (S-oligo) and in the 3-min stair-climb test (3MSCT). Mean relative change in S-oligo in the VA arm was -77.6% [95% confidence interval (CI) -81.6 to -72.8] at week 52 and -62.9% (95% CI -85.8 to -40.0) at LO; mean relative change in the placebo arm was -24.1% (95% CI -40.3 to -3.6) at week 52 and -55.7% (95% CI -76.4 to -34.9) at LO after switch to active treatment. Mean relative change in 3MSCT at week 52 was -1.1% (95% CI -9.0 to 7.6) and - % (95% CI -13.4 to 6.5) for VA and placebo, respectively. At LO, the mean relative change was 3.9% (95% CI -5.5 to 13.2) in the VA arm and 9.0% (95% CI -10.3 to 28.3) in placebo patients after switch to active treatment. Similar improvement pattern was observed in secondary parameters. A post hoc analysis investigated whether some factors at baseline could account for treatment outcome; none of those factors were predictive of the response to VA, besides age. These findings support the utility of VA for the treatment of AM, with more evident benefit over time and when treatment is started in the paediatric age.
PB Wiley
YR 2018
FD 2018-04-05
LK http://hdl.handle.net/10668/12519
UL http://hdl.handle.net/10668/12519
LA en
NO Borgwardt L, Guffon N, Amraoui Y, Dali CI, De Meirleir L, Gil-Campos M, et al. Efficacy and safety of Velmanase alfa in the treatment of patients with alpha-mannosidosis: results from the core and extension phase analysis of a phase III multicentre, double-blind, randomised, placebo-controlled trial. J Inherit Metab Dis. 2018 Nov;41(6):1215-1223
DS RISalud
RD Apr 5, 2025