TY - JOUR
T1 - Efficacy and safety of Velmanase alfa in the treatment of patients with alpha-mannosidosis
T2 - results from the core and extension phase analysis of a phase III multicentre, double-blind, randomised, placebo-controlled trial
AU - Borgwardt, Line
AU - Guffon, Nathalie
AU - Amraoui, Yasmina
AU - Dali, Christine I
AU - De Meirleir, Linda
AU - Gil-Campos, Mercedes
AU - Heron, Bénédicte
AU - Geraci, Silvia
AU - Ardigò, Diego
AU - Cattaneo, Federica
AU - Fogh, Jens
AU - Van den Hout, J M Hannerieke
AU - Beck, Michael
AU - Jones, Simon A
AU - Tylki-Szymanska, Anna
AU - Haugsted, Ulla
AU - Lund, Allan M
PY - 2018/11
Y1 - 2018/11
N2 - INTRODUCTION: 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.METHODS: 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).RESULTS: 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.CONCLUSIONS: 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.
AB - INTRODUCTION: 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.METHODS: 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).RESULTS: 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.CONCLUSIONS: 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.
U2 - 10.1007/s10545-018-0185-0
DO - 10.1007/s10545-018-0185-0
M3 - Journal article
C2 - 29846843
SN - 0141-8955
VL - 41
SP - 1215
EP - 1223
JO - Journal of Inherited Metabolic Disease
JF - Journal of Inherited Metabolic Disease
IS - 6
ER -