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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
Author(s) -
Borgwardt Line,
Guffon Nathalie,
Amraoui Yasmina,
Dali Christine I.,
De Meirleir Linda,
GilCampos Mercedes,
Heron Bénédicte,
Geraci Silvia,
Ardigò Diego,
Cattaneo Federica,
Fogh Jens,
Van den Hout J. M. Hannerieke,
Beck Michael,
Jones Simon A.,
TylkiSzymanska Anna,
Haugsted Ulla,
Lund Allan M.
Publication year - 2018
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-018-0185-0
Subject(s) - placebo , medicine , clinical endpoint , confidence interval , relative risk , randomized controlled trial , surgery , gastroenterology , alternative medicine , pathology
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.