Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

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

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Increased risk of sudden death in untreated Primary Carnitine Deficiency

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Newborn screening for homocystinurias: recent recommendations versus current practice

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Cholesteryl ester storage disease of clinical and genetic characterisation: A case report and review of literature

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Impaired lipolysis in propionic acidemia: A new metabolic myopathy?

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Increased risk of sudden death in untreated Primary Carnitine Deficiency

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Cystic fibrosis newborn screening in Denmark: Experience from the first 2 years

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. Danish expanded newborn screening is a successful preventive public health programme

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

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.

Original languageEnglish
JournalJournal of Inherited Metabolic Disease
Volume41
Issue number6
Pages (from-to)1215-1223
Number of pages9
ISSN0141-8955
DOIs
Publication statusPublished - Nov 2018

ID: 56309962