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.
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.
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DOI：
10.1007/s10545-018-0185-0
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发表时间：
2018-11
影响因子：
4.2
通讯作者：
Lund AM
中科院分区：
文献类型：
--
作者：
Borgwardt L;Guffon N;Amraoui Y;Dali CI;De Meirleir L;Gil-Campos M;Heron B;Geraci S;Ardigò D;Cattaneo F;Fogh J;Van den Hout JMH;Beck M;Jones SA;Tylki-Szymanska A;Haugsted U;Lund AM
这项III期、双盲、随机、安慰剂对照试验（和扩展期）旨在评估维马那酶α（VA）在α-甘露糖苷沉积症（AM）患者中的疗效和安全性。25例患者随机接受每周1 mg/kg VA或安慰剂治疗，持续52周。研究结束时，安慰剂组患者转为VA治疗; 23例患者在体恤使用/随访研究中继续接受VA治疗，并在扩展期[末次观察（LO）]进行评价。联合主要终点为血清低聚糖（S-oligo）和3分钟爬楼梯试验（3 MSCT）的变化。第52周时，VA组S-oligo的平均相对变化为−77.6% [95%置信区间（CI）为−81.6至−72.8]，（95% CI −85.8至−40.0），LO;转换为活性治疗后，安慰剂组第52周的平均相对变化为−24.1%（95% CI −40.3至−3.6），LO组为−55.7%（95% CI −76.4至−34.9）。VA组和安慰剂组第52周3 MSCT的平均相对变化分别为−1.1%（95%CI −9.0至7.6）和− %（95%CI −13.4至6.5）。在LO时，转换为活性治疗后，VA组的平均相对变化为3.9%（95% CI −5.5至13.2），安慰剂组为9.0%（95% CI −10.3至28.3）。在次要参数中观察到相似的改善模式。一项事后分析研究了基线时的一些因素是否可以解释治疗结局;除年龄外，这些因素均不能预测VA的应答。这些发现支持VA治疗AM的效用，随着时间的推移以及在儿科年龄开始治疗时具有更明显的益处。本文的在线版本（10.1007/s10545-018-0185-0）包含补充材料，可供授权用户使用。
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. The online version of this article (10.1007/s10545-018-0185-0) contains supplementary material, which is available to authorized users.
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