Brain Research Institute, Niigata University, Niigata, Japan
Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan.
J Neurol Neurosurg Psychiatry. 2020 Mar;91(3):254-262. doi: 10.1136/jnnp-2019-322168. Epub 2020 Jan 14.
To investigate the efficacy of rovatirelin, a thyrotropin-releasing hormone analogue, for ataxias in patients with spinocerebellar degeneration (SCD).
Two multicentre, randomised, double-blind, placebo-controlled phase 3 studies (KPS1301, KPS1305) enrolled patients with predominant cerebellar ataxia, including SCA6, SCA31 or cortical cerebellar atrophy. KPS1301 enrolled patients with truncal ataxia and KPS1305 enrolled patients with truncal and limb ataxia. Each study included 4 weeks of pretreatment, a 28-week or 24-week treatment period and 4 weeks of follow-up. Patients were randomised (1:1:1) to rovatirelin (1.6 or 2.4 mg) or placebo in KPS1301, and randomised (1:1) to rovatirelin 2.4 mg or placebo in KPS1305. The primary endpoint was change in Scale for the Assessment and Rating of Ataxia (SARA) total scores. Pooled analysis was performed in patients who met the SARA recruitment criteria of KPS1305.
From October 2013 to May 2014, KPS1301 enrolled 411 patients; 374 were randomised to rovatirelin 1.6 mg (n=125), rovatirelin 2.4 mg (n=126) or placebo (n=123). From November 2016 to August 2017, KPS1305 enrolled 241 patients; 203 were randomised to rovatirelin 2.4 mg (n=101) or placebo (n=102). The primary endpoint showed no significant difference between rovatirelin and placebo in these two studies. In the pooled analysis (n=278), the difference between rovatirelin 2.4 mg (n=140) and placebo (n=138) was -0.61 (-1.64 vs -1.03; 95% CI -1.16 to -0.06; p=0.029) in the adjusted mean change in the SARA total score.
Rovatirelin is a potentially effective treatment option for SCD.
NCT01970098; NCT02889302.
研究促甲状腺素释放激素类似物罗瓦替林治疗脊髓小脑变性（SCD）患者共济失调的疗效。
两项多中心、随机、双盲、安慰剂对照 3 期研究（KPS1301、KPS1305）纳入以小脑共济失调为主的患者，包括 SCA6、SCA31 或皮质小脑萎缩。KPS1301 纳入躯干共济失调患者，KPS1305 纳入躯干和肢体共济失调患者。每项研究包括 4 周预处理期、28 或 24 周治疗期和 4 周随访期。患者按 1:1:1 比例随机分为罗瓦替林（1.6 或 2.4mg）或安慰剂组（KPS1301），KPS1305 中患者按 1:1 比例随机分为罗瓦替林 2.4mg 或安慰剂组。主要终点为共济失调评定量表（SARA）总分的变化。KPS1305 符合 SARA 纳入标准的患者进行汇总分析。
2013 年 10 月至 2014 年 5 月，KPS1301 纳入 411 例患者；其中 374 例随机分为罗瓦替林 1.6mg 组（n=125）、罗瓦替林 2.4mg 组（n=126）或安慰剂组（n=123）。2016 年 11 月至 2017 年 8 月，KPS1305 纳入 241 例患者；其中 203 例随机分为罗瓦替林 2.4mg 组（n=101）或安慰剂组（n=102）。这两项研究中，罗瓦替林与安慰剂在主要终点方面无显著差异。汇总分析（n=278）中，罗瓦替林 2.4mg 组（n=140）与安慰剂组（n=138）的 SARA 总分调整平均变化差值为-0.61（-1.64 比-1.03；95%CI-1.16 至-0.06；p=0.029）。
罗瓦替林可能是 SCD 的有效治疗选择。
NCT01970098；NCT02889302。
