Davunetide in patients with progressive supranuclear palsy: a randomised, double-blind, placebo-controlled phase 2/3 trial.
Davunetide in patients with progressive supranuclear palsy: a randomised, double-blind, placebo-controlled phase 2/3 trial.
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DOI：
10.1016/s1474-4422(14)70088-2
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发表时间：
2014-07
期刊：
影响因子：
48
通讯作者：
Morimoto, Bruce H.
中科院分区：
文献类型：
--
作者：
Boxer, Adam L.;Lang, Anthony E.;Grossman, Murray;Knopman, David S.;Miller, Bruce L.;Schneider, Lon S.;Doody, Rachelle S.;Lees, Andrew;Golbe, Lawrence I.;Williams, David R.;Corvol, Jean-Cristophe;Ludolph, Albert;Burn, David;Lorenzl, Stefan;Litvan, Irene;Roberson, Erik D.;Hoeglinger, Guenter U.;Koestler, Mary;Jack, Clifford R., Jr.;Van Deerlin, Viviana;Randolph, Christopher;Lobach, Iryna V.;Heuer, Hilary W.;Gozes, Illana;Parker, Lesley;Whitaker, Steve;Hirman, Joe;Stewart, Alistair J.;Gold, Michael;Morimoto, Bruce H.
Davunide（AL-108，NAP）是一种促进微管稳定性并降低tau磷酸化的八氨基酸肽，因为PSP与TAU病理密切相关，Davunide可能是PSP的有效治疗方法。我们将评估Davunette在PSP中的效率和安全性。
第2/3阶段的双盲，平行组，Davunette 30 mg或安慰剂（随机1：1）每天两次在48个中心进行鼻内两次。主要的终点是PSP评级量表（PSPRS）和Schwab和England ADL（Seadl）量表的变化，最多可达52周的数据。使用基于等级的方法比较了至少一剂的药物，并进行了基线后的有效性评估。专有结果包括变化的临床全球印象（CGIC）和区域脑体积MRI的变化。 NCT01110720。
筛选了360名参与者，313位随机分配，243（77.6％）完成了研究。 [-2，4％]，p = 0.76）从基线（CFB）和平均52周CFB PSPRS分数变化相似（11.3 [9.8,12.8]）和安慰剂组（10.9 [9.1，[9.1，， 13.0]。
Davunide的耐受性良好，但对于PSP的临床试验不是有效的治疗方法。
Allon Therapeutics
Davunetide (AL-108, NAP) is an eightamino acid peptide that promotes microtubule stability and decreases tau phosphorylation in pre-clinical studies. Since PSP is tightly linked to tau pathology, davunetide could be an effective treatment for PSP.The goals of this study were to evaluate the efficacy and safety of davunetide in PSP. A phase 2/3 double-blind, parallel group, clinical trial of davunetide 30 mg or placebo (randomized 1:1) administered intranasally twice daily for 52 weeks was conducted at 48centers. Participants met modifiedNNIPPS criteria for possible or probable PSP. Co-primary endpointswere the change from baseline in PSP Rating Scale (PSPRS) and Schwab and England ADL(SEADL) scale at up to 52 weeks. Data from all individuals who received at least one dose of medication and had a post-baseline efficacy assessment were compared using a rank-based method.Secondary outcomes included the Clinical Global Impression of Change (CGIC) and the change in regional brain volumeon MRI. Clinicaltrials.gov identifier: NCT01110720. 360 participants were screened, 313 were randomized and 243 (77.6%) completed the study. There were no group differences in PSPRS (mean difference: 0.49 [95% CI: −1.5, 2.5], p = 0.72) or SEADL (1% [−2, 4%], p = 0.76) change from baseline (CFB) and mean 52 week CFB PSPRS scores were similar between the davunetide (11.3 [9.8,12.8]) and placebo groups (10.9 [9.1, 13.0]). There wereno differences in any of the secondary or exploratory endpoints. There were 11deaths in the davunetide group and tenin the placebo group. There were more nasal adverse events in the davunetide group. Davunetide is well tolerated but is not an effective treatment for PSP. Clinical trials of disease modifying therapy are feasible in PSP and should be pursued with other promising tau-directed therapies. Allon Therapeutics