Krivickas Brooke, Scirocco Erica, Giacomelli Elisa, Sharma Saloni, Benson Molly, Keegan Mackenzie, Kulesa-Kelley Jennifer, Chibnik Lori B, Casagrande Gabriella, Heyd Lindsay, Chase Marianne, Drake Kristin, Mohapatra Silpa, Hagar Jennifer Linn, Hasenoehrl Meredith Gibbons, Dagostino Derek, Sherman Alexander V, Leite Alex, Yu Hong, Rosenthal Jesse, Miller Timothy, McCaffrey Alexandra, Gwathmey Kelly, Locatelli Eduardo, Bayat Elham, Heitzman Daragh, Young Eufrosina, Goyal Namita A, Whitesell Jackie, Felice Kevin, Ilieva Hristelina, Swenson Andrea, Walk David, Alameda Gustavo, Foster Laura, McIlduff Courtney E, Walsh Alison, Zilliox Lindsay, Ajroud-Driss Senda, Bodkin Cynthia, Katz Jonathan, Ladha Shafeeq, Rivner Michael, Rosow Laura, Twydell Paul, Wasiewski Warren, Babu Suma, Berry James D, Paganoni Sabrina
Sean M. Healey & AMG Center for ALS and Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Washington University School of Medicine, St. Louis, Missouri, USA.
Muscle Nerve. 2025 Aug 26. doi: 10.1002/mus.70011.
INTRODUCTION/AIMS: Expanded access protocols (EAPs) allow individuals ineligible for clinical trials to receive investigational products. EAP data can be collected in parallel to randomized clinical trials (RCTs) and serve as a source of evidence in clinical practice. Here, we present the results of a National Institutes of Health (NIH)-funded EAP for amyotrophic lateral sclerosis (ALS).
Participants received trehalose, a drug studied in a parallel RCT, for up to 24 weeks; clinical and biomarker data were collected throughout the study.
Seventy participants were enrolled at 20 study centers across the United States. Treatment with trehalose did not affect the levels of neurofilament light chain [estimated flat slope per month was -0.005, SE = 0.0078; 95% CI (-0.021, 0.011)] or disease progression [estimated least square mean change of the ALS Functional Rating Scale-Revised total score and slow vital capacity (percent predicted) from baseline to Week 24 were -5.6 (0.67); 95% CI (-7.0, -4.3) and -4.53 (4.308); 95% CI (-13.55, 4.48)], respectively. No unexpected treatment-related risks were identified. Serious adverse events were deemed not related to trehalose (20 occurrences in 13 [18.6%] participants with eight deaths).
This EAP establishes a framework for implementing multi-center EAPs that complement data collected from RCTs. Additional NIH-funded EAPs are currently underway. Data and additional serum samples collected in this study are available to the research community for further study.
ClinicalTrials.gov: NCT05597436.
引言/目的：扩大准入协议（EAPs）允许不符合临床试验条件的个体获得研究性产品。EAP数据可与随机临床试验（RCTs）并行收集，并作为临床实践中的证据来源。在此，我们展示了一项由美国国立卫生研究院（NIH）资助的针对肌萎缩侧索硬化症（ALS）的EAP的结果。
参与者接受海藻糖治疗长达24周，海藻糖是在一项平行RCT中研究的药物；在整个研究过程中收集临床和生物标志物数据。
在美国20个研究中心招募了70名参与者。海藻糖治疗不影响神经丝轻链水平[每月估计平缓斜率为-0.005，标准误=0.0078；95%置信区间（-0.021，0.011）]或疾病进展[从基线到第24周，ALS功能评定量表修订版总分和慢肺活量（预测百分比）的估计最小二乘均值变化分别为-5.6（0.67）；95%置信区间（-7.0，-4.3）和-4.53（4.308）；95%置信区间（-13.55，4.48）]。未发现意外的治疗相关风险。严重不良事件被认为与海藻糖无关（13名[18.6%]参与者发生20次，8例死亡）。
该EAP建立了一个实施多中心EAP的框架，以补充从RCTs收集的数据。目前正在进行其他由NIH资助的EAP。本研究中收集的数据和额外的血清样本可供研究界进一步研究。
ClinicalTrials.gov：NCT05597436。
