Multicenter Expanded Access Protocol for Research Through Access to Trehalose in People With Amyotrophic Lateral Sclerosis

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). Methods Participants received trehalose, a drug studied in a parallel RCT, for up to 24 weeks; clinical and biomarker data were collected throughout the study. Results 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). Discussion 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. Trial Registration: ClinicalTrials.gov: NCT05597436