A randomized, placebo‐controlled, double‐blind, Phase 1b study to evaluate the safety, tolerability and pharmacodynamics of PRI‐002 in early AD

Background PRI‐002 is an all‐D‐enantiomeric peptide developed to disassemble Abeta oligomers, which has shown to improve cognition in animal models and which has demonstrated its safety profile in healthy young volunteers (Kutzsche et al. 2020). Method 20 AD patients in early disease stages fulfilling the ATN‐criteria were recruited to participate in a single center, randomized, placebo –controlled, double‐blind study. Patients received once daily oral doses of 300 mg PRI‐002 or placebo for 28 days. Safety and efficacy assessments were executed at baseline, day 14, day 28 and day 56 (follow up). Blood sampling was carried out at each time point, EEG and CSF measurements before and at the end of treatment. Imaging (MRI) and functional tests (CERAD, CDR) were performed in parallel to EEG/CSF and additionally at follow up. Result 10 patients (age 76.9±3.4, MMSE 28±1.6) received placebo and 9 patients PRI‐002 (72.4±6.9, 27.2±2.9). One patient withdraw informed consent before treatment was started. 13 patients reported in total 27 adverse events while no serious adverse event was noted. There was no statistical difference regarding adverse events between treatment and placebo. EEG and MRI revealed no changes after treatment. While no significant changes were detected in p‐TAU, Abeta1‐42 and Abeta oligomers in CSF before and after treatment, patients receiving PRI‐002 significantly performed better than those receiving placebo in the CERAD word list at follow up (p≤0.05). Conclusion PRI‐002 showed an excellent safety profile in AD patients. While no biomarker changes were detected after 4 weeks of treatment interestingly, an improvement of memory function was noted at follow up. A phase 2 study is scheduled. Kutzsche J, Jürgens D, Willuweit A, Adermann K, Fuchs C, Simons S, Windisch M, Hümpel M, Rossberg W, Wolzt M, Willbold D. Safety and pharmacokinetics of the orally available antiprionic compound PRI‐002: A single and multiple ascending dose phase I study. Alzheimers Dement (N Y). 2020 Mar 20;6(1):e12001. https://doi.org/10.1002/trc2.12001.