Objective: We present preliminary findings from PRAX-944-221, a Phase 2a clinical trial evaluating efficacy, safety, tolerability, and pharmacokinetics of PRAX-944 in adults with essential tremor (ET).

Background: ET is the most common movement disorder with high unmet patient needs. Treatment options are limited, with high discontinuation rates due to poor tolerability and modest efficacy. PRAX-944 is a novel selective T-type calcium channel blocker in clinical development for treatment of ET.

Method: PRAX-944-221 is a Phase 2a trial in adults (18-75yrs) with ET (NCT05021978). Eligible participants were receiving no medications or a stable dose of 1 tremor medication excluding primidone. In Part A, participants received PRAX-944 20mg orally once-daily for 7 days, followed by 40mg for 7 days. Part B is a 42-day open-label phase followed by a 14-day randomized, double-blind, placebo-controlled withdrawal phase (ongoing). Daily dose levels are titrated from 20-120mg during the open-label phase with ≥14 days at the highest tolerated dose for each participant. The primary outcome in Part A was upper limb tremor assessed by The Essential Tremor Rating Assessment Scale (TETRAS-UL); and in Part B is safety and tolerability. Secondary outcomes in Part A included other measures of tremor severity, and safety and tolerability. Part B secondary outcomes include TETRAS-UL and other measures of disease impact including TETRAS activities of daily living (TETRAS-ADL).

Results: Seven participants received PRAX-944 in Part A, with 6 completing all study visits. Mean baseline TETRAS-UL score was 12.4 (range 10-15). Preliminary results revealed a mean reduction in TETRAS-UL score of 2.83 points on Day 14, corresponding to a 42% reduction in UL tremor amplitude. PRAX-944 20 and 40mg doses were generally well-tolerated, with only mild-moderate AEs. Twelve participants were enrolled in Part B, with 8 completing all study visits thus far. Preliminary results indicate TETRAS-ADL improvements and a safety profile consistent with Part A findings across the wide dose range tested.

Conclusion: Our findings provide preliminary evidence that PRAX-944 can reduce tremor symptoms of ET at well-tolerated doses. Part B topline results are expected in 1H2022 following completion of the randomized withdrawal phase and will inform dose selection in later phase studies.

References: This abstract contains material (Part A data) that has been accepted for presentation at the American Academy of Neurology Annual Meeting; April 2022.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/a-phase-2-clinical-trial-evaluating-the-efficacy-safety-tolerability-and-pharmacokinetics-of-prax-944-in-adults-with-essential-tremor/