An Innovative Multi-study Phase 3 Program to Evaluate the Efficacy and Safety of Ulixacaltamide: The Future of Clinical Trial Design in Essential Tremor
Monique Giroux1, Jeff Zhao1, Henry Jacotin1, Megan Sniecinski1, Aubryn Samaroo1, Alex La Croix1, Richard Able1, Alyssa Wyant1, Claudio Santos1, Marcio Souza1
1Praxis Precision Medicines
Objective:
An innovative, multi-study Phase 3 program to definitively assess safety and efficacy of ulixacaltamide (PRAX-944) in essential tremor (ET).
Background:
Phase 2 studies of ulixacaltamide, a selective T-type calcium channel blocker, have demonstrated improvement in TETRAS Activities of Daily Living (ADL) measures and favorable tolerability. Combining learnings from Essential1 (NCT05021991) and FDA guidance, the upcoming Essential3 program (NCT06087276) addresses critical trial design considerations to facilitate definitive assessment of the safety and efficacy of 60 mg once-daily ulixacaltamide in adults with ET.
Design/Methods:
The Essential3 program uses an innovative trial design including functionally relevant endpoints and disease-appropriate analyses, and is optimized to: minimize variability due to disease heterogeneity and temporal fluctuation; mitigate placebo effects and potential confounds; while maximizing speed, efficiency, accessibility and diversity. Two simultaneous, 12-week, decentralized, pivotal studies will combine in-home and telehealth visits to assess efficacy of ulixacaltamide (60 mg QAM) vs. placebo, and maintenance and durability of effect in responders following randomized withdrawal (RW). Participants will undergo a long-term safety study up to ~1 year. Essential3 will recruit ~600 adults aged 18–80 years with ET (symptoms for at least 3 years; no more than 1 ET medication for at least 1 month before screening). Eligible participants will be randomized 1:1 to ulixacaltamide or placebo, with three stratification factors.
Results:
Primary endpoints will be change from baseline to Day 84 in mADL11 (TETRAS-ADL items 1-11 with modified score), and the proportion of participants maintaining response following RW. Secondary endpoints will include responder rates and mADL11 change after 12 weeks, as well as change in TETRAS-ADL, clinician and patient measures of severity, Archimedes Spiral, and safety assessments. Enrollment will commence in 4Q2023.
Conclusions:
In addition to providing evidence of ulixacaltamide safety and efficacy, the Essential3 program is expected to set the foundation for future clinical trial design in ET and other neurologic disorders.