Abstract Details

Title An Innovative Multi-study Phase 3 Program to Evaluate the Efficacy and Safety of Ulixacaltamide: The Future of Clinical Trial Design in Essential Tremor

Topic Movement Disorders

Presentation(s) P3 - Poster Session 3 (5:30 PM-6:30 PM)

Poster/Presentation
Number 3-003

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.

Authors/Disclosures
Richard A. Able, Jr., PhD PRESENTER	Dr. Able has received personal compensation for serving as an employee of Praxis Medicines. Dr. Able has received personal compensation for serving as an employee of PTC Therapeutics. Dr. Able has stock in Praxis Medicines. Dr. Able has received personal compensation in the range of $0-$499 for serving as a Employee with PTC therapeutics.
Monique L. Giroux, MD	Dr. Giroux has received personal compensation for serving as an employee of Praxis Precision Medicine.
Jeff Zhao	No disclosure on file
Henry Jacotin (Praxis)	Henry Jacotin has received personal compensation for serving as an employee of Praxis Precision Medicines. Henry Jacotin has stock in Praxis Precision Medicines. Henry Jacotin has stock in Clover Health. Henry Jacotin has stock in Certara. Henry Jacotin has stock in Takeda. Henry Jacotin has received personal compensation in the range of $500,000-$999,999 for serving as a VP Clinical Development and Pharmacovigilance with Praxis Precision Medicines.
Megan Sniecinski	Megan Sniecinski has received personal compensation for serving as an employee of Praxis Precision Medicines. Megan Sniecinski has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Praxis Precision Medicines.
Aubryn Samaroo (Praxis Precision Medicines)	No disclosure on file
Alex La Croix (Praxis Precision Medicines)	Mr. La Croix has received personal compensation for serving as an employee of Praxis Precision Medicines. Mr. La Croix has stock in Praxis Precision Medicines.
Alyssa Wyant (Praxis Precision Medicines)	Alyssa Wyant has received personal compensation for serving as an employee of Praxis Precision Medicines. Alyssa Wyant has stock in Praxis Precision Medicines. Alyssa Wyant has received intellectual property interests from a discovery or technology relating to health care.
Claudio Santos	No disclosure on file
Marcio Souza	Marcio Souza has received personal compensation for serving as an employee of Praxis Precision Medicines.

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