Abstract Details

Title Efficacy Result from a Phase 2, Double-Blind, Placebo-Controlled Study of CX-8998 a State-Dependent T-Type Calcium (Cav3) Channel Modulator in Essential Tremor Patients (T-CALM)

Topic Movement Disorders

Presentation(s) S4 - Clinical Trials in Movement Disorders (2:17 PM-2:28 PM)

Poster/Presentation
Number 008

Background

ET is among the most prevalent of movement disorders in adults. Propranolol is the only medication approved for the treatment of ET. The T-type calcium channel is a mediator of subthreshold oscillations and excessive rhythmicity in pathophysiologic states found in tremor and is highly expressed in functional tremor network regions. Tremor-related oscillations are a neuronal signature for ET and T-Type calcium channels play a critical role in their generation. CX-8998 is a potent, selective, and state-dependent small molecule modulator of T-Type calcium channels.

Objective

To determine the efficacy of CX-8998 in patients with moderate to severe essential tremor (ET) with inadequate response to standard of care anti-tremor medications.

Design/Methods

We recently completed a randomized, double-blind, placebo-controlled, parallel-group study (NCT03101241) of 95 patients with ET. Following consent and screening, subjects were randomized to receive either CX-8998 (titrated to 10mg BID) or placebo for 28 days. Clinical rating scales, patient-reported outcomes and digital markers were collected at baseline (visit 1), day 15 (visit 3) and day 28 (visit 4).

Results

Investigator-rated TETRAS (The Essential Tremor Rating Assessment Scale) Performance Subscale (p=0.017), TETRAS-ADL (p=0.049), TETRAS total score (p=0.007) and Clinician Global Impression of Improvement (p=0.001) significantly improved. Centrally video-rated TETRAS Performance Subscale (primary endpoint) did not reach significance due to methodological issues. The significant differences on the TETRAS-ADL were confirmed by goal attainment scaling (GAS; p=0.034) and supported by the subject’s impressions of improvement (PGIC; p=0.089). Digital spirography using iMotor was qualified as a digital marker in a subset of patients.

Conclusions

The study achieved proof-of-concept in ET and identified key pivotal study design parameters including primary and secondary efficacy endpoints, patient population, dose and titration scheme. Further studies are needed to evaluate the efficacy of CX-8998 in ET patients. These results are expected to enable late-stage development of CX-8998 in ET.

Authors/Disclosures
Spyridon Papapetropoulos, MD, PhD (SPIRIDON PAPAPETROPOULOS, MD, PHD) PRESENTER	Dr. Papapetropoulos has received personal compensation for serving as an employee of Vigil Neuroscience . Dr. Papapetropoulos has received personal compensation for serving as an employee of Bionomics Ltd. Dr. Papapetropoulos has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Lipocine Inc. Dr. Papapetropoulos has stock in Vigil Neuroscience. Dr. Papapetropoulos has stock in Lipocine. Dr. Papapetropoulos has stock in Bionomics Ltd.
Margaret S. Lee, PhD	No disclosure on file
	No disclosure on file
	No disclosure on file
Rajesh Pahwa, MD, FAAN (University of Kansas Medical Center)	Dr. Pahwa has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Abbott. Dr. Pahwa has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for AbbVie. Dr. Pahwa has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for ACADIA. Dr. Pahwa has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Acorda. Dr. Pahwa has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Amneal. Dr. Pahwa has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Kyowa. Dr. Pahwa has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lundbeck. Dr. Pahwa has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurocrine. Dr. Pahwa has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Supernus. Dr. Pahwa has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Allevion. Dr. Pahwa has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Insightec. Dr. Pahwa has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Jaaz. Dr. Pahwa has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Neuroderm. Dr. Pahwa has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Photopharmics. Dr. Pahwa has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sage. Dr. Pahwa has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Fasikl. Dr. Pahwa has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genetech. Dr. Pahwa has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merz. Dr. Pahwa has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sun Biopharma. The institution of Dr. Pahwa has received research support from Abbott. The institution of Dr. Pahwa has received research support from Abbvie. The institution of Dr. Pahwa has received research support from Biogen. The institution of Dr. Pahwa has received research support from Biohaven. The institution of Dr. Pahwa has received research support from EIP. The institution of Dr. Pahwa has received research support from Amneal. The institution of Dr. Pahwa has received research support from Parkinson Foundation. The institution of Dr. Pahwa has received research support from Roche. The institution of Dr. Pahwa has received research support from Sage. The institution of Dr. Pahwa has received research support from Sun Pharma. The institution of Dr. Pahwa has received research support from Theranexus. The institution of Dr. Pahwa has received research support from Theravance. The institution of Dr. Pahwa has received research support from Voyager. The institution of Dr. Pahwa has received research support from Neuroderm. The institution of Dr. Pahwa has received research support from Annovis. The institution of Dr. Pahwa has received research support from Ask Bio. The institution of Dr. Pahwa has received research support from Blue Rock. The institution of Dr. Pahwa has received research support from Cerevance. The institution of Dr. Pahwa has received research support from Fasikl. The institution of Dr. Pahwa has received research support from Praxis. The institution of Dr. Pahwa has received research support from Scion. The institution of Dr. Pahwa has received research support from UCB.
Kelly E. Lyons, PhD (University of Kansas Medical Center)	Dr. Lyons has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Praxis. Dr. Lyons has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sage. Dr. Lyons has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Parkinson's Foundation. Dr. Lyons has a non-compensated relationship as a President with International Essential Tremor Foundation that is relevant to AAN interests or activities.
William Ondo, MD (Methodist Neurological Institute)	Dr. Ondo has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Cerevel. Dr. Ondo has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Supernus. Dr. Ondo has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amneal. Dr. Ondo has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ipsen. Dr. Ondo has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for BlueRock. Dr. Ondo has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Neurocrine. Dr. Ondo has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for ACADIA. Dr. Ondo has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Allergan. Dr. Ondo has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Kyowa Kirin. The institution of Dr. Ondo has received research support from Cerevel. The institution of Dr. Ondo has received research support from Sun. The institution of Dr. Ondo has received research support from SCION. The institution of Dr. Ondo has received research support from Harmony. Dr. Ondo has received publishing royalties from a publication relating to health care.
H. A. Jinnah, MD, PhD, FAAN (Emory University)	Dr. Jinnah has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Takaha/Ene. Dr. Jinnah has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Ipsen. Dr. Jinnah has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ipsen. Dr. Jinnah has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abbvie. The institution of Dr. Jinnah has received research support from Addex. The institution of Dr. Jinnah has received research support from Aeon. The institution of Dr. Jinnah has received research support from Revance. The institution of Dr. Jinnah has received research support from Jazz.
Rodger J. Elble, MD, PhD, FAAN (Southern IL Univ Sch of Med)	Dr. Elble has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Jazz. Dr. Elble has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sage . Dr. Elble has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ES Therapeutics. Dr. Elble has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Applied Therapeutics. Dr. Elble has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Praxis.