2:55 PM
Oct 08, 2018
 |  BC Extra  |  Clinical News

Cavion planning Phase III for essential tremor candidate despite Phase II miss

Cavion Inc. (Charlottesville, Va.) said CX-8998 missed the primary endpoint in the Phase II T-CALM trial to treat moderate to severe essential tremor. Despite the miss, the company plans to start a Phase III trial by 4Q19 of the compound in the indication that will use a different primary endpoint than that of the Phase II trial. CX-8998 is a calcium channel T-type blocker.

On the Phase II trial's primary endpoint, CX-8998 failed to improve tremor severity from baseline to day 28 measured using remote video rating of the Tremor Research Group Essential Tremor Rating Assessment Scale - Performance Subscale (TETRAS-PS) vs. placebo (p=0.696). However, in-person investigator ratings of TETRAS-PS did show a significant improvement in tremor severity at day 28 vs. placebo (p=0.027). According to the company, an independent analysis of the video rating process uncovered "unexpected complications in implementation."

Cavion's Spyros Papapetropoulos told BioCentury that following discussions with KOLs and academics, video rating was chosen for the trial to reduce variability and control for placebo effects. He said issues in implementing video ratings include lack of sensitivity for certain subitems of TETRAS-PS that require spatial discrimination, and calibration of raters at the beginning of the trial. Papapetropoulos added that the company is "very confident that what investigators observed is actually the true outcome of the study." Papapetropoulos is EVP of R&D and CMO at Cavion.

Cavion said CX-8998 met several secondary and exploratory endpoints vs. placebo in the trial, including TETRAS Activities of Daily Living (TETRAS-ADL) scale (p=0.049), Clinician Global Impression of Improvement (CGI-I) (p=0.001), TETRAS Total Score (p=0.029) and Goal Attainment Scale (GAS) (p=0.034). Data were presented at the Parkinson’s Disease and Movement Disorders meeting in Hong Kong.

Based on discussions with FDA, Papapetropoulos said the company plans to move forward with a Phase III trial evaluating a primary endpoint that is focused around TETRAS- ADL and other quality of life (QOL) endpoints.

The double-blind, U.S. Phase II trial enrolled 95 patients with moderate to severe essential tremor to receive placebo or twice-daily CX-8998 for 28 days. About 64% of the patients were on concurrent standard of care (SOC) antitremor medication.

The company also expects data in 1Q19 from the Phase II T-WAVE trial of CX-8998 to treat generalized epilepsy with absence seizures.

Idorsia Ltd. (SIX:IDIA) is also developing a calcium channel T-type blocker, ACT-709478, which is in Phase I testing to treat epilepsy.

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