Randomized Controlled ELATE Study to Test OnabotulinumtoxinA in Upper Limb Essential Tremor

Lynn James, a global development lead at AbbVie

At the 2024 International Congress of Parkinson’s Disease and Movement Disorders (MDS), held September 27-October 1, in Philadelphia, Pennsylvania, investigators presented the design of ELATE, a phase 2b clinical trial evaluating the safety and efficacy of onabotulinumtoxinA (onabotA) compared with placebo for the treatment of adult upper limb essential tremor (ULET). The trial, which seeks to enroll 174 participants across 40 sites in the United States and Canada, is expected to be completed in 2024.¹

The hope is that the ELATE study results could reveal valuable insights into the effectiveness and safety of onabotA for ULET, potentially offering a better risk-benefit profile than current oral therapies. ELATE, an 18-week trial, will test 4 regimens, involving onabotA or placebo administered unilaterally or bilaterally. Study investigators will use changes on the Tremor Disability Scale-Revised (TREDS-R) score across 7 unliteral items over that time as the primary efficacy measure.

Senior author Lynn James, a global development lead at AbbVie, and colleagues presented the outline of the study, which acts as a double-blind, placebo-controlled, parallel-group trial. To be included in the study, patients must have a diagnosis of essential tremor according to modified Tremor Research Group criteria, aged 18-80 years, and have TREDS-R scores of greater than 3 on any of the 7 unilateral items. Furthermore, patients must score at least 3 on any of the 5 unilateral items of the Essential Tremor Rating Assessment Scale Activities of Daily Living TETRAS ADL, and must have either TETRAS UL score of at least 2 or TETRAS Archimedes spiral task score of at least 2 in the dominant limb.

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The study includes several notable secondary end points, including change in TETRAS ADL total score across 5 unilateral items, change in TETRAS Archimedes Spiral Score, change in TETRAS Handwriting score, and change in TETRAS UL score. ELATE will also record changes from baseline in Clinical Global Impression of Severity and Patient Global Impression of Severity scales. The study consists of 2 treatment cycles of unilateral onabotA or placebo during the double-blind, placebo-controlled phase, followed by a single unilateral or bilateral treatment of onabotA.

Essential tremor is one of the most common movement disorders in adults, with prevalences of approximately 1% in the general population and 4% to 5% among persons older than 65 years of age. BotulinumxotinA, which has been effective to varying degrees in the treatment of essential limb tremor, prevents the release of acetylcholine in synapses, leading to a reduction in aberrant muscle movement. The therapy has been used for the treatment of tremor, particularly in the hands and arms.

A 2023 study published in the New England Journal of Medicine showed that electromyographically guided injections of botulinum toxin into each splenius capitis muscle led to inconsistent effects in treating essential head tremor. The study, which featured 120 patients, showed that injections on day 0 and during week 12 was more effective than placebo in reducing the severity of isolated or essential head tremor at 18 weeks but not at 24 weeks, when the effects of injection might be expected to wane. The treatment was also associated with adverse events, such as head and neck pain, posterior cervical weakness, and dysphagia.²

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REFERENCES
1. Patterson K, Alibhai N, Khosla D, James L. A Phase 2b Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of OnabotulinumtoxinA for the Treatment of Upper Limb Essential Tremor: ELATE Trial. Presented at: 2024 MDS Congress; September 27-October 1; Philadelphia, PA. ABSTRACT 1551
2. Marques A, Pereira B, Simonetta-Moreau M, et al. Trial of botulinum toxin for isolated or essential head tremor. NEJM. 2023;389:1753-1765. doi:10.1056/NEJMoa2304192