A Randomized Phase 2 KINETIC Trial Evaluating SAGE-324/BIIB124 in Individuals with Essential Tremor

Rodger J. Elble; William G. Ondo; Kelly E. Lyons; Min Qin; Svetlana Garafola; Bonnie Hersh; Tina Marie Lieu; Dimitrios Arkilo; Rosalind Chuang; Kemi Bankole; Rajesh Pahwa

doi:10.1002/mds.29731

A Randomized Phase 2 KINETIC Trial Evaluating SAGE-324/BIIB124 in Individuals with Essential Tremor

Rodger J. Elble, William G. Ondo, Kelly E. Lyons, Min Qin, Svetlana Garafola, Bonnie Hersh, Tina Marie Lieu, Dimitrios Arkilo, Rosalind Chuang, Kemi Bankole, Rajesh Pahwa

Research output: Contribution to journal › Article › peer-review

Abstract

Background: SAGE-324/BIIB124 is an investigational positive allosteric modulator of GABA_A receptors. Objective: KINETIC (NCT04305275), a double-blind, randomized, placebo-controlled, phase 2 study, evaluated SAGE-324/BIIB124 in individuals with essential tremor (ET). Methods: Individuals aged 18 to 80 years were randomly assigned 1:1 to orally receive 60 mg of SAGE-324/BIIB124 or placebo once daily for 28 days. The primary endpoint was change from baseline in The Essential Tremor Rating Assessment Scale-Performance Subscale (TETRAS-PS) Item 4 (upper-limb tremor) at day 29 with SAGE-324/BIIB124 versus placebo. Results: Between May 2020 and February 2021, 69 U.S. participants were randomly assigned to receive SAGE-324/BIIB124 (n = 34) or placebo (n = 35). There was a significant reduction from baseline in TETRAS-PS Item 4 at day 29 with SAGE-324/BIIB124 versus placebo (least squares mean [standard error]: –2.31 [0.401] vs. –1.24 [0.349], P = 0.0491). The most common treatment-emergent adverse events included somnolence, dizziness, fatigue, and balance disorder. Conclusion: These results support further development of SAGE-324/BIIB124 for potential ET treatment.

Original language	English (US)
Journal	Movement Disorders
DOIs	https://doi.org/10.1002/mds.29731
State	Accepted/In press - 2024

Keywords

essential tremor
neuroactive steroid
positive allosteric modulator
γ-aminobutyric acid

ASJC Scopus subject areas

Neurology
Clinical Neurology

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10.1002/mds.29731

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@article{8b3be7bd27f74d3d95638ae2ba5e98b8,

title = "A Randomized Phase 2 KINETIC Trial Evaluating SAGE-324/BIIB124 in Individuals with Essential Tremor",

abstract = "Background: SAGE-324/BIIB124 is an investigational positive allosteric modulator of GABAA receptors. Objective: KINETIC (NCT04305275), a double-blind, randomized, placebo-controlled, phase 2 study, evaluated SAGE-324/BIIB124 in individuals with essential tremor (ET). Methods: Individuals aged 18 to 80 years were randomly assigned 1:1 to orally receive 60 mg of SAGE-324/BIIB124 or placebo once daily for 28 days. The primary endpoint was change from baseline in The Essential Tremor Rating Assessment Scale-Performance Subscale (TETRAS-PS) Item 4 (upper-limb tremor) at day 29 with SAGE-324/BIIB124 versus placebo. Results: Between May 2020 and February 2021, 69 U.S. participants were randomly assigned to receive SAGE-324/BIIB124 (n = 34) or placebo (n = 35). There was a significant reduction from baseline in TETRAS-PS Item 4 at day 29 with SAGE-324/BIIB124 versus placebo (least squares mean [standard error]: –2.31 [0.401] vs. –1.24 [0.349], P = 0.0491). The most common treatment-emergent adverse events included somnolence, dizziness, fatigue, and balance disorder. Conclusion: These results support further development of SAGE-324/BIIB124 for potential ET treatment.",

keywords = "essential tremor, neuroactive steroid, positive allosteric modulator, γ-aminobutyric acid",

author = "Elble, {Rodger J.} and Ondo, {William G.} and Lyons, {Kelly E.} and Min Qin and Svetlana Garafola and Bonnie Hersh and Lieu, {Tina Marie} and Dimitrios Arkilo and Rosalind Chuang and Kemi Bankole and Rajesh Pahwa",

note = "Publisher Copyright: {\textcopyright} 2024 Sage Therapeutics, Inc and The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.",

year = "2024",

doi = "10.1002/mds.29731",

language = "English (US)",

journal = "Movement Disorders",

issn = "0885-3185",

publisher = "Wiley",

}

TY - JOUR

T1 - A Randomized Phase 2 KINETIC Trial Evaluating SAGE-324/BIIB124 in Individuals with Essential Tremor

AU - Elble, Rodger J.

AU - Ondo, William G.

AU - Lyons, Kelly E.

AU - Qin, Min

AU - Garafola, Svetlana

AU - Hersh, Bonnie

AU - Lieu, Tina Marie

AU - Arkilo, Dimitrios

AU - Chuang, Rosalind

AU - Bankole, Kemi

AU - Pahwa, Rajesh

PY - 2024

Y1 - 2024

N2 - Background: SAGE-324/BIIB124 is an investigational positive allosteric modulator of GABAA receptors. Objective: KINETIC (NCT04305275), a double-blind, randomized, placebo-controlled, phase 2 study, evaluated SAGE-324/BIIB124 in individuals with essential tremor (ET). Methods: Individuals aged 18 to 80 years were randomly assigned 1:1 to orally receive 60 mg of SAGE-324/BIIB124 or placebo once daily for 28 days. The primary endpoint was change from baseline in The Essential Tremor Rating Assessment Scale-Performance Subscale (TETRAS-PS) Item 4 (upper-limb tremor) at day 29 with SAGE-324/BIIB124 versus placebo. Results: Between May 2020 and February 2021, 69 U.S. participants were randomly assigned to receive SAGE-324/BIIB124 (n = 34) or placebo (n = 35). There was a significant reduction from baseline in TETRAS-PS Item 4 at day 29 with SAGE-324/BIIB124 versus placebo (least squares mean [standard error]: –2.31 [0.401] vs. –1.24 [0.349], P = 0.0491). The most common treatment-emergent adverse events included somnolence, dizziness, fatigue, and balance disorder. Conclusion: These results support further development of SAGE-324/BIIB124 for potential ET treatment.

AB - Background: SAGE-324/BIIB124 is an investigational positive allosteric modulator of GABAA receptors. Objective: KINETIC (NCT04305275), a double-blind, randomized, placebo-controlled, phase 2 study, evaluated SAGE-324/BIIB124 in individuals with essential tremor (ET). Methods: Individuals aged 18 to 80 years were randomly assigned 1:1 to orally receive 60 mg of SAGE-324/BIIB124 or placebo once daily for 28 days. The primary endpoint was change from baseline in The Essential Tremor Rating Assessment Scale-Performance Subscale (TETRAS-PS) Item 4 (upper-limb tremor) at day 29 with SAGE-324/BIIB124 versus placebo. Results: Between May 2020 and February 2021, 69 U.S. participants were randomly assigned to receive SAGE-324/BIIB124 (n = 34) or placebo (n = 35). There was a significant reduction from baseline in TETRAS-PS Item 4 at day 29 with SAGE-324/BIIB124 versus placebo (least squares mean [standard error]: –2.31 [0.401] vs. –1.24 [0.349], P = 0.0491). The most common treatment-emergent adverse events included somnolence, dizziness, fatigue, and balance disorder. Conclusion: These results support further development of SAGE-324/BIIB124 for potential ET treatment.

KW - essential tremor

KW - neuroactive steroid

KW - positive allosteric modulator

KW - γ-aminobutyric acid

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U2 - 10.1002/mds.29731

DO - 10.1002/mds.29731

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JO - Movement Disorders

JF - Movement Disorders

ER -

A Randomized Phase 2 KINETIC Trial Evaluating SAGE-324/BIIB124 in Individuals with Essential Tremor

Abstract

Keywords

ASJC Scopus subject areas

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