Clinical trial NCT05173012: Study to Evaluate SAGE-324 in Participants With Essential Tremor
Official title: A Phase 2, Double-Blind, Randomized, Placebo-Controlled, Dose-Response Study of SAGE-324 for the Treatment of Essential Tremor
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Essential Tremor
Keywords: Essential Tremor
SAGE-324
Lead sponsor: Sage Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Biogen
First posted: 2021-12-29
Enrollment: 146
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary purpose of this study is to evaluate the dose-response relationship of different doses of SAGE-324 on upper extremity tremor in participants with essential tremor (ET) in the monotherapy cohort.


Eligibility criteria: Inclusion Criteria:

1. Diagnosis of ET, as defined by all of the following criteria:

   * Isolated tremor syndrome consisting of bilateral upper limb action tremor
   * At least 3 years duration
   * With or without tremor in other locations (eg, head, voice, or lower limbs)
2. Absence of other neurological signs, such as dystonia, ataxia, or parkinsonism, isolated focal tremors (eg, voice, head), task- and position-specific tremors, sudden tremor onset, or evidence of stepwise deterioration of tremor.
3. Participant has the following:

   * Scores of at least 12 in the combined TETRAS Performance Subscale Item 4 (upper limb tremor) at both Screening and pre-dose on Day 1
   * Scores of at least 6 in the total TETRAS Performance Subscale Item 4 score for the dominant upper limb (the sum of the three items for either the right or left upper limb, whichever is dominant) at both Screening and pre-dose on Day 1
4. Participant has a baseline TETRAS ADL Subscale score of at least 20 at Screening.
5. Willing to discontinue medications taken for the treatment of ET except propranolol at least 14 days or 5 half-lives (whichever is longer) prior to receiving the investigational product (IP). Medications taken for the treatment of ET that were discontinued prior to receiving IP may be resumed following Day 97. Participants in the adjunct therapy cohort must be on a stable dose of propranolol (maximum total daily propranolol dose up to 320 mg allowed) for the treatment of ET from 3 months prior to Screening through Day 97 of the study.
6. Participant is willing to limit use of alcohol to 2 units per day for males and 1 unit per day for females starting at least 1 week prior to Day 1 and through Day 97 of the study.
7. Participant is willing to maintain prestudy consumption of products that contain nicotine starting at least 1 week prior to Day 1 and through Day 97 of the study.

Exclusion Criteria:

1. Presence of known causes of enhanced physiological tremor.
2. Participant has had newly administered tremorgenic drugs (14 days or 5 half-lives \[whichever is longer\] prior to Day 1) or presence of alcohol withdrawal state.
3. Direct or indirect injury or trauma to the nervous system within 3 months before the onset of tremor.
4. Previous procedure for the treatment of ET, deep brain stimulation, brain lesioning, or magnetic resonance (MR) guided procedure, eg, MR-guided focused ultrasound. Use of Cala Trio bracelet for the treatment of ET from two weeks prior to Day 1 through Day 97 is prohibited.
5. Participant has had botulinum toxin for treatment of ET within 6 months of Screening.
6. Historical or clinical evidence of tremor with functional neurological syndrome origin.
7. Participant currently requires propranolol treatment for a medical condition other than ET.
8. Participant has history of substance abuse or dependence prior to Screening, has a positive screen for drugs of abuse at Screening or predose on Day 1. Participants with nicotine use disorder that impacts their tremor are excluded.

Primary outcomes:
measure: Change From Baseline in The Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale Item 4 (Upper Limb) Total Score on Day 91 in the Monotherapy Cohort
timeFrame: Baseline, Day 91
Secondary outcomes:
measure: Change From Baseline in TETRAS Activities of Daily Living (ADL) Composite Score in the Monotherapy Cohort
timeFrame: Baseline, Day 91
Other outcomes:
Locations:
city: Hoover
country: United States
facility: Sage Investigational Site
state: Alabama
city: Phoenix
country: United States
facility: Sage Investigational Site
state: Arizona
city: Scottsdale
country: United States
facility: Sage Investigational Site
state: Arizona
city: Sun City
country: United States
facility: Sage Investigational Site
state: Arizona
city: Fountain Valley
country: United States
facility: Sage Investigational Site
state: California
city: Fullerton
country: United States
facility: Sage Investigational Site
state: California
city: Los Angeles
country: United States
facility: Sage Investigational Site
state: California
city: Englewood
country: United States
facility: Sage Investigational Site
state: Colorado
city: Boca Raton
country: United States
facility: Sage Investigational Site
state: Florida
city: Boynton Beach
country: United States
facility: Sage Investigational Site
state: Florida
city: Bradenton
country: United States
facility: Sage Investigational Site
state: Florida
city: Coral Springs
country: United States
facility: Sage Investigational Site
state: Florida
city: Gainesville
country: United States
facility: Sage Investigational Site
state: Florida
city: Hollywood
country: United States
facility: Sage Investigational Site
state: Florida
city: Kendall
country: United States
facility: Sage Investigational Site
state: Florida
city: Miami
country: United States
facility: Sage Investigational Site
state: Florida
city: Miami
country: United States
facility: Sage Investigational Site
state: Florida
city: Miami
country: United States
facility: Sage Investigational Site
state: Florida
city: Naples
country: United States
facility: Sage Investigational Site
state: Florida
city: Orlando
country: United States
facility: Sage Investigational Site
state: Florida
city: Pensacola
country: United States
facility: Sage Investigational Site
state: Florida
city: Port Charlotte
country: United States
facility: Sage Investigational Site
state: Florida
city: Tampa
country: United States
facility: Sage Investigational Site
state: Florida
city: Atlanta
country: United States
facility: Sage Investigational Site
state: Georgia
city: Decatur
country: United States
facility: Sage Investigational Site
state: Georgia
city: Chicago
country: United States
facility: Sage Investigational Site
state: Illinois
city: Springfield
country: United States
facility: Sage Investigational Site
state: Illinois
city: Kansas City
country: United States
facility: Sage Investigational Site
state: Kansas
city: Lexington
country: United States
facility: Sage Investigational Site
state: Kentucky
city: Shreveport
country: United States
facility: Sage Investigational Site
state: Louisiana
city: Boston
country: United States
facility: Sage Investigational Site
state: Massachusetts
city: Farmington Hills
country: United States
facility: Sage Investigational Site
state: Michigan
city: Lansing
country: United States
facility: Sage Investigational Site
state: Michigan
city: Las Vegas
country: United States
facility: Sage Investigational Site
state: Nevada
city: New York
country: United States
facility: Sage Investigational Site
state: New York
city: New York
country: United States
facility: Sage Investigational Site
state: New York
city: Asheville
country: United States
facility: Sage Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: Sage Investigational Site
state: Ohio
city: Dayton
country: United States
facility: Sage Investigational Site
state: Ohio
city: Tulsa
country: United States
facility: Sage Investigational Site
state: Oklahoma
city: Memphis
country: United States
facility: Sage Investigational Site
state: Tennessee
city: Austin
country: United States
facility: Sage Investigational Site
state: Texas
city: Fort Worth
country: United States
facility: Sage Investigational Site
state: Texas
city: Houston
country: United States
facility: Sage Investigational Site
state: Texas
city: Katy
country: United States
facility: Sage Investigational Site
state: Texas
city: Round Rock
country: United States
facility: Sage Investigational Site
state: Texas
city: San Antonio
country: United States
facility: Sage Investigational Site
state: Texas
city: McLean
country: United States
facility: Sage Investigational Site
state: Virginia
city: W. Falls Church
country: United States
facility: Sage Investigational Site
state: Virginia
city: Kirkland
country: United States
facility: Sage Investigational Site
state: Washington
city: Spokane
country: United States
facility: Sage Investigational Site
state: Washington
Study officials:
References: