Study to Evaluate SAGE-324 in Participants With Essential Tremor

Essential Tremor Clinical Trial

Official title:

A Phase 2, Double-Blind, Randomized, Placebo-Controlled, Dose-Response Study of SAGE-324 for the Treatment of Essential Tremor

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05173012
• Other study ID #: 324-ETD-202
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 24, 2022
• Est. completion date: May 2024

Study information

• Verified date: March 2024
• Source: Sage Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 160
• Est. completion date: May 2024
• Est. primary completion date: May 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Essential Tremor
• Tremor

Intervention

Drug:
• SAGE-324
SAGE-324 oral tablets.
• SAGE-324 Matched Placebo
SAGE-324 matched placebo oral tablets.

Locations

Country	Name	City	State
United States	Sage Investigational Site	Asheville	North Carolina
United States	Sage Investigational Site	Atlanta	Georgia
United States	Sage Investigational Site	Austin	Texas
United States	Sage Investigational Site	Boca Raton	Florida
United States	Sage Investigational Site	Boston	Massachusetts
United States	Sage Investigational Site	Bradenton	Florida
United States	Sage Investigational Site	Chicago	Illinois
United States	Sage Investigational Site	Coral Springs	Florida
United States	Sage Investigational Site	Dayton	Ohio
United States	Sage Investigational Site	Decatur	Georgia
United States	Sage Investigational Site	Englewood	Colorado
United States	Sage Investigational Site	Fairfax	Virginia
United States	Sage Investigational Site	Farmington Hills	Michigan
United States	Sage Investigational Site	Fort Worth	Texas
United States	Sage Investigational Site	Fountain Valley	California
United States	Sage Investigational Site	Fullerton	California
United States	Sage Investigational Site	Gainesville	Florida
United States	Sage Investigational Site	Hollywood	Florida
United States	Sage Investigational Site	Hoover	Alabama
United States	Sage Investigational Site	Houston	Texas
United States	Sage Investigational Site	Kansas City	Kansas
United States	Sage Investigational Site	Katy	Texas
United States	Sage Investigational Site	Kendall	Florida
United States	Sage Investigational Site	Kirkland	Washington
United States	Sage Investigational Site	Lexington	Kentucky
United States	Sage Investigational Site	Los Angeles	California
United States	Sage Investigational Site	McLean	Virginia
United States	Sage Investigational Site	Memphis	Tennessee
United States	Sage Investigational Site	Miami	Florida
United States	Sage Investigational Site	Miami	Florida
United States	Sage Investigational Site	Miami	Florida
United States	Sage Investigational Site	Naples	Florida
United States	Sage Investigational Site	New York	New York
United States	Sage Investigational Site	New York	New York
United States	Sage Investigational Site	Pensacola	Florida
United States	Sage Investigational Site	Round Rock	Texas
United States	Sage Investigational Site	San Antonio	Texas
United States	Sage Investigational Site	Scottsdale	Arizona
United States	Sage Investigational Site	Shreveport	Louisiana
United States	Sage Investigational Site	Spokane	Washington
United States	Sage Investigational Site	Springfield	Illinois
United States	Sage Investigational Site	Tampa	Florida
United States	Sage Investigational Site	Tulsa	Oklahoma
United States	Sage Investigational Site	Winter Park	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Sage Therapeutics	Biogen

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	TETRAS is a validated, comprehensive clinical assessment of essential tremor. For the performance subscale item 4 upper limb (UL) tremor score, all 3 maneuvers in the UL assessments of item 4 (subscale 4a, 4b, and 4c) will be completed for both arms, first for the left arm and then for the right. The item 4 subscale ordinally rates postural (limbs extended forward and wing-beating [elbows flexed]), and kinetic (finger-nose-finger maneuver) tremor on a 0 to 4 severity scale in 0.5-point increments. TETRAS Item 4 score for each upper limb ranges from 0 to 12 and for both upper limbs from 0 to 24.	Baseline up to Day 91
Secondary	Change From Baseline in TETRAS Activities of Daily Living (ADL) Composite Score in the Monotherapy Cohort	TETRAS ADL subscale assesses how ET affects typical ADL (i.e., speech, eating, drinking, dressing, personal hygiene, writing, occupational impairment, social impact, and activities affected by upper limb tremor). It consists of 12 items, each item rated on a scale from 0 (normal activity) to 4 (severe abnormality). The performance subscale assesses the overall rating of tremor in the voice, limbs, head, face, trunk, while performing prespecified tasks, and also measures functional task capabilities, i.e., handwriting, spirography, and holding a pen over a dot. It consists of 16 items, each item rated on a scale from 0 (no tremor) to 4 (severe tremor). The ADL composite score comprises items 1 to 11 of the ADL subscale and item 6 of the performance subscale, each item rated on a scale from 0 (normal/slightly abnormal) to 3 (severely abnormal) and the overall score range is 0 to 36. A negative change from baseline will indicate improvement.	Baseline up to Day 91