Study to Evaluate SAGE-324 in Participants With Essential Tremor

NCT05173012 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 324-ETD-202
• Study Type: interventional
• Target: 146
• Locations: 1 country
• Sites: 51

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.

Conditions

Essential Tremor

Keywords

Essential Tremor; SAGE-324

Outcome Measures

Primary Outcomes (1)

• 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 clinical evaluation of essential tremor. The TETRAS performance subscale upper limb tremor score is a component of TETRAS. For the TETRAS Performance Subscale Item 4 (upper limb), three maneuvers/assessments were to be completed for both arms, first for the right arm and then for the left, specifically Item 4a, limbs extended forward maneuver (postural tremor), Item 4b, wing-beating \[elbows flexed\] maneuver (postural tremor), and Item 4c finger-nose-finger maneuver (kinetic tremor). Each assessment is rated on a 0 to 4 scale of severity in 0.5-point increments, with higher scores indicating more severe tremor. The Performance Subscale Item 4 (upper limb) total score range for a given side (left or right) is 0 to 12, and for both sides combined is 0 to 24. A negative change from baseline indicates improvement. Mixed model for repeated measures (MMRM) was used for the analysis.

  Baseline, Day 91

Secondary Outcomes (1)

• Change From Baseline in TETRAS Activities of Daily Living (ADL) Composite Score in the Monotherapy Cohort

  Baseline, Day 91

Study Arms (4)

SAGE-324 Matched Placebo

PLACEBO COMPARATOR

Participants will receive SAGE-324 matched placebo, stratified by baseline propranolol use. Monotherapy: Participants will receive SAGE-324 matched placebo, oral tablets, once daily (QD), in the evening, from Day 1 to Day 90 in a double-blind treatment period. Adjunct therapy: Participants will receive SAGE-324 matched placebo, oral tablets, QD, in the evening, from Day 1 to Day 90 along with a stable dose of up to 320 milligrams (mg) of propranolol from 3 months prior to Screening up to Day 90 in a double-blind treatment period.

Drug: SAGE-324 Matched Placebo

SAGE-324 15 mg

EXPERIMENTAL

Participants will receive SAGE-324, 15 mg, stratified by baseline propranolol use. Monotherapy: Participants will receive SAGE-324, 15 mg, oral tablets, QD, in the evening, from Day 1 to Day 90 in a double-blind treatment period. Adjunct therapy: Participants will receive SAGE-324, 15 mg, oral tablets, QD, in the evening, from Day 1 to Day 90 along with a stable dose of up to 320 mg of propranolol from 3 months prior to Screening up to Day 90 in a double-blind treatment period.

Drug: SAGE-324

SAGE-324 30 mg

EXPERIMENTAL

Participants will receive SAGE-324, 30 mg, stratified by baseline propranolol use. Monotherapy: Participants will receive SAGE-324, 30 mg, oral tablets, QD, in the evening, from Day 1 to Day 90 in a double-blind treatment period. Adjunct therapy: Participants will receive SAGE-324, 30 mg, oral tablets, QD, in the evening, from Day 1 to Day 90 along with a stable dose of up to 320 mg of propranolol from 3 months prior to Screening up to Day 90 in a double-blind treatment period.

Drug: SAGE-324

SAGE-324 60 mg

EXPERIMENTAL

Participants will receive SAGE-324: 15 mg, 30 mg, 45 mg, and 60 mg, stratified by baseline propranolol use. Monotherapy: Participants will receive SAGE-324, 15 mg from Day 1 to 14, followed by up-titration to 30 mg from Day 15 to 28, then to 45 mg from Day 29 to 42, and then to 60 mg from Day 43 to 90, oral tablets, QD, in the evening, from Day 1 to Day 90 in a double-blind treatment period. Adjunct therapy: Participants will receive SAGE-324, 15 mg from Day 1 to 14, followed by up-titration to 30 mg from Day 15 to 28, then to 45 mg from Day 29 to 42, and then to 60 mg from Day 43 to 90, oral tablets, QD, in the evening, from Day 1 to Day 90 along with a stable dose of up to 320 mg of propranolol from 3 months prior to Screening up to Day 90 in a double-blind treatment period.

Drug: SAGE-324

Interventions

SAGE-324 DRUG

SAGE-324 oral tablets.

SAGE-324 15 mg; SAGE-324 30 mg; SAGE-324 60 mg

SAGE-324 Matched Placebo DRUG

SAGE-324 matched placebo oral tablets.

SAGE-324 Matched Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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.
• 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
• Participant has a baseline TETRAS ADL Subscale score of at least 20 at Screening.
• 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.
• 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.
• 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.

You may not qualify if:

• Presence of known causes of enhanced physiological tremor.
• 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.
• Direct or indirect injury or trauma to the nervous system within 3 months before the onset of tremor.
• 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.
• Participant has had botulinum toxin for treatment of ET within 6 months of Screening.
• Historical or clinical evidence of tremor with functional neurological syndrome origin.
• Participant currently requires propranolol treatment for a medical condition other than ET.
• 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.

Sponsors & Collaborators

• Sage Therapeutics: lead
• Biogen: collaborator

Study Sites (51)

Sage Investigational Site

Hoover, Alabama, 35244, United States

Location

Sage Investigational Site

Phoenix, Arizona, 85012, United States

Location

Sage Investigational Site

Scottsdale, Arizona, 85258, United States

Location

Sage Investigational Site

Sun City, Arizona, 85351, United States

Location

Sage Investigational Site

Fountain Valley, California, 92708, United States

Location

Sage Investigational Site

Fullerton, California, 92835, United States

Location

Sage Investigational Site

Los Angeles, California, 90095, United States

Location

Sage Investigational Site

Englewood, Colorado, 80113, United States

Location

Sage Investigational Site

Boca Raton, Florida, 33486, United States

Location

Sage Investigational Site

Boynton Beach, Florida, 33437, United States

Location

Sage Investigational Site

Bradenton, Florida, 34205, United States

Location

Sage Investigational Site

Coral Springs, Florida, 33067, United States

Location

Sage Investigational Site

Gainesville, Florida, 32608, United States

Location

Sage Investigational Site

Hollywood, Florida, 33024, United States

Location

Sage Investigational Site

Kendall, Florida, 33176, United States

Location

Sage Investigational Site

Miami, Florida, 33136, United States

Location

Sage Investigational Site

Miami, Florida, 33175, United States

Location

Sage Investigational Site

Miami, Florida, 33176, United States

Location

Sage Investigational Site

Naples, Florida, 34105, United States

Location

Sage Investigational Site

Orlando, Florida, 32803, United States

Location

Sage Investigational Site

Pensacola, Florida, 32503, United States

Location

Sage Investigational Site

Port Charlotte, Florida, 33980, United States

Location

Sage Investigational Site

Tampa, Florida, 33612, United States

Location

Sage Investigational Site

Atlanta, Georgia, 30329, United States

Location

Sage Investigational Site

Decatur, Georgia, 30030, United States

Location

Sage Investigational Site

Chicago, Illinois, 60612, United States

Location

Sage Investigational Site

Springfield, Illinois, 62702, United States

Location

Sage Investigational Site

Kansas City, Kansas, 66160, United States

Location

Sage Investigational Site

Lexington, Kentucky, 40509, United States

Location

Sage Investigational Site

Shreveport, Louisiana, 71105, United States

Location

Sage Investigational Site

Boston, Massachusetts, 02131, United States

Location

Sage Investigational Site

Farmington Hills, Michigan, 48334, United States

Location

Sage Investigational Site

Lansing, Michigan, 48824, United States

Location

Sage Investigational Site

Las Vegas, Nevada, 89102, United States

Location

Sage Investigational Site

New York, New York, 10003, United States

Location

Sage Investigational Site

New York, New York, 10032, United States

Location

Sage Investigational Site

Asheville, North Carolina, 28806, United States

Location

Sage Investigational Site

Cincinnati, Ohio, 45219, United States

Location

Sage Investigational Site

Dayton, Ohio, 45417, United States

Location

Sage Investigational Site

Tulsa, Oklahoma, 74136, United States

Location

Sage Investigational Site

Memphis, Tennessee, 38157, United States

Location

Sage Investigational Site

Austin, Texas, 78746, United States

Location

Sage Investigational Site

Fort Worth, Texas, 76104, United States

Location

Sage Investigational Site

Houston, Texas, 77030, United States

Location

Sage Investigational Site

Katy, Texas, 77450, United States

Location

Sage Investigational Site

Round Rock, Texas, 78681, United States

Location

Sage Investigational Site

San Antonio, Texas, 78229, United States

Location

Sage Investigational Site

McLean, Virginia, 22101, United States

Location

Sage Investigational Site

West Falls Church, Virginia, 22042, United States

Location

Sage Investigational Site

Kirkland, Washington, 98034, United States

Location

Sage Investigational Site

Spokane, Washington, 99202, United States

Location

MeSH Terms

Conditions

Essential Tremor

Condition Hierarchy (Ancestors)

Movement Disorders; Central Nervous System Diseases; Nervous System Diseases

Results Point of Contact

• Title: Carrie Vaudreuil
• Organization: Sage Therapeutics

carrie.vaudreuil@sagerx.com

(857) 259-4766

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2021
• First Posted: December 29, 2021
• Study Start: January 5, 2022
• Primary Completion: May 2, 2024
• Study Completion: May 16, 2024
• Last Updated: May 16, 2025
• Results First Posted: May 16, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (51)