Study to Evaluate SAGE-324 in Participants With Essential Tremor

NCT ID: NCT05173012

Last Updated: 2025-05-16

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

146 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-01-05

Study Completion Date

2024-05-16

Brief Summary

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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.

Detailed Description

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Conditions

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Essential Tremor

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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SAGE-324 Matched Placebo

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.

Group Type PLACEBO_COMPARATOR

SAGE-324 Matched Placebo

Intervention Type DRUG

SAGE-324 matched placebo oral tablets.

SAGE-324 15 mg

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.

Group Type EXPERIMENTAL

SAGE-324

Intervention Type DRUG

SAGE-324 oral tablets.

SAGE-324 30 mg

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.

Group Type EXPERIMENTAL

SAGE-324

Intervention Type DRUG

SAGE-324 oral tablets.

SAGE-324 60 mg

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.

Group Type EXPERIMENTAL

SAGE-324

Intervention Type DRUG

SAGE-324 oral tablets.

Interventions

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SAGE-324

SAGE-324 oral tablets.

Intervention Type DRUG

SAGE-324 Matched Placebo

SAGE-324 matched placebo oral tablets.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Biogen

INDUSTRY

Sponsor Role collaborator

Sage Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Sage Investigational Site

Hoover, Alabama, United States

Site Status

Sage Investigational Site

Phoenix, Arizona, United States

Site Status

Sage Investigational Site

Scottsdale, Arizona, United States

Site Status

Sage Investigational Site

Sun City, Arizona, United States

Site Status

Sage Investigational Site

Fountain Valley, California, United States

Site Status

Sage Investigational Site

Fullerton, California, United States

Site Status

Sage Investigational Site

Los Angeles, California, United States

Site Status

Sage Investigational Site

Englewood, Colorado, United States

Site Status

Sage Investigational Site

Boca Raton, Florida, United States

Site Status

Sage Investigational Site

Boynton Beach, Florida, United States

Site Status

Sage Investigational Site

Bradenton, Florida, United States

Site Status

Sage Investigational Site

Coral Springs, Florida, United States

Site Status

Sage Investigational Site

Gainesville, Florida, United States

Site Status

Sage Investigational Site

Hollywood, Florida, United States

Site Status

Sage Investigational Site

Kendall, Florida, United States

Site Status

Sage Investigational Site

Miami, Florida, United States

Site Status

Sage Investigational Site

Miami, Florida, United States

Site Status

Sage Investigational Site

Miami, Florida, United States

Site Status

Sage Investigational Site

Naples, Florida, United States

Site Status

Sage Investigational Site

Orlando, Florida, United States

Site Status

Sage Investigational Site

Pensacola, Florida, United States

Site Status

Sage Investigational Site

Port Charlotte, Florida, United States

Site Status

Sage Investigational Site

Tampa, Florida, United States

Site Status

Sage Investigational Site

Atlanta, Georgia, United States

Site Status

Sage Investigational Site

Decatur, Georgia, United States

Site Status

Sage Investigational Site

Chicago, Illinois, United States

Site Status

Sage Investigational Site

Springfield, Illinois, United States

Site Status

Sage Investigational Site

Kansas City, Kansas, United States

Site Status

Sage Investigational Site

Lexington, Kentucky, United States

Site Status

Sage Investigational Site

Shreveport, Louisiana, United States

Site Status

Sage Investigational Site

Boston, Massachusetts, United States

Site Status

Sage Investigational Site

Farmington Hills, Michigan, United States

Site Status

Sage Investigational Site

Lansing, Michigan, United States

Site Status

Sage Investigational Site

Las Vegas, Nevada, United States

Site Status

Sage Investigational Site

New York, New York, United States

Site Status

Sage Investigational Site

New York, New York, United States

Site Status

Sage Investigational Site

Asheville, North Carolina, United States

Site Status

Sage Investigational Site

Cincinnati, Ohio, United States

Site Status

Sage Investigational Site

Dayton, Ohio, United States

Site Status

Sage Investigational Site

Tulsa, Oklahoma, United States

Site Status

Sage Investigational Site

Memphis, Tennessee, United States

Site Status

Sage Investigational Site

Austin, Texas, United States

Site Status

Sage Investigational Site

Fort Worth, Texas, United States

Site Status

Sage Investigational Site

Houston, Texas, United States

Site Status

Sage Investigational Site

Katy, Texas, United States

Site Status

Sage Investigational Site

Round Rock, Texas, United States

Site Status

Sage Investigational Site

San Antonio, Texas, United States

Site Status

Sage Investigational Site

McLean, Virginia, United States

Site Status

Sage Investigational Site

West Falls Church, Virginia, United States

Site Status

Sage Investigational Site

Kirkland, Washington, United States

Site Status

Sage Investigational Site

Spokane, Washington, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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324-ETD-202

Identifier Type: -

Identifier Source: org_study_id

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