Study to Evaluate SAGE-324 in Participants With Essential Tremor

• ClinicalTrials.gov Identifier: NCT05173012
• Recruitment Status: Active, not recruiting
• First Posted: December 29, 2021
• Last Update Posted: March 4, 2024
• Sponsor: Sage Therapeutics
• Collaborator: Biogen
• Information provided by (Responsible Party): Sage Therapeutics

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Essential Tremor	Drug: SAGE-324; Drug: SAGE-324 Matched Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 160 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Double-Blind, Randomized, Placebo-Controlled, Dose-Response Study of SAGE-324 for the Treatment of Essential Tremor
• Actual Study Start Date: January 24, 2022
• Estimated Primary Completion Date: May 2024
• Estimated Study Completion Date: May 2024

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: 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.	Drug: SAGE-324 Matched Placebo; SAGE-324 matched placebo oral tablets.
Experimental: 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.	Drug: SAGE-324; SAGE-324 oral tablets.
Experimental: 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.	Drug: SAGE-324; SAGE-324 oral tablets.
Experimental: 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.	Drug: SAGE-324; SAGE-324 oral tablets.

Outcome Measures

Primary Outcome Measures :

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 [ Time Frame: Baseline up to Day 91 ]
   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.

Secondary Outcome Measures :

1. Change From Baseline in TETRAS Activities of Daily Living (ADL) Composite Score in the Monotherapy Cohort [ Time Frame: Baseline up to Day 91 ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Alabama

Sage Investigational Site

Hoover, Alabama, United States, 35244

United States, Arizona

Sage Investigational Site

Scottsdale, Arizona, United States, 85258

United States, California

Sage Investigational Site

Fountain Valley, California, United States, 92708

Sage Investigational Site

Fullerton, California, United States, 92835

Sage Investigational Site

Los Angeles, California, United States, 90095

United States, Colorado

Sage Investigational Site

Englewood, Colorado, United States, 80113

United States, Florida

Sage Investigational Site

Boca Raton, Florida, United States, 33486

Sage Investigational Site

Bradenton, Florida, United States, 34205

Sage Investigational Site

Coral Springs, Florida, United States, 33067

Sage Investigational Site

Gainesville, Florida, United States, 32608

Sage Investigational Site

Hollywood, Florida, United States, 33024

Sage Investigational Site

Kendall, Florida, United States, 33176

Sage Investigational Site

Miami, Florida, United States, 33136

Sage Investigational Site

Miami, Florida, United States, 33175

Sage Investigational Site

Miami, Florida, United States, 33176

Sage Investigational Site

Naples, Florida, United States, 34105

Sage Investigational Site

Pensacola, Florida, United States, 32503

Sage Investigational Site

Tampa, Florida, United States, 33612

Sage Investigational Site

Winter Park, Florida, United States, 32792

United States, Georgia

Sage Investigational Site

Atlanta, Georgia, United States, 30329

Sage Investigational Site

Decatur, Georgia, United States, 30030

United States, Illinois

Sage Investigational Site

Chicago, Illinois, United States, 60612

Sage Investigational Site

Springfield, Illinois, United States, 62702

United States, Kansas

Sage Investigational Site

Kansas City, Kansas, United States, 66160

United States, Kentucky

Sage Investigational Site

Lexington, Kentucky, United States, 40509

United States, Louisiana

Sage Investigational Site

Shreveport, Louisiana, United States, 71105

United States, Massachusetts

Sage Investigational Site

Boston, Massachusetts, United States, 02131

United States, Michigan

Sage Investigational Site

Farmington Hills, Michigan, United States, 48334

United States, New York

Sage Investigational Site

New York, New York, United States, 10003

Sage Investigational Site

New York, New York, United States, 10032

United States, North Carolina

Sage Investigational Site

Asheville, North Carolina, United States, 28806

United States, Ohio

Sage Investigational Site

Dayton, Ohio, United States, 45417

United States, Oklahoma

Sage Investigational Site

Tulsa, Oklahoma, United States, 74136

United States, Tennessee

Sage Investigational Site

Memphis, Tennessee, United States, 38157

United States, Texas

Sage Investigational Site

Austin, Texas, United States, 78746

Sage Investigational Site

Fort Worth, Texas, United States, 76104

Sage Investigational Site

Houston, Texas, United States, 77030

Sage Investigational Site

Katy, Texas, United States, 77450

Sage Investigational Site

Round Rock, Texas, United States, 78681

Sage Investigational Site

San Antonio, Texas, United States, 78229

United States, Virginia

Sage Investigational Site

Fairfax, Virginia, United States, 22042

Sage Investigational Site

McLean, Virginia, United States, 22101

United States, Washington

Sage Investigational Site

Kirkland, Washington, United States, 98034

Sage Investigational Site

Spokane, Washington, United States, 99202

Sponsors and Collaborators

Sage Therapeutics

Biogen

More Information

• Responsible Party: Sage Therapeutics
• ClinicalTrials.gov Identifier: NCT05173012
• Other Study ID Numbers: 324-ETD-202
• First Posted: December 29, 2021
• Last Update Posted: March 4, 2024
• Last Verified: March 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: Data sharing will be consistent with the results submission policy of ClinicalTrials.gov.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sage Therapeutics:

Essential Tremor; SAGE-324

Additional relevant MeSH terms:

Tremor; Essential Tremor; Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Movement Disorders; Central Nervous System Diseases