A Study to Evaluate the Efficacy, Safety, and Tolerability of SAGE-324 in Participants With Essential Tremor

• ClinicalTrials.gov Identifier: NCT04305275
• Recruitment Status: Completed
• First Posted: March 12, 2020
• Last Update Posted: March 5, 2021
• Sponsor: Sage Therapeutics
• Information provided by (Responsible Party): Sage Therapeutics

Study Description

Brief Summary:

This is a phase 2, double-blind, placebo-controlled study to evaluate the safety and efficacy of SAGE-324 compared to placebo on upper limb tremor reduction in individuals with essential tremor (ET).

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 69 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, Placebo-controlled, Randomized Study Evaluating the Efficacy, Safety, and Tolerability of Sage-324 in the Treatment of Individuals With Essential Tremor
• Actual Study Start Date: June 15, 2020
• Actual Primary Completion Date: February 1, 2021
• Actual Study Completion Date: February 15, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: SAGE-324 60 mg; Participants will receive SAGE-324 60 mg dose (tablets) orally in the morning for 28 days.	Drug: SAGE-324; SAGE-324 oral tablet
Placebo Comparator: SAGE-324 Matched Placebo; Participants will receive SAGE-324 matched placebo, oral tablets for 28 days.	Drug: SAGE-324 Placebo; SAGE-324 matched placebo oral tablet

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline Compared to Placebo in The Essential Tremor Rating Assessment (TETRAS) Performance Subscale Part 4 Upper Limb Tremor Score on Day 29 [ Time Frame: Baseline, Day 29 ]
   TETRAS is a validated, comprehensive clinical assessment of essential tremor. For the performance subscale part 4 upper limb (UL) tremor score, all 3 maneuvers in the UL assessments of part 4 (subscale 4a, 4b, and 4c) will be completed for both arms, first for the left arm and then for the right. The part 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 Part 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 Compared to Placebo in TETRAS Performance Subscale Part 4 Upper Limb Tremor Score at all Other Timepoints [ Time Frame: Baseline, Day 1, 8, 15, 22 and on Day 42 (or Early Termination Visit [ETV] / End of Study [EOS]) ]
   For the performance subscale part 4 upper limb (UL) tremor score, all 3 maneuvers in the UL assessments of part 4 (subscale 4a, 4b, and 4c) will be completed for both arms, first for the left arm and then for the right. The part 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 Part 4 score for each upper limb ranges from 0 to 12 and for both upper limbs from 0 to 24.
2. Change From Baseline Compared to Placebo in Kinesia ONE Accelerometer Scores [ Time Frame: Baseline, Day 1, 8, 15, 22, 29 and on Day 42 (or ETV / EOS) ]
   Kinesia ONE is a wireless motion sensor worn distally on the index finger, which utilizes 3 orthogonal accelerometers and 3 orthogonal gyroscopes to monitor three-dimensional motion. Via the Kinesia ONE software application, measures of three-dimensional motion are converted to scores ranging from 0 to 4. Higher scores indicate greater tremor severity. Motion in each arm will be captured separately.
3. Change From Baseline Compared to Placebo in TETRAS Scale Activities of Daily Living (ADL) Score [ Time Frame: Baseline, Day 1, 8, 15, 22, 29 and on Day 42 (or ETV / EOS) ]
   The ADL subscale will assess how ET impacts typical activities of daily living (speech, eating, drinking, dressing, personal hygiene, writing, occupational impairment, social impact and activities affected by upper limb (UL) tremor). It consists of 12 items, each rated from 0 (normal activity) to 4 (severe abnormality) with overall ADL score range of 0 to 48.
4. Change From Baseline Compared to Placebo in TETRAS Total Performance Score [ Time Frame: Baseline, Day 1, 8, 15, 22, 29 and on Day 42 (or ETV / EOS) ]
   The total performance score is based on overall rating of tremor amplitude in the voice, limbs, head, face, trunk, while performing pre-specified tasks, and functional task capabilities (handwriting, spiral drawing, and holding a pen over a dot). Each of these items is rated from 0 (no tremor) to 4 (severe tremor) with an overall performance score of 0 to 64.
5. Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Up to Day 42 ]
   A TEAE is defined as an AE with onset after the start of investigational product (IP), or any worsening of a pre-existing medical condition/AE with onset after the start of IP and throughout the study.

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:

• Participant has a diagnosis of ET, defined as isolated tremor syndrome consisting of bilateral upper limb action tremor for at least 3 years prior to screening, with or without tremor in other locations and 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 step-wise deterioration of tremor.
• Participant scores at least 1.5 for each of the six items that comprise the combined total upper limb TETRAS (total performance subscale part 4) with the total score for the dominant upper limb (the sum of the three items for either the right or left upper limb, whichever is dominant) being at least 5.5, at both Screening and predose on Day 1.
• Participant is willing to discontinue medications taken for the treatment of ET within 14 days or 5 half-lives prior to receiving IP. Medications taken for the treatment of ET that were discontinued prior to receiving IP may be resumed following Day 29.
• Participant has no clinically significant findings, as determined by the investigator, on Screening and pre-dose Day 1 physical examination including mental state examination (MSE) and neurologic examination, 12-lead electrocardiogram (ECG), or screening clinical laboratory tests.

Exclusion Criteria:

• Participant has a presence of known causes of enhanced physiological tremor.
• Participant has had recent exposure (14 days prior to Day 1) to tremorgenic drugs.
• Participant has had direct or indirect injury or trauma to the nervous system within 3 months before the onset of tremor.
• Participant has had a previous procedure for the treatment of ET, deep brain stimulation, brain lesioning, or magnetic resonance (MR)-guided procedure, eg, MR-guided focused ultrasound.
• Participant has historical or clinical evidence of tremor with psychogenic origin (including but not limited to eating disorders, major depression, etc.).
• Participant has history of suicidal behavior within 2 years or answers "YES" to questions 3, 4, or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening or at Day 1 or is currently at risk for suicide in the opinion of the investigator.
• Participant has used any known moderate or strong cytochrome P450 3A4 and/or inducers within 14 days or 5 half-lives (whichever is longer) prior to Day 1 or consumed grapefruit juice, grapefruit, Seville oranges, pomegranates, tangelos, or St. John's Wort or products containing these within 30 days prior to Day 1. Use of mild cytochrome inhibitors and/or inducers may be permitted.
• Participant has concurrent or recent exposure (14 days or 5 half-lives, whichever is longer, prior to the Day 1 visit) to sedative/hypnotic drugs, stimulants, highly-caffeinated beverages or dietary supplements containing high doses of caffeine, or recent increase above regular daily consumption of caffeine.
• Participant currently uses or has used within 14 days or 5 half-lives (whichever is longer) prior to Day 1, any prescription or over-the-counter medication that is a substrate of the OATP1B1 transporter.

Contacts and Locations

Locations

United States, Arizona

Sage Investigational Site

Phoenix, Arizona, United States, 85258

United States, Arkansas

Sage Investigational Site

Rogers, Arkansas, United States, 72758

United States, California

Sage Investigational Site

Fresno, California, United States, 93710

Sage Investigational Site

Long Beach, California, United States, 90806

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

Gainesville, Florida, United States, 32608

Sage Investigational Site

Hollywood, Florida, United States, 33024

Sage Investigational Site

Miami, Florida, United States, 33136

Sage Investigational Site

Miami, Florida, United States, 33176

Sage Investigational Site

Port Charlotte, Florida, United States, 33980

Sage Investigational Site

Saint Petersburg, Florida, United States, 33713

Sage Investigational Site

Tampa, Florida, United States, 33609

United States, Georgia

Sage Investigational Site

Decatur, Georgia, United States, 30030

Sage Investigational Site

Savannah, Georgia, United States, 31406

United States, Illinois

Sage Investigational Site

Springfield, Illinois, United States, 62702

United States, Kansas

Sage Investigational Site

Kansas City, Kansas, United States, 66160

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, 10032

United States, North Carolina

Sage Investigational Site

Asheville, North Carolina, United States, 28806

United States, Ohio

Sage Investigational Site

Cincinnati, Ohio, United States, 45212

Sage Investigational Site

Dayton, Ohio, United States, 45417

United States, Oklahoma

Sage Investigational Site

Tulsa, Oklahoma, United States, 74136

United States, Texas

Sage Investigational Site

Houston, Texas, United States, 77030

United States, Virginia

Sage Investigational Site

Richmond, Virginia, United States, 23229

United States, Washington

Sage Investigational Site

Spokane, Washington, United States, 99202

United States, West Virginia

Sage Investigational Site

Huntington, West Virginia, United States, 25701

Sponsors and Collaborators

Sage Therapeutics

More Information

• Responsible Party: Sage Therapeutics
• ClinicalTrials.gov Identifier: NCT04305275
• Other Study ID Numbers: 324-ETD-201
• First Posted: March 12, 2020
• Last Update Posted: March 5, 2021
• Last Verified: March 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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
• Product Manufactured in and Exported from the U.S.: 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