A Study to Evaluate the Efficacy of Sage-217 in the Treatment of Adult Participants With Major Depressive Disorder (MDD)

• ClinicalTrials.gov Identifier: NCT04442490
• Recruitment Status: Completed
• First Posted: June 22, 2020
• Last Update Posted: March 29, 2022
• Sponsor: Sage Therapeutics
• Information provided by (Responsible Party): Sage Therapeutics

Study Description

Brief Summary:

The purpose of this study to evaluate the efficacy of SAGE-217 in the treatment of participants with MDD.

Condition or disease	Intervention/treatment	Phase
Depressive Disorder, Major	Drug: SAGE-217; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 543 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study Evaluating the Efficacy of SAGE-217 in the Treatment of Adult Subjects With Major Depressive Disorder
• Actual Study Start Date: May 7, 2020
• Actual Primary Completion Date: March 26, 2021
• Actual Study Completion Date: April 21, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: SAGE-217; Participants will receive SAGE-217 capsules, once daily for 14 days. The dose may be decreased based on safety and tolerability.	Drug: SAGE-217; SAGE-217 oral capsules.
Placebo Comparator: SAGE-217 Matched Placebo; Participants will receive SAGE-217 matched-placebo capsules, once daily for 14 days.	Drug: Placebo; SAGE-217 matched-placebo oral capsules.

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D) Total Score at Day 15 [ Time Frame: Baseline and Day 15 ]
   The 17-item HAM-D scale is used to assess the severity of depression. It is comprised of individual ratings related to the following symptoms: depressed mood, feelings of guilt, suicide, insomnia, work and activities, retardation, agitation, anxiety, somatic symptoms, genital symptoms, hypochondriasis, loss of weight, and insight. Individual items are scored on either a 3-point (0 to 2) or a 5-point scale (0 to 4), with 0=none/absent and 4=most severe. The total score is the sum of individual items, ranging from 0 to 52; where a higher score indicates more depression.

Secondary Outcome Measures :

1. Clinical Global Impression - Severity (CGI-S) Score [ Time Frame: Day 15 ]
   The CGI-S is a 7-point Likert scale to rate the severity of the participant's illness at the time of assessment, relative to the clinician's past experience with participants who have the same diagnosis. A participant is assessed on severity of mental illness at the time of rating as 1=normal, not at all ill; 2=borderline ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; and 7= among the most extremely ill participants.
2. HAM-D Total Score [ Time Frame: Baseline and Days 3, 28, and 42 ]
   The 17-item HAM-D scale is used to assess the severity of depression. It is comprised of individual ratings related to the following symptoms: depressed mood, feelings of guilt, suicide, insomnia, work and activities, retardation, agitation, anxiety, somatic symptoms, genital symptoms, hypochondriasis, loss of weight, and insight. Individual items are scored on either a 3-point (0 to 2) or a 5-point scale (0 to 4), with 0=none/absent and 4=most severe. The total score is the sum of individual items, ranging from 0 to 52; where a higher score indicates more depression.
3. Percentage of Participants With HAM-D Response [ Time Frame: Days 15 and 42 ]
   The time to response is defined as time from first administration of study drug to the time when ≥50% reduction in HAM-D score from baseline is achieved.
4. Percentage of Participants With HAM-D Remission [ Time Frame: Days 15 and 42 ]
   HAM-D remission is defined as HAM-D total score ≤7.
5. Percentage of Participants With Clinical Global Impression - Improvement (CGI-I) Response [ Time Frame: Day 15 ]
   CGI-I response is defined as having a CGI-I score of "very much improved" or "much improved." The CGI-I employs a 7-point Likert scale to measure the overall improvement in the participant's condition posttreatment. Response choices include 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, and 7=very much worse.
6. Montgomery Åsberg Depression Rating Scale (MADRS) Total Score [ Time Frame: Day 15 ]
   The MADRS is a 10-item diagnostic questionnaire used to measure the severity of depressive episodes in participants with mood disorders. Each item is rated on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score ranges from 0 to 60 with a higher score indicating more depression.
7. Hamilton Rating Scale for Anxiety (HAM-A) Total Score [ Time Frame: Day 15 ]
   The 14-item HAM-A is comprised of a series of symptoms, and measures both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints related to anxiety). The HAM-A total score will be calculated as the sum of the 14 individual item scores. The scoring for HAM-A is calculated by assigning scores of 0 (not present) to 4 (very severe), with a total score range of 0 to 56.
8. Time to First HAM-D Response [ Time Frame: Days 1, 3, 8, 12, 15, 21, 28, 35 and 42 ]
   The time to response is defined as time from first administration of study drug to the time when ≥50% reduction in HAM-D score from baseline is achieved.
9. Change From Baseline in PRO Measures of Health-Related Quality of Life, as Assessed by the 36-item Short Form version 2 (SF-36v2) Score [ Time Frame: Baseline and Days 1, 8, 15, 28 and 42 ]
   Participant's health will be assessed using Patient-reported outcome (PRO) health related quality of life (HRQOL) SF-36 V2. The SF-36v2 is a 36-item measure including eight health dimensions which are four physical health status domains and four mental health status domains. Scores on each item are summed and averaged (range = 0 "worst"-100 "best"). Higher SF-36v2 scores will indicate a better state of health.
10. Change From Baseline in PRO Measures of Depressive Symptoms, as Assessed by the 9-item Patient Health Questionnaire (PHQ-9) Score [ Time Frame: Baseline and Days 1, 8, 15, 28 and 42 ]
    The PHQ-9 is a participant-rated depressive symptom severity scale where scoring is based on responses to specific questions. The score will be calculated as the sum of the 9 individual item scores. The PHQ-9 total score ranges from 1 to 27 with a higher score indicating more depression.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 64 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Participant with diagnosis of MDD as diagnosed by Structured Clinical Interview for Diagnostic and Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) Clinical Trial Version [SCID-5-CT], with symptoms that have been present for at least a 4-week period.
2. Participant has a Hamilton Rating Scale for Depression (HAM-D) total score ≥24 at screening and Day 1 (prior to dosing).
3. Participants taking antidepressants must have been taking these medications at the same dose for at least 60 days prior to Day 1. Participants who have stopped taking antidepressants within 60 days must have stopped for longer than 5 half-lives of the antidepressant prior to Day 1. Participants receiving psychotherapy must have been receiving therapy on a regular schedule for at least 60 days prior to Day 1.
4. Participant is willing to delay start of other antidepressant or antianxiety medications and any new pharmacotherapy regimens, including as-needed benzodiazepine anxiolytics and sleep aids, until after completion of the Day 42 visit.

Exclusion Criteria:

1. Participant is currently at significant risk of suicide, as judged by the Investigator, or has attempted suicide associated with the current episode of MDD.
2. Participant has onset of the current depressive episode during pregnancy or 4 weeks postpartum, or the participant has presented for screening during the 6-month postpartum period.
3. Participant has a body mass index (BMI) ≤18 or ≥45 kg/m^2 at Screening, which is subject to a broader evaluation of medical comorbidities.
4. Participant has treatment-resistant depression, defined as persistent depressive symptoms despite treatment with adequate doses of antidepressants within the current major depressive episode (excluding antipsychotics) from two different classes for at least 4 weeks of treatment.
5. Participant has a medical history of seizures, bipolar disorder, schizophrenia, and/or schizoaffective disorder.
6. Participant has a history of mild, moderate, or severe substance use disorder (including benzodiazepines) diagnosed using DSM-5 criteria in the 12 months prior to screening.
7. Participant is taking psychostimulants (eg, methylphenidate, amphetamine) or opioids, regularly or as-needed, at Day -28.

Contacts and Locations

Locations

United States, Arkansas

Sage Investigational Site

Rogers, Arkansas, United States, 72758

United States, California

Sage Investigational Site

Bellflower, California, United States, 90706

Sage Investigational Site

Garden Grove, California, United States, 92845

Sage Investigational Site

Glendale, California, United States, 91206

Sage Investigational Site

Lemon Grove, California, United States, 91945

Sage Investigational Site

Orange, California, United States, 92868

Sage Investigational Site

Pico Rivera, California, United States, 90660

Sage Investigational Site

Redlands, California, United States, 92374

Sage Investigational Site

San Diego, California, United States, 92103

Sage Investigational Site

Sherman Oaks, California, United States, 91403

Sage Investigational Site

Temecula, California, United States, 92591

United States, Florida

Sage Investigational Site

Coral Springs, Florida, United States, 33067

Sage Investigational Site

Hollywood, Florida, United States, 33024

Sage Investigational Site

Jacksonville, Florida, United States, 32256

Sage Investigational Site

Lauderhill, Florida, United States, 33319

Sage Investigational Site

Orange City, Florida, United States, 32763

Sage Investigational Site

Orlando, Florida, United States, 32801

Sage Investigational Site

Orlando, Florida, United States, 32807

United States, Georgia

Sage Investigational Site

Alpharetta, Georgia, United States, 30022

Sage Investigational Site

Atlanta, Georgia, United States, 30328

Sage Investigational Site

Atlanta, Georgia, United States, 30331

Sage Investigational Site

Decatur, Georgia, United States, 30030

United States, Illinois

Sage Investigational Site

Skokie, Illinois, United States, 60076

United States, Mississippi

Sage Investigational Site

Flowood, Mississippi, United States, 39232

United States, Missouri

Sage Investigational Site

O'Fallon, Missouri, United States, 63368

United States, Nevada

Sage Investigational Site

Las Vegas, Nevada, United States, 89102

United States, New Jersey

Sage Investigational Site

Marlton, New Jersey, United States, 08053

United States, North Carolina

Sage Investigational Site

Charlotte, North Carolina, United States, 28211

United States, Ohio

Sage Investigational Site

Cincinnati, Ohio, United States, 45215

Sage Investigational Site

Dayton, Ohio, United States, 45417

Sage Investigational Site

North Canton, Ohio, United States, 44720

United States, Oklahoma

Sage Investigational Site

Oklahoma City, Oklahoma, United States, 73112

United States, Oregon

Sage Investigational Site

Portland, Oregon, United States, 97210

United States, Pennsylvania

Sage Investigational Site

Allentown, Pennsylvania, United States, 18104

United States, Tennessee

Sage Investigational Site

Memphis, Tennessee, United States, 38119

United States, Texas

Sage Investigational Site

DeSoto, Texas, United States, 75115

Sage Investigational Site

Wichita Falls, Texas, United States, 76309

United States, Virginia

Sage Investigational Site

Charlottesville, Virginia, United States, 22903

Sponsors and Collaborators

Sage Therapeutics

More Information

• Responsible Party: Sage Therapeutics
• ClinicalTrials.gov Identifier: NCT04442490
• Other Study ID Numbers: 217-MDD-301B
• First Posted: June 22, 2020
• Last Update Posted: March 29, 2022
• Last Verified: March 2022

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
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Sage Therapeutics:

Depression; Depressive disorder; SAGE-217

Additional relevant MeSH terms:

Disease; Depressive Disorder; Depression; Depressive Disorder, Major; Pathologic Processes; Mood Disorders; Mental Disorders; Behavioral Symptoms