A Study to Evaluate SAGE-217 for Prevention of Relapse in Adult Participants With Major Depressive Disorder

A Phase 3, Randomized, Double-Blind, Placebo-controlled Study of the Efficacy and Safety of SAGE-217 With a Fixed, Repeated Treatment Regimen on Relapse Prevention in Adults With Major Depressive Disorder

This is a study with an Open-Label (OL) phase followed by a randomized, Double-Blind (DB), placebo-controlled phase to assess efficacy and safety of SAGE-217 on relapse prevention in adults with major depressive disorder (MDD).

Study Overview

• Status: Terminated
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: SAGE-217; Drug: Placebo

Detailed Description

This study was previously posted by Sage Therapeutics. In November 2023, sponsorship of the trial was transferred to Biogen.

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Bentonville, Arkansas, United States, 72712
      • Sage Investigational Site
  • California
    • Bellflower, California, United States, 90706
      • Sage Investigational Site
    • Garden Grove, California, United States, 92845
      • Sage Investigational Site
    • Lemon Grove, California, United States, 91945
      • Sage Investigational Site
    • Oceanside, California, United States, 92056
      • Sage Investigational Site
    • Orange, California, United States, 92868
      • Sage Investigational Site
    • Riverside, California, United States, 92503
      • Sage Investigational Site
    • San Diego, California, United States, 92103
      • Sage Investigational Site
    • San Marcos, California, United States, 92078
      • Sage Investigational Site
    • Sherman Oaks, California, United States, 91403
      • Sage Investigational Site
  • Florida
    • Coral Springs, Florida, United States, 33067
      • Sage Investigational Site
    • Jacksonville, Florida, United States, 32256
      • Sage Investigational Site
    • Lauderhill, Florida, United States, 33319
      • Sage Investigational Site
    • Orlando, Florida, United States, 32801
      • Sage Investigational Site
  • Georgia
    • Alpharetta, Georgia, United States, 30022
      • Sage Investigational Site
    • Atlanta, Georgia, United States, 30331
      • Sage Investigational Site
    • Atlanta, Georgia, United States, 30328
      • Sage Investigational Site
    • Atlanta, Georgia, United States, 30329
      • Sage Investigational Site
    • Decatur, Georgia, United States, 30030
      • Sage Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60634
      • Sage Investigational Site
    • Lincolnwood, Illinois, United States, 60712
      • Sage Investigational Site
  • Louisiana
    • Lake Charles, Louisiana, United States, 70629
      • Sage Investigational Site
  • Maryland
    • Gaithersburg, Maryland, United States, 20877
      • Sage Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02131
      • Sage Investigational Site
    • Methuen, Massachusetts, United States, 01844
      • Sage Investigational Site
    • Watertown, Massachusetts, United States, 02472
      • Sage Investigational Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Sage Investigational Site
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • Sage Investigational Site
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Sage Investigational Site
    • Cherry Hill, New Jersey, United States, 08002
      • Sage Investigational Site
    • Marlton, New Jersey, United States, 08053
      • Sage Investigational Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Sage Investigational Site
  • New York
    • Jamaica, New York, United States, 11432
      • Sage Investigational Site
    • New York, New York, United States, 10017
      • Sage Investigational Site
    • New York, New York, United States, 10128
      • Sage Investigational Site
    • Rochester, New York, United States, 14618
      • Sage Investigational Site
  • Ohio
    • Dayton, Ohio, United States, 454117
      • Sage Investigational Site
    • North Canton, Ohio, United States, 44720
      • Sage Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73106
      • Sage Investigational Site
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18104
      • Sage Investigational Site
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Sage Investigational Site
  • Texas
    • Austin, Texas, United States, 78737
      • Sage Investigational Site
    • Dallas, Texas, United States, 75231
      • Sage Investigational Site
    • Richardson, Texas, United States, 75080
      • Sage Investigational Site
    • Wichita Falls, Texas, United States, 76309
      • Sage Investigational Site
  • Washington
    • Everett, Washington, United States, 98201
      • Sage Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participant had a diagnosis of MDD as diagnosed by Structured Clinical Interview for Diagnostic and DSM-5 Clinical Trial Version (SCID-5-CT), with symptoms that had been present for at least a 4-week period.
2. Participant had at least 1 prior major depressive episode (MDE) in the 5 years prior to Screening (not including the current episode).
3. Participant was willing to delay the start of any antidepressant, anxiolytic, insomnia, psychostimulant, prescription opioid regimens, and new psychotherapy (including Cognitive Behavioral Therapy for Insomnia [CBT-I]) until after study completion.

Exclusion Criteria:

1. Participant had attempted suicide associated with the current episode of MDD.
2. Participant had 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. Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (MGH ATRQ) was used for this purpose.
3. Participant had a positive pregnancy test at screening or on Day 1 prior to dosing.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Open-Label Phase: SAGE-217; Participants self-administered SAGE-217, 30 milligrams (mg), oral capsule, once daily (QD) in the evening from Day 1 to Day 14.	Drug: SAGE-217; SAGE-217 capsule
Placebo Comparator: Double-Blind Phase: Placebo; Following the OL Phase, participants who exhibited a Hamilton Rating Scale for Depression (HAM-D) response, defined as a greater than or equal to (≥) 50% reduction from baseline in HAM-D total score were to be randomized to receive SAGE-217 matching placebo capsule, orally, QD, in the evening, in a total of five, 14-day treatment periods, each separated by a 6-week follow-up period during the 40-week DB Phase of the study. However, no participants were randomized to receive SAGE-217 matching placebo due to early study termination.	Drug: Placebo; SAGE-217 matching placebo capsule
Experimental: Double-Blind Phase: SAGE-217; Following the OL Phase, participants who exhibited a HAM-D response defined as a ≥ 50% reduction from baseline in HAM-D total score to SAGE-217 were randomized to receive SAGE-217, 30 mg, oral capsule, QD, in the evening, up to study termination date (i.e., up to approximately 22 weeks) during the DB Phase of the study.	Drug: SAGE-217; SAGE-217 capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Relapse During the DB Phase	Time to relapse was defined as days from the first dose of the study drug in the DB Phase to the day of relapse during the DB Phase. Participant was considered to have relapsed if: 2 consecutive HAM-D scores were ≥ 18 assessed 7 to 14 days apart, any worsening of depression requiring hospitalization, Investigator-determined risk of suicide, or any other clinically relevant event whether or not hospitalization was required. HAM-D is a scale used to rate depression in participants who were already diagnosed as depressed. The HAM-D total score comprised a sum of 17 individual item scores. Items scored in a range of 0 to 2 included: insomnia, somatic symptoms, genital symptoms, loss of weight, and insight. Items scored in a range of 0 to 4 included: agitation, depressed mood, feelings of guilt, suicide, work and activities, retardation, anxiety, hypochondriasis. The HAM-D total score could range from 0 (not depressed) to 52 (severely depressed). Higher scores indicated more depression.	Day 56 (Day 1 of DB Phase) up to Day 153 (i.e., up to 22 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Relapsed During the DB Phase	Participant was considered to have relapsed if: 2 consecutive HAM-D scores were ≥ 18 assessed 7 to 14 days apart, worsening of depression requiring hospitalization, Investigator-determined risk of suicide, or other clinically relevant events whether hospitalization was required. HAM-D scale was used to rate depression in participants who were diagnosed as depressed. Total score is a sum of 17 individual item scores. Items in a range of 0-2 included: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. Items in a range of 0-4 included: agitation, depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, work and activities, retardation (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), anxiety (psychic and somatic), hypochondriasis. Total score could range from 0 (not depressed)- 52 (severely depressed). Higher scores indicated more depression.	Day 56 (Day 1 of DB Phase) up to Day 153 (i.e., up to 22 weeks)
Change From Baseline in the 17-Item HAM-D Total Score at the End of Each 14-Day Treatment Period in the DB Phase	The 17-item HAM-D scale was used to rate the severity of depression in participants who were already diagnosed as depressed. The HAM-D total score comprised a sum of 17 individual item scores. Items scored in a range of 0 to 2 included: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. Items scored in a range of 0 to 4 included: agitation, depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, work and activities, retardation (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), anxiety (psychic and somatic), hypochondriasis. The HAM-D total score could range from 0 (not depressed) to 52 (severely depressed). Higher scores indicated more depression. A negative change from baseline indicated improvement.	Day 56 (Baseline [Day 1] of DB Phase) up to Day 153 (i.e., up to 22 weeks)
Percentage of Participants With HAM-D Response at the End of Each 14-Day Treatment Period in the DB Phase	HAM-D response was defined as having a 50% or greater reduction from baseline in HAM-D total score. The HAM-D total score comprised a sum of 17 individual item scores. Items scored in a range of 0 to 2 included: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. Items scored in a range of 0 to 4 included: agitation, depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, work and activities, retardation (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), anxiety (psychic and somatic), hypochondriasis. The HAM-D total score could range from 0 (not depressed) to 52 (severely depressed). Higher scores indicated more depression.	Day 56 (Day 1 of DB Phase) up to Day 153 (i.e., up to 22 weeks)
Percentage of Participants With HAM-D Remission at the End of Each 14-Day Treatment Period in the DB Phase	HAM-D remission was defined as having a HAM-D total score of ≤ 7. The HAM-D total score comprised a sum of 17 individual item scores. Items scored in a range of 0 to 2 included: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. Items scored in a range of 0 to 4 included: agitation, depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, work and activities, retardation (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), anxiety (psychic and somatic), hypochondriasis. The HAM-D total score could range from 0 (not depressed) to 52 (severely depressed). Higher scores indicated more depression.	Day 56 (Day 1 of DB Phase) up to Day 153 (i.e., up to 22 weeks)
Percentage of Participants With Clinical Global Impression - Improvement (CGI-I) Response at the End of Each 14-Day Treatment Period in the DB Phase	The CGI-I employs a 7-point Likert scale to measure the overall improvement in the participant's condition posttreatment. The Investigator rated the participant's total improvement whether or not it was due entirely to drug treatment. Response choices included: 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, and 7=very much worse. The CGI-I is only rated at posttreatment assessments. By definition, all CGI-I assessments are evaluated against baseline conditions. Higher score indicated worse condition. CGI-I response was defined as having a CGI-I score of "very much improved" or "much improved."	Day 56 (Day 1 of DB Phase) up to Day 153 (i.e., up to 22 weeks)
Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at the End of Each 14-Day Treatment Period in the DB Phase	The CGI-S uses 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 had the same diagnosis. Considering total clinical experience, a participant was assessed on severity of mental illness at the time of rating as 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; and 7= among the most extremely ill participant. A higher score indicated extreme illness. A negative change from baseline indicated improvement (a higher absolute number indicating more illness).	Day 56 (Baseline [Day 1] of DB Phase) up to Day 153 (i.e., up to 22 weeks)
Change From Baseline in 9-Item Patient Health Questionnaire (PHQ-9) Score at the End of Each 14-Day Treatment Period in the DB Phase	The PHQ-9 is a participant-rated depressive symptom severity scale. To monitor severity over time participants in current treatment for depression, participants completed the questionnaires at baseline and at regular intervals thereafter. Scoring was based on responses to specific questions, as follows: 0=not at all; 1=several days; 2=more than half the days; and 3=nearly every day. The PHQ-9 total score was calculated as the sum of the 9 individual item scores and ranged from 0 to 27. The PHQ-9 total score was categorized as follows: 1 to 4=minimal depression, 5 to 9=mild depression, 10 to 14=moderate depression, 15 to 19=moderately severe depression; and 20 to 27=severe depression. Higher score indicated severe depression. A negative change from baseline indicated improvement.	Day 56 (Baseline [Day 1] of DB Phase) up to Day 153 (i.e, up to 22 weeks)
Time to Relapse During The DB Phase for Participants Who Achieved HAM-D Remission in the OL Phase	Time to relapse was defined as days from the first dose of the study drug in the DB Phase to the day of relapse during the DB Phase. Participant was considered to have relapsed if: 2 consecutive HAM-D scores were ≥18 assessed 7 to 14 days apart, any worsening of depression requiring hospitalization, Investigator-determined risk of suicide, or any other clinically relevant event whether or not hospitalization was required. HAM-D is a scale used to rate depression in participants who were already diagnosed as depressed. The HAM-D total score comprised a sum of 17 individual item scores. Items scored in a range of 0 to 2 included: insomnia, somatic symptoms, genital symptoms, loss of weight, and insight. Items scored in a range of 0 to 4 included: agitation, depressed mood, feelings of guilt, suicide, work and activities, retardation, anxiety, hypochondriasis. The HAM-D total score could range from 0 (not depressed) to 52 (severely depressed). Higher scores indicated more depression.	Day 56 (Day 1 of DB Phase) up to Day 153 (i.e., up to 22 weeks)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	An adverse event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. A TEAE was defined as an AE with onset after the start of study drug, or any worsening of a pre-existing medical condition/AE with onset after the start of study drug and throughout the study.	From the first dose of study drug up to the end of the study (i.e., up to approximately 22 weeks)

Collaborators and Investigators

• Sponsor: Biogen

Study record dates

Study Major Dates

• Study Start (Actual): August 6, 2019
• Primary Completion (Actual): January 6, 2020
• Study Completion (Actual): January 6, 2020

Study Registration Dates

• First Submitted: July 2, 2019
• First Submitted That Met QC Criteria: July 2, 2019
• First Posted (Actual): July 5, 2019

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 27, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: MDD; SAGE-217
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: 217-MDD-302; 2019-002640-25 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No