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

Study Overview
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Brief Summary
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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).

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

Official Title
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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

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: SAGE-217
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Participant had at least 1 prior major depressive episode (MDE) in the 5 years prior to Screening (not including the current episode). 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: Participant had attempted suicide associated with the current episode of MDD. 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. Participant had a positive pregnancy test at screening or on Day 1 prior to dosing.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open-Label Phase: SAGE-217<br>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<br>* SAGE-217 capsule<br>|
| Placebo Comparator: Double-Blind Phase: Placebo<br>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<br>* SAGE-217 matching placebo capsule<br>|
| Experimental: Double-Blind Phase: SAGE-217<br>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<br>* SAGE-217 capsule<br>|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MDD, SAGE-217