A Study to Evaluate SAGE-217 in Adult Participants With Major Depressive Disorder (MDD)

Study Overview
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Brief Summary
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This is a Phase 3, open-label, 1-year study of the safety, tolerability, and need for re-treatment with SAGE-217 in adult participants with MDD.

Official Title
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A Phase 3, Open-Label, 1-Year Study of the Safety, Tolerability, and Need for Re-Treatment With SAGE-217 in Adult Subjects With Major Depressive Disorder

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: SAGE-217


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant has a diagnosis of MDD as diagnosed by the Structured Clinical Interview for 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. Participant is in good physical health and has no clinically significant findings, as determined by the Investigator, on physical examination, 12-lead electrocardiogram (ECG), or clinical laboratory tests. Participant has a Montgomery-Åsberg Depression Rating Scale (MADRS) total score of ≥28 and a HAM-D total score of ≥20 at Screening and Day 1 (prior to dosing). Exclusion Criteria: Participant has attempted suicide associated with the current episode of MDD. Participant has a medical history of bipolar disorder, schizophrenia, and/or schizoaffective disorder. Participant has had vagus nerve stimulation, electroconvulsive therapy, or has taken ketamine (including esketamine) within the current major depressive episode.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SAGE-217<br> | Drug: SAGE-217<br>* SAGE-217<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of the initial treatment with SAGE-217 and/or re-treatment with SAGE-217, as assessed by the incidence and severity of adverse events. |  | 52 Weeks | 
| Safety and tolerability of the initial treatment with SAGE-217 and/or re-treatment with SAGE-217, as assessed by the incidence of clinically significant changes from baseline in clinical laboratory measures. |  | 52 Weeks | 
| Safety and tolerability of the initial treatment with SAGE-217 and/or re-treatment with SAGE-217, as assessed by the incidence of clinically significant changes from baseline in vital signs. |  | 52 Weeks | 
| Safety and tolerability of the initial treatment with SAGE-217 and/or re-treatment with SAGE-217, as assessed by the incidence of clinically significant changes from baseline in electrocardiograms (ECGs). |  | 52 Weeks | 
| The safety and tolerability of the initial treatment with SAGE-217 and/or re-treatment with SAGE-217, as assessed by suicidal ideation and behavior using the Columbia Suicide Severity Rating Scale (C-SSRS). | The C-SSRS consists of a baseline evaluation that assesses the lifetime experience of the participants with suicidal ideation and behavior, and a post-baseline evaluation that focuses on suicidality since the last study visit. The C-SSRS includes 'yes' or 'no' responses for assessment of suicidal ideation and behavior as well as numeric ratings for severity of ideation, if present (from 1 to 5, with 5 being the most severe). | 52 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The need for re-treatment with SAGE-217 as assessed by the time to first re-treatment. |  | Up to 52 weeks | 
| The need for re-treatment with SAGE-217 as assessed by the number of participants achieving the requirements for re-treatment. |  | Up to 52 weeks | 
| The need for re-treatment with SAGE-217 as assessed by the number of re-treatment cycles for each participant. |  | Up to 52 weeks | 
| The response of initial treatment and/or re-treatment as assessed by change from baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D) score. | The 17-item HAM-D scale is used for measuring severity of depression. The HAM-D comprises individual ratings of the following symptoms scored in a range of 0 to 2: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. The following symptoms are scored in a range of 0 to 4: agitation, depressed mood, feelings of guilt, suicide, work and activities, retardation, anxiety (psychic and somatic), and hypochondriasis. The total score can range from 0 to 52, and higher scores indicate a greater degree of depression. | Up to 52 weeks | 
| The response of initial treatment and/or re-treatment as assessed by percent of participants achieving HAM-D response at the end of each 14-day treatment period, defined as a ≥50% reduction in HAM-D score from baseline. | The 17-item HAM-D scale is used for measuring severity of depression. The HAM-D comprises individual ratings of the following symptoms scored in a range of 0 to 2: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. The following symptoms are scored in a range of 0 to 4: agitation, depressed mood, feelings of guilt, suicide, work and activities, retardation, anxiety (psychic and somatic), and hypochondriasis. The total score can range from 0 to 52, and higher scores indicate a greater degree of depression. | Up to 52 weeks | 
| The response of initial treatment and/or re-treatment as assessed by percent of participants achieving HAM-D remission at the end of each 14-day treatment (initial and/or re-treatment) period, defined as HAM-D total score ≤7. | The 17-item HAM-D scale is used for measuring severity of depression. The HAM-D total score comprises a sum of the 17 individual item scores. Items scored in a range of 0 to 2 include: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. The following items are scored in a range of 0 to 4: agitation, depressed mood, feelings of guilt, suicide, work and activities, retardation, anxiety (psychic and somatic), and hypochondriasis. The total score can range from 0 to 52, and higher scores indicate a greater degree of depression. | Up to 52 weeks | 
| The response of initial treatment and/or re-treatment as assessed by percent of participants achieving Clinical Global Impression - Improvement (CGI-I) score. | The CGI-I employs a 7-point Likert scale to measure the overall improvement in the participant's condition posttreatment. The Investigator will rate the participant's total improvement compared to baseline, whether or not it is due entirely to drug treatment. Response choices include: 0=not assessed, 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, and 7=very much worse. | Up to 52 weeks | 
| The response of initial treatment and/or re-treatment as assessed by change from baseline in Clinical Global Impression - Severity (CGI-S) score. | The CGI-S uses a 7-point Likert scale to rate the severity of the participant's mental illness at the time of assessment, relative to the clinician's past experience with participants who have the same diagnosis. Considering total clinical experience, a participant is 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=extremely ill. | Up to 52 weeks |