A Study to Evaluate SAGE-217 in Participants With Severe Postpartum Depression

Study Overview
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Brief Summary
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The primary purpose of this study was to determine if treatment with SAGE-217 reduces depressive symptoms in participants with severe postpartum depression (PPD) compared to placebo as assessed by the change from baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D) total score at Day 15 and to evaluate the safety and tolerability of SAGE-217 compared to placebo as assessed by the incidence of adverse events, vital sign measurements, clinical laboratory evaluations, electrocardiogram (ECG) parameters, and the Columbia Suicide Severity Rating Scale (C-SSRS).

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 Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study Evaluating the Efficacy, Safety, and Pharmacokinetics of SAGE-217 in the Treatment of Adult Female Subjects With Severe Postpartum Depression

Conditions
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Postpartum Depression

Intervention / Treatment
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* Drug: SAGE-217 15/20 mg Oral Solution
* Drug: Placebo
* Drug: SAGE 217 30 mg Capsules


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Participant either must have ceased lactating at screening or, if still lactating or actively breastfeeding at screening, must agree to temporarily cease giving breast milk to her infant(s) Participant has had a Major Depressive Episode that began no earlier than the third trimester and no later than the first 4 weeks following delivery, as diagnosed by the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 Axis I Disorders (SCID-I) Participant was <=six months postpartum. Key Exclusion Criteria: Active psychosis Attempted suicide associated with current episode of postpartum depression Medical history of seizures Medical history of bipolar disorder, schizophrenia, and/or schizoaffective disorder. Note: suicidal ideation was not an exclusion. Other protocol-defined inclusion/exclusion criteria might apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: SAGE-217 15/20 mg Oral Solution<br>Participants received SAGE-217, 15 milligrams (mg), oral solution, twice daily (BID) for first 2 days followed by SAGE-217, 15 or 20 mg, oral solution, BID, starting on Day 3 for up to 14 days as tolerated. | Drug: SAGE-217 15/20 mg Oral Solution<br>* SAGE-217, 15 mg oral solution, BID for Days 1 to 2 followed by 20 mg oral solution BID for Days 3 to 14. If not tolerated, 15 mg for the rest of study (Days 3 to 14).<br>|
| Placebo Comparator: Part B: Placebo<br>Participants received SAGE-217 matching placebo, capsules, orally, once daily, for up to 14 days. | Drug: Placebo<br>* SAGE-217 matching placebo, capsules, orally, once daily, for up to 14 days.<br>|
| Experimental: Part B: SAGE 217 30 mg Capsules<br>Participants received SAGE-217, 30 mg, capsules, orally, once daily, for up to 14 days. | Drug: SAGE 217 30 mg Capsules<br>* SAGE-217, 30 mg, capsules, orally, once daily, for up to 14 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Parts A and B: Change From Baseline in the 17-Item Hamilton Rating Scale for Depression (HAM-D) Total Score at Day 15 | The 17-item HAM-D is used to rate the severity of depression in participants who are already diagnosed as depressed. 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 HAM-D total score was calculated as the sum of the 17 individual item scores and could range from 0 to 52. Higher scores indicated more severe depression. A negative change from Baseline indicates less depression. | Parts A and B: Baseline, Day 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Parts A and B: Change From Baseline in the HAM-D Total Score at Days 3, 8, 21 and 45 | The 17-item HAM-D is used to rate the severity of depression in participants who are already diagnosed as depressed. 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 HAM-D total score was calculated as the sum of the 17 individual item scores and could range from 0 to 52. Higher scores indicated more severe depression. A negative change from Baseline indicates less depression. | Part B: Baseline, Days 3, 8, 21 and 45 | 
| Parts A and B: Percentage of Participants With HAM-D Response | HAM-D Response was defined as having a 50 percent (%) or greater reduction from Baseline in HAM-D total score. The HAM-D total score was calculated as the sum of the 17 individual item scores and could range from 0 to 52. The items on HAM-D included: depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, insomnia (early night, middle night, early hours [morning]), work and activities, retardation (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), agitation, anxiety (psychic and somatic), somatic symptoms (gastrointestinal and general), genital symptoms, hypochondriasis, loss of weight, and insight. Higher scores indicated more depression. | Part B: Days 3, 8, 15, 21 and 45 | 
| Parts A and B: Percentage of Participants With HAM-D Remission | HAM-D Remission was defined as a HAM-D total score of less than or equal to (<=)7. The HAM-D total score was calculated as the sum of the 17 individual item scores and could range from 0 to 52. The items on HAM-D included: depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, insomnia (early night, middle night, early hours [morning]), work and activities, retardation (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), agitation, anxiety (psychic and somatic), somatic symptoms (gastrointestinal and general), genital symptoms, hypochondriasis, loss of weight, and insight. Higher scores indicated more depression. | Part B: Days 3, 8, 15, 21 and 45 | 
| Parts A and B: Change From Baseline in HAM-D Subscales Scores | HAM-D is used to rate the severity of depression in participants who are already diagnosed as depressed. HAM-D subscales: Core subscale (symptoms-depressed mood, feelings of guilt, suicide, work and activities, and retardation ); Anxiety subscale (symptoms-anxiety [psychic and somatic], somatic symptoms [gastrointestinal and general], hypochondriasis, loss of weight); Bech-6 subscale (symptoms-depressed mood, feelings of guilt, work and activities, retardation, anxiety psychic, and somatic symptoms general); Meier subscale (symptoms-depressed mood, feelings of guilt, work and activities, retardation, agitation, and anxiety psychic). Each item was scored in a range of 0 to 2 or 0 to 4, higher scores=greater degree of depression. Subscale scores were calculated as the sum of the individual item scores comprising each subscale. Scores were transformed to a scale of 0 to 100, with higher scores indicated more severe depression. A negative change from Baseline indicates less depression. | Part B: Baseline, Days 3, 8, 15, 21 and 45 | 
| Parts A and B: Change From Baseline in HAM-D Individual Item Scores | The 17-item HAM-D is used to rate the severity of depression in participants who are already diagnosed as depressed. Individual items on the scale were scored in a range of 0 to 2 or 0 to 4. 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 were 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. Higher scores indicated a greater degree of depression. A negative change from Baseline indicates less depression. | Part B: Baseline, Days 3, 8, 15, 21 and 45 | 
| Parts A and B: Change From Baseline in Montgomery and Åsberg Depression Rating Scale (MADRS) Total Score | The MADRS is a 10-item questionnaire used to measure the severity of depressive episodes in participants with mood disorders. It includes questions on the following symptoms: apparent sadness; reported sadness; inner tension; reduced sleep; reduced appetite; concentration difficulties; lassitude; inability to feel; pessimistic thoughts; and suicidal thoughts. Each item was scored in a range of 0 (no symptoms) to 6 (symptoms of maximum severity). The MADRS total score was calculated as the sum of the 10 individual item scores and could range from 0 to 60. Higher scores indicated more severe depression. A negative change from Baseline indicates less depression. | Part B: Baseline, Days 3, 8, 15, 21 and 45 | 
| Parts A and B: Percentage of Participants With Clinical Global Impression - Improvement (CGI-I) Response | The Clinical Global Impression - Improvement (CGI-I) item of the CGI scale uses 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: 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. CGI response was defined as a CGI-I score of 1 (very much improved) or 2 (much improved). The percentage of participants with overall improvement in post-treatment condition, rated by investigator as very much improved (CGI-I score of 1) or much improved (CGI-I score of 2) is reported. | Part B: Days 3, 8, 15, 21 and 45 | 
| Parts A and B: Change From Baseline in Hamilton Anxiety Rating Scale (HAM-A) Total Score | The 14-item HAM-A was used to rate the severity of symptoms of anxiety. Each of the 14 items was defined by a series of symptoms and measured both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints related to anxiety). The individual items were scored in a range of 0 (not present) to 4 (very severe). The HAM-A total score was calculated as the sum of the 14 individual item scores and could range from 0 to 56 where a score of <17=mild severity; 18-24= mild to moderate severity and 25-30=moderate to severe severity. A negative change from Baseline indicates less anxiety. | Part B: Baseline, Days 3, 8, 15, 21 and 45 | 
| Parts A and B: Percentage of Participants With MADRS Response | MADRS response was defined as having a 50% or greater reduction from Baseline in MADRS total score. The MADRS is a 10-item questionnaire used to measure the severity of depressive episodes in participants with mood disorders. It includes questions on the following symptoms: apparent sadness; reported sadness; inner tension; reduced sleep; reduced appetite; concentration difficulties; lassitude; inability to feel; pessimistic thoughts; and suicidal thoughts. Each item was scored in a range of 0 (no symptoms) to 6 (symptoms of maximum severity). The MADRS total score was calculated as the sum of the 10 individual item scores and could range from 0 to 60. Higher scores indicated more depression. | Part B: Days 3, 8, 15, 21 and 45 | 
| Parts A and B: Percentage of Participants With MADRS Remission | MADRS Remission was defined as a MADRS total score of <=10. The MADRS is a 10-item questionnaire used to measure the severity of depressive episodes in participants with mood disorders. It includes questions on the following symptoms: apparent sadness; reported sadness; inner tension; reduced sleep; reduced appetite; concentration difficulties; lassitude; inability to feel; pessimistic thoughts; and suicidal thoughts. Each item was scored in a range of 0 (no symptoms) to 6 (symptoms of maximum severity). The MADRS total score was calculated as the sum of the 10 individual item scores and could range from 0 to 60. Higher scores indicated more depression. | Part B: Days 3, 8, 15, 21 and 45 | 
| Parts A and B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | An Adverse Event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE was defined as an AE with an onset that occurs after receiving study drug. | Part A: Up to Day 75; Part B: Up to Day 45 | 
| Part B: Number of Participants With Potentially Clinically Significant Vital Sign Measurements | Vital signs included assessments of supine and standing systolic blood pressure (SBP), supine and standing diastolic blood pressure (DBP), and heart rate. | Part B: From first dose of study drug up to 45 days | 
| Part B: Number of Participants With Potentially Clinically Significant Laboratory Evaluations | Laboratory tests included tests of Hematology, Chemistry, and Urinalysis. | Part B: From first dose of study drug up to 45 days | 
| Part B: Change From Baseline in Electrocardiogram (ECG) Parameter Heart Rate | ECG parameters included assessment of the standard 12-lead ECG intervals: QT, QTcF, PR, RR, QRS, and heart rate. Heart rate was measured in terms of beats per minute. Change from Baseline in heart rate at specified time points were reported. | Part B: Baseline, Days 8, 15, and 21 | 
| Part B: Change From Baseline in ECG Parameters-PR Interval, RR Interval, QRS Duration, QT Interval, QTcF Interval | ECG parameters included assessment of the standard 12-lead ECG intervals: QT, QTcF, PR, RR, QRS, and heart rate. Change from Baseline in PR Interval, RR Interval, QRS Duration, QT Interval, QTcF Interval is reported. | Part B: Baseline, Days 8, 15, and 21 | 
| Part B: Number of Participants With a Response of Yes to Any Suicidal Ideation or Suicidal Behaviors Item Using the Columbia Suicide Severity Rating Scale (C-SSRS) | C-SSRS was used to assess the suicidality of participants during the study. The assessment included yes or no responses for 5 questions, each related to suicidal ideation (wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods, active suicidal ideation with some intent, active suicidal ideation with specific plan) and suicidal behavior (preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, suicide). Numeric ratings were provided for severity of ideation (if present), from 1 to 5, with 5 being the most severe. Number of participants with a response of 'yes' to any suicidal ideation or suicidal behavior item as measured by C-SSRS is reported. | Part B: Up to Day 45 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Postpartum Care