A Study to Evaluate the Efficacy and Safety of SAGE-217 in Participants With Severe Postpartum Depression (PPD)

Study Overview
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Brief Summary
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The purpose of this study is to determine if treatment with SAGE-217 reduces depressive symptoms in females with severe postpartum depression (PPD) as compared to placebo.

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 Randomized, Double-Blind, Placebo-controlled Study Evaluating the Efficacy and Safety of SAGE-217 in the Treatment of Adults With Severe Postpartum Depression

Conditions
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Depression, Postpartum

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 has ceased lactating or agrees not to provide breastmilk to her infant(s) from just prior to receiving the investigational product (IP) on Day 1 until 7 days after the last dose of IP. 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 Structured Clinical Interview for Diagnostic and DSM-5 Clinical Trial Version (SCID-5-CT). Participant is ≤12 months postpartum at screening and Day 1. Exclusion Criteria: Participant is at significant risk of suicide or has attempted suicide associated with the current episode of PPD. Participant has active psychosis per investigator assessment. Participant has a medical history of nonfebrile seizures. Participant has a medical history of bipolar disorder, schizophrenia, and/or schizoaffective disorder. Participant has a history of sleep apnea. Note: Other protocol-defined inclusion/exclusion criteria applied.

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 |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants received SAGE-217 matched-placebo capsules, orally, once daily for 14 days. | Drug: Placebo<br>* SAGE-217 matched-placebo oral capsules.<br>|
| Experimental: SAGE-217 50 mg<br>Participants received SAGE-217, 50 mg, capsules, orally, once daily for 14 days. | Drug: SAGE-217<br>* SAGE-217 oral capsules.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline (CFB) in the 17-item Hamilton Rating Scale for Depression (HAM-D) Total Score at Day 15 | The 17-item HAM-D scale is used to assess the severity of depression. It is comprised of 17 individual items related to the following symptoms: depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, insomnia (early, middle, late), work and activities (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), retardation, agitation, anxiety (psychic and somatic), somatic symptoms (gastrointestinal and general), 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 the 17 individual items, ranges from 0 to 52; where a higher score indicates more depression. Negative change from baseline indicates improvement. Mixed Model for Repeated Measures (MMRM) was used for the analysis. | Baseline and Day 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the 17-item HAM-D Total Score | The 17-item HAM-D scale is used to assess the severity of depression. It is comprised of 17 individual items related to the following symptoms: depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, insomnia (early, middle, late), work and activities (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), retardation, agitation, anxiety (psychic and somatic), somatic symptoms (gastrointestinal and general), 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 the 17 individual items, ranges from 0 to 52; where a higher score indicates more depression. Negative change from baseline indicates improvement. MMRM was used for the analysis. | Baseline, Days 3, 28 and 45 | 
| Change From Baseline in Clinical Global Impressions - Severity Scale (CGI-S) Score | 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 had the same diagnosis. 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= extremely ill participants. A lower score indicates a better outcome. A negative change from baseline indicates improvement. MMRM was used for the analysis. | Baseline and Day 15 | 
| Percentage of Participants With HAM-D Response | The 17-item HAM-D scale is used to assess the severity of depression. It is comprised of 17 individual items related to the following symptoms: depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, insomnia (early, middle, late), work and activities (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), retardation, agitation, anxiety (psychic and somatic), somatic symptoms (gastrointestinal and general), 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 the 17 individual items, ranges from 0 to 52; where a higher score indicates more depression. Negative change from baseline indicates improvement. HAM-D response was defined as a ≥50% reduction in HAM-D total score from baseline. | Days 15 and 45 | 
| Percentage of Participants With HAM-D Remission | The 17-item HAM-D scale is used to assess the severity of depression. It is comprised of 17 individual items related to the following symptoms: depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, insomnia (early, middle, late), work and activities (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), retardation, agitation, anxiety (psychic and somatic), somatic symptoms (gastrointestinal and general), 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 the 17 individual items, ranges from 0 to 52; where a higher score indicates more depression. Negative change from baseline indicates improvement. HAM-D remission was defined as having a HAM-D total score of ≤7. | Days 15 and 45 | 
| Percentage of Participants With Clinical Global Impression - Improvement (CGI-I) Response | 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 is due entirely to drug treatment. 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. The CGI-I was only rated at posttreatment assessments. By definition, all CGI-I assessments are evaluated against baseline conditions. CGI-I response was defined as having a CGI-I score of very much improved or much improved. | Day 15 | 
| Change From Baseline in Hamilton Rating Scale for Anxiety (HAM-A) Total Score | The 14-item HAM-A was used to rate the severity of symptoms of anxiety. Each 14-items were 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 HAM-A total score was 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 where <17 indicated mild severity, 18 to 24, mild to moderate severity, and 25 to 30, moderate to severe severity. A negative change from baseline in HAM-A total score indicated improvement. | Baseline and Day 15 | 
| Change From Baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) Total Score | The MADRS is a 10-item diagnostic 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 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. A negative change from baseline in MADRS total score indicated improvement. | Baseline and Day 15 | 
| Change From Baseline in HAM-D Subscale | 17-item HAM-D scale is used for severity of depression. HAM-D subscales: Core subscale(depressed mood, feelings of guilt, suicide, work and activities, and retardation/20x100; Anxiety subscale[anxiety(psychic and somatic), somatic symptoms (gastrointestinal and general), hypochondriasis, and insight loss of weight]/18x100; Bech-6 subscale(depressed mood, feelings of guilt, work and activities, retardation, anxiety psychic, and somatic symptoms general)/22x100; Maier score(depressed mood, feelings of guilt, work and activities, retardation, agitation, and anxiety psychic)/24x100. Each item was scored in range of 0 to 2 or 0 to 4 (0=none to 2 or 4=severe), higher score=more depression. 4 Subscale scores were calculated as sum of individual rating scores related to each subscale, divided by total possible score within subscale, multiplied by 100. Scores were transformed to scale of 0 to 100, with higher scores=more severe depression. Negative CFB=improvement. MMRM was used for analysis. | Baseline and Day 15 | 
| Change From Baseline in Self-Reported Measures of Depressive Symptoms, as Assessed by the Edinburgh Postnatal Depression Scale (EPDS) Total Score | The EPDS is a self-rated depressive symptom severity scale specific to the perinatal period which consists of 10 individual items. Each item is rated on a 4-point scale ranging from 0 to 3 points. The EPDS total score is calculated as the sum of the 10 individual item scores, ranging from 0 points to 30 points with a higher score indicating more depression. A negative change indicates improvement. | Baseline, Days 3, 8,15, 21, 28 and 45 | 
| Change From Baseline in Self-Reported Measures of Depressive Symptoms, as Assessed by the 9-item Patient Health Questionnaire (PHQ-9) Score | The PHQ-9 is a self-rated depressive symptom severity scale to monitor severity over time for newly diagnosed participants or participants in current treatment for depression. Scoring was based on participants responses to 9 specific questions as follows: 0 = not at all; 1 = several days; 2 = more than half the days; and 3 = nearly every day. The score were calculated as the sum of the 9 individual item scores. 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. The PHQ-9 total score ranges from 1 to 27 with a higher score indicating more depression. A negative change from baseline indicates reduced depression. MMRM was used for the analysis. | Baseline, Days 3, 8,15, 21, 28 and 45 | 
| Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) | An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a medicinal (investigational) product whether or not related to the medicinal (investigational) product. A TEAE is defined as an AE with onset after the start of IP, or any worsening of a pre-existing medical condition/AE with onset after the start of IP and throughout the study. | Up to Day 45 | 

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