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

• ClinicalTrials.gov Identifier: NCT04442503
• Recruitment Status: Completed
• First Posted: June 22, 2020
• Results First Posted: June 22, 2023
• Last Update Posted: November 30, 2023
• Sponsor: Biogen
• Information provided by (Responsible Party): Biogen

Tracking Information

• First Submitted Date: June 18, 2020
• First Posted Date: June 22, 2020
• Results First Submitted Date: April 11, 2023
• Results First Posted Date: June 22, 2023
• Last Update Posted Date: November 30, 2023
• Actual Study Start Date: June 8, 2020
• Actual Primary Completion Date: March 15, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 21, 2023)

Change From Baseline (CFB) in the 17-item Hamilton Rating Scale for Depression (HAM-D) Total Score at Day 15 [ Time Frame: Baseline and 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.

Original Primary Outcome Measures (submitted: June 18, 2020)

Change From Baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D) Total Score at Day 15 [ Time Frame: Baseline and Day 15 ]

The 17-item HAM-D scale is used to assess the severity of depression. It is comprised of individual ratings related to the following symptoms: depressed mood, feelings of guilt, suicide, insomnia, work and activities, retardation, agitation, anxiety, somatic symptoms, 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 individual items, ranging from 0 to 52; where a higher score indicates more depression.

Current Secondary Outcome Measures (submitted: June 21, 2023)

• Change From Baseline in the 17-item HAM-D Total Score [ Time Frame: Baseline, Days 3, 28 and 45 ]
  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.
• Change From Baseline in Clinical Global Impressions - Severity Scale (CGI-S) Score [ Time Frame: Baseline and Day 15 ]
  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.
• Percentage of Participants With HAM-D Response [ Time Frame: Days 15 and 45 ]
  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.
• Percentage of Participants With HAM-D Remission [ Time Frame: Days 15 and 45 ]
  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.
• Percentage of Participants With Clinical Global Impression - Improvement (CGI-I) Response [ Time Frame: Day 15 ]
  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."
• Change From Baseline in Hamilton Rating Scale for Anxiety (HAM-A) Total Score [ Time Frame: Baseline and Day 15 ]
  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.
• Change From Baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) Total Score [ Time Frame: Baseline and Day 15 ]
  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.
• Change From Baseline in HAM-D Subscale [ Time Frame: Baseline and Day 15 ]
  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.
• Change From Baseline in Self-Reported Measures of Depressive Symptoms, as Assessed by the Edinburgh Postnatal Depression Scale (EPDS) Total Score [ Time Frame: Baseline, Days 3, 8,15, 21, 28 and 45 ]
  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.
• Change From Baseline in Self-Reported Measures of Depressive Symptoms, as Assessed by the 9-item Patient Health Questionnaire (PHQ-9) Score [ Time Frame: Baseline, Days 3, 8,15, 21, 28 and 45 ]
  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.
• Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) [ Time Frame: Up to Day 45 ]
  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.

Original Secondary Outcome Measures (submitted: June 18, 2020)

• Change From Baseline in the 17-item HAM-D Total Score [ Time Frame: Baseline and Days 3, 28 and 45 ]
  The 17-item HAM-D scale is used to assess the severity of depression. It is comprised of individual ratings related to the following symptoms: depressed mood, feelings of guilt, suicide, insomnia, work and activities, retardation, agitation, anxiety, somatic symptoms, 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 individual items, ranging from 0 to 52; where a higher score indicates more depression.
• Change From Baseline in Clinical Global Impressions - Severity (CGI-S) Score [ Time Frame: Baseline and Day 15 ]
  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 have the same diagnosis. A participant is assessed on severity of mental illness at the time of rating as 1=normal, not at all ill; 2=borderline ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; and 7=among the most extremely ill participants.
• Percentage of Participants With HAM-D Response [ Time Frame: Baseline and Days 15 and 45 ]
  HAM-D response is defined as a ≥50% reduction in HAM-D score from baseline.
• Percentage of Participants With HAM-D Remission [ Time Frame: Days 15 and 45 ]
  HAM-D remission is defined as HAM-D total score ≤7.
• Percentage of Participants With Clinical Global Impression - Improvement (CGI-I) Response [ Time Frame: Day 15 ]
  CGI-I response is defined as having a CGI-I score of "very much improved" or "much improved." The CGI-I employs a 7-point Likert scale to measure the overall improvement in the participant's condition posttreatment. 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.
• Change From Baseline in Hamilton Rating Scale for Anxiety (HAM-A) Total Score [ Time Frame: Baseline and Day 15 ]
  The 14-item HAM-A is comprised of a series of symptoms, and measures both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints related to anxiety). The HAM-A total score will be 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.
• Change From Baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) Total Score [ Time Frame: Baseline and Day 15 ]
  The MADRS is a 10-item diagnostic questionnaire used to measure the severity of depressive episodes in participants with mood disorders. 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.
• Change From Baseline in HAM-D Subscale [ Time Frame: Baseline and Day 15 ]
  The 17-item HAM-D is comprised of individual ratings related to the following symptoms: depressed mood, feelings of guilt, suicide, insomnia, work and activities, retardation, agitation, anxiety, somatic symptoms, genital symptoms, hypochondriasis, loss of weight, and insight. HAM-D subscale scores will be calculated as the sum of the items comprising each subscale. 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.
• Change From Baseline in Self-Reported Measures of Depressive Symptoms, as Assessed by the Edinburgh Postnatal Depression Scale (EPDS) Total Score [ Time Frame: Baseline and up to Day 45 ]
  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.
• Change From Baseline in Self-Reported Measures of Depressive Symptoms, as Assessed by the 9-item Patient Health Questionnaire (PHQ-9) Score [ Time Frame: Baseline and up to Day 45 ]
  The PHQ-9 is a participant-rated depressive symptom severity scale where scoring is based on responses to specific questions. The score will be calculated as the sum of the 9 individual item scores. The PHQ-9 total score ranges from 1 to 27 with a higher score indicating more depression.
• Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) [ Time Frame: Up to Day 45 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate the Efficacy and Safety of SAGE-217 in Participants With Severe Postpartum Depression (PPD)
• Official Title: A Randomized, Double-Blind, Placebo-controlled Study Evaluating the Efficacy and Safety of SAGE-217 in the Treatment of Adults With Severe Postpartum Depression
• Brief Summary: 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: This study was previously posted by Sage Therapeutics. In November 2023, sponsorship of the trial was transferred to Biogen.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Depression, Postpartum

Intervention

• Drug: SAGE-217
  SAGE-217 oral capsules.
• Drug: Placebo
  SAGE-217 matched-placebo oral capsules.

Study Arms

• Placebo Comparator: Placebo
  Participants received SAGE-217 matched-placebo capsules, orally, once daily for 14 days.
  Intervention: Drug: Placebo
• Experimental: SAGE-217 50 mg
  Participants received SAGE-217, 50 mg, capsules, orally, once daily for 14 days.
  Intervention: Drug: SAGE-217

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 30, 2022): 200
• Original Estimated Enrollment (submitted: June 18, 2020): 192
• Actual Study Completion Date: April 12, 2022
• Actual Primary Completion Date: March 15, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes

• Ages: 18 Years to 45 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT04442503
• Other Study ID Numbers: 217-PPD-301; 2020-001424-34 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/
• URL: https://vivli.org/

• Current Responsible Party: Biogen
• Original Responsible Party: Sage Therapeutics
• Current Study Sponsor: Biogen
• Original Study Sponsor: Sage Therapeutics
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Biogen
• Verification Date: November 2023