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

• ClinicalTrials.gov Identifier: NCT02978326
• Recruitment Status: Completed
• First Posted: November 30, 2016
• Results First Posted: December 16, 2021
• Last Update Posted: December 15, 2023
• Sponsor: Biogen
• Information provided by (Responsible Party): Biogen

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Postpartum Depression	Drug: SAGE-217 15/20 mg Oral Solution; Drug: Placebo; Drug: SAGE 217 30 mg Capsules	Phase 3

Detailed Description:

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 276 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: January 4, 2017
• Actual Primary Completion Date: November 15, 2018
• Actual Study Completion Date: December 11, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: Part A: SAGE-217 15/20 mg Oral Solution; 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; 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).
Placebo Comparator: Part B: Placebo; Participants received SAGE-217 matching placebo, capsules, orally, once daily, for up to 14 days.	Drug: Placebo; SAGE-217 matching placebo, capsules, orally, once daily, for up to 14 days.
Experimental: Part B: SAGE 217 30 mg Capsules; Participants received SAGE-217, 30 mg, capsules, orally, once daily, for up to 14 days.	Drug: SAGE 217 30 mg Capsules; SAGE-217, 30 mg, capsules, orally, once daily, for up to 14 days.

Outcome Measures

Primary Outcome Measures :

1. Parts A and B: Change From Baseline in the 17-Item Hamilton Rating Scale for Depression (HAM-D) Total Score at Day 15 [ Time Frame: Parts A and B: Baseline, 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.

Secondary Outcome Measures :

1. Parts A and B: Change From Baseline in the HAM-D Total Score at Days 3, 8, 21 and 45 [ Time Frame: Part B: Baseline, 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.
2. Parts A and B: Percentage of Participants With HAM-D Response [ Time Frame: Part B: Days 3, 8, 15, 21 and 45 ]
   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.
3. Parts A and B: Percentage of Participants With HAM-D Remission [ Time Frame: Part B: Days 3, 8, 15, 21 and 45 ]
   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.
4. Parts A and B: Change From Baseline in HAM-D Subscales Scores [ Time Frame: Part B: Baseline, Days 3, 8, 15, 21 and 45 ]
   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.
5. Parts A and B: Change From Baseline in HAM-D Individual Item Scores [ Time Frame: Part B: Baseline, Days 3, 8, 15, 21 and 45 ]
   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.
6. Parts A and B: Change From Baseline in Montgomery and Åsberg Depression Rating Scale (MADRS) Total Score [ Time Frame: Part B: Baseline, Days 3, 8, 15, 21 and 45 ]
   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.
7. Parts A and B: Percentage of Participants With Clinical Global Impression - Improvement (CGI-I) Response [ Time Frame: Part B: Days 3, 8, 15, 21 and 45 ]
   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.
8. Parts A and B: Change From Baseline in Hamilton Anxiety Rating Scale (HAM-A) Total Score [ Time Frame: Part B: Baseline, Days 3, 8, 15, 21 and 45 ]
   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.
9. Parts A and B: Percentage of Participants With MADRS Response [ Time Frame: Part B: Days 3, 8, 15, 21 and 45 ]
   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.
10. Parts A and B: Percentage of Participants With MADRS Remission [ Time Frame: Part B: Days 3, 8, 15, 21 and 45 ]
    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.
11. Parts A and B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Part A: Up to Day 75; Part B: Up to Day 45 ]
    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.
12. Part B: Number of Participants With Potentially Clinically Significant Vital Sign Measurements [ Time Frame: Part B: From first dose of study drug up to 45 days ]
    Vital signs included assessments of supine and standing systolic blood pressure (SBP), supine and standing diastolic blood pressure (DBP), and heart rate.
13. Part B: Number of Participants With Potentially Clinically Significant Laboratory Evaluations [ Time Frame: Part B: From first dose of study drug up to 45 days ]
    Laboratory tests included tests of Hematology, Chemistry, and Urinalysis.
14. Part B: Change From Baseline in Electrocardiogram (ECG) Parameter Heart Rate [ Time Frame: Part B: Baseline, Days 8, 15, and 21 ]
    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.
15. Part B: Change From Baseline in ECG Parameters-PR Interval, RR Interval, QRS Duration, QT Interval, QTcF Interval [ Time Frame: Part B: Baseline, Days 8, 15, and 21 ]
    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.
16. 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) [ Time Frame: Part B: Up to Day 45 ]
    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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Arkansas

Sage Investigational Site

Little Rock, Arkansas, United States, 72209

United States, California

Sage Investigational Site

Beverly Hills, California, United States, 90212

Sage Investigational Site

Oceanside, California, United States, 92056

Sage Investigational Site

Wildomar, California, United States, 92595

United States, District of Columbia

Sage Investigational Site

Washington, District of Columbia, United States, 20011

United States, Florida

Sage Investigational Site

Aventura, Florida, United States, 33027

Sage Investigational Site

Miami, Florida, United States, 33173

Sage Investigational Site

Orlando, Florida, United States, 32807

Sage Investigational Site

Pensacola, Florida, United States, 32502

Sage Investigational SIte

Pinellas Park, Florida, United States, 33782

United States, Georgia

Sage Investigational Site

Atlanta, Georgia, United States, 30331

Sage Investigational Site

Decatur, Georgia, United States, 30030

United States, Illinois

Sage Investigational Site

Hoffman Estates, Illinois, United States, 60169

United States, Kentucky

Sage Investigational Site

Owensboro, Kentucky, United States, 42303

United States, Louisiana

Sage Investigational Site

Lake Charles, Louisiana, United States, 70629

Sage Investigational Site

New Orleans, Louisiana, United States, 70115

United States, Missouri

Sage Investigational Site

Saint Charles, Missouri, United States, 63304

United States, Nevada

Sage Investigational Site

Las Vegas, Nevada, United States, 89102

United States, New York

Sage Investigational Site

Manhasset, New York, United States, 11030

Sage Investigational Site

New York, New York, United States, 10036

United States, North Carolina

Sage Investigational Site

Chapel Hill, North Carolina, United States, 27599

Sage Investigational Site

Raleigh, North Carolina, United States, 27612

United States, Rhode Island

Sage Investigational Site

Providence, Rhode Island, United States, 02904

United States, Texas

Sage Investigational Site

Fort Worth, Texas, United States, 76060

Sage Investigational Site

Houston, Texas, United States, 77058

Sage Investigational Site

Richardson, Texas, United States, 75080

United States, Utah

Sage Investigational Site

Orem, Utah, United States, 84058

Sponsors and Collaborators

Biogen

  Study Documents (Full-Text)

Documents provided by Biogen:

Study Protocol  [PDF] July 2, 2018

Statistical Analysis Plan  [PDF] December 11, 2018

More Information

Additional Information:

Related Info 

Publications of Results:

Deligiannidis K, Lasser R, Gunduz-Bruce H, Silber C, Sankoh AJ, Li Si, et al. A Phase 3, Double-Blind, Placebo- Controlled Trial of SAGE-217 in Postpartum Depression: Assessment of Depressive Symptoms Across Multiple Measures. Abstract presented at: American Society of Clinical Psychopharmacology 2019 Annual Meeting; May 28-31, 2019; Scottsdale, AZ.

Lasser R, Deligiannidis K, Gunduz-Bruce H, Silber C, Sankoh AJ, Li Si, et al. A Phase 3, Double-Blind, Placebo- Controlled Trial of SAGE-217 in Postpartum Depression: Topline Assessment of Secondary Efficacy Measures of Anxiety and Depression. Abstract presented at: American Society of Clinical Psychopharmacology 2019 Annual Meeting; May 28-31, 2019; Scottsdale, AZ.

Deligiannidis KM, Meltzer-Brody S, Gunduz-Bruce H, Doherty J, Jonas J, Li S, Sankoh AJ, Silber C, Campbell AD, Werneburg B, Kanes SJ, Lasser R. Effect of Zuranolone vs Placebo in Postpartum Depression: A Randomized Clinical Trial. JAMA Psychiatry. 2021 Sep 1;78(9):951-959. doi: 10.1001/jamapsychiatry.2021.1559. Erratum In: JAMA Psychiatry. 2022 Jul 1;79(7):740. JAMA Psychiatry. 2023 Feb 1;80(2):191.

• Responsible Party: Biogen
• ClinicalTrials.gov Identifier: NCT02978326
• Other Study ID Numbers: 217-PPD-201
• First Posted: November 30, 2016
• Results First Posted: December 16, 2021
• Last Update Posted: December 15, 2023
• Last Verified: November 2023

Individual Participant Data (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/

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

Keywords provided by Biogen:

Postpartum Care

Additional relevant MeSH terms:

Depression, Postpartum; Depression; Depressive Disorder; Behavioral Symptoms; Mood Disorders; Mental Disorders; Puerperal Disorders; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Zuranolone; Antidepressive Agents; Psychotropic Drugs