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CompletedNCT04442490Updated Dec 22, 2023Results posted

A Study to Evaluate the Efficacy of Sage-217 in the Treatment of Adult Participants With Major Depressive Disorder (MDD)

A Phase 3 interventional study of SAGE-217 and Placebo in Depressive Disorder, Major, sponsored by Biogen. Completed at 39 sites in United States. Open to participants aged 18 Years to 64 Years. Per ClinicalTrials.gov, last updated 2023-12-22.

Sponsored by Biogen · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
543
Allocation
Randomized
Ages
18 Years to 64 Years
Sex
All
01

Study summary

The purpose of this study to evaluate the efficacy of SAGE-217 in the treatment of participants with MDD.

Read the detailed description

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

02

Conditions studied

  • Depressive Disorder, Major

Keywords

  • Depression
  • Depressive disorder
  • SAGE-217
03

In context

Depressive Disorder

4,845 studies on the registry are indexed under Depressive Disorder; 514 are open to participants now.

This study's enrollment of 543 is above the median of 80 across 3,999 interventional studies indexed under Depressive Disorder.

Browse Depressive Disorder studies →

Lead sponsor

Biogen is the lead sponsor of 494 studies on the registry; 22 are open to participants now.

Of its 98 completed or terminated interventional studies of FDA-regulated products, 49 (50%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 64 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Participant with diagnosis of MDD as diagnosed by Structured Clinical Interview for Diagnostic and 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.
  2. Participant has a Hamilton Rating Scale for Depression (HAM-D) total score ≥24 at screening and Day 1 (prior to dosing).
  3. Participants taking antidepressants must have been taking these medications at the same dose for at least 60 days prior to Day 1. Participants who have stopped taking antidepressants within 60 days must have stopped for longer than 5 half-lives of the antidepressant prior to Day 1. Participants receiving psychotherapy must have been receiving therapy on a regular schedule for at least 60 days prior to Day 1.
  4. Participant is willing to delay start of other antidepressant or antianxiety medications and any new pharmacotherapy regimens, including as-needed benzodiazepine anxiolytics and sleep aids, until after completion of the Day 42 visit.

Exclusion criteria

Exclusion Criteria:

  1. Participant is currently at significant risk of suicide, as judged by the Investigator, or has attempted suicide associated with the current episode of MDD.
  2. Participant has onset of the current depressive episode during pregnancy or 4 weeks postpartum, or the participant has presented for screening during the 6-month postpartum period.
  3. Participant has a body mass index (BMI) ≤18 or ≥45 kg/m\^2 at Screening, which is subject to a broader evaluation of medical comorbidities.
  4. Participant has treatment-resistant depression, defined as persistent depressive symptoms despite treatment with adequate doses of antidepressants within the current major depressive episode (excluding antipsychotics) from two different classes for at least 4 weeks of treatment.
  5. Participant has a medical history of seizures, bipolar disorder, schizophrenia, and/or schizoaffective disorder.
  6. Participant has a history of mild, moderate, or severe substance use disorder (including benzodiazepines) diagnosed using DSM-5 criteria in the 12 months prior to screening.
  7. Participant is taking psychostimulants (eg, methylphenidate, amphetamine) or opioids, regularly or as-needed, at Day -28.
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
543 participants (actual)

Study arms

  • Placebo comparator
    Placebo

    Participants self-administered SAGE-217 matched-placebo capsules, once daily at approximately 8 PM with fat-containing food for 14 days.

    Drug: Placebo

  • Experimental
    SAGE-217 50 mg

    Participants self-administered SAGE-217 50 mg capsules, once daily at approximately 8 PM with fat-containing food for 14 days. Participants who could not tolerate 50 mg received 40 mg for the remainder of the treatment period as per discretion of investigator.

    Drug: SAGE-217

Interventions

  • DrugSAGE-217

    SAGE-217 oral capsules.

  • DrugPlacebo

    SAGE-217 matched-placebo oral capsules.

06

What researchers measure

Primary outcomes

  1. Change From Baseline in the 17-item 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 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 HAM-D score is the sum of individual items, ranging from 0 to 52; where a higher score indicates more depression. A negative change indicates improvement. A mixed Model for Repeated Measures (MMRM)was used for the analysis.

    Time frame: Baseline, Day 15

Secondary outcomes

  1. Change From Baseline in the CGI-S Score at 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. A negative change from baseline indicates improvement. MMRM was used for the analysis. A negative change from baseline indicates improvement. MMRM was used for the analysis.

    Time frame: Baseline, Day 15

  2. Change From Baseline in the HAM-D Total Score at Days 3, 8 and 42

    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 HAM-D score is the sum of individual items, ranging from 0 to 52; where a higher score indicates more depression. A negative change from baseline indicates improvement. MMRM was used for the analysis.

    Time frame: Baseline, Days 3, 8, and 42

  3. Percentage of Participants Achieving HAM-D Response

    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 HAM-D score is the sum of individual items, ranging from 0 to 52; where a higher score indicates more depression. HAM-D response is defined as having a greater than or equal to (≥) 50% reduction in HAM-D score from baseline. Generalized Estimating Equation (GEE) method was used for the analysis.

    Time frame: Days 15 and 42

  4. Percentage of Participants Achieving HAM-D Remission

    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 HAM-D score is the sum of individual items, ranging from 0 to 52; where a higher score indicates more depression. HAM-D remission is defined as HAM-D total score less than or equal to (≤) 7. GEE model was used for the analysis.

    Time frame: Days 15 and 42

  5. Percentage of Participants With Clinical Global Impression - Improvement (CGI-I) Response at Day 15

    CGI-I response is defined as having a CGI-I score of "very much improved" (score of 1) or "much improved" (score of 2)". 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. GEE model was used for the analysis.

    Time frame: Day 15

  6. Change From Baseline in MADRS Total Score at Day 15

    The MADRS is a 10-item diagnostic questionnaire used to measure the severity of depressive episodes in participants with mood disorders. The MADRS total score was calculated as the sum of the 10 individual item scores and each item yields a score of 0 to 6. The overall MADRS score ranges from 0 to 60 where higher MADRS scores indicate more severe depression. A negative change indicates improvement. MMRM was used analysis.

    Time frame: Baseline, Day 15

  7. Change From Baseline in HAM-A Total Score at 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 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) to each item, with a total HAM-A score range of 0 to 56, where \<17 indicates mild severity, 18 to 24 indicates mild to moderate severity, and 25 to 30 indicates moderate to severe severity. A negative change from baseline indicates improvement. MMRM was used for the analysis.

    Time frame: Baseline, Day 15

  8. Time to First HAM-D Response

    17-item HAM-D scale is used to assess the severity of depression. It is comprised of individual ratings related to 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. Total HAM-D score is sum of individual items, ranging from 0 to 52; where higher score indicates more depression. Time to first HAM-D response is defined as time from first administration of the study drug to first time when ≥50% reduction in HAM-D score from baseline is achieved.

    Time frame: Up to Day 57

  9. Change From Baseline in Patient- Reported Outcome (PRO) Measures of Health-Related Quality of Life, as Assessed by the 36-item Short Form Version 2 (SF-36v2) Score at Days 8, 15, 28 and 42

    Participant's health was assessed using PRO health related quality of life (HRQOL) SF-36 V2. SF-36v2 covers 8 health dimensions, including 4 physical health status domains (physical functioning, role participation with physical health problems \[role-physical\], bodily pain, and general health) and 4 mental health status domains (vitality, social functioning, role participation with emotional health problems \[role-emotional\], and mental health). Physical Component Summary and the Mental Component Summary are derived from the 8 domains. Each domain is scored by summing the individual items, scores varying between 0 and 100. Both the domain scores and the component summary scores are norm-based. A higher score indicates a better state of health. Positive change indicates improvement. MMRM was used for the analysis.

    Time frame: Baseline, Days 8, 15, 28 and 42

  10. Change From Baseline in PRO Measures of Depressive Symptoms, as Assessed by the 9-item Patient Health Questionnaire (PHQ-9) Total Score at Days 8, 15, 28 and 42

    The PHQ-9 is a participant-rated depressive symptom severity scale where scoring is based on responses to specific questions. The score was calculated as the sum of the 9 individual item scores. The PHQ-9 total score ranges from 0 to 27 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 with a higher score indicating more depression. A negative change indicates improvements. MMRM was used for analysis.

    Time frame: Baseline, Days 8, 15, 28 and 42

07

Results

Posted Dec 5, 2023

Participant flow

Participants were enrolled in the study at 39 centers in the United States from 12 May 2020 to 21 April 2021.

Participant flow — Overall Study
MilestonePlaceboSAGE-217 50 mg
Started272271
Safety set269268
Completed235242
Not completed3729
Withdrew: Withdrawal by subject1810
Withdrew: Lost to follow-up77
Withdrew: Adverse event26
Withdrew: Noncompliance31
Withdrew: Physician decision21
Withdrew: Reason not specified21
Withdrew: Randomized but not treated33

Outcome measures

PrimaryChange From Baseline in the 17-item 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 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 HAM-D score is the sum of individual items, ranging from 0 to 52; where a higher score indicates more depression. A negative change indicates improvement. A mixed Model for Repeated Measures (MMRM)was used for the analysis.

Time frame:
Baseline, Day 15
Reported as:
Least squares mean · score on a scale
Change From Baseline in the 17-item HAM-D Total Score at Day 15
score on a scalePlaceboSAGE-217 50 mg
Change From Baseline in the 17-item HAM-D Total Score at Day 15-12.3 ± 0.50-14.1 ± 0.51
Statistical analysis
  • Placebo vs SAGE-217 50 mg · MMRM · p = 0.0141 · Least squares (ls) mean difference: -1.7 · 95% CI -3.1 to -0.3Model used was the MMRM with treatment, baseline HAM-D total score, antidepressant use at baseline (Yes or No), assessment time point, and time point-by-treatment interaction as fixed effects with Unstructured covariance structure.
SecondaryChange From Baseline in the CGI-S Score at 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. A negative change from baseline indicates improvement. MMRM was used for the analysis. A negative change from baseline indicates improvement. MMRM was used for the analysis.

Time frame:
Baseline, Day 15
Reported as:
Least squares mean · score on a scale
Change From Baseline in the CGI-S Score at Day 15
score on a scalePlaceboSAGE-217 50 mg
Change From Baseline in the CGI-S Score at Day 15-1.6 ± 0.08-1.8 ± 0.08
Statistical analysis
  • Placebo vs SAGE-217 50 mg · MMRM · p = 0.1193 · Ls mean difference: -0.2 · 95% CI -0.4 to 0.0Model used was the MMRM with treatment (SAGE-217 or placebo), baseline CGI-S score, antidepressant use at baseline (Yes or No), assessment time point, and time point-by-treatment interaction as fixed effects with Unstructured covariance structure.
SecondaryChange From Baseline in the HAM-D Total Score at Days 3, 8 and 42

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 HAM-D score is the sum of individual items, ranging from 0 to 52; where a higher score indicates more depression. A negative change from baseline indicates improvement. MMRM was used for the analysis.

Time frame:
Baseline, Days 3, 8, and 42
Reported as:
Least squares mean · score on a scale
Change From Baseline in the HAM-D Total Score at Days 3, 8 and 42
score on a scalePlaceboSAGE-217 50 mg
Change from Baseline at Day 3-6.8 ± 0.38-9.8 ± 0.38
Change from Baseline at Day 8-9.5 ± 0.45-12.0 ± 0.45
Change from Baseline at Day 42-12.6 ± 0.55-13.5 ± 0.55
Statistical analysis
  • Placebo vs SAGE-217 50 mg · MMRM · p = <0.0001 · Ls mean difference: -3.0 · 95% CI -4.0 to -2.0Model used was the MMRM with treatment, baseline HAM-D total score, antidepressant use at baseline (Yes or No), assessment time point, and time point-by-treatment interaction as fixed effects with Unstructured covariance structure.
  • Placebo vs SAGE-217 50 mg · MMRM · p = <0.0001 · Ls mean difference: -2.6 · 95% CI -3.8 to -1.4Model used was the MMRM with treatment, baseline HAM-D total score, antidepressant use at baseline (Yes or No), assessment time point, and time point-by-treatment interaction as fixed effects with Unstructured covariance structure.
  • Placebo vs SAGE-217 50 mg · MMRM · p = 0.2344 · Ls mean difference: -0.9 · 95% CI -2.4 to 0.6Model used was the MMRM with treatment, baseline HAM-D total score, antidepressant use at baseline (Yes or No), assessment time point, and time point-by-treatment interaction as fixed effects with Unstructured covariance structure.
SecondaryPercentage of Participants Achieving HAM-D Response

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 HAM-D score is the sum of individual items, ranging from 0 to 52; where a higher score indicates more depression. HAM-D response is defined as having a greater than or equal to (≥) 50% reduction in HAM-D score from baseline. Generalized Estimating Equation (GEE) method was used for the analysis.

Time frame:
Days 15 and 42
Reported as:
Number · percentage of participants
Percentage of Participants Achieving HAM-D Response
percentage of participantsPlaceboSAGE-217 50 mg
Day 1547.056.0
Day 4245.952.9
Statistical analysis
  • Placebo vs SAGE-217 50 mg · Generalized Estimating Equation Model · p = 0.0599 · Odds ratio (or): 1.40 · 95% CI 0.99 to 1.98
  • Placebo vs SAGE-217 50 mg · GEE Model · p = 0.0889 · Odds ratio (or): 1.36 · 95% CI 0.95 to 1.94
SecondaryPercentage of Participants Achieving HAM-D Remission

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 HAM-D score is the sum of individual items, ranging from 0 to 52; where a higher score indicates more depression. HAM-D remission is defined as HAM-D total score less than or equal to (≤) 7. GEE model was used for the analysis.

Time frame:
Days 15 and 42
Reported as:
Number · percentage of participants
Percentage of Participants Achieving HAM-D Remission
percentage of participantsPlaceboSAGE-217 50 mg
Day 1527.129.8
Day 4229.630.8
Statistical analysis
  • Placebo vs SAGE-217 50 mg · GEE Model · p = 0.5495 · Odds ratio (or): 1.13 · 95% CI 0.76 to 1.66
  • Placebo vs SAGE-217 50 mg · GEE Model · p = 0.6790 · Odds ratio (or): 1.09 · 95% CI 0.74 to 1.60
SecondaryPercentage of Participants With Clinical Global Impression - Improvement (CGI-I) Response at Day 15

CGI-I response is defined as having a CGI-I score of "very much improved" (score of 1) or "much improved" (score of 2)". 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. GEE model was used for the analysis.

Time frame:
Day 15
Reported as:
Number · percentage of participants
Percentage of Participants With Clinical Global Impression - Improvement (CGI-I) Response at Day 15
percentage of participantsPlaceboSAGE-217 50 mg
Percentage of Participants With Clinical Global Impression - Improvement (CGI-I) Response at Day 1551.062.1
Statistical analysis
  • Placebo vs SAGE-217 50 mg · GEE Model · p = 0.0191 · Odds ratio (or): 1.52 · 95% CI 1.07 to 2.16
SecondaryChange From Baseline in MADRS Total Score at Day 15

The MADRS is a 10-item diagnostic questionnaire used to measure the severity of depressive episodes in participants with mood disorders. The MADRS total score was calculated as the sum of the 10 individual item scores and each item yields a score of 0 to 6. The overall MADRS score ranges from 0 to 60 where higher MADRS scores indicate more severe depression. A negative change indicates improvement. MMRM was used analysis.

Time frame:
Baseline, Day 15
Reported as:
Least squares mean · score on a scale
Change From Baseline in MADRS Total Score at Day 15
score on a scalePlaceboSAGE-217 50 mg
Change From Baseline in MADRS Total Score at Day 15-15.1 ± 0.76-17.5 ± 0.77
Statistical analysis
  • Placebo vs SAGE-217 50 mg · MMRM · p = 0.0238 · Ls mean difference: -2.4 · 95% CI -4.4 to -0.3Model used was the MMRM with treatment (SAGE-217/placebo), baseline MADRS total score, antidepressant use at baseline (Yes or No), assessment time point, and time point-by-treatment interaction as fixed effects with Unstructured covariance structure
SecondaryChange From Baseline in HAM-A Total Score at 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 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) to each item, with a total HAM-A score range of 0 to 56, where \<17 indicates mild severity, 18 to 24 indicates mild to moderate severity, and 25 to 30 indicates moderate to severe severity. A negative change from baseline indicates improvement. MMRM was used for the analysis.

Time frame:
Baseline, Day 15
Reported as:
Least squares mean · score on a scale
Change From Baseline in HAM-A Total Score at Day 15
score on a scalePlaceboSAGE-217 50 mg
Change From Baseline in HAM-A Total Score at Day 15-9.1 ± 0.43-10.4 ± 0.43
Statistical analysis
  • Placebo vs SAGE-217 50 mg · MMRM · p = 0.0199 · Ls mean difference: -1.4 · 95% CI -2.5 to -0.2Model used was MMRM with treatment (SAGE-217/placebo), baseline HAM-A total score, antidepressant use at baseline (Yes or No), assessment time point, and time point-by-treatment interaction as fixed effects with Unstructured covariance structure.
SecondaryTime to First HAM-D Response

17-item HAM-D scale is used to assess the severity of depression. It is comprised of individual ratings related to 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. Total HAM-D score is sum of individual items, ranging from 0 to 52; where higher score indicates more depression. Time to first HAM-D response is defined as time from first administration of the study drug to first time when ≥50% reduction in HAM-D score from baseline is achieved.

Time frame:
Up to Day 57
Reported as:
Median · days
Time to First HAM-D Response
daysPlaceboSAGE-217 50 mg
Time to First HAM-D Response15 (2 to 57)11 (2 to 54)
SecondaryChange From Baseline in Patient- Reported Outcome (PRO) Measures of Health-Related Quality of Life, as Assessed by the 36-item Short Form Version 2 (SF-36v2) Score at Days 8, 15, 28 and 42

Participant's health was assessed using PRO health related quality of life (HRQOL) SF-36 V2. SF-36v2 covers 8 health dimensions, including 4 physical health status domains (physical functioning, role participation with physical health problems \[role-physical\], bodily pain, and general health) and 4 mental health status domains (vitality, social functioning, role participation with emotional health problems \[role-emotional\], and mental health). Physical Component Summary and the Mental Component Summary are derived from the 8 domains. Each domain is scored by summing the individual items, scores varying between 0 and 100. Both the domain scores and the component summary scores are norm-based. A higher score indicates a better state of health. Positive change indicates improvement. MMRM was used for the analysis.

Time frame:
Baseline, Days 8, 15, 28 and 42
Reported as:
Least squares mean · score on a scale
Change From Baseline in Patient- Reported Outcome (PRO) Measures of Health-Related Quality of Life, as Assessed by the 36-item Short Form Version 2 (SF-36v2) Score at Days 8, 15, 28 and 42
score on a scalePlaceboSAGE-217 50 mg
Physical Functioning Domain Score: Change from Baseline at Day 81.9 ± 0.362.4 ± 0.37
Physical Functioning Domain Score: Change from Baseline at Day 152.3 ± 0.383.1 ± 0.39
Physical Functioning Domain Score: Change from Baseline at Day 282.3 ± 0.403.2 ± 0.41
Physical Functioning Domain Score: Change from Baseline at Day 422.4 ± 0.433.3 ± 0.43
Role-Physical Domain Score: Change from Baseline at Day 81.9 ± 0.431.8 ± 0.44
Role-Physical Domain Score: Change from Baseline at Day 153.2 ± 0.453.1 ± 0.46
Role-Physical Domain Score: Change from Baseline at Day 283.1 ± 0.463.0 ± 0.46
Role-Physical Domain Score: Change from Baseline at Day 423.2 ± 0.463.5 ± 0.46
Bodily Pain Domain Score: Change from Baseline at Day 83.3 ± 0.463.8 ± 0.47
Bodily Pain Domain Score: Change from Baseline at Day 154.7 ± 0.494.9 ± 0.50
Bodily Pain Domain Score: Change from Baseline at Day 284.7 ± 0.515.0 ± 0.51
Bodily Pain Domain Score: Change from Baseline at Day 424.2 ± 0.545.2 ± 0.54
General Health Domain Score: Change from Baseline at Day 82.4 ± 0.363.6 ± 0.37
General Health Domain Score: Change from Baseline at Day 153.4 ± 0.394.4 ± 0.40
General Health Domain Score: Change from Baseline at Day 283.3 ± 0.433.8 ± 0.43
General Health Domain Score: Change from Baseline at Day 423.5 ± 0.454.6 ± 0.45
Vitality Domain Score: Change from Baseline at Day 87.2 ± 0.649.8 ± 0.65
Vitality Domain Score: Change from Baseline at Day 159.7 ± 0.7512.8 ± 0.76
Vitality Domain Score: Change from Baseline at Day 289.1 ± 0.7510.9 ± 0.76
Vitality Domain Score: Change from Baseline at Day 429.7 ± 0.8111.7 ± 0.81
Social Functioning Domain Score: Change from Baseline at Day 88.2 ± 0.669.5 ± 0.67
Social Functioning Domain Score: Change from Baseline at Day 1511.4 ± 0.7212.5 ± 0.73
Social Functioning Domain Score: Change from Baseline at Day 2811.6 ± 0.7611.9 ± 0.76
Social Functioning Domain Score: Change from Baseline at Day 4211.4 ± 0.7813.2 ± 0.78
Role-Emotional Domain Score: Change from Baseline at Day 89.4 ± 0.7710.5 ± 0.78
Role-Emotional Domain Score: Change from Baseline at Day 1512.1 ± 0.8213.6 ± 0.83
Role-Emotional Domain Score: Change from Baseline at Day 2811.8 ± 0.8413.7 ± 0.84
Role-Emotional Domain Score: Change from Baseline at Day 4212.3 ± 0.8913.5 ± 0.89
Mental Health Domain Score: Change from Baseline at Day 89.4 ± 0.6811.0 ± 0.69
Mental Health Domain Score: Change from Baseline at Day 1512.2 ± 0.7614.0 ± 0.77
Mental Health Domain Score: Change from Baseline at Day 2811.6 ± 0.8112.7 ± 0.81
Mental Health Domain Score: Change from Baseline at Day 4212.2 ± 0.8513.9 ± 0.85
Statistical analysis
  • Placebo vs SAGE-217 50 mg · MMRM · p = 0.3216 · Ls mean difference: 0.5 · 95% CI -0.5 to 1.5Model used is MMRM with treatment(SAGE-217/placebo), baseline SF-36v2 domain/component score, antidepressant use at baseline(Yes/No)assessment time point and time point-by-treatment interaction as fixed effects with Unstructured covariance structure.
  • Placebo vs SAGE-217 50 mg · MMRM · p = 0.1247 · Ls mean difference: 0.8 · 95% CI -0.2 to 1.8Model used is MMRM with treatment(SAGE-217/placebo), baseline SF-36v2 domain/component score, antidepressant use at baseline(Yes/No)assessment time point and time point-by-treatment interaction as fixed effects with Unstructured covariance structure.
  • Placebo vs SAGE-217 50 mg · MMRM · p = 0.1111 · Ls mean difference: 0.9 · 95% CI -0.2 to 2.0Model used is MMRM with treatment(SAGE-217/placebo), baseline SF-36v2 domain/component score, antidepressant use at baseline(Yes/No)assessment time point and time point-by-treatment interaction as fixed effects with Unstructured covariance structure.
  • Placebo vs SAGE-217 50 mg · MMRM · p = 0.1449 · Ls mean difference: 0.9 · 95% CI -0.3 to 2.0Model used is MMRM with treatment(SAGE-217/placebo), baseline SF-36v2 domain/component score, antidepressant use at baseline(Yes/No)assessment time point and time point-by-treatment interaction as fixed effects with Unstructured covariance structure.
  • Placebo vs SAGE-217 50 mg · MMRM · p = 0.8242 · Ls mean difference: -0.1 · 95% CI -1.3 to 1.0Model used is MMRM with treatment(SAGE-217/placebo), baseline SF-36v2 domain/component score, antidepressant use at baseline(Yes/No)assessment time point and time point-by-treatment interaction as fixed effects with Unstructured covariance structure.
  • Placebo vs SAGE-217 50 mg · MMRM · p = 0.8329 · Ls mean difference: -0.1 · 95% CI -1.4 to 1.1
  • Placebo vs SAGE-217 50 mg · MMRM · p = 0.8127 · Ls mean difference: -0.1 · 95% CI -1.4 to 1.1
  • Placebo vs SAGE-217 50 mg · MMRM · p = 0.5435 · Ls mean difference: 0.4 · 95% CI -0.9 to 1.6
  • Placebo vs SAGE-217 50 mg · MMRM · p = 0.3551 · Ls mean difference: 0.6 · 95% CI -0.7 to 1.8
  • Placebo vs SAGE-217 50 mg · MMRM · p = 0.7495 · Ls mean difference: 0.2 · 95% CI -1.1 to 1.6
  • Placebo vs SAGE-217 50 mg · MMRM · p = 0.6471 · Ls mean difference: 0.3 · 95% CI -1.1 to 1.7
  • Placebo vs SAGE-217 50 mg · MMRM · p = 0.1832 · Ls mean difference: 1.0 · 95% CI -0.5 to 2.5
  • Placebo vs SAGE-217 50 mg · MMRM · p = 0.0168 · Ls mean difference: 1.2 · 95% CI 0.2 to 2.2
  • Placebo vs SAGE-217 50 mg · MMRM · p = 0.0787 · Ls mean difference: 1.0 · 95% CI -0.1 to 2.0
  • Placebo vs SAGE-217 50 mg · MMRM · p = 0.4273 · Ls mean difference: 0.5 · 95% CI -0.7 to 1.6
  • Placebo vs SAGE-217 50 mg · MMRM · p = 0.0938 · Ls mean difference: 1.0 · 95% CI -0.2 to 2.2
  • Placebo vs SAGE-217 50 mg · MMRM · p = 0.0033 · Ls mean difference: 2.6 · 95% CI 0.9 to 4.3
  • Placebo vs SAGE-217 50 mg · MMRM · p = 0.0029 · Ls mean difference: 3.1 · 95% CI 1.1 to 5.1
  • Placebo vs SAGE-217 50 mg · MMRM · p = 0.0791 · Ls mean difference: 1.8 · 95% CI -0.2 to 3.9
  • Placebo vs SAGE-217 50 mg · MMRM · p = 0.0761 · Ls mean difference: 2.0 · 95% CI -0.2 to 4.2
  • Placebo vs SAGE-217 50 mg · MMRM · p = 0.1568 · Ls mean difference: 1.3 · 95% CI -0.5 to 3.1
  • Placebo vs SAGE-217 50 mg · MMRM · p = 0.2807 · Ls mean difference: 1.1 · 95% CI -0.9 to 3.0
  • Placebo vs SAGE-217 50 mg · MMRM · p = 0.7751 · Ls mean difference: 0.3 · 95% CI -1.8 to 2.4
  • Placebo vs SAGE-217 50 mg · MMRM · p = 0.0913 · Ls mean difference: 1.8 · 95% CI -0.3 to 3.9
  • Placebo vs SAGE-217 50 mg · MMRM · p = 0.2863 · Ls mean difference: 1.1 · 95% CI -0.9 to 3.2
  • Placebo vs SAGE-217 50 mg · MMRM · p = 0.1801 · Ls mean difference: 1.5 · 95% CI -0.7 to 3.7
  • Placebo vs SAGE-217 50 mg · MMRM · p = 0.1107 · Ls mean difference: 1.8 · 95% CI -0.4 to 4.1
  • Placebo vs SAGE-217 50 mg · MMRM · p = 0.3274 · Ls mean difference: 1.2 · 95% CI -1.2 to 3.6
  • Placebo vs SAGE-217 50 mg · MMRM · p = 0.0873 · Ls mean difference: 1.6 · 95% CI -0.2 to 3.4
  • Placebo vs SAGE-217 50 mg · MMRM · p = 0.0871 · Ls mean difference: 1.8 · 95% CI -0.3 to 3.9
  • Placebo vs SAGE-217 50 mg · MMRM · p = 0.3095 · Ls mean difference: 1.1 · 95% CI -1.1 to 3.3
  • Placebo vs SAGE-217 50 mg · MMRM · p = 0.1477 · Ls mean difference: 1.7 · 95% CI -0.6 to 4.0
SecondaryChange From Baseline in PRO Measures of Depressive Symptoms, as Assessed by the 9-item Patient Health Questionnaire (PHQ-9) Total Score at Days 8, 15, 28 and 42

The PHQ-9 is a participant-rated depressive symptom severity scale where scoring is based on responses to specific questions. The score was calculated as the sum of the 9 individual item scores. The PHQ-9 total score ranges from 0 to 27 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 with a higher score indicating more depression. A negative change indicates improvements. MMRM was used for analysis.

Time frame:
Baseline, Days 8, 15, 28 and 42
Reported as:
Least squares mean · score on a scale
Change From Baseline in PRO Measures of Depressive Symptoms, as Assessed by the 9-item Patient Health Questionnaire (PHQ-9) Total Score at Days 8, 15, 28 and 42
score on a scalePlaceboSAGE-217 50 mg
Change from Baseline at Day 8-6.8 ± 0.42-7.8 ± 0.42
Change from Baseline at Day 15-8.3 ± 0.45-9.4 ± 0.46
Change from Baseline at Day 28-7.8 ± 0.46-8.8 ± 0.46
Change from Baseline at Day 42-8.5 ± 0.48-9.0 ± 0.48
Statistical analysis
  • Placebo vs SAGE-217 50 mg · MMRM · p = 0.0828 · Ls mean difference: -1.0 · 95% CI -2.1 to 0.1Model used was the MMRM with treatment (SAGE-217/placebo), baseline PHQ-9 total score, antidepressant use at baseline (Yes or No), assessment time point, and time point-by-treatment interaction as fixed effects with Unstructured covariance structure.
  • Placebo vs SAGE-217 50 mg · MMRM · p = 0.0606 · Ls mean difference: -1.2 · 95% CI -2.4 to 0.1Model used was the MMRM with treatment (SAGE-217/placebo), baseline PHQ-9 total score, antidepressant use at baseline (Yes or No), assessment time point, and time point-by-treatment interaction as fixed effects with Unstructured covariance structure.
  • Placebo vs SAGE-217 50 mg · MMRM · p = 0.1079 · Ls mean difference: -1.0 · 95% CI -2.3 to 0.2Model used was the MMRM with treatment (SAGE-217/placebo), baseline PHQ-9 total score, antidepressant use at baseline (Yes or No), assessment time point, and time point-by-treatment interaction as fixed effects with Unstructured covariance structure.
  • Placebo vs SAGE-217 50 mg · MMRM · p = 0.3951 · Ls mean difference: -0.6 · 95% CI -1.9 to 0.7Model used was the MMRM with treatment (SAGE-217/placebo), baseline PHQ-9 total score, antidepressant use at baseline (Yes or No), assessment time point, and time point-by-treatment interaction as fixed effects with Unstructured covariance structure.

Adverse events

Collected over From inform consent signing up to 28 days after the last dose (Up to 70 days). Non-serious events are listed at a 2% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo0/269 (0%)2/269 (0.7%)59/269 (21.9%)
SAGE-217 50 mg0/268 (0%)2/268 (0.7%)111/268 (41.4%)
Most frequent serious events
Most frequent serious events
EventPlaceboSAGE-217 50 mg
Lower Limb FractureInjury, poisoning and procedural complications0/2691/268
Slow SpeechNervous system disorders0/2691/268
Psychotic DisorderPsychiatric disorders0/2691/268
Deep Vein ThrombosisVascular disorders0/2691/268
Retinal DetachmentEye disorders1/2690/268
Alanine Aminotransferase IncreasedInvestigations1/2690/268
Aspartate Aminotransferase IncreasedInvestigations1/2690/268
Blood Alkaline Phosphatase IncreasedInvestigations1/2690/268
Gamma-glutamyltransferase IncreasedInvestigations1/2690/268
Most frequent other events
Most frequent other events
EventPlaceboSAGE-217 50 mg
SomnolenceNervous system disorders8/26941/268
DizzinessNervous system disorders6/26937/268
HeadacheNervous system disorders21/26929/268
SedationNervous system disorders1/26920/268
DiarrhoeaGastrointestinal disorders14/2698/268
NauseaGastrointestinal disorders12/26911/268
Dry MouthGastrointestinal disorders10/26910/268
TremorNervous system disorders0/2698/268

Baseline characteristics

Safety Set included all participants who were administered IP.

Age, Continuous
Age, Continuous(years)PlaceboSAGE-217 50 mgTotal
Mean40.1 ± 12.6439.4 ± 12.3039.7 ± 12.46
Sex: Female, Male
Sex: Female, Male(Participants)PlaceboSAGE-217 50 mgTotal
Female166186352
Male10382185
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)PlaceboSAGE-217 50 mgTotal
Hispanic or Latino5458112
Not Hispanic or Latino215210425
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)PlaceboSAGE-217 50 mgTotal
American Indian or Alaska Native314
Asian41317
Native Hawaiian or Other Pacific Islander112
Black or African American4675121
White206169375
More than one race5712
Unknown or Not Reported426
17-item Hamilton Rating Scale for Depression (HAM-D) Total Score
17-item Hamilton Rating Scale for Depression (HAM-D) Total Score(score on a scale)PlaceboSAGE-217 50 mgTotal
Mean26.9 ± 2.6726.8 ± 2.6026.9 ± 2.64
Clinical Global Impression - Severity (CGIS) Score
Clinical Global Impression - Severity (CGIS) Score(score on a scale)PlaceboSAGE-217 50 mgTotal
Mean4.8 ± 0.524.7 ± 0.554.7 ± 0.54
Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score
Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score(score on a scale)PlaceboSAGE-217 50 mgTotal
Mean35.0 ± 4.7335.2 ± 4.8335.1 ± 4.78
Hamilton Anxiety Rating Scale (HAM-A) Total Score
Hamilton Anxiety Rating Scale (HAM-A) Total Score(score on a scale)PlaceboSAGE-217 50 mgTotal
Mean20.7 ± 5.5121.4 ± 5.1521.0 ± 5.34
08

Study locations

39 sites
  • Sage Investigational Site
    Rogers, Arkansas 72758, United States
  • Sage Investigational Site
    Bellflower, California 90706, United States
  • Sage Investigational Site
    Garden Grove, California 92845, United States
  • Sage Investigational Site
    Glendale, California 91206, United States
  • Sage Investigational Site
    Lemon Grove, California 91945, United States
  • Sage Investigational Site
    Orange, California 92868, United States
  • Sage Investigational Site
    Pico Rivera, California 90660, United States
  • Sage Investigational Site
    Redlands, California 92374, United States
  • Sage Investigational Site
    San Diego, California 92103, United States
  • Sage Investigational Site
    Sherman Oaks, California 91403, United States
  • Sage Investigational Site
    Temecula, California 92591, United States
  • Sage Investigational Site
    Coral Springs, Florida 33067, United States
  • Sage Investigational Site
    Hollywood, Florida 33024, United States
  • Sage Investigational Site
    Jacksonville, Florida 32256, United States
  • Sage Investigational Site
    Lauderhill, Florida 33319, United States
  • Sage Investigational Site
    Orange City, Florida 32763, United States
  • Sage Investigational Site
    Orlando, Florida 32801, United States
  • Sage Investigational Site
    Orlando, Florida 32807, United States
  • Sage Investigational Site
    Alpharetta, Georgia 30022, United States
  • Sage Investigational Site
    Atlanta, Georgia 30328, United States
  • Sage Investigational Site
    Atlanta, Georgia 30331, United States
  • Sage Investigational Site
    Decatur, Georgia 30030, United States
  • Sage Investigational Site
    Skokie, Illinois 60076, United States
  • Sage Investigational Site
    Flowood, Mississippi 39232, United States
  • Sage Investigational Site
    O'Fallon, Missouri 63368, United States
  • Sage Investigational Site
    Las Vegas, Nevada 89102, United States
  • Sage Investigational Site
    Marlton, New Jersey 08053, United States
  • Sage Investigational Site
    Charlotte, North Carolina 28211, United States
  • Sage Investigational Site
    Cincinnati, Ohio 45215, United States
  • Sage Investigational Site
    Dayton, Ohio 45417, United States
  • Sage Investigational Site
    North Canton, Ohio 44720, United States
  • Sage Investigational Site
    Oklahoma City, Oklahoma 73112, United States
  • Sage Investigational Site
    Portland, Oregon 97210, United States
  • Sage Investigational Site
    Allentown, Pennsylvania 18104, United States
  • Sage Investigational Site
    Charleston, South Carolina 29407, United States
  • Sage Investigational Site
    Memphis, Tennessee 38119, United States
  • Sage Investigational Site
    DeSoto, Texas 75115, United States
  • Sage Investigational Site
    Wichita Falls, Texas 76309, United States
  • Sage Investigational Site
    Charlottesville, Virginia 22903, United States
09

References and documents

Study documents

  • Study protocol · Dec 14, 2020
  • Statistical analysis plan · May 25, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Dec 22, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT04442490
Lead sponsor
Biogen
Responsible party
Sponsor
First posted
Jun 22, 2020
Start date
May 12, 2020
Primary completion
Mar 26, 2021
Completion
Apr 21, 2021
Results posted
Dec 5, 2023
Last update
Dec 22, 2023

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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