Trial · NCT04476030

A Comparative Study of Sage-217 Plus an Antidepressant (ADT) Versus Placebo Plus an ADT in Adults With Major Depressive Disorder

NCT04476030, Phase 3, Completed, Biogen; results first posted 2023-11-07

3 sourcestrials-2026-11-12-0.5.0

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ConductScience Library. A Comparative Study of Sage-217 Plus an Antidepressant (ADT) Versus Placebo Plus an ADT in Adults With Major Depressive Disorder. Trials, record NCT04476030. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT04476030

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Trial

As registered on ClinicalTrials.gov, in the graph's capture of the registry.

Title: A Comparative Study of Sage-217 Plus an Antidepressant (ADT) Versus Placebo Plus an ADT in Adults With Major Depressive Disorder
NCT number: NCT04476030
Status: Completed
Phases: Phase 3
Enrollment: 440 participants, actual
Lead sponsor: Biogen
Conditions: Depressive Disorder, Major
Interventions: SAGE-217, Matching Placebo, Sertraline, Escitalopram, Citalopram, Duloxetine, Desvenlafaxine
First posted: 2020-07-17
Last updated: 2023-12-22
Results first posted: 2023-11-07

Source ClinicalTrials.gov

Registered outcomes16

Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.

List	Outcome	Time frame	Description
Primary	Change From Baseline in the HAMD-17 Total Score at Day 3	Baseline, Day 3	The 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 3-point (0=none to 2=severe) or 5-point scale (0=none/absent to 4=most severe). Total score is the sum of individual items, ranging from 0 (not depressed) to 52 (severely depressed); where a higher score indicates more depression. A negative change from baseline indicated improvement. Least Squares (LS) mean was estimated using mixed effects model for repeated measures (MMRM) analysis.
Secondary	Change From Baseline in the HAMD-17 Total Score Over the Double-Blind Treatment Period	Baseline through Day 15	The 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 3-point (0=none to 2=severe) or 5-point scale (0=none/absent to 4=most severe). Total score is the sum of individual items, ranging from 0 (not depressed) to 52 (severely depressed); where a higher score indicates more depression. A negative change from baseline indicated improvement. LS mean was estimated using MMRM analysis. The data reported is summary of data collected and analyzed during double-blind treatment period at Baseline, Day 3, Day 8, Day 12, and Day 15 using equal weights for the scheduled visits.
Secondary	Change From Baseline in the HAMD-17 Total Score at Days 15 and 42	Baseline, Days 15 and 42	The 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 3-point (0=none to 2=severe) or 5-point scale (0=none/absent to 4=most severe). Total score is the sum of individual items, ranging from 0 (not depressed) to 52 (severely depressed); where a higher score indicates more depression. A negative change from baseline indicated improvement. LS mean was estimated using MMRM analysis. The missing values were imputed for the analysis.
Secondary	Change From Baseline in the HAMD-17 Total Score Around End of Blinded Treatment	Baseline, End of blinded treatment assessment (i.e., average of Days 12, 15 , and 18)	The 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 3-point (0=none to 2=severe) or 5-point scale (0=none/absent to 4=most severe). Total score is the sum of individual items, ranging from 0 (not depressed) to 52 (severely depressed); where a higher score indicates more depression. A negative change from baseline indicated improvement. End of blinded treatment was defined as the average of change from baseline values of Days 12, 15 and 18. LS mean was estimated using MMRM analysis.
Secondary	Percentage of Participants With HAMD-17 Response at Day 15 and Day 42	At Days 15 and 42	HAM-D response was defined as having a 50% or greater reduction from baseline in HAM-D total score. The 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 3-point (0=none to 2=severe) or 5-point scale (0=none/absent to 4=most severe). Total score is the sum of individual items, ranging from 0 (not depressed) to 52 (severely depressed); where a higher score indicates more depression. Percentages were rounded off to the first decimal point.
Secondary	Percentage of Participants With HAMD-17 Remission at Day 15 and Day 42	Days 15 and 42	HAM-D remission was defined as having a HAM-D total score of ≤7. The 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 3-point (0=none to 2=severe) or 5-point scale (0=none/absent to 4=most severe). Total score is the sum of individual items, ranging from 0 (not depressed) to 52 (severely depressed); where a higher score indicates more depression. Percentages were rounded off to the first decimal point.
Secondary	Change From Baseline in CGI-S Score at Day 15	Baseline and Day 15	The CGI-S uses 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. Considering total clinical experience, the investigator rated the participant 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. A higher score indicated extreme illness. A negative change from baseline indicated improvement. LS mean was estimated using MMRM analysis.
Secondary	Percentage of Participants With CGI-I Response, at Day 3 and Day 15	Days 3 and 15	CGI-I response was 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 post-treatment. The investigator rated the participant's total improvement whether or not it was due entirely to IP. 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. By definition, all CGI-I assessments are evaluated against baseline conditions. Higher scores indicated worse condition. Percentages were rounded off to the first decimal point.
Secondary	Change From Baseline in MADRS Total Score at Day 15	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. The MADRS total score was calculated as the sum of the 10 individual item scores. Each item yields a score of 0 (no symptoms) to 6 (symptoms of maximum severity). The total MADRS score (sum of all individual items) ranges from 0 (symptoms absent) to 60 (severe depression). Higher MADRS scores indicated more severe depression. A negative change from baseline indicated improvement. LS mean was estimated using MMRM analysis.
Secondary	Percentage of Participants With MADRS Response at Day 15	Day 15	MADRS response was defined as having a 50% or greater reduction from baseline in MADRS total score. 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. Each item yields a score of 0 (no symptoms) to 6 (symptoms of maximum severity). The total MADRS score (sum of all individual items) ranges from 0 (symptoms absent) to 60 (severe depression). Higher MADRS scores indicated more severe depression. Percentages were rounded off to the first decimal point.

1 to 10 of 16Source ClinicalTrials.gov

See all 16 registered outcomes

Outcomes16

Each outcome the trial posted results for, in ClinicalTrials.gov's words.

Type	Outcome	Time frame	Population	Units	Measured as
PRIMARY	Change From Baseline in the HAMD-17 Total Score at Day 3	Baseline, Day 3	Full analysis set included all randomized participants who administered blinded IP with a valid baseline total score and at least 1 valid postbaseline total score in at least 1 of HAMD-17, HAM-A, MADRS, 9-item Patient Health Questionnaire (PHQ-9) or had a valid baseline and at least 1 valid postbaseline value in at least 1 of CGI-S or Clinical Global Impression - Improvement (CGI-I) score. Overall number of participants analyzed is the number of participants with data available for analysis.	score on a scale	LEAST_SQUARES_MEAN
SECONDARY	Change From Baseline in the HAMD-17 Total Score Over the Double-Blind Treatment Period	Baseline through Day 15	Full analysis set included all randomized participants who administered blinded IP with a valid baseline total score and at least 1 valid postbaseline total score in at least 1 of HAMD-17, HAM-A, MADRS, PHQ-9 or had a valid baseline and at least 1 valid postbaseline value in at least 1 of CGI-S or CGI-I score.	score on a scale	LEAST_SQUARES_MEAN
SECONDARY	Change From Baseline in the HAMD-17 Total Score at Days 15 and 42	Baseline, Days 15 and 42	Full analysis set included all randomized participants who administered blinded IP with a valid baseline total score and at least 1 valid postbaseline total score in at least 1 of HAMD-17, HAM-A, MADRS, PHQ-9 or had a valid baseline and at least 1 valid postbaseline value in at least 1 of CGI-S or CGI-I score.	score on a scale	LEAST_SQUARES_MEAN
SECONDARY	Change From Baseline in the HAMD-17 Total Score Around End of Blinded Treatment	Baseline, End of blinded treatment assessment (i.e., average of Days 12, 15 , and 18)	Full analysis set included all randomized participants who administered blinded IP with a valid baseline total score and at least 1 valid postbaseline total score in at least 1 of HAMD-17, HAM-A, MADRS, PHQ-9 or had a valid baseline and at least 1 valid postbaseline value in at least 1 of CGI-S or CGI-I score.	score on a scale	LEAST_SQUARES_MEAN
SECONDARY	Percentage of Participants With HAMD-17 Response at Day 15 and Day 42	At Days 15 and 42	Full analysis set included all randomized participants who administered blinded IP with a valid baseline total score and at least 1 valid postbaseline total score in at least 1 of HAMD-17, HAM-A, MADRS, PHQ-9 or had a valid baseline and at least 1 valid postbaseline value in at least 1 of CGI-S or CGI-I score. Number analyzed is the number of participants with data available for analysis at the specified time points.	percentage of participants	NUMBER
SECONDARY	Percentage of Participants With HAMD-17 Remission at Day 15 and Day 42	Days 15 and 42	Full analysis set included all randomized participants who administered blinded IP with a valid baseline total score and at least 1 valid postbaseline total score in at least 1 of HAMD-17, HAM-A, MADRS, PHQ-9 or had a valid baseline and at least 1 valid postbaseline value in at least 1 of CGI-S or CGI-I score. Number analyzed is number of participants with data available for analysis at the specified time points.	percentage of participants	NUMBER
SECONDARY	Change From Baseline in CGI-S Score at Day 15	Baseline and Day 15	Full analysis set included all randomized participants who administered blinded IP with a valid baseline total score and at least 1 valid postbaseline total score in at least 1 of HAMD-17, HAM-A, MADRS, PHQ-9 or had a valid baseline and at least 1 valid postbaseline value in at least 1 of CGI-S or CGI-I score. Overall number of participants analyzed is the number of participants with data available for analysis.	score on a scale	LEAST_SQUARES_MEAN
SECONDARY	Percentage of Participants With CGI-I Response, at Day 3 and Day 15	Days 3 and 15	Full analysis set included all randomized participants who administered blinded IP with a valid baseline total score and at least 1 valid postbaseline total score in at least 1 of HAMD-17, HAM-A, MADRS, PHQ-9 or had a valid baseline and at least 1 valid postbaseline value in at least 1 of CGI-S or CGI-I score. Number analyzed is the number of participants with data available for analysis at the specified time points.	percentage of participants	NUMBER
SECONDARY	Change From Baseline in MADRS Total Score at Day 15	Baseline and Day 15	Full analysis set included all randomized participants who administered blinded IP with a valid baseline total score and at least 1 valid postbaseline total score in at least 1 of HAMD-17, HAM-A, MADRS, PHQ-9 or had a valid baseline and at least 1 valid postbaseline value in at least 1 of CGI-S or CGI-I score. Overall number of participants analyzed is the number of participants with data available for analysis.	score on a scale	LEAST_SQUARES_MEAN
SECONDARY	Percentage of Participants With MADRS Response at Day 15	Day 15	Full analysis set included all randomized participants who administered blinded IP with a valid baseline total score and at least 1 valid postbaseline total score in at least 1 of HAMD-17, HAM-A, MADRS, PHQ-9 or had a valid baseline and at least 1 valid postbaseline value in at least 1 of CGI-S or CGI-I score. Overall number of participants analyzed is the number of participants with data available for analysis.	percentage of participants	NUMBER

1 to 10 of 16Source ClinicalTrials.gov

See all 16 outcomes

Results by group44

Each measurement the trial posted, group by group, in the words and numbers it posted.

Outcome	Group	Category	Value	Spread	Units
Change From Baseline in the HAMD-17 Total Score at Day 3	Placebo + Assigned ADT		-7.0	Standard Error 0.38	score on a scale
Change From Baseline in the HAMD-17 Total Score at Day 3	SAGE-217 + Assigned ADT		-8.9	Standard Error 0.39	score on a scale
Change From Baseline in the HAMD-17 Total Score Over the Double-Blind Treatment Period	Placebo + Assigned ADT		-10.1	Standard Error 0.39	score on a scale
Change From Baseline in the HAMD-17 Total Score Over the Double-Blind Treatment Period	SAGE-217 + Assigned ADT		-11.7	Standard Error 0.40	score on a scale
Change From Baseline in the HAMD-17 Total Score at Days 15 and 42	Placebo + Assigned ADT	Day 15	-12.9	Standard Error 0.49	score on a scale
Change From Baseline in the HAMD-17 Total Score at Days 15 and 42	SAGE-217 + Assigned ADT	Day 15	-13.7	Standard Error 0.50	score on a scale
Change From Baseline in the HAMD-17 Total Score at Days 15 and 42	Placebo + Assigned ADT	Day 42	-14.9	Standard Error 0.56	score on a scale
Change From Baseline in the HAMD-17 Total Score at Days 15 and 42	SAGE-217 + Assigned ADT	Day 42	-14.9	Standard Error 0.56	score on a scale
Change From Baseline in the HAMD-17 Total Score Around End of Blinded Treatment	Placebo + Assigned ADT		-12.7	Standard Error 0.45	score on a scale
Change From Baseline in the HAMD-17 Total Score Around End of Blinded Treatment	SAGE-217 + Assigned ADT		-13.2	Standard Error 0.46	score on a scale

1 to 10 of 44Source ClinicalTrials.gov

See all 44 results by group

Participant flow8

How many started, completed or left each group, period by period.

Period	Milestone	Group	Participants
Overall Study	STARTED	Placebo + Assigned ADT	220
Overall Study	STARTED	SAGE-217 + Assigned ADT	220
Overall Study	Safety Population	Placebo + Assigned ADT	218
Overall Study	Safety Population	SAGE-217 + Assigned ADT	212
Overall Study	COMPLETED	Placebo + Assigned ADT	177
Overall Study	COMPLETED	SAGE-217 + Assigned ADT	180
Overall Study	NOT COMPLETED	Placebo + Assigned ADT	43
Overall Study	NOT COMPLETED	SAGE-217 + Assigned ADT	40

Source ClinicalTrials.gov

Adverse events26

Each adverse event the trial posted, group by group: the participants affected out of those at risk.

Type	Event	Organ system	Group	Affected	At risk
other	Somnolence	Nervous system disorders	Placebo + Assigned ADT	18	218
other	Somnolence	Nervous system disorders	SAGE-217 + Assigned ADT	39	212
other	Dizziness	Nervous system disorders	Placebo + Assigned ADT	16	218
other	Dizziness	Nervous system disorders	SAGE-217 + Assigned ADT	28	212
other	Headache	Nervous system disorders	Placebo + Assigned ADT	32	218
other	Headache	Nervous system disorders	SAGE-217 + Assigned ADT	25	212
other	Sedation	Nervous system disorders	Placebo + Assigned ADT	6	218
other	Sedation	Nervous system disorders	SAGE-217 + Assigned ADT	12	212
other	Tremor	Nervous system disorders	Placebo + Assigned ADT	3	218
other	Tremor	Nervous system disorders	SAGE-217 + Assigned ADT	11	212

1 to 10 of 26Source ClinicalTrials.gov

See all 26 adverse events

Adverse event totals6

The totals the trial posted for each group.

Total	Group	Affected	At risk
Total, all-cause mortality	Placebo + Assigned ADT	0	220
Total, all-cause mortality	SAGE-217 + Assigned ADT	0	220
Total, other adverse events	Placebo + Assigned ADT	113	218
Total, other adverse events	SAGE-217 + Assigned ADT	123	212
Total, serious adverse events	Placebo + Assigned ADT	0	218
Total, serious adverse events	SAGE-217 + Assigned ADT	2	212

Source ClinicalTrials.gov

Papers1

The papers the trial lists on ClinicalTrials.gov.

PMID	Listed as
37875578	DERIVED

Source PubMed

Grants0

The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.

None in this release.

Trial comparisons2

Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.

Comparison	Source
Placebo + Assigned ADT vs SAGE-217 + Assigned ADT: deaths from any cause	Trial comparisons
Placebo + Assigned ADT vs SAGE-217 + Assigned ADT: serious adverse events	Trial comparisons

Tests0

The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.

None in this release.

Data dates

The day each source was copied for this release.

ClinicalTrials.gov: 2026-11-12; ClinicalTrials.gov
Results, from AACT: 2026-03-23; AACT
NIH grant links: 2026-11-13; NIH RePORTER

Sources 3

ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
ClinicalTrials.govNo license stated
NIH RePORTER's clinical studies and project filesPublic domain

Each source's terms

ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
ClinicalTrials.govnone stated
NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)

ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.

For software

Read this trial from software.

The record and each of its lists are JSON, twenty rows a page. No key.

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