A Comparative Study of Sage-217 Plus an Antidepressant (ADT) Versus Placebo Plus an ADT in Adults With Major Depressive Disorder
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| ClinicalTrials.gov Identifier: NCT04476030 |
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Recruitment Status :
Completed
First Posted : July 17, 2020
Results First Posted : November 7, 2023
Last Update Posted : December 22, 2023
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Sponsor:
Biogen
Information provided by (Responsible Party):
Biogen
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Brief Summary:
The primary purpose of this study is to evaluate the efficacy of SAGE-217 plus an ADT in the treatment of major depressive disorder (MDD) compared to placebo plus an ADT.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Depressive Disorder, Major | Drug: SAGE-217 Drug: Matching Placebo Drug: Sertraline Drug: Escitalopram Drug: Citalopram Drug: Duloxetine Drug: Desvenlafaxine | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 440 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 3, Randomized, Double-Blind Study Comparing the Efficacy and Safety of SAGE-217 Plus an Antidepressant Versus Placebo Plus an Antidepressant in Adults With Major Depressive Disorder |
| Actual Study Start Date : | November 9, 2020 |
| Actual Primary Completion Date : | October 25, 2021 |
| Actual Study Completion Date : | December 22, 2021 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Depression
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: Placebo + Assigned ADT
Participants received SAGE-217-matching placebo capsules, orally, once daily along with an assigned ADT (sertraline, escitalopram, citalopram, duloxetine, or desvenlafaxine administered per labeled prescribing information), daily, from Day 1 through 14, followed by the same ADT, per labeled prescribing information, daily, up to Day 42.
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Drug: Matching Placebo
Oral capsules Drug: Sertraline Oral tablets Drug: Escitalopram Oral tablets Drug: Citalopram Oral tablets Drug: Duloxetine Oral capsules Drug: Desvenlafaxine Oral tablets |
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Experimental: SAGE-217 + Assigned ADT
Participants received SAGE-217, 50 milligrams (mg), orally, once daily along with an assigned ADT (sertraline, escitalopram, citalopram, duloxetine, or desvenlafaxine administered per labeled prescribing information), daily from Day 1 through 14, followed by the same ADT, per labeled prescribing information, daily, up to Day 42.
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Drug: SAGE-217
Oral capsules Drug: Sertraline Oral tablets Drug: Escitalopram Oral tablets Drug: Citalopram Oral tablets Drug: Duloxetine Oral capsules Drug: Desvenlafaxine Oral tablets |
Primary Outcome Measures :
- Change From Baseline in the HAMD-17 Total Score at Day 3 [ Time Frame: 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 Outcome Measures :
- Change From Baseline in the HAMD-17 Total Score Over the Double-Blind Treatment Period [ Time Frame: 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.
- Change From Baseline in the HAMD-17 Total Score at Days 15 and 42 [ Time Frame: 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.
- Change From Baseline in the HAMD-17 Total Score Around End of Blinded Treatment [ Time Frame: 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.
- Percentage of Participants With HAMD-17 Response at Day 15 and Day 42 [ Time Frame: 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.
- Percentage of Participants With HAMD-17 Remission at Day 15 and Day 42 [ Time Frame: 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.
- Change From Baseline in CGI-S Score at Day 15 [ Time Frame: 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.
- Percentage of Participants With CGI-I Response, at Day 3 and Day 15 [ Time Frame: 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.
- Change From Baseline in MADRS Total Score at Day 15 [ 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. 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.
- Percentage of Participants With MADRS Response at Day 15 [ Time Frame: 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.
- Percentage of Participants With MADRS Remission at Day 15 [ Time Frame: Day 15 ]MADRS remission was defined as having a MADRS total score of ≤10. 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.
- Change From Baseline in HAM-A Total Score at Day 15 [ Time Frame: Baseline, Day 15 ]Each of the 14 items in the HAM-A was defined by a series of symptoms, and measured both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints). The HAM-A total score was calculated as sum of the 14 individual item scores, each rated on a five point scale ranging from 0 (not present) to 4 (very severe). The total score (sum of all individual items) range from 0 to 56, where <17 indicated mild severity, 18 to 24 indicated mild to moderate severity, and 25 to 30 indicated moderate to severe severity. Higher scores indicated more severe disease. Negative change from baseline indicated improvement. LS mean was estimated using MMRM analysis.
- Time to First HAMD-17 Response [ Time Frame: From first dose of study drug up to first HAMD-17 response (up to approximately 65 days) ]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. Time (in days) from first dose of study drug to time of first HAMD response was reported in this outcome measure.
- Change From Baseline in Depressive Symptoms at Day 15, as Assessed by PHQ-9 [ Time Frame: Baseline and Day 15 ]The PHQ-9 is a participant-rated depressive symptom severity scale. The PHQ-9 total score is calculated as the sum of the 9 individual item scores. For individual items, scoring is based on responses to specific questions, as follows: 0 = not at all; 1 = several days; 2 = more than half the days; and 3 = nearly every day. The PHQ-9 possible total score range is 0 to 27, with higher scores reflecting greater depressive symptoms, and is categorized as follows: 0 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. Negative change from baseline indicated improvement. LS mean was estimated using MMRM analysis.
- Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Up to approximately 58 weeks ]An adverse event (AE) was any untoward medical occurrence in a participant 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, symptom or disease temporally associated with the use of a medicinal (investigational) product whether or not related to the medicinal (investigational) product. A TEAE was 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.
- Percentage of Participants With TEAEs, Graded by Severity [ Time Frame: Up to approximately 58 weeks ]An AE was any untoward medical occurrence in a participant 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, symptom or disease temporally associated with the use of a medicinal (investigational) product whether or not related to the medicinal (investigational) product. A TEAE was 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. The severity was graded as mild, moderate and severe.
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| Ages Eligible for Study: | 18 Years to 64 Years (Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Diagnosis of MDD as diagnosed by Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition Clinical Trials Version (SCID-5-CT), with symptoms that have been present for at least a 4-week period
- 17-item Hamilton Rating Scale for Depression (HAM-D-17) total score of ≥24 at Screening and Day 1
- Participant in good physical health and has no clinically significant findings, as determined by the investigator, on physical examination, 12-lead electrocardiogram (ECG), or clinical laboratory tests
- Participant is willing, able, and eligible to take at least 1 of the 5 ADTs specified in the protocol (an eligible ADT is an ADT that has not been taken during the current depressive episode and for which the participant has no contraindications; further, a participant is not eligible for citalopram if escitalopram has been taken during the current depressive episode, and vice versa)
Exclusion Criteria:
- Has attempted suicide associated with the current episode of MDD
- Participant had 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
- Participant has treatment-resistant depression
- History of bipolar disorder, schizophrenia, and/or schizoaffective disorder
- Known allergy to SAGE-217, allopregnanolone, or related compounds
- Has taken antidepressants within 30 days prior to Day 1, and/or has taken fluoxetine within 60 days prior to Day 1
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04476030
Locations
Show 51 study locations
Sponsors and Collaborators
Biogen
Study Documents (Full-Text)
Documents provided by Biogen:
Documents provided by Biogen:
Study Protocol [PDF] January 10, 2022
Statistical Analysis Plan [PDF] January 11, 2022
| Responsible Party: | Biogen |
| ClinicalTrials.gov Identifier: | NCT04476030 |
| Other Study ID Numbers: |
217-MDD-305 |
| First Posted: | July 17, 2020 Key Record Dates |
| Results First Posted: | November 7, 2023 |
| Last Update Posted: | December 22, 2023 |
| Last Verified: | December 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 |
| Product Manufactured in and Exported from the U.S.: | No |
Keywords provided by Biogen:
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Major Depressive Disorder MDD SAGE-217 |
Additional relevant MeSH terms:
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Depressive Disorder Depression Depressive Disorder, Major Mood Disorders Mental Disorders Behavioral Symptoms Duloxetine Hydrochloride Citalopram Sertraline Desvenlafaxine Succinate Zuranolone Escitalopram Selective Serotonin Reuptake Inhibitors Neurotransmitter Uptake Inhibitors |
Membrane Transport Modulators Molecular Mechanisms of Pharmacological Action Neurotransmitter Agents Serotonin Agents Physiological Effects of Drugs Peripheral Nervous System Agents Antidepressive Agents, Second-Generation Antidepressive Agents Psychotropic Drugs Serotonin and Noradrenaline Reuptake Inhibitors Analgesics Sensory System Agents Dopamine Agents |