Major Depressive Disorder
Conditions
Keywords
MDD, SAGE-217
Brief summary
This is a study with an Open-Label (OL) phase followed by a randomized, Double-Blind (DB), placebo-controlled phase to assess efficacy and safety of SAGE-217 on relapse prevention in adults with major depressive disorder (MDD).
Detailed description
This study was previously posted by Sage Therapeutics. In November 2023, sponsorship of the trial was transferred to Biogen.
Interventions
DRUGSAGE-217
SAGE-217 capsule
DRUGPlacebo
SAGE-217 matching placebo capsule
Sponsors
Biogen
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Participant had a diagnosis of MDD as diagnosed by Structured Clinical Interview for Diagnostic and DSM-5 Clinical Trial Version (SCID-5-CT), with symptoms that had been present for at least a 4-week period. 2. Participant had at least 1 prior major depressive episode (MDE) in the 5 years prior to Screening (not including the current episode). 3. Participant was willing to delay the start of any antidepressant, anxiolytic, insomnia, psychostimulant, prescription opioid regimens, and new psychotherapy (including Cognitive Behavioral Therapy for Insomnia \[CBT-I\]) until after study completion.
Exclusion criteria
1. Participant had attempted suicide associated with the current episode of MDD. 2. Participant had 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. Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (MGH ATRQ) was used for this purpose. 3. Participant had a positive pregnancy test at screening or on Day 1 prior to dosing.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Relapse During the DB Phase | Day 56 (Day 1 of DB Phase) up to Day 153 (i.e., up to 22 weeks) | Time to relapse was defined as days from the first dose of the study drug in the DB Phase to the day of relapse during the DB Phase. Participant was considered to have relapsed if: 2 consecutive HAM-D scores were ≥ 18 assessed 7 to 14 days apart, any worsening of depression requiring hospitalization, Investigator-determined risk of suicide, or any other clinically relevant event whether or not hospitalization was required. HAM-D is a scale used to rate depression in participants who were already diagnosed as depressed. The HAM-D total score comprised a sum of 17 individual item scores. Items scored in a range of 0 to 2 included: insomnia, somatic symptoms, genital symptoms, loss of weight, and insight. Items scored in a range of 0 to 4 included: agitation, depressed mood, feelings of guilt, suicide, work and activities, retardation, anxiety, hypochondriasis. The HAM-D total score could range from 0 (not depressed) to 52 (severely depressed). Higher scores indicated more depression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the 17-Item HAM-D Total Score at the End of Each 14-Day Treatment Period in the DB Phase | Day 56 (Baseline [Day 1] of DB Phase) up to Day 153 (i.e., up to 22 weeks) | The 17-item HAM-D scale was used to rate the severity of depression in participants who were already diagnosed as depressed. The HAM-D total score comprised a sum of 17 individual item scores. Items scored in a range of 0 to 2 included: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. Items scored in a range of 0 to 4 included: agitation, depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, work and activities, retardation (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), anxiety (psychic and somatic), hypochondriasis. The HAM-D total score could range from 0 (not depressed) to 52 (severely depressed). Higher scores indicated more depression. A negative change from baseline indicated improvement. |
| Percentage of Participants With HAM-D Response at the End of Each 14-Day Treatment Period in the DB Phase | Day 56 (Day 1 of DB Phase) up to Day 153 (i.e., up to 22 weeks) | HAM-D response was defined as having a 50% or greater reduction from baseline in HAM-D total score. The HAM-D total score comprised a sum of 17 individual item scores. Items scored in a range of 0 to 2 included: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. Items scored in a range of 0 to 4 included: agitation, depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, work and activities, retardation (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), anxiety (psychic and somatic), hypochondriasis. The HAM-D total score could range from 0 (not depressed) to 52 (severely depressed). Higher scores indicated more depression. |
| Percentage of Participants With HAM-D Remission at the End of Each 14-Day Treatment Period in the DB Phase | Day 56 (Day 1 of DB Phase) up to Day 153 (i.e., up to 22 weeks) | HAM-D remission was defined as having a HAM-D total score of ≤ 7. The HAM-D total score comprised a sum of 17 individual item scores. Items scored in a range of 0 to 2 included: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. Items scored in a range of 0 to 4 included: agitation, depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, work and activities, retardation (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), anxiety (psychic and somatic), hypochondriasis. The HAM-D total score could range from 0 (not depressed) to 52 (severely depressed). Higher scores indicated more depression. |
| Percentage of Participants With Clinical Global Impression - Improvement (CGI-I) Response at the End of Each 14-Day Treatment Period in the DB Phase | Day 56 (Day 1 of DB Phase) up to Day 153 (i.e., up to 22 weeks) | The CGI-I employs a 7-point Likert scale to measure the overall improvement in the participant's condition posttreatment. The Investigator rated the participant's total improvement whether or not it was due entirely to drug treatment. Response choices included: 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, and 7=very much worse. The CGI-I is only rated at posttreatment assessments. By definition, all CGI-I assessments are evaluated against baseline conditions. Higher score indicated worse condition. CGI-I response was defined as having a CGI-I score of very much improved or much improved. |
| Percentage of Participants Who Relapsed During the DB Phase | Day 56 (Day 1 of DB Phase) up to Day 153 (i.e., up to 22 weeks) | Participant was considered to have relapsed if: 2 consecutive HAM-D scores were ≥ 18 assessed 7 to 14 days apart, worsening of depression requiring hospitalization, Investigator-determined risk of suicide, or other clinically relevant events whether hospitalization was required. HAM-D scale was used to rate depression in participants who were diagnosed as depressed. Total score is a sum of 17 individual item scores. Items in a range of 0-2 included: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. Items in a range of 0-4 included: agitation, depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, work and activities, retardation (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), anxiety (psychic and somatic), hypochondriasis. Total score could range from 0 (not depressed)- 52 (severely depressed). Higher scores indicated more depression. |
| Change From Baseline in 9-Item Patient Health Questionnaire (PHQ-9) Score at the End of Each 14-Day Treatment Period in the DB Phase | Day 56 (Baseline [Day 1] of DB Phase) up to Day 153 (i.e, up to 22 weeks) | The PHQ-9 is a participant-rated depressive symptom severity scale. To monitor severity over time participants in current treatment for depression, participants completed the questionnaires at baseline and at regular intervals thereafter. Scoring was 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 total score was calculated as the sum of the 9 individual item scores and ranged from 0 to 27. The PHQ-9 total score was categorized as follows: 1 to 4=minimal depression, 5 to 9=mild depression, 10 to 14=moderate depression, 15 to 19=moderately severe depression; and 20 to 27=severe depression. Higher score indicated severe depression. A negative change from baseline indicated improvement. |
| Time to Relapse During The DB Phase for Participants Who Achieved HAM-D Remission in the OL Phase | Day 56 (Day 1 of DB Phase) up to Day 153 (i.e., up to 22 weeks) | Time to relapse was defined as days from the first dose of the study drug in the DB Phase to the day of relapse during the DB Phase. Participant was considered to have relapsed if: 2 consecutive HAM-D scores were ≥18 assessed 7 to 14 days apart, any worsening of depression requiring hospitalization, Investigator-determined risk of suicide, or any other clinically relevant event whether or not hospitalization was required. HAM-D is a scale used to rate depression in participants who were already diagnosed as depressed. The HAM-D total score comprised a sum of 17 individual item scores. Items scored in a range of 0 to 2 included: insomnia, somatic symptoms, genital symptoms, loss of weight, and insight. Items scored in a range of 0 to 4 included: agitation, depressed mood, feelings of guilt, suicide, work and activities, retardation, anxiety, hypochondriasis. The HAM-D total score could range from 0 (not depressed) to 52 (severely depressed). Higher scores indicated more depression. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | From the first dose of study drug up to the end of the study (i.e., up to approximately 22 weeks) | An adverse event (AE) was defined as 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. A TEAE was defined as an AE with onset after the start of study drug, or any worsening of a pre-existing medical condition/AE with onset after the start of study drug and throughout the study. |
| Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at the End of Each 14-Day Treatment Period in the DB Phase | Day 56 (Baseline [Day 1] of DB Phase) up to Day 153 (i.e., up to 22 weeks) | 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 had the same diagnosis. Considering total clinical experience, a participant was assessed on severity of mental illness at the time of rating as 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; and 7= among the most extremely ill participant. A higher score indicated extreme illness. A negative change from baseline indicated improvement (a higher absolute number indicating more illness). |
Countries
United States
Participant flow
Recruitment details
Participants took part in this study at 28 investigative sites in the United States from 06 August 2019 to 06 January 2020.
Pre-assignment details
The study was conducted in 2 parts: Open-Label (OL) and Double-Blind (DB) Phase. Participants received SAGE-217 during treatment period in OL Phase. Participants who exhibited a Hamilton Rating Scale for Depression response in OL Phase were to be randomized in a ratio of 1:1 to receive either SAGE-217 matching placebo or SAGE-217 oral capsule in DB Phase. However, the study was terminated by sponsor due to business decisions and only 2 participants entered the DB Phase and did not complete it.
Participants by arm
| Arm | Count |
|---|---|
| Open-Label Phase: SAGE-217 Participants self-administered SAGE-217, 30 mg, oral capsule, QD in the evening from Day 1 to Day 14. | 53 |
| Total | 53 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double-Blind Phase (14-Weeks) | Withdrawal by Participant | 0 | 0 | 2 |
| Open-Label Phase (8-Weeks) | Adverse Event | 2 | 0 | 0 |
| Open-Label Phase (8-Weeks) | Non-compliance | 1 | 0 | 0 |
| Open-Label Phase (8-Weeks) | Study Terminated by Sponsor | 43 | 0 | 0 |
| Open-Label Phase (8-Weeks) | Withdrawal by Participant | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Open-Label Phase: SAGE-217 |
|---|---|
| Age, Continuous | 39.6 years STANDARD_DEVIATION 12.16 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 45 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants |
| Race (NIH/OMB) More than one race | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 37 Participants |
| Sex: Female, Male Female | 37 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 53 | 0 / 0 | 0 / 2 |
| other Total, other adverse events | 19 / 53 | 0 / 0 | 0 / 2 |
| serious Total, serious adverse events | 0 / 53 | 0 / 0 | 0 / 2 |
Outcome results
Primary
Time to Relapse During the DB Phase
Time to relapse was defined as days from the first dose of the study drug in the DB Phase to the day of relapse during the DB Phase. Participant was considered to have relapsed if: 2 consecutive HAM-D scores were ≥ 18 assessed 7 to 14 days apart, any worsening of depression requiring hospitalization, Investigator-determined risk of suicide, or any other clinically relevant event whether or not hospitalization was required. HAM-D is a scale used to rate depression in participants who were already diagnosed as depressed. The HAM-D total score comprised a sum of 17 individual item scores. Items scored in a range of 0 to 2 included: insomnia, somatic symptoms, genital symptoms, loss of weight, and insight. Items scored in a range of 0 to 4 included: agitation, depressed mood, feelings of guilt, suicide, work and activities, retardation, anxiety, hypochondriasis. The HAM-D total score could range from 0 (not depressed) to 52 (severely depressed). Higher scores indicated more depression.
Time frame: Day 56 (Day 1 of DB Phase) up to Day 153 (i.e., up to 22 weeks)
Population: Due to early termination of the study by the sponsor, no data was collected, and no efficacy analysis was performed as planned, thus data is not available for this outcome measure.
Secondary
Change From Baseline in 9-Item Patient Health Questionnaire (PHQ-9) Score at the End of Each 14-Day Treatment Period in the DB Phase
The PHQ-9 is a participant-rated depressive symptom severity scale. To monitor severity over time participants in current treatment for depression, participants completed the questionnaires at baseline and at regular intervals thereafter. Scoring was 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 total score was calculated as the sum of the 9 individual item scores and ranged from 0 to 27. The PHQ-9 total score was categorized as follows: 1 to 4=minimal depression, 5 to 9=mild depression, 10 to 14=moderate depression, 15 to 19=moderately severe depression; and 20 to 27=severe depression. Higher score indicated severe depression. A negative change from baseline indicated improvement.
Time frame: Day 56 (Baseline [Day 1] of DB Phase) up to Day 153 (i.e, up to 22 weeks)
Population: Due to early termination of the study by the sponsor, no data was collected, and no efficacy analysis was performed as planned, thus data is not available for this outcome measure.
Secondary
Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at the End of Each 14-Day Treatment Period in the DB Phase
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 had the same diagnosis. Considering total clinical experience, a participant was assessed on severity of mental illness at the time of rating as 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; and 7= among the most extremely ill participant. A higher score indicated extreme illness. A negative change from baseline indicated improvement (a higher absolute number indicating more illness).
Time frame: Day 56 (Baseline [Day 1] of DB Phase) up to Day 153 (i.e., up to 22 weeks)
Population: Due to early termination of the study by the sponsor, no data was collected, and no efficacy analysis was performed as planned, thus data is not available for this outcome measure.
Secondary
Change From Baseline in the 17-Item HAM-D Total Score at the End of Each 14-Day Treatment Period in the DB Phase
The 17-item HAM-D scale was used to rate the severity of depression in participants who were already diagnosed as depressed. The HAM-D total score comprised a sum of 17 individual item scores. Items scored in a range of 0 to 2 included: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. Items scored in a range of 0 to 4 included: agitation, depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, work and activities, retardation (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), anxiety (psychic and somatic), hypochondriasis. The HAM-D total score could range from 0 (not depressed) to 52 (severely depressed). Higher scores indicated more depression. A negative change from baseline indicated improvement.
Time frame: Day 56 (Baseline [Day 1] of DB Phase) up to Day 153 (i.e., up to 22 weeks)
Population: Due to early termination of the study by the sponsor, no data was collected, and no efficacy analysis was performed as planned, thus data is not available for this outcome measure.
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) was defined as 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. A TEAE was defined as an AE with onset after the start of study drug, or any worsening of a pre-existing medical condition/AE with onset after the start of study drug and throughout the study.
Time frame: From the first dose of study drug up to the end of the study (i.e., up to approximately 22 weeks)
Population: Safety Set included all participants who were administered the study drug. Data for this outcome measure was not collected for DB Phase: Placebo arm because none of the participants were enrolled into this group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double-Blind Phase: Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 26 Participants |
| Double-Blind Phase: SAGE-217 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 0 Participants |
Secondary
Percentage of Participants Who Relapsed During the DB Phase
Participant was considered to have relapsed if: 2 consecutive HAM-D scores were ≥ 18 assessed 7 to 14 days apart, worsening of depression requiring hospitalization, Investigator-determined risk of suicide, or other clinically relevant events whether hospitalization was required. HAM-D scale was used to rate depression in participants who were diagnosed as depressed. Total score is a sum of 17 individual item scores. Items in a range of 0-2 included: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. Items in a range of 0-4 included: agitation, depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, work and activities, retardation (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), anxiety (psychic and somatic), hypochondriasis. Total score could range from 0 (not depressed)- 52 (severely depressed). Higher scores indicated more depression.
Time frame: Day 56 (Day 1 of DB Phase) up to Day 153 (i.e., up to 22 weeks)
Population: Due to early termination of the study by the sponsor, no data was collected, and no efficacy analysis was performed as planned, thus data is not available for this outcome measure.
Secondary
Percentage of Participants With Clinical Global Impression - Improvement (CGI-I) Response at the End of Each 14-Day Treatment Period in the DB Phase
The CGI-I employs a 7-point Likert scale to measure the overall improvement in the participant's condition posttreatment. The Investigator rated the participant's total improvement whether or not it was due entirely to drug treatment. Response choices included: 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, and 7=very much worse. The CGI-I is only rated at posttreatment assessments. By definition, all CGI-I assessments are evaluated against baseline conditions. Higher score indicated worse condition. CGI-I response was defined as having a CGI-I score of very much improved or much improved.
Time frame: Day 56 (Day 1 of DB Phase) up to Day 153 (i.e., up to 22 weeks)
Population: Due to early termination of the study by the sponsor, no data was collected, and no efficacy analysis was performed as planned, thus data is not available for this outcome measure.
Secondary
Percentage of Participants With HAM-D Remission at the End of Each 14-Day Treatment Period in the DB Phase
HAM-D remission was defined as having a HAM-D total score of ≤ 7. The HAM-D total score comprised a sum of 17 individual item scores. Items scored in a range of 0 to 2 included: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. Items scored in a range of 0 to 4 included: agitation, depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, work and activities, retardation (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), anxiety (psychic and somatic), hypochondriasis. The HAM-D total score could range from 0 (not depressed) to 52 (severely depressed). Higher scores indicated more depression.
Time frame: Day 56 (Day 1 of DB Phase) up to Day 153 (i.e., up to 22 weeks)
Population: Due to early termination of the study by the sponsor, no data was collected, and no efficacy analysis was performed as planned, thus data is not available for this outcome measure.
Secondary
Percentage of Participants With HAM-D Response at the End of Each 14-Day Treatment Period in the DB Phase
HAM-D response was defined as having a 50% or greater reduction from baseline in HAM-D total score. The HAM-D total score comprised a sum of 17 individual item scores. Items scored in a range of 0 to 2 included: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. Items scored in a range of 0 to 4 included: agitation, depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, work and activities, retardation (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), anxiety (psychic and somatic), hypochondriasis. The HAM-D total score could range from 0 (not depressed) to 52 (severely depressed). Higher scores indicated more depression.
Time frame: Day 56 (Day 1 of DB Phase) up to Day 153 (i.e., up to 22 weeks)
Population: Due to early termination of the study by the sponsor, no data was collected, and no efficacy analysis was performed as planned, thus data is not available for this outcome measure.
Secondary
Time to Relapse During The DB Phase for Participants Who Achieved HAM-D Remission in the OL Phase
Time to relapse was defined as days from the first dose of the study drug in the DB Phase to the day of relapse during the DB Phase. Participant was considered to have relapsed if: 2 consecutive HAM-D scores were ≥18 assessed 7 to 14 days apart, any worsening of depression requiring hospitalization, Investigator-determined risk of suicide, or any other clinically relevant event whether or not hospitalization was required. HAM-D is a scale used to rate depression in participants who were already diagnosed as depressed. The HAM-D total score comprised a sum of 17 individual item scores. Items scored in a range of 0 to 2 included: insomnia, somatic symptoms, genital symptoms, loss of weight, and insight. Items scored in a range of 0 to 4 included: agitation, depressed mood, feelings of guilt, suicide, work and activities, retardation, anxiety, hypochondriasis. The HAM-D total score could range from 0 (not depressed) to 52 (severely depressed). Higher scores indicated more depression.
Time frame: Day 56 (Day 1 of DB Phase) up to Day 153 (i.e., up to 22 weeks)
Population: Due to early termination of the study by the sponsor, no data was collected, and no efficacy analysis was performed as planned, thus data is not available for this outcome measure.