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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04476030
Recruitment Status : Completed
First Posted : July 17, 2020
Last Update Posted : March 15, 2022
Sponsor:
Information provided by (Responsible Party):
Sage Therapeutics

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

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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 16, 2020
Actual Primary Completion Date : November 30, 2021
Actual Study Completion Date : November 30, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Experimental: SAGE-217 + Assigned ADT
Participants will receive SAGE-217 capsules, orally, daily 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 for up to 42 days, with fat-containing food.
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

Active Comparator: Active Comparator: Placebo + Assigned ADT
Participants will receive SAGE-217-matching placebo capsules, orally, daily 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 for up to 42 days, with fat-containing food.
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




Primary Outcome Measures :
  1. Change from Baseline in 17-item Hamilton Rating Scale for Depression (HAM-D) Total Score at Day 3 [ Time Frame: Baseline and Day 3 ]
    HAM-D total score will be the sum of the 17 individual item scores. Items with score range of 0 to 2 include insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. Items with score range of 2 to 4 include 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), and hypochondriasis. The total score ranges from 0 to 52, where higher score indicates more depression.


Secondary Outcome Measures :
  1. Change from Baseline in 17-item HAM-D Total Score over the Blinded Treatment Period Using Equal Weights for the Scheduled Visits [ Time Frame: Baseline, Days 3, 8, 12, and 15 ]
    HAM-D total score will be the sum of the 17 individual item scores. Items with score range of 0 to 2 include insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. Items with score range of 2 to 4 include 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), and hypochondriasis. The total score ranges from 0 to 52, where higher score indicates more depression.

  2. Change from Baseline in 17-item HAM-D Total Score at Days 15 and 42 [ Time Frame: Baseline, Days 15 and 42 ]
  3. Change from Baseline in 17-item HAM-D Total Score Around the End of Blinded Treatment Using Equal Weights for the Scheduled Visits [ Time Frame: Baseline, Days 12, 15, and 18 ]
  4. Percentage of Participants with HAM-D Response [ Time Frame: Days 15 and 42 ]
    HAM-D response is defined as having a 50% or greater reduction from baseline in HAM-D total score.

  5. Percentage of Participants with HAM-D Remission [ Time Frame: Days 15 and 42 ]
    HAM-D remission is defined as having a HAM-D total score of ≤7.

  6. Change from Baseline in Clinical Global Impression - Severity (CGI-S) Score [ Time Frame: Baseline and Day 15 ]
    CGI-S uses a 7-point Likert scale to rate the severity of the participant's illness at the time of assessment. Severity of mental illness is assessed using ratings 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.

  7. Percentage of Participants with Clinical Global Impression - Improvement (CGI-I) Response [ Time Frame: Days 3 and 15 ]
    CGI-I response will be defined as having a CGI-I score of 1 (very much improved) or 2 (much improved). CGI-I employs a 7-point Likert scale to measure the overall improvement (whether or not due entirely to drug treatment) in 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.

  8. Change from Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score [ Time Frame: Baseline and Day 15 ]
    MADRS is a 10-item diagnostic questionnaire used to measure the severity of depressive episodes in participants with mood disorders. Each item has a score range of 0 to 6. MADRS total score (ranging from 0 to 60) will be sum of the 10 individual item scores. The higher MADRS scores indicate more severe depression.

  9. Percentage of Participants with MADRS Response [ Time Frame: Day 15 ]
    MADRS response is defined as having a 50% or greater reduction from baseline in MADRS total score.

  10. Percentage of Participants with MADRS Remission [ Time Frame: Day 15 ]
    MADRS remission is defined as having a MADRS total score of ≤10.

  11. Change from Baseline in Hamilton Anxiety Rating Scale (HAM-A) Total Score [ Time Frame: Baseline and Day 15 ]
    14-item HAM-A will be used to rate the severity of symptoms of anxiety. HAM-A total score will be the sum of the 14 individual item scores. Each of the 14 items measures both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints related to anxiety). Scores of 0 (not present) to 4 (very severe) are assigned, with a total score range of 0 to 56, where <17 = mild severity, 18 to 24 = mild to moderate severity, and 25 to 30 = moderate to severe severity.

  12. Time to First HAM-D Response [ Time Frame: Up to Day 42 ]
    HAM-D response is defined as having a 50% or greater reduction from baseline in HAM-D total score.

  13. Change from Baseline in Depressive Symptoms Assessed by 9-item Patient Health Questionnaire (PHQ-9) [ Time Frame: Baseline and Day 15 ]
    PHQ-9 is a participant-rated depressive symptom severity scale consisting of 9 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. PHQ-9 total score will be the sum of the 9 individual item scores, where, 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.

  14. Percentage of Participants with Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Up to Day 42 ]
  15. Percentage of Participants with TEAEs, Graded by Severity [ Time Frame: Up to Day 42 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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
  • 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
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Sponsors and Collaborators
Sage Therapeutics
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Responsible Party: Sage Therapeutics
ClinicalTrials.gov Identifier: NCT04476030    
Other Study ID Numbers: 217-MDD-305
First Posted: July 17, 2020    Key Record Dates
Last Update Posted: March 15, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Data sharing will be consistent with the results submission policy of ClinicalTrials.gov.

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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 Sage Therapeutics:
Major Depressive Disorder
MDD
SAGE-217
Additional relevant MeSH terms:
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Disease
Depressive Disorder
Depression
Depressive Disorder, Major
Pathologic Processes
Mood Disorders
Mental Disorders
Behavioral Symptoms
Duloxetine Hydrochloride
Citalopram
Sertraline
Desvenlafaxine Succinate
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Peripheral Nervous System Agents
Serotonin and Noradrenaline Reuptake Inhibitors
Analgesics
Sensory System Agents
Dopamine Agents