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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

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ClinicalTrials.gov Identifier: NCT04476030
Recruitment Status : Recruiting
First Posted : July 17, 2020
Last Update Posted : March 29, 2021
Sponsor:
Information provided by (Responsible Party):
Sage Therapeutics

Tracking Information
First Submitted Date  ICMJE July 15, 2020
First Posted Date  ICMJE July 17, 2020
Last Update Posted Date March 29, 2021
Actual Study Start Date  ICMJE November 16, 2020
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 15, 2020)
Change from Baseline in 17-item Hamilton Rating Scale for Depression (HAM-D) Total Score at Day 15 [ Time Frame: Baseline and Day 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 15, 2020)
  • 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.
  • Change from Baseline in 17-item HAM-D Total Score [ Time Frame: Baseline, Days 3, 8 and 42 ]
    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.
  • 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.
  • 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.
  • Percentage of Participants with Clinical Global Impression - Improvement (CGI-I) Response [ Time Frame: Day 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: 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.
  • 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.
  • 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.
  • 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.
  • Change from Baseline in Depressive Symptoms Assessed by 9-item Patient Health Questionnaire (PHQ-9) [ Time Frame: Baseline up to 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, 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.
  • Percentage of Participants with Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Up to Day 42 ]
  • Percentage of Participants with TEAEs, Graded by Severity [ Time Frame: Up to Day 42 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Comparative Study of Sage-217 Plus an Antidepressant (ADT) Versus Placebo Plus an ADT in Adults With Major Depressive Disorder
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Depressive Disorder, Major
Intervention  ICMJE
  • Drug: SAGE-217
    Oral capsules
  • 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
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: SAGE-217
    • Drug: Sertraline
    • Drug: Escitalopram
    • Drug: Citalopram
    • Drug: Duloxetine
    • Drug: Desvenlafaxine
  • 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.
    Interventions:
    • Drug: Matching Placebo
    • Drug: Sertraline
    • Drug: Escitalopram
    • Drug: Citalopram
    • Drug: Duloxetine
    • Drug: Desvenlafaxine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 15, 2020)
424
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 64 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Handan Gunduz-Bruce, MD, MBA +1 617-949-2883 handan.gunduz-bruce@sagerx.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04476030
Other Study ID Numbers  ICMJE 217-MDD-305
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Data sharing will be consistent with the results submission policy of ClinicalTrials.gov.
Responsible Party Sage Therapeutics
Study Sponsor  ICMJE Sage Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Sage Therapeutics
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP