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

• Sponsor: Sage Therapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04476030
• Collaborator: (none)
• Enrollment: 440
• Locations: 51
• Arms: 2
• Actual Duration (Months): 12.5
• Patients Per Site: 8.6
• Patients Per Site Per Month: 0.7

Study Details

Study Description

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 Design

• Study Type: Interventional
• 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: Nov 16, 2020
• Actual Primary Completion Date: Nov 30, 2021
• Actual Study Completion Date: Nov 30, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Change from Baseline in 17-item Hamilton Rating Scale for Depression (HAM-D) Total Score at Day 3 [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 [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 [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 [Baseline, Days 12, 15, and 18]

4. Percentage of Participants with HAM-D Response [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 [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 [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 [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 [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 [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 [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 [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 [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) [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) [Up to Day 42]

15. Percentage of Participants with TEAEs, Graded by Severity [Up to Day 42]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 64 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sage Investigational Site	Dothan	Alabama	United States	36303
2	Sage Investigational Site	Phoenix	Arizona	United States	85012
3	Sage Investigational Site	Anaheim	California	United States	92805
4	Sage Investigational Site	Costa Mesa	California	United States	92626
5	Sage Investigational Site	Glendale	California	United States	91206
6	Sage Investigational Site	Irvine	California	United States	92614
7	Sage Investigational Site	Los Alamitos	California	United States	90720
8	Sage Investigational Site	Oceanside	California	United States	92056
9	Sage Investigational Site	Orange	California	United States	92868
10	Sage Investigational Site	Riverside	California	United States	92503
11	Sage Investigational Site	San Diego	California	United States	92103
12	Sage Investigational Site	Temecula	California	United States	92591
13	Sage Investigational Site	Colorado Springs	Colorado	United States	80910
14	Sage Investigational Site	Cromwell	Connecticut	United States	06416
15	Sage Investigational Site	Norwich	Connecticut	United States	06360
16	Sage Investigational Site	Coral Springs	Florida	United States	33067
17	Sage Investigational Site	Jacksonville	Florida	United States	32256
18	Sage Investigational Site	Orlando	Florida	United States	32801
19	Sage Investigational Site	Orlando	Florida	United States	32807
20	Sage Investigational Site	Pensacola	Florida	United States	32502
21	Sage Investigational Site	Alpharetta	Georgia	United States	30022
22	Sage Investigational Site	Atlanta	Georgia	United States	30331
23	Sage Investigational Site	Marietta	Georgia	United States	30060
24	Sage Investigational Site	Savannah	Georgia	United States	31405
25	Sage Investigational Site	Chicago	Illinois	United States	60634
26	Sage Investigational Site	Chicago	Illinois	United States	60640
27	Sage Investigational Site	Towson	Maryland	United States	21204
28	Sage Investigational Site	Watertown	Massachusetts	United States	02472
29	Sage Investigational Site	Ann Arbor	Michigan	United States	48109
30	Sage Investigational Site	Saint Charles	Missouri	United States	63304
31	Sage Investigational Site	Lincoln	Nebraska	United States	68526
32	Sage Investigational Site	Cherry Hill	New Jersey	United States	08002
33	Sage Investigational Site	Marlton	New Jersey	United States	08053
34	Sage Investigational Site	Princeton	New Jersey	United States	08540
35	Sage Investigational Site	Albuquerque	New Mexico	United States	87109
36	Sage Investigational Site	Brooklyn	New York	United States	11229
37	Sage Investigational Site	Brooklyn	New York	United States	11235
38	Sage Investigational Site	Mount Kisco	New York	United States	10549
39	Sage Investigational Site	Beachwood	Ohio	United States	44122
40	Sage Investigational Site	Cincinnati	Ohio	United States	45212
41	Sage Investigational Site	Cincinnati	Ohio	United States	45215
42	Sage Investigational Site	Cincinnati	Ohio	United States	45219
43	Sage Investigational Site	North Canton	Ohio	United States	44720
44	Sage Investigational Site	Oklahoma City	Oklahoma	United States	73112
45	Sage Investigational Site	Plymouth Meeting	Pennsylvania	United States	19462
46	Sage Investigational Site	Austin	Texas	United States	78759
47	Sage Investigational Site	Dallas	Texas	United States	75231
48	Sage Investigational Site	Houston	Texas	United States	77030
49	Sage Investigational Site	Houston	Texas	United States	77081
50	Sage Investigational Site	Wichita Falls	Texas	United States	76309
51	Sage Investigational Site	Bellevue	Washington	United States	98007

Sponsors and Collaborators

• Sage Therapeutics

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sage Therapeutics
• ClinicalTrials.gov Identifier: NCT04476030
• Other Study ID Numbers: 217-MDD-305
• First Posted: Jul 17, 2020
• Last Update Posted: Mar 15, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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: Disease; Depressive Disorder; Depression; Depressive Disorder, Major; Duloxetine Hydrochloride; Citalopram; Sertraline; Desvenlafaxine Succinate

Study Results

No Results Posted as of Mar 15, 2022