A Study to Evaluate the Efficacy of Sage-217 in the Treatment of Adult Participants With Major Depressive Disorder (MDD)

• Sponsor: Sage Therapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04442490
• Collaborator: (none)
• Enrollment: 543
• Locations: 38
• Arms: 2
• Actual Duration (Months): 11.5
• Patients Per Site: 14.3
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

The purpose of this study to evaluate the efficacy of SAGE-217 in the treatment of participants with MDD.

Condition or Disease	Intervention/Treatment	Phase
Depressive Disorder, Major	Drug: SAGE-217; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 543 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study Evaluating the Efficacy of SAGE-217 in the Treatment of Adult Subjects With Major Depressive Disorder
• Actual Study Start Date: May 7, 2020
• Actual Primary Completion Date: Mar 26, 2021
• Actual Study Completion Date: Apr 21, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SAGE-217 Participants will receive SAGE-217 capsules, once daily for 14 days. The dose may be decreased based on safety and tolerability.	Drug: SAGE-217; SAGE-217 oral capsules.
Placebo Comparator: SAGE-217 Matched Placebo Participants will receive SAGE-217 matched-placebo capsules, once daily for 14 days.	Drug: Placebo; SAGE-217 matched-placebo oral capsules.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D) Total Score at Day 15 [Baseline and Day 15]

   The 17-item HAM-D scale is used to assess the severity of depression. It is comprised of individual ratings related to the 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 a 3-point (0 to 2) or a 5-point scale (0 to 4), with 0=none/absent and 4=most severe. The total score is the sum of individual items, ranging from 0 to 52; where a higher score indicates more depression.

Secondary Outcome Measures

1. Clinical Global Impression - Severity (CGI-S) Score [Day 15]

   The CGI-S is 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. A participant is assessed on severity of mental illness at the time of rating as 1=normal, not at all ill; 2=borderline ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; and 7= among the most extremely ill participants.

2. HAM-D Total Score [Baseline and Days 3, 28, and 42]

   The 17-item HAM-D scale is used to assess the severity of depression. It is comprised of individual ratings related to the 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 a 3-point (0 to 2) or a 5-point scale (0 to 4), with 0=none/absent and 4=most severe. The total score is the sum of individual items, ranging from 0 to 52; where a higher score indicates more depression.

3. Percentage of Participants With HAM-D Response [Days 15 and 42]

   The time to response is defined as time from first administration of study drug to the time when ≥50% reduction in HAM-D score from baseline is achieved.

4. Percentage of Participants With HAM-D Remission [Days 15 and 42]

   HAM-D remission is defined as HAM-D total score ≤7.

5. Percentage of Participants With Clinical Global Impression - Improvement (CGI-I) Response [Day 15]

   CGI-I response is 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 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.

6. Montgomery Åsberg Depression Rating Scale (MADRS) Total Score [Day 15]

   The MADRS is a 10-item diagnostic questionnaire used to measure the severity of depressive episodes in participants with mood disorders. Each item is rated on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score ranges from 0 to 60 with a higher score indicating more depression.

7. Hamilton Rating Scale for Anxiety (HAM-A) Total Score [Day 15]

   The 14-item HAM-A is comprised of a series of symptoms, and measures both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints related to anxiety). The HAM-A total score will be calculated as the sum of the 14 individual item scores. The scoring for HAM-A is calculated by assigning scores of 0 (not present) to 4 (very severe), with a total score range of 0 to 56.

8. Time to First HAM-D Response [Days 1, 3, 8, 12, 15, 21, 28, 35 and 42]

   The time to response is defined as time from first administration of study drug to the time when ≥50% reduction in HAM-D score from baseline is achieved.

9. Change From Baseline in PRO Measures of Health-Related Quality of Life, as Assessed by the 36-item Short Form version 2 (SF-36v2) Score [Baseline and Days 1, 8, 15, 28 and 42]

   Participant's health will be assessed using Patient-reported outcome (PRO) health related quality of life (HRQOL) SF-36 V2. The SF-36v2 is a 36-item measure including eight health dimensions which are four physical health status domains and four mental health status domains. Scores on each item are summed and averaged (range = 0 "worst"-100 "best"). Higher SF-36v2 scores will indicate a better state of health.

10. Change From Baseline in PRO Measures of Depressive Symptoms, as Assessed by the 9-item Patient Health Questionnaire (PHQ-9) Score [Baseline and Days 1, 8, 15, 28 and 42]

    The PHQ-9 is a participant-rated depressive symptom severity scale where scoring is based on responses to specific questions. The score will be calculated as the sum of the 9 individual item scores. The PHQ-9 total score ranges from 1 to 27 with a higher score indicating more depression.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Participant with diagnosis of MDD as diagnosed by Structured Clinical Interview for Diagnostic and Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) Clinical Trial Version [SCID-5-CT], with symptoms that have been present for at least a 4-week period.

2. Participant has a Hamilton Rating Scale for Depression (HAM-D) total score ≥24 at screening and Day 1 (prior to dosing).

3. Participants taking antidepressants must have been taking these medications at the same dose for at least 60 days prior to Day 1. Participants who have stopped taking antidepressants within 60 days must have stopped for longer than 5 half-lives of the antidepressant prior to Day 1. Participants receiving psychotherapy must have been receiving therapy on a regular schedule for at least 60 days prior to Day 1.

4. Participant is willing to delay start of other antidepressant or antianxiety medications and any new pharmacotherapy regimens, including as-needed benzodiazepine anxiolytics and sleep aids, until after completion of the Day 42 visit.

Exclusion Criteria:

1. Participant is currently at significant risk of suicide, as judged by the Investigator, or has attempted suicide associated with the current episode of MDD.

2. Participant has 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.

3. Participant has a body mass index (BMI) ≤18 or ≥45 kg/m^2 at Screening, which is subject to a broader evaluation of medical comorbidities.

4. Participant has 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.

5. Participant has a medical history of seizures, bipolar disorder, schizophrenia, and/or schizoaffective disorder.

6. Participant has a history of mild, moderate, or severe substance use disorder (including benzodiazepines) diagnosed using DSM-5 criteria in the 12 months prior to screening.

7. Participant is taking psychostimulants (eg, methylphenidate, amphetamine) or opioids, regularly or as-needed, at Day -28.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sage Investigational Site	Rogers	Arkansas	United States	72758
2	Sage Investigational Site	Bellflower	California	United States	90706
3	Sage Investigational Site	Garden Grove	California	United States	92845
4	Sage Investigational Site	Glendale	California	United States	91206
5	Sage Investigational Site	Lemon Grove	California	United States	91945
6	Sage Investigational Site	Orange	California	United States	92868
7	Sage Investigational Site	Pico Rivera	California	United States	90660
8	Sage Investigational Site	Redlands	California	United States	92374
9	Sage Investigational Site	San Diego	California	United States	92103
10	Sage Investigational Site	Sherman Oaks	California	United States	91403
11	Sage Investigational Site	Temecula	California	United States	92591
12	Sage Investigational Site	Coral Springs	Florida	United States	33067
13	Sage Investigational Site	Hollywood	Florida	United States	33024
14	Sage Investigational Site	Jacksonville	Florida	United States	32256
15	Sage Investigational Site	Lauderhill	Florida	United States	33319
16	Sage Investigational Site	Orange City	Florida	United States	32763
17	Sage Investigational Site	Orlando	Florida	United States	32801
18	Sage Investigational Site	Orlando	Florida	United States	32807
19	Sage Investigational Site	Alpharetta	Georgia	United States	30022
20	Sage Investigational Site	Atlanta	Georgia	United States	30328
21	Sage Investigational Site	Atlanta	Georgia	United States	30331
22	Sage Investigational Site	Decatur	Georgia	United States	30030
23	Sage Investigational Site	Skokie	Illinois	United States	60076
24	Sage Investigational Site	Flowood	Mississippi	United States	39232
25	Sage Investigational Site	O'Fallon	Missouri	United States	63368
26	Sage Investigational Site	Las Vegas	Nevada	United States	89102
27	Sage Investigational Site	Marlton	New Jersey	United States	08053
28	Sage Investigational Site	Charlotte	North Carolina	United States	28211
29	Sage Investigational Site	Cincinnati	Ohio	United States	45215
30	Sage Investigational Site	Dayton	Ohio	United States	45417
31	Sage Investigational Site	North Canton	Ohio	United States	44720
32	Sage Investigational Site	Oklahoma City	Oklahoma	United States	73112
33	Sage Investigational Site	Portland	Oregon	United States	97210
34	Sage Investigational Site	Allentown	Pennsylvania	United States	18104
35	Sage Investigational Site	Memphis	Tennessee	United States	38119
36	Sage Investigational Site	DeSoto	Texas	United States	75115
37	Sage Investigational Site	Wichita Falls	Texas	United States	76309
38	Sage Investigational Site	Charlottesville	Virginia	United States	22903

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: NCT04442490
• Other Study ID Numbers: 217-MDD-301B
• First Posted: Jun 22, 2020
• Last Update Posted: Mar 29, 2022
• Last Verified: Mar 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: Depression; Depressive disorder; SAGE-217
• Additional relevant MeSH terms: Disease; Depressive Disorder; Depression; Depressive Disorder, Major

Study Results

No Results Posted as of Mar 29, 2022