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A Study to Evaluate SAGE-217 for Prevention of Relapse in Adult Participants With Major Depressive Disorder

Primary Purpose

Major Depressive Disorder

Status

Terminated

Phase

Phase 3

Locations

United States

Study Type

Interventional

Intervention

SAGE-217

Placebo

About this trial

This is an interventional treatment trial for Major Depressive Disorder focused on measuring MDD, SAGE-217

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.
Participant had at least 1 prior major depressive episode (MDE) in the 5 years prior to Screening (not including the current episode).
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:

Participant had attempted suicide associated with the current episode of MDD.
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.
Participant had a positive pregnancy test at screening or on Day 1 prior to dosing.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Experimental

Arm Label

Open-Label Phase: SAGE-217

Double-Blind Phase: Placebo

Double-Blind Phase: SAGE-217

Arm Description

Participants self-administered SAGE-217, 30 milligrams (mg), oral capsule, once daily (QD) in the evening from Day 1 to Day 14.

Following the OL Phase, participants who exhibited a Hamilton Rating Scale for Depression (HAM-D) response, defined as a greater than or equal to (≥) 50% reduction from baseline in HAM-D total score were to be randomized to receive SAGE-217 matching placebo capsule, orally, QD, in the evening, in a total of five, 14-day treatment periods, each separated by a 6-week follow-up period during the 40-week DB Phase of the study. However, no participants were randomized to receive SAGE-217 matching placebo due to early study termination.

Following the OL Phase, participants who exhibited a HAM-D response defined as a ≥ 50% reduction from baseline in HAM-D total score to SAGE-217 were randomized to receive SAGE-217, 30 mg, oral capsule, QD, in the evening, up to study termination date (i.e., up to approximately 22 weeks) during the DB Phase of the study.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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.

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.

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."

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).

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 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.

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.

Full Information

NCT ID

NCT04007367

First Posted

July 2, 2019

Last Updated

August 31, 2022

Sponsor

Sage Therapeutics

1. Study Identification

Unique Protocol Identification Number

NCT04007367

Brief Title

A Study to Evaluate SAGE-217 for Prevention of Relapse in Adult Participants With Major Depressive Disorder

Official Title

A Phase 3, Randomized, Double-Blind, Placebo-controlled Study of the Efficacy and Safety of SAGE-217 With a Fixed, Repeated Treatment Regimen on Relapse Prevention in Adults With Major Depressive Disorder

Study Type

Interventional

2. Study Status

Record Verification Date

April 2022

Overall Recruitment Status

Terminated

Why Stopped

Internal company decision

Study Start Date

August 6, 2019 (Actual)

Primary Completion Date

January 6, 2020 (Actual)

Study Completion Date

January 6, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Sage Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Major Depressive Disorder

Keywords

MDD, SAGE-217

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Sequential Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

53 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Open-Label Phase: SAGE-217

Arm Type

Experimental

Arm Description

Participants self-administered SAGE-217, 30 milligrams (mg), oral capsule, once daily (QD) in the evening from Day 1 to Day 14.

Arm Title

Double-Blind Phase: Placebo

Arm Type

Placebo Comparator

Arm Description

Arm Title

Double-Blind Phase: SAGE-217

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

SAGE-217

Intervention Description

SAGE-217 capsule

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

SAGE-217 matching placebo capsule

Primary Outcome Measure Information:

Title

Time to Relapse During the DB Phase

Description

Time Frame

Day 56 (Day 1 of DB Phase) up to Day 153 (i.e., up to 22 weeks)

Secondary Outcome Measure Information:

Title

Percentage of Participants Who Relapsed During the DB Phase

Description

Time Frame

Day 56 (Day 1 of DB Phase) up to Day 153 (i.e., up to 22 weeks)

Title

Change From Baseline in the 17-Item HAM-D Total Score at the End of Each 14-Day Treatment Period in the DB Phase

Description

Time Frame

Day 56 (Baseline [Day 1] of DB Phase) up to Day 153 (i.e., up to 22 weeks)

Title

Percentage of Participants With HAM-D Response at the End of Each 14-Day Treatment Period in the DB Phase

Description

Time Frame

Day 56 (Day 1 of DB Phase) up to Day 153 (i.e., up to 22 weeks)

Title

Percentage of Participants With HAM-D Remission at the End of Each 14-Day Treatment Period in the DB Phase

Description

Time Frame

Day 56 (Day 1 of DB Phase) up to Day 153 (i.e., up to 22 weeks)

Title

Percentage of Participants With Clinical Global Impression - Improvement (CGI-I) Response at the End of Each 14-Day Treatment Period in the DB Phase

Description

Time Frame

Day 56 (Day 1 of DB Phase) up to Day 153 (i.e., up to 22 weeks)

Title

Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at the End of Each 14-Day Treatment Period in the DB Phase

Description

Time Frame

Day 56 (Baseline [Day 1] of DB Phase) up to Day 153 (i.e., up to 22 weeks)

Title

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

Description

Time Frame

Day 56 (Baseline [Day 1] of DB Phase) up to Day 153 (i.e, up to 22 weeks)

Title

Time to Relapse During The DB Phase for Participants Who Achieved HAM-D Remission in the OL Phase

Description

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)

Title

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

Description

Time Frame

From the first dose of study drug up to the end of the study (i.e., up to approximately 22 weeks)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Participant had at least 1 prior major depressive episode (MDE) in the 5 years prior to Screening (not including the current episode). 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: Participant had attempted suicide associated with the current episode of MDD. 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. Participant had a positive pregnancy test at screening or on Day 1 prior to dosing.

Facility Information:

Facility Name

Sage Investigational Site

City

Bentonville

State/Province

Arkansas

ZIP/Postal Code

72712

Country

United States

Facility Name

Sage Investigational Site

City

Bellflower

State/Province

California

ZIP/Postal Code

90706

Country

United States

Facility Name

Sage Investigational Site

City

Garden Grove

State/Province

California

ZIP/Postal Code

92845-2506

Country

United States

Facility Name

Sage Investigational Site

City

Lemon Grove

State/Province

California

ZIP/Postal Code

91945

Country

United States

Facility Name

Sage Investigational Site

City

Oceanside

State/Province

California

ZIP/Postal Code

92056-4500

Country

United States

Facility Name

Sage Investigational Site

City

Orange

State/Province

California

ZIP/Postal Code

92868-2847

Country

United States

Facility Name

Sage Investigational Site

City

Riverside

State/Province

California

ZIP/Postal Code

92503

Country

United States

Facility Name

Sage Investigational Site

City

San Diego

State/Province

California

ZIP/Postal Code

92103

Country

United States

Facility Name

Sage Investigational Site

City

San Marcos

State/Province

California

ZIP/Postal Code

92078

Country

United States

Facility Name

Sage Investigational Site

City

Sherman Oaks

State/Province

California

ZIP/Postal Code

91403-2131

Country

United States

Facility Name

Sage Investigational Site

City

Coral Springs

State/Province

Florida

ZIP/Postal Code

33067-4644

Country

United States

Facility Name

Sage Investigational Site

City

Jacksonville

State/Province

Florida

ZIP/Postal Code

32256

Country

United States

Facility Name

Sage Investigational Site

City

Lauderhill

State/Province

Florida

ZIP/Postal Code

33319

Country

United States

Facility Name

Sage Investigational Site

City

Orlando

State/Province

Florida

ZIP/Postal Code

32801

Country

United States

Facility Name

Sage Investigational Site

City

Alpharetta

State/Province

Georgia

ZIP/Postal Code

30022

Country

United States

Facility Name

Sage Investigational Site

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30328

Country

United States

Facility Name

Sage Investigational Site

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30329

Country

United States

Facility Name

Sage Investigational Site

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30331

Country

United States

Facility Name

Sage Investigational Site

City

Decatur

State/Province

Georgia

ZIP/Postal Code

30030

Country

United States

Facility Name

Sage Investigational Site

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60634

Country

United States

Facility Name

Sage Investigational Site

City

Lincolnwood

State/Province

Illinois

ZIP/Postal Code

60712

Country

United States

Facility Name

Sage Investigational Site

City

Lake Charles

State/Province

Louisiana

ZIP/Postal Code

70629

Country

United States

Facility Name

Sage Investigational Site

City

Gaithersburg

State/Province

Maryland

ZIP/Postal Code

20877

Country

United States

Facility Name

Sage Investigational Site

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02131

Country

United States

Facility Name

Sage Investigational Site

City

Methuen

State/Province

Massachusetts

ZIP/Postal Code

01844

Country

United States

Facility Name

Sage Investigational Site

City

Watertown

State/Province

Massachusetts

ZIP/Postal Code

02472-4153

Country

United States

Facility Name

Sage Investigational Site

City

Ann Arbor

State/Province

Michigan

ZIP/Postal Code

48109-2700

Country

United States

Facility Name

Sage Investigational Site

City

Las Vegas

State/Province

Nevada

ZIP/Postal Code

89102

Country

United States

Facility Name

Sage Investigational Site

City

Berlin

State/Province

New Jersey

ZIP/Postal Code

08009

Country

United States

Facility Name

Sage Investigational Site

City

Cherry Hill

State/Province

New Jersey

ZIP/Postal Code

08002-3008

Country

United States

Facility Name

Sage Investigational Site

City

Marlton

State/Province

New Jersey

ZIP/Postal Code

08053

Country

United States

Facility Name

Sage Investigational Site

City

Albuquerque

State/Province

New Mexico

ZIP/Postal Code

87109

Country

United States

Facility Name

Sage Investigational Site

City

Jamaica

State/Province

New York

ZIP/Postal Code

11432

Country

United States

Facility Name

Sage Investigational Site

City

New York

State/Province

New York

ZIP/Postal Code

10017

Country

United States

Facility Name

Sage Investigational Site

City

New York

State/Province

New York

ZIP/Postal Code

10128

Country

United States

Facility Name

Sage Investigational Site

City

Rochester

State/Province

New York

ZIP/Postal Code

14618-1609

Country

United States

Facility Name

Sage Investigational Site

City

Dayton

State/Province

Ohio

ZIP/Postal Code

454117

Country

United States

Facility Name

Sage Investigational Site

City

North Canton

State/Province

Ohio

ZIP/Postal Code

44720

Country

United States

Facility Name

Sage Investigational Site

City

Oklahoma City

State/Province

Oklahoma

ZIP/Postal Code

73106

Country

United States

Facility Name

Sage Investigational Site

City

Allentown

State/Province

Pennsylvania

ZIP/Postal Code

18104-5051

Country

United States

Facility Name

Sage Investigational Site

City

Memphis

State/Province

Tennessee

ZIP/Postal Code

38119

Country

United States

Facility Name

Sage Investigational Site

City

Austin

State/Province

Texas

ZIP/Postal Code

78737

Country

United States

Facility Name

Sage Investigational Site

City

Dallas

State/Province

Texas

ZIP/Postal Code

75231-3442

Country

United States

Facility Name

Sage Investigational Site

City

Richardson

State/Province

Texas

ZIP/Postal Code

75080

Country

United States

Facility Name

Sage Investigational Site

City

Wichita Falls

State/Province

Texas

ZIP/Postal Code

76309

Country

United States

Facility Name

Sage Investigational Site

City

Everett

State/Province

Washington

ZIP/Postal Code

98201

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

Data sharing will be consistent with the results submission policy of ClinicalTrials.gov.

Learn more about this trial

A Study to Evaluate SAGE-217 for Prevention of Relapse in Adult Participants With Major Depressive Disorder

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A Study to Evaluate SAGE-217 for Prevention of Relapse in Adult Participants With Major Depressive Disorder

Major Depressive Disorder

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial