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NCT03672175

A Study to Evaluate the Efficacy of SAGE-217 in the Treatment of Adult Participants With Major Depressive Disorder

Completed Phase 3 Results posted Last updated 29 November 2023
What this trial tests

Phase 3 trial testing SAGE-217 in Major Depressive Disorder in 581 participants. Completed in 17 March 2020.

Timeline
19 November 2018
Primary endpoint
24 September 2019
17 March 2020

Quick facts

Lead sponsorBiogen
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment581
Start date19 November 2018
Primary completion24 September 2019
Estimated completion17 March 2020
Sites53 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Biogen — full company profile →

Who can join

Adults 18 to 65, any sex, with Major Depressive Disorder. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in the 17-item HAM-D Total Score at Day 15 Primary · Baseline (BL), Day 15

The 17-item HAM-D is used to rate the severity of depression in participants who were already diagnosed as depressed. The HAM-D total score comprises a sum of the 17 individual item scores. 8 items scored in a range of 0 to 2 include: Insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. The following 9 items are scored in a range of 0 to 4: Agitation, depressed mood, feelings of guilt, suicide, work and activities, retardation, anxiety (psychic and somatic), and hypochondriasis. Total HAM-D score can range from 0 to 52,

GroupValue95% CI
SAGE-217 Matched Placebo-11.1± 0.59
SAGE-217 20 mg-11.5± 0.62
SAGE-217 30 mg-12.5± 0.68
Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Day 15 Secondary · Baseline, Day 15

The CGI-S uses a 7-point Likert scale to rate the severity of the participant's illness 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=extremely ill. A higher score indicates extreme illness/more severity. A negative change from baseline indicates less severe illness.

GroupValue95% CI
SAGE-217 Matched Placebo-1.5± 0.10
SAGE-217 20 mg-1.6± 0.11
SAGE-217 30 mg-1.7± 0.11
Change From Baseline in the 17-item HAM-D Total Score Secondary · Baseline, Days 3, 8, 42, and 182

The 17-item HAM-D is used to rate the severity of depression in participants who were already diagnosed as depressed. The HAM-D total score comprises a sum of the 17 individual item scores. 8 items scored in a range of 0 to 2 include: Insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. The following 9 items are scored in a range of 0 to 4: Agitation, depressed mood, feelings of guilt, suicide, work and activities, retardation, anxiety (psychic and somatic), and hypochondriasis. Total HAM-D score can range from 0 to 52,

Change from Baseline at Day 3
GroupValue95% CI
SAGE-217 Matched Placebo-6.7± 0.46
SAGE-217 20 mg-7.1± 0.48
SAGE-217 30 mg-8.3± 0.47
Change from Baseline at Day 8
GroupValue95% CI
SAGE-217 Matched Placebo-7.8± 0.53
SAGE-217 20 mg-8.4± 0.54
SAGE-217 30 mg-9.9± 0.60
Change from Baseline at Day 42
GroupValue95% CI
SAGE-217 Matched Placebo-11.7± 0.64
SAGE-217 20 mg-11.5± 0.70
SAGE-217 30 mg-11.9± 0.67
Change from Baseline at Day 182
GroupValue95% CI
SAGE-217 Matched Placebo-13.2± 0.74
SAGE-217 20 mg-13.4± 0.83
SAGE-217 30 mg-13.9± 0.72
Number of Participants Achieving HAM-D Response Secondary · Days 15, 42, and 182

HAM-D response is defined as a ≥50% reduction in HAM-D score from baseline. The HAM-D total score comprises a sum of the 17 individual item scores. 8 items scored in a range of 0 to 2 include: Insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. The following 9 items are scored in a range of 0 to 4: Agitation, depressed mood, feelings of guilt, suicide, work and activities, retardation, anxiety (psychic and somatic), and hypochondriasis. Total HAM-D score can range from 0 to 52, and higher scores indicate severe depress

Day 15
GroupValue95% CI
SAGE-217 Matched Placebo60
SAGE-217 20 mg65
SAGE-217 30 mg77
Day 42
GroupValue95% CI
SAGE-217 Matched Placebo56
SAGE-217 20 mg59
SAGE-217 30 mg59
Day 182
GroupValue95% CI
SAGE-217 Matched Placebo51
SAGE-217 20 mg39
SAGE-217 30 mg51
Number of Participants Achieving HAM-D Remission Secondary · Days 15, 42, and 182

HAM-D remission is defined as HAM-D total score ≤7. The HAM-D total score comprises a sum of the 17 individual item scores. 8 items scored in a range of 0 to 2 include: Insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. The following 9 items are scored in a range of 0 to 4: Agitation, depressed mood, feelings of guilt, suicide, work and activities, retardation, anxiety (psychic and somatic), and hypochondriasis. Total HAM-D score can range from 0 to 52, and higher scores indicate severe depression.

Day 15
GroupValue95% CI
SAGE-217 Matched Placebo33
SAGE-217 20 mg35
SAGE-217 30 mg48
Day 42
GroupValue95% CI
SAGE-217 Matched Placebo35
SAGE-217 20 mg39
SAGE-217 30 mg33
Day 182
GroupValue95% CI
SAGE-217 Matched Placebo32
SAGE-217 20 mg29
SAGE-217 30 mg34
Number of Participants Achieving Clinical Global Impression - Improvement (CGI-I) Response at Day 15 Secondary · Day 15

CGI-I response is defined as 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 post-treatment. 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.

GroupValue95% CI
SAGE-217 Matched Placebo65
SAGE-217 20 mg71
SAGE-217 30 mg84
Change From Baseline in Hamilton Anxiety Rating Scale (HAM-A) Total Score at Day 15 Secondary · Baseline, Day 15

The 14-item HAM-A is used to rate the severity of symptoms of anxiety. Each of the 14 items is defined by a series of symptoms and measures both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints related to anxiety). Scoring for HAM-A is calculated by assigning scores of 0 (not present) to 4 (very severe) to each item. Total HAM-A score is calculated as the sum of the 14 individual item scores with a total score range of 0 to 56, where the score of \<17 indicates mild severity, 18 to 24 indicates mild to moderate severity, and 25 to 30 indica

GroupValue95% CI
SAGE-217 Matched Placebo-8.7± 0.49
SAGE-217 20 mg-9.1± 0.54
SAGE-217 30 mg-9.4± 0.53
Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Day 15 Secondary · Baseline, 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). Total MADRS score, calculated as the sum of the 10 individual items, ranges from 0 to 60 with a higher score indicating more depression. A negative change from baseline indicates less severe symptoms.

GroupValue95% CI
SAGE-217 Matched Placebo-16.0± 0.93
SAGE-217 20 mg-16.7± 1.00
SAGE-217 30 mg-18.0± 1.03
Change From Baseline in HAM-D Core Subscale Score Secondary · Baseline, Days 15, and 42

The 17-item HAM-D is used to rate the severity of depression in participants who were already diagnosed as depressed. HAM-D subscale scores are calculated as the sum of the items comprising each subscale. The core subscale score is the sum of the following symptom scores, scored in a range of 0 to 4: Depressed mood, feelings of guilt, suicide, work and activities, and retardation. Total HAM-D core subscale scores were transformed to a scale of 0 to 100. Higher scores indicate more severe depression. A negative change from baseline indicates less depression.

Change from Baseline at Day 15
GroupValue95% CI
SAGE-217 Matched Placebo-21.7± 1.33
SAGE-217 20 mg-21.3± 1.31
SAGE-217 30 mg-22.6± 1.38
Change from Baseline at Day 42
GroupValue95% CI
SAGE-217 Matched Placebo-23.1± 1.36
SAGE-217 20 mg-22.4± 1.44
SAGE-217 30 mg-23.6± 1.40
Change From Baseline in HAM-D Anxiety Subscale Score Secondary · Baseline, Days 15, and 42

The 17-item HAM-D is used to rate the severity of depression in participants who were already diagnosed as depressed. HAM-D subscale scores are calculated as the sum of the items comprising each subscale. The anxiety subscale score is the sum of the following symptom scores: Anxiety (psychic and somatic) \[scored in a range of 0 to 4\], somatic symptoms (gastrointestinal and general) \[scored in a range of 0 to 2\], hypochondriasis \[scored in a range of 0 to 4\], and loss of weight \[scored in a range of 0 to 2\]. Total HAM-D anxiety subscale scores were transformed to a scale of 0 to 100. Hi

Change from Baseline at Day 15
GroupValue95% CI
SAGE-217 Matched Placebo-19.4± 1.19
SAGE-217 20 mg-20.1± 1.28
SAGE-217 30 mg-22.1± 1.30
Change from Baseline at Day 42
GroupValue95% CI
SAGE-217 Matched Placebo-22.0± 1.27
SAGE-217 20 mg-20.7± 1.38
SAGE-217 30 mg-21.7± 1.29
Change From Baseline in HAM-D Bech-6 Subscale Score Secondary · Baseline, Days 15, and 42

The 17-item HAM-D is used to rate the severity of depression in participants who were already diagnosed as depressed. HAM-D subscale scores are calculated as the sum of the items comprising each subscale. The Bech-6 subscale score is the sum of the following symptom scores, scored in a range of 0 to 4: Depressed mood, feelings of guilt, work and activities, retardation, anxiety psychic, and somatic symptoms general. Total HAM-D Bech-6 subscale scores were transformed to a scale of 0 to 100. Higher scores indicate more severe depression. A negative change from baseline indicates less depression

Change from Baseline at Day 15
GroupValue95% CI
SAGE-217 Matched Placebo-26.2± 1.57
SAGE-217 20 mg-26.3± 1.62
SAGE-217 30 mg-28.7± 1.70
Change from Baseline at Day 42
GroupValue95% CI
SAGE-217 Matched Placebo-28.0± 1.66
SAGE-217 20 mg-27.4± 1.77
SAGE-217 30 mg-28.7± 1.70
Change From Baseline in HAM-D Maier Subscale Score Secondary · Baseline, Days 15, and 42

The 17-item HAM-D is used to rate the severity of depression in participants who were already diagnosed as depressed. HAM-D subscale scores are calculated as the sum of the items comprising each subscale. The Maier subscale score is the sum of the following symptom scores, scored in a range of 0 to 4: Depressed mood, feelings of guilt, work and activities, retardation, agitation, and anxiety psychic. Total HAM-D Maier subscale scores were transformed to a scale of 0 to 100. Higher scores indicate more severe depression. A negative change from baseline indicates less depression.

Change from Baseline at Day 15
GroupValue95% CI
SAGE-217 Matched Placebo-23.4± 1.34
SAGE-217 20 mg-23.1± 1.37
SAGE-217 30 mg-25.9± 1.45
Change from Baseline at Day 42
GroupValue95% CI
SAGE-217 Matched Placebo-25.0± 1.42
SAGE-217 20 mg-24.8± 1.53
SAGE-217 30 mg-26.2± 1.49

Adverse events — posted to ClinicalTrials.gov

Time frame: Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Treatment Period: SAGE-217 Matched Placebo
Serious: 0/190 (0%)
Deaths: 0/190
Treatment Period: SAGE-217 20 mg
Serious: 0/188 (0%)
Deaths: 0/188
Treatment Period: SAGE-217 30 mg
Serious: 2/192 (1%)
Deaths: 0/192
FU Period: SAGE-217 Matched Placebo
Serious: 1/190 (1%)
Deaths: 0/190
FU Period: SAGE-217 20 mg
Serious: 1/188 (1%)
Deaths: 0/188
FU Period: SAGE-217 30 mg
Serious: 1/192 (1%)
Deaths: 0/192
Extended FU Period: SAGE-217 Matched Placebo
Serious: 1/129 (1%)
Deaths: 0/129
Extended FU Period: SAGE-217 20 mg
Serious: 3/127 (2%)
Deaths: 1/127
Extended FU Period: SAGE-217 30 mg
Serious: 1/131 (1%)
Deaths: 0/131

Serious adverse events (20 terms)

ReactionSystemTreatment Period: SAGE-217…Treatment Period: SAGE-217…Treatment Period: SAGE-217…FU Period: SAGE-217 Matche…FU Period: SAGE-217 20 mgFU Period: SAGE-217 30 mgExtended FU Period: SAGE-2…Extended FU Period: SAGE-2…Extended FU Period: SAGE-2…
Bile duct stoneHepatobiliary disorders
Suicide attemptPsychiatric disorders
AgitationPsychiatric disorders
DeliriumPsychiatric disorders
Drug abusePsychiatric disorders
Suicidal ideationPsychiatric disorders
DepressionPsychiatric disorders
ManiaPsychiatric disorders
SyncopeNervous system disorders
Toxic encephalopathyNervous system disorders
Ankle fractureInjury, poisoning and procedural complications
Cervical vertebral fractureInjury, poisoning and procedural complications
Tibia fractureInjury, poisoning and procedural complications
PneumoniaInfections and infestations
RhabdomyolysisMusculoskeletal and connective tissue disorders
Acute kidney injuryRenal and urinary disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
HypertensionVascular disorders
DeathGeneral disorders
Diabetic footSkin and subcutaneous tissue disorders
Other adverse events (7 terms — click to expand)

ReactionSystemTreatment Period: SAGE-217…Treatment Period: SAGE-217…Treatment Period: SAGE-217…FU Period: SAGE-217 Matche…FU Period: SAGE-217 20 mgFU Period: SAGE-217 30 mgExtended FU Period: SAGE-2…Extended FU Period: SAGE-2…Extended FU Period: SAGE-2…
HeadacheNervous system disorders
DizzinessNervous system disorders
SomnolenceNervous system disorders
FatigueGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
SedationNervous system disorders
NauseaGastrointestinal disorders

Most-reported serious reactions: Bile duct stone, Suicide attempt, Agitation, Delirium, Drug abuse, Suicidal ideation, Depression, Mania.

Data from ClinicalTrials.gov NCT03672175 adverse events section.

Sponsor's own description

This study is a phase 3, multicenter, double-blind, randomized, placebo-controlled study evaluating the efficacy of SAGE-217 in the treatment of adult participants with major depressive disorder (MDD).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. The future of psychopharmacology: a critical appraisal of ongoing phase 2/3 trials, and of some current trends aiming to de-risk trial programmes of novel agents.
    Correll CU, Solmi M, Cortese S, Fava M, et al · · 2023 · cited 90× · PMID 36640403 · DOI 10.1002/wps.21056
  2. Zuranolone in Major Depressive Disorder: Results From MOUNTAIN-A Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial.
    Clayton AH, Lasser R, Nandy I, Sankoh AJ, et al · · 2023 · cited 50× · PMID 36811520 · DOI 10.4088/jcp.22m14445
  3. Clinical specificity profile for novel rapid acting antidepressant drugs.
    Scala M, Fanelli G, De Ronchi D, Serretti A, et al · · 2023 · cited 33× · PMID 37381161 · DOI 10.1097/yic.0000000000000488
  4. Novel Antidepressants in the Pipeline (Phase II and III): A Systematic Review of the US Clinical Trials Registry.
    Sakurai H, Yonezawa K, Tani H, Mimura M, et al · · 2022 · cited 21× · PMID 35045580 · DOI 10.1055/a-1714-9097
  5. Emerging Therapeutics Based on the Amino Acid Neurotransmitter System: An Update on the Pharmaceutical Pipeline for Mood Disorders.
    Hecking J, Davoudian PA, Wilkinson ST. · · 2021 · cited 13× · PMID 34124495 · DOI 10.1177/24705470211020446
  6. Key considerations in the pharmacological management of treatment-resistant depression.
    Yavi M, Henter ID, Park LT, Zarate C. · · 2021 · cited 10× · PMID 34252320 · DOI 10.1080/14656566.2021.1951225
  7. The efficacy and safety of Zuranolone for treatment of depression: A systematic review and meta-analysis.
    Fayoud AM, Orebi HA, Elshnoudy IA, Elsebaie MAT, et al · · 2024 · cited 3× · PMID 38802705 · DOI 10.1007/s00213-024-06611-y
  8. Neuroendocrine insights into neurosteroid therapy for postpartum depression.
    Reddy DS. · · 2023 · cited 3× · PMID 37541828 · DOI 10.1016/j.molmed.2023.07.006

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing