NCT03692910

A Study to Evaluate SAGE-217 in Participants With Bipolar I/II Disorder With a Current Major Depressive Episode

Completed Phase 2 Results posted Last updated 13 December 2023

What this trial tests

Phase 2 trial testing SAGE-217 in Bipolar Disorder I in 35 participants. Completed in 21 May 2019.

Timeline

23 August 2018

Primary endpoint
21 May 2019

21 May 2019

Quick facts

Lead sponsor	Biogen
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	35
Start date	23 August 2018
Primary completion	21 May 2019
Estimated completion	21 May 2019
Sites	11 locations across United States

Drugs / interventions tested

• SAGE-217 — full drug profile →
• Placebo

Conditions studied

• Bipolar Disorder I — all drugs for Bipolar Disorder I →
• Bipolar Disorder II — all drugs for Bipolar Disorder II →
• Major Depressive Episode — all drugs for Major Depressive Episode →

Sponsor

Biogen — full company profile →

Who can join

Adults 18 to 65, any sex, with Bipolar Disorder I or Bipolar Disorder II. 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.

Part A: Number of Participants With at Least One Treatment-Emergent Adverse Events (TEAEs) Primary · From first dose of study drug up to Day 42

An adverse event (AE) was 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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not related to the medicinal (investigational) product. A TEAE was defined as an adverse event with onset after the start of study through Day 42/early terminati

Group	Value	95% CI
Part A (Open-label): SAGE-217	16

Part A: Number of Participants With TEAEs, Graded by Severity Primary · From first dose of study drug up to Day 42

An adverse event (AE) was 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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not related to the medicinal (investigational) product. A TEAE was defined as an adverse event with onset after the start of study through Day 42/early terminati

Mild

Group	Value	95% CI
Part A (Open-label): SAGE-217	11

Moderate

Group	Value	95% CI
Part A (Open-label): SAGE-217	5

Severe

Group	Value	95% CI
Part A (Open-label): SAGE-217	0

Part A: Percentages of Participants With Response to Suicidal Ideation and Suicidal Behavior Based on the Columbia-Suicide Severity Rating Scale (C-SSRS) Primary · Baseline, Post-baseline (any time up to Day 42)

Suicidality was monitored using the C-SSRS. This scale consists of a baseline evaluation that assesses the lifetime experience of the participant with suicidal ideation and behavior, and a post-baseline evaluation that focuses on suicidality since the last study visit. The C-SSRS includes 'yes' or 'no' responses for assessment of suicidal ideation (wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods, active suicidal ideation with some intent, active suicidal ideation with specific plan) and behavior (preparatory acts or behavior, aborted attempt, i

Suicidal Ideation: Baseline

Group	Value	95% CI
Part A (Open-label): SAGE-217	22.9

Suicidal Ideation: Post-Baseline (Any Time up to Day 42)

Group	Value	95% CI
Part A (Open-label): SAGE-217	9.4

Suicidal Behavior: Baseline

Group	Value	95% CI
Part A (Open-label): SAGE-217	0

Suicidal Behavior: Post-Baseline (Any Time up to Day 42)

Group	Value	95% CI
Part A (Open-label): SAGE-217	0

Part A: Change From Baseline in the Young Mania Rating Scale (YMRS) Total Score Primary · Baseline, Days 3, 8, 12, 15, 21, 28, 35, and 42, Last value on treatment (up to Day 14), Last value on study (up to Day 42)

Manic symptoms were assessed during the study using the YMRS. The clinician-administered scale is based on 11 items of core symptoms of mania. Four of the items (irritability, speech, thought content, and disruptive/aggressive behavior) were graded on a scale of 0 to 8 (choices given as even numbers), with the remaining 7 items graded on a scale of 0 to 4. Scoring between the points given (whole or half points) is possible. The YMRS total score ranges from 0 (no symptoms) to 60 (extreme severity of symptoms). A higher total score indicates a greater degree of mania. A negative change indicates

Baseline

Group	Value	95% CI
Part A (Open-label): SAGE-217	4.9	± 3.23

Change From Baseline at Day 3

Group	Value	95% CI
Part A (Open-label): SAGE-217	-0.9	± 2.24

Change From Baseline at Day 8

Group	Value	95% CI
Part A (Open-label): SAGE-217	-0.9	± 2.66

Change From Baseline at Day 12

Group	Value	95% CI
Part A (Open-label): SAGE-217	-0.7	± 3.35

Change From Baseline at Day 15

Group	Value	95% CI
Part A (Open-label): SAGE-217	0.3	± 3.10

Change From Baseline at Day 21

Group	Value	95% CI
Part A (Open-label): SAGE-217	-0.7	± 3.08

Change From Baseline at Day 28

Group	Value	95% CI
Part A (Open-label): SAGE-217	-0.9	± 2.92

Change From Baseline at Day 35

Group	Value	95% CI
Part A (Open-label): SAGE-217	-0.9	± 3.29

Part A: Change From Baseline in the 17-Item HAM-D Total Score at Day 15 Secondary · Baseline, Day 15

The 17-item HAM-D was used to rate the severity of depression in participants who were identified as experiencing an MDE. 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. Items scored in a range of 0 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), hypochondri

Baseline

Group	Value	95% CI
Part A (Open-label): SAGE-217	25.7	± 2.97

Day 15

Group	Value	95% CI
Part A (Open-label): SAGE-217	-11.4	± 8.69

Part A: Percentage of Participants With HAM-D Response at Day 15 Secondary · Day 15

HAM-D response was defined as having a 50% or greater reduction from baseline in HAM-D total score. The HAM-D total score was calculated as the sum of the 17 individual item scores. The 17-item HAM-D comprises individual ratings related to the following symptoms: depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, insomnia (early, middle, late), work and activities, retardation (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), agitation, anxiety (psychic and somatic), somatic symptoms (gastrointestinal and general), ge

Group	Value	95% CI
Part A (Open-label): SAGE-217	43.5

Part A: Percentage of Participants With HAM-D Remission at Day 15 Secondary · Day 15

HAM-D remission was defined as having a HAM-D total score of ≤7. The HAM-D total score was calculated as the sum of the 17 individual item scores. The 17-item HAM-D comprises individual ratings related to the following symptoms: depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, insomnia (early, middle, late), work and activities, retardation (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), agitation, anxiety (psychic and somatic), somatic symptoms (gastrointestinal and general), genital symptoms, hypochondriasis, lo

Group	Value	95% CI
Part A (Open-label): SAGE-217	30.4

Part A: 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. It includes questions on the following symptoms: apparent sadness; reported sadness; inner tension; reduced sleep; reduced appetite; concentration difficulties; lassitude; inability to feel; pessimistic thoughts; and suicidal thoughts. Each item was scored in a range of 0 (no symptoms) to 6 (symptoms of maximum severity). The MADRS total score was calculated as the sum of the ten individual item scores and ranges from 0 (symptoms absent) to 60 (severe depress

Baseline

Group	Value	95% CI
Part A (Open-label): SAGE-217	34.4	± 4.58

Change From Baseline at Day 15

Group	Value	95% CI
Part A (Open-label): SAGE-217	-15.5	± 11.67

Part A: Change From Baseline in Response to the Clinical Global Impression - Severity (CGI-S) 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 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=extremely ill. A negative change from baseline indicates improvement (higher absolute number indicating more illness).

Baseline

Group	Value	95% CI
Part A (Open-label): SAGE-217	4.4	± 0.62

Change From Baseline at Day 15

Group	Value	95% CI
Part A (Open-label): SAGE-217	-1.4	± 1.24

Part A: Percentage of Participants With Response to Clinical Global Impression - Improvement (CGI-I) at Day 15 Secondary · Day 15

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. Higher number indicating more illness. The CGI-I is only rated at posttreatment assessments. CGI-I response were defined as having a CGI-I score "very much improved" or "much improved."

Group	Value	95% CI
Part A (Open-label): SAGE-217	47.8

Part A: Insomnia Severity Index (ISI) at Day 15 Secondary · Day 15

The ISI is a validated questionnaire designed to assess the nature, severity, and impact of insomnia. The ISI uses a 5-point Likert Scale to measure various aspects of insomnia severity (0 = none, 1 = mild, 2 = moderate; 3 = severe; 4 = very severe), satisfaction with current sleep pattern (0 = very satisfied, 1 = satisfied, 2 = neutral, 3 = dissatisfied, 4 = very dissatisfied), and various aspects of the impact of insomnia on daily functioning (0 = not at all, 1 = a little, 2 = somewhat, 3 = much, 4 = very much). ISI total score ranges from 0 to 28, where a total score of 0 to 7 = no clinical

Group	Value	95% CI
Part A (Open-label): SAGE-217	13.1	± 6.97

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose of study drug up to Day 42. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Part A (Open-label): SAGE-217

Serious: 0/35 (0%)

Deaths: 0/35

Other adverse events (5 terms — click to expand)

Reaction	System	Part A (Open-label): SAGE-…
Somnolence	Nervous system disorders	—
Headache	Nervous system disorders	—
Diarrhoea	Gastrointestinal disorders	—
Hypomania	Psychiatric disorders	—
Sedation	Nervous system disorders	—

Data from ClinicalTrials.gov NCT03692910 adverse events section.

Sponsor's own description

This is an open-label study evaluating the safety, tolerability, pharmacokinetics, and efficacy of SAGE-217 in the treatment of participants with bipolar I/II disorder with a current major depressive episode.

Publications & conference data

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

1. Review of Allopregnanolone Agonist Therapy for the Treatment of Depressive Disorders.
   Walkery A, Leader LD, Cooke E, VandenBerg A. · · 2021 · cited 37× · PMID 34267503 · DOI 10.2147/dddt.s240856
2. 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
3. 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
4. New agents and perspectives in the pharmacological treatment of major depressive disorder.
   Sanches M, Quevedo J, Soares JC. · · 2021 · cited 9× · PMID 33159975 · DOI 10.1016/j.pnpbp.2020.110157