Phase 2 N=102 Randomized Quadruple-blind Treatment

A Study to Evaluate SAGE-217 in Participants With Moderate to Severe Major Depressive Disorder

Major Depression

Bottom Line

View on ClinicalTrials.gov: NCT03000530 ↗

Enrolled (actual)

102

Serious AEs

0.0%

Results posted

Dec 2020

Primary outcome: Primary: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) - Part A — 92.3 percentage of participants

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: SAGE-217 (Drug); Placebo (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Biogen
Primary completion: Oct 2017

Outcome Measures

Outcome	Result	p-value
PRIMARY Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) - Part A	92.3	—
PRIMARY Percentage of Participants With TEAEs, Graded by Severity - Part A	69.2; 23.1; 0	—
PRIMARY Change From Baseline in Basophils - Part A	0.032; -0.002; 0.005; -0.003; -0.007	—
PRIMARY Change From Baseline in Basophils to Leukocytes Ratio [Percentage (%)] - Part A	0.56; 0.38; 0.13; 0.02; -0.05	—
PRIMARY Change From Baseline in Eosinophils - Part A	0.155; 0.031; 0.044; 0.018; 0.011	—
PRIMARY Change From Baseline in Eosinophils to Leukocytes Ratio (%) - Part A	2.20; 0.68; 0.98; 0.52; 0.43	—
PRIMARY Change From Baseline in Hematocrit - Part A	0.419; 0.001; -0.006; -0.020; -0.017	—
PRIMARY Change From Baseline in Hemoglobin - Part A	136.7; 0.2; -2.4; -5.7; -4.8	—
PRIMARY Change From Baseline in Lymphocytes - Part A	2.356; -0.302; -0.339; -0.260; -0.204	—
PRIMARY Change From Baseline in Lymphocytes to Leukocytes Ratio (%) - Part A	34.89; -1.75; -1.25; -1.11; -0.62	—
PRIMARY Change From Baseline in Monocytes - Part A	0.485; -0.042; -0.074; -0.090; -0.103	—
PRIMARY Change From Baseline in Monocytes to Leukocytes Ratio (%) - Part A	6.72; 0.35; -0.03; -0.67; -0.82	—
PRIMARY Change From Baseline in Neutrophils - Part A	4.126; -0.485; -0.528; -0.411; -0.190	—
PRIMARY Change From Baseline in Neutrophils to Leukocytes Ratio (%) - Part A	55.63; 0.76; 0.16; 1.23; 1.06	—
PRIMARY Change From Baseline in Platelets - Part A	265.5; -13.4; -7.8; 8.8; -9.9	—
PRIMARY Change From Baseline in Erythrocytes - Part A	4.661; 0.021; -0.050; -0.198; -0.164	—
PRIMARY Change From Baseline in Reticulocytes - Part A	51.926; -3.694; -6.163; 6.174; 13.012	—
PRIMARY Change From Baseline in Leukocytes - Part A	7.16; -0.82; -0.91; -0.75; -0.49	—
PRIMARY Change From Baseline in Albumin - Part A	42.8; -1.5; -1.0; -1.5; -0.8	—
PRIMARY Change From Baseline in Alkaline Phosphatase - Part A	84.3; 6.1; 16.5; 2.3; 2.5	—
PRIMARY Change From Baseline in Alanine Aminotransferase - Part A	18.8; 8.8; 11.0; 2.8; -1.7	—
PRIMARY Change From Baseline in Aspartate Aminotransferase - Part A	18.7; 3.7; 5.7; 0.0; 0.5	—
PRIMARY Change From Baseline in Bilirubin - Part A	8.945; -1.052; -1.973; -1.842; -1.184	—
PRIMARY Change From Baseline in Chloride - Part A	102.9; 1.2; 1.5; 1.3; 1.1	—
PRIMARY Change From Baseline in Carbon Dioxide - Part A	26.4; -1.0; -0.8; 0.0; -0.5	—
PRIMARY Change From Baseline in Creatinine - Part A	73.848; -0.748; 0.136; 0.952; 0.816	—
PRIMARY Change From Baseline in Potassium - Part A	4.25; 0.12; 0.02; -0.04; -0.10	—
PRIMARY Change From Baseline in Protein - Part A	71.8; -0.6; -0.2; -2.5; -0.1	—
PRIMARY Change From Baseline in Sodium - Part A	138.5; -0.2; -0.1; 0.5; 0.5	—
PRIMARY Change From Baseline in Urea Nitrogen - Part A	4.888; -0.275; -0.412; -0.357; -0.741	—
PRIMARY Change From Baseline in Activated Partial Thromboplastin Time - Part A	28.00; 1.00; 1.20; 0.70; 1.00	—
PRIMARY Change From Baseline in Prothrombin International Normalized Ratio (%) - Part A	1.02; 0.04; -0.04; -0.01; -0.02	—
PRIMARY Change From Baseline in Prothrombin Time - Part A	10.50; 0.10; -0.40; -0.10; 0.00	—
PRIMARY Change From Baseline in pH - Part A	6.46; -0.15; -0.35; -0.31; -0.19	—
PRIMARY Change From Baseline in Specific Gravity - Part A	1.014; 0.001; 0.000; 0.003; -0.001	—
PRIMARY Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A	122.8; -1.7; -4.2; -2.4; -4.9; -0.8	—
PRIMARY Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A	79.4; -1.1; -1.6; -2.0; -5.2; 1.3	—
PRIMARY Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A	126.8; -0.1; -3.8; -6.5; -3.9; -4.2	—
PRIMARY Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A	83.9; -0.2; -1.5; -1.8; -1.5; -3.5	—
PRIMARY Change From Baseline (CFB) in Heart Rate - Part A	80.0; -2.7; -5.9; -4.6; -2.6; -2.2	—
PRIMARY Change From Baseline (CFB) in Respiratory Rate - Part A	16.9; 0.5; 0.5; 0.3; 0.4; -0.1	—
PRIMARY Change From Baseline (CFB) in Oral Temperature - Part A	36.71; -0.17; 0.12; 0.11; 0.03; -0.09	—
PRIMARY Change From Baseline (CFB) in Oxygen Saturation - Part A	98.6; 0.0; -0.4; 0.3; -0.3; 0.3	—
PRIMARY Change From Baseline in QT Interval - Part A	401.0; -8.0; -12.0; -22.0; -16.0; -17.5	—
PRIMARY Change From Baseline in QTcF Interval - Part A	423.0; 2.0; -5.0; -4.0; -8.0; -7.0	—
PRIMARY Change From Baseline in ECG Mean Heart Rate - Part A	65.6; 5.8; 5.6; 8.8; 6.0; 7.0	—
PRIMARY Change From Baseline in RR Interval - Part A	952.0; -65.0; -45.0; -88.0; -107.0; -97.0	—
PRIMARY Change From Baseline in PR Interval - Part A	158.0; 1.0; -8.0; 2.0; 5.0; -3.5	—
PRIMARY Change From Baseline in QRS Interval - Part A	94.0; 0.0; -2.0; -1.0; 4.0; -0.5	—
PRIMARY Percentage of Participants With a Response of 'Yes' to Any Columbia Suicide Severity Rating Scale (C-SSRS) Suicidal Ideation Item - Part A	—	—
PRIMARY Change From Baseline in Stanford Sleepiness Scale (SSS) Score at Day 15 - Part A	2.3; -0.6	—
PRIMARY Change From Baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D) Total Score at Day 15 - Part B	-10.3; -17.4	< 0.0001 sig
SECONDARY Change From Baseline in the HAM-D Total Score at Day 15 and All Other Time Points - Part A	27.2; -5.9; -9.1; -12.4; -14.4; -16.0	—
SECONDARY Percentage of Participants With TEAEs - Part B	45.5; 53.3	—
SECONDARY Percentage of Participants With AEs During Post-TEAE Period	22.7; 8.9	—
SECONDARY Percentage of Participants With TEAEs, Graded by Severity - Part B	5; 6; 0; 0	—
SECONDARY Change From Baseline in Basophils - Part B	0.038; 0.041; 0.012; -0.004; 0.005; 0.001	—
SECONDARY Change From Baseline in Basophils to Leukocytes Ratio (%) - Part B	0.63; 0.63; 0.11; 0.04; 0.05; 0.11	—
SECONDARY Change From Baseline in Eosinophils - Part B	0.147; 0.126; 0.004; 0.025; 0.027; 0.037	—
SECONDARY Change From Baseline in Eosinophils to Leukocytes Ratio (%) - Part B	1.95; 1.96; 0.15; 0.44; 0.53; 0.60	—
SECONDARY Change From Baseline in Hematocrit - Part B	0.424; 0.436; -0.004; -0.004; -0.006; -0.010	—
SECONDARY Change From Baseline in Hemoglobin - Part B	136.1; 141.0; -1.3; -2.3; -1.8; -3.8	—
SECONDARY Change From Baseline in Lymphocytes - Part B	2.294; 2.162; -0.053; -0.054; 0.066; 0.025	—
SECONDARY Change From Baseline in Lymphocytes to Leukocytes Ratio (%) - Part B	33.06; 33.87; -0.43; 1.86; 1.25; 1.96	—
SECONDARY Change From Baseline in Monocytes - Part B	0.442; 0.438; 0.003; 0.035; 0.017; 0.028	—
SECONDARY Change From Baseline in Monocytes to Leukocytes Ratio (%) - Part B	6.33; 6.78; 0.20; 0.98; 0.40; 0.79	—
SECONDARY Change From Baseline in Neutrophils - Part B	4.174; 3.852; -0.100; -0.399; -0.389; -0.406	—
SECONDARY Change From Baseline in Neutrophils to Leukocytes Ratio (%) - Part B	58.03; 56.76; -0.03; -3.32; -2.23; -3.46	—
SECONDARY Change From Baseline in Platelets - Part B	287.0; 272.2; -8.5; -0.9; 6.8; 3.7	—
SECONDARY Change From Baseline in Erythrocytes - Part B	4.811; 4.902; -0.041; -0.074; -0.069; -0.128	—
SECONDARY Change From Baseline in Reticulocytes - Part B	32.313; 78.735; -19.035; 9.240	—
SECONDARY Change From Baseline in Reticulocytes to Erythrocytes Ratio (%) - Part B	1.32; 1.40; -0.02; -0.07; -0.03; 0.00	—
SECONDARY Change From Baseline in Leukocytes - Part B	7.08; 6.63; -0.11; -0.40; -0.27; -0.34	—
SECONDARY Change From Baseline in Albumin - Part B	44.6; 44.6; -1.1; -0.8; -0.8; -0.9	—
SECONDARY Change From Baseline in Alkaline Phosphatase - Part B	80.9; 85.5; -0.1; 1.3; 1.6; 3.1	—
SECONDARY Change From Baseline in Alanine Aminotransferase - Part B	22.9; 22.2; 4.1; 11.0; 7.3; 9.1	—
SECONDARY Change From Baseline in Aspartate Aminotransferase - Part B	23.0; 23.5; -0.5; 10.0; 2.2; 5.0	—
SECONDARY Change From Baseline in Bilirubin - Part B	8.157; 9.422; -1.095; -1.670; -0.652; -1.673	—
SECONDARY Change From Baseline in Calcium - Part B	2.359; 2.364; -0.021; -0.033; -0.019; -0.041	—
SECONDARY Change From Baseline in Chloride - Part B	104.7; 104.4; -0.2; -0.2; -0.4; -0.1	—
SECONDARY Change From Baseline in Carbon Dioxide - Part B	29.3; 28.8; -1.1; 0.0; -0.3; 0.7	—
SECONDARY Change From Baseline in Creatinine - Part B	76.363; 77.894; 0.036; -1.710; 1.028; 0.566	—
SECONDARY Change From Baseline in Glucose - Part B	5.438; 5.114; 0.103; 0.045; 0.203; 0.390	—
SECONDARY Change From Baseline in Potassium - Part B	4.33; 4.36; 0.05; 0.09; 0.05; 0.03	—
SECONDARY Change From Baseline in Magnesium - Part B	0.891; 0.879; -0.020; -0.011; -0.025; -0.014	—
SECONDARY Change From Baseline in Phosphate - Part B	1.245; 1.212; 0.053; 0.048; 0.019; 0.010	—
SECONDARY Change From Baseline in Protein - Part B	75.0; 76.0; -2.1; -1.3; -1.3; -1.6	—
SECONDARY Change From Baseline in Sodium - Part B	140.8; 140.5; -0.7; 0.1; -0.6; 0.0	—
SECONDARY Change From Baseline in Thyrotropin - Part B	1.328; 1.398; 0.464; 0.445; 0.668; 0.315	—
SECONDARY Change From Baseline in Urea Nitrogen - Part B	4.186; 4.644; 0.322; 0.334; 0.330; 0.189	—
SECONDARY Change From Baseline in Activated Partial Thromboplastin Time - Part B	27.60; 27.80; 0.20; -0.20; 0.10; 0.40	—
SECONDARY Change From Baseline in Prothrombin International Normalized Ratio (%) - Part B	1.006; 1.032; 0.011; -0.016; -0.003; -0.010	—
SECONDARY Change From Baseline in Prothrombin Time - Part B	10.40; 10.60; 0.00; -0.20; 0.00; -0.20	—
SECONDARY Change From Baseline in pH - Part B	6.22; 6.23; -0.32; -0.16; -0.37; -0.23	—
SECONDARY Change From Baseline in Specific Gravity - Part B	1.016; 1.018; 0.002; 0.000; 0.003; -0.001	—
SECONDARY Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B	120.5; 120.6; 1.7; 0.6; 1.3; 0.7	—
SECONDARY Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B	76.1; 75.2; 0.8; 1.0; -0.1; 0.6	—
SECONDARY Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B	125.9; 125.1; 0.3; 0.8; -0.7; -1.7	—
SECONDARY Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B	81.9; 80.1; 1.0; 2.6; 0.7; 1.5	—
SECONDARY Change From Baseline (CFB) in Heart Rate - Part B	74.3; 76.8; -1.9; -2.8; -2.1; -2.5	—
SECONDARY Change From Baseline (CFB) in Respiratory Rate - Part B	16.7; 16.8; 0.2; -0.1; 0.4; 0.0	—
SECONDARY Change From Baseline (CFB) in Oral Temperature - Part B	36.72; 36.72; 0.03; 0.03; 0.03; 0.05	—
SECONDARY Change From Baseline (CFB) in Oxygen Saturation - Part B	97.95; 98.02; -0.11; -0.02; 0.12; 0.00	—
SECONDARY Change From Baseline in QT Interval - Part B	403.5; 398.0; -9.0; -7.0; -12.0; -15.0	—
SECONDARY Change From Baseline in QTcF Interval - Part B	406.0; 410.0; 0.0; -2.0; -2.5; -4.0	—
SECONDARY Change From Baseline in ECG Mean Heart Rate - Part B	65.0; 64.8; 3.2; 4.5; 6.0; 4.7	—
SECONDARY Change From Baseline in RR Interval - Part B	952.0; 938.0; -50.0; -52.5; -46.0; -51.0	—
SECONDARY Change From Baseline in PR Interval - Part B	149.5; 162.0; 1.0; 2.0; 1.5; 4.0	—
SECONDARY Change From Baseline in QRS Duration - Part B	88.0; 89.0; 0.5; 0.5; 1.0; 1.0	—
SECONDARY Percentage of Participants With a Response of "Yes" to Any C-SSRS Suicidal Ideation (SI) Item - Part B	11; 8; 3; 0; 1; 0	—
SECONDARY Percentage of Participants With HAM-D Response - Part A	15.4; 15.4; 30.8; 53.8; 61.5; 61.5	—
SECONDARY Percentage of Participants With HAM-D Remission - Part A	0; 0; 15.4; 15.4; 38.5; 38.5	—
SECONDARY Change From Baseline in the Montgomery and Åsberg Depression Rating Scale (MADRS) Total Score at Day 15 and All Other Time Points - Part A	36.9; -6.4; -9.6; -14.2; -16.2; -18.9	—
SECONDARY Change From Baseline in HAM-D Subscale Scores at Day 15 and All Other Time Points - Part A	45.0; -5.4; -12.3; -18.5; -21.9; -25.4	—
SECONDARY Change From Baseline (CFB) in HAM-D Individual Item Scores at Day 15 and All Other Time Points - Part A	3.2; -0.2; -0.8; -1.3; -1.4; -1.6	—
SECONDARY Change From Baseline in Hamilton Anxiety Rating Scale (HAM-A) Total Score at All Time Points - Part A	23.2; -2.8; -5.6; -13.3; -15.5; -15.6	—
SECONDARY Percentage of Participants With Clinical Global Impression - Improvement (CGI-I) Response - Part A	7.7; 15.4; 84.6; 92.3; 84.6; 76.9	—
SECONDARY Change From Baseline (CFB) in the SSS Score - Part B	2.7; 2.6; 0.0; 0.0; -0.1; 0.0	—
SECONDARY Change From Baseline in the 17-item HAM-D Total Score at All Time Points - Part B	-3.5; -5.8; -5.2; -9.3; -7.7; -10.6	0.0223 sig
SECONDARY Percentage of Participants With HAM-D Response - Part B	4.5; 15.6; 47.6; 59.1; 40.5; 78.6	0.0884
SECONDARY Percentage of Participants With HAM-D Remission - Part B	0; 2.2; 28.6; 36.4; 26.2; 64.3	0.4300
SECONDARY Change From Baseline in the MADRS Total Score at Day 15 and All Other Time Points - Part B	-4.5; -6.9; -15.4; -19.4; -15.0; -22.5	0.0836
SECONDARY Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B	47.3; 46.9; -5.9; -7.2; -9.4; -14.1	—
SECONDARY Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B	3.1; 3.1; -0.3; -0.5; -0.5; -0.8	—
SECONDARY Change From Baseline in HAM-A Total Score at Day 15 and All Other Time Points - Part B	-3.7; -5.5; -8.9; -11.4; -8.6; -13.2	0.0391 sig
SECONDARY Percentage of Participants With CGI-I Response - Part B	0; 15.6; 45.2; 70.5; 45.2; 78.6	0.0048 sig

Summary

This is a two-part (open-label followed by double-blind) study evaluating the safety, tolerability, pharmacokinetics, and efficacy of SAGE-217 in 102 participants diagnosed with moderate to severe Major Depressive Disorder.

Eligibility Criteria

Inclusion Criteria

Participant has a diagnosis of Major Depressive Disorder that has been present for at least a 4-week period as diagnosed by Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I)

Exclusion Criteria

Participant has a history of suicide attempt
Participant has a history of treatment-resistant depression, defined as persistent depressive symptoms despite treatment with adequate doses of antidepressants from two different classes for an adequate amount of time
Participant has active psychosis
Participant has a medical history of seizures
Participant has a medical history of bipolar disorder, schizophrenia, and/or schizoaffective disorder

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03000530). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.