Phase 2 N=25 Randomized Treatment

Study to Evaluate SAGE-547 Injection as Adjunctive Therapy for the Treatment of Super-Refractory Status Epilepticus

Super-refractory Status Epilepticus

Bottom Line

View on ClinicalTrials.gov: NCT02052739 ↗

Enrolled (actual)

Serious AEs

64.0%

Results posted

May 2022

Primary outcome: Primary: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) — 17; 6 Participants

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: SAGE-547 (Drug)
Age: Pediatric, Adult, Older Adult · 2+ yrs
Sex: All
Sponsor: Supernus Pharmaceuticals, Inc.
Primary completion: May 2015

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	17; 6	—
PRIMARY Change From Baseline (CFB) in National Institutes of Health Stroke Scale (NIH-SS) Total Score	34.2; 33.0; 0.7; 0.3; 0.8; -1.5	—
PRIMARY Change From Baseline in Vital Sign Parameter: Body Weight	78.263; 81.667; 0.253; 0.250; 1.095; 1.083	—
PRIMARY Change From Baseline in Vital Sign Parameter: Heart Rate	89.3; 81.8; -2.3; -0.5; -0.7; 0.6	—
PRIMARY Change From Baseline in Vital Sign Parameter: Blood Pressure - SBP and DBP	111.1; 111.8; 1.3; 20.0; -3.2; 5.0	—
PRIMARY Change From Baseline in Vital Sign Parameter: Respiratory Rate	17.4; 13.4; 0.3; -2.0; 0.2; -0.6	—
PRIMARY Change From Baseline in Vital Sign Parameter: Body Temperature	99.21; 98.98; -0.80; -0.30; -0.38; -0.04	—
PRIMARY Change From Baseline in Vital Sign Parameter: Oxygen Saturation	98.8; 98.6; 0.0; 0.5; 0.0; 0.2	—
PRIMARY Change From Baseline in Serum Chemistry Parameter: Alanine Aminotransferase Levels	48.7; 40.0; 8.2; 17.0; 11.0; 39.3	—
PRIMARY Change From Baseline in Serum Chemistry Parameter: Albumin Levels	26.7; 21.3; -0.3; -1.3; -0.5; -0.7	—
PRIMARY Change From Baseline in Serum Chemistry Parameter: Aspartate Aminotransferase Levels	43.8; 44.8; 0.9; 18.3; 7.5; 32.7	—
PRIMARY Change From Baseline in Serum Chemistry Parameter: Bicarbonate Levels	22.29; 24.52; 0.29; -0.85; 0.68; -0.90	—
PRIMARY Change From Baseline in Serum Chemistry Parameter: Bilirubin Levels	15.3900; 6.8400; -2.8165; 0.8550; -3.0176; 0.0000	—
PRIMARY Change From Baseline in Serum Chemistry Parameter: Blood Urea Nitrogen Levels	4.7162; 4.9980; 0.5752; -0.1785; 1.2025; -0.7140	—
PRIMARY Change From Baseline in Serum Chemistry Parameter: Calcium Levels	0.2037; 0.1950; 0.0015; 0.0021; 0.0036; 0.0017	—
PRIMARY Change From Baseline in Serum Chemistry Parameter: Chloride Levels	110.0; 109.7; 0.2; -3.5; -0.6; -0.5	—
PRIMARY Change From Baseline in Serum Chemistry Parameter: Creatine Kinase Levels	164.6; 1056.4; -5.4; 80.0; -41.5; -77.0	—
PRIMARY Change From Baseline in Serum Chemistry Parameter: Creatinine Levels	61.8335; 66.1527; 3.5851; -4.2727; -0.3257; -2.7993	—
PRIMARY Change From Baseline in Serum Chemistry Parameter: Glucose Levels	7.0731; 7.1238; 0.7247; 2.5905; 0.2542; 0.6661	—
PRIMARY Change From Baseline in Serum Chemistry Parameter: Lipase Levels	69.7; 48.3; -13.4; 3.3; -7.5; 9.3	—
PRIMARY Change From Baseline in Serum Chemistry Parameter: Magnesium Levels	0.8969; 0.8607; -0.0219; -0.0441; -0.0194; -0.0319	—
PRIMARY Change From Baseline in Serum Chemistry Parameter: Potassium Levels	3.76; 3.87; 0.01; -0.03; 0.15; -0.10	—
PRIMARY Change From Baseline in Serum Chemistry Parameter: Protein Levels	56.5; 52.2; 0.4; 1.0; 1.1; 1.5	—
PRIMARY Change From Baseline in Serum Chemistry Parameter: Sodium Levels	140.6; 141.7; 0.1; -3.8; 0.7; 0.3	—
PRIMARY Change From Baseline in Hematology Parameter: Basophil Levels	0.031; 0.037; 0.013; 0.003; -0.008; -0.023	—
PRIMARY Change From Baseline in Hematology Parameter: Basophils to Leukocytes Ratio Reported in Percentage of Cells	0.50; 0.00; 0.00; 0.00; 0.00; 1.00	—
PRIMARY Change From Baseline in Hematology Parameter: Eosinophil Levels	0.3364; 0.7433; 0.0580; -0.2700; 0.0660; -0.2333	—
PRIMARY Change From Baseline in Hematology Parameter: Eosinophils to Leukocytes Ratio Reported in Percentage of Cells	3.00; 3.00; 5.00; -2.00; 0.50; 0.00	—
PRIMARY Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin Concentration Levels	328.4; 322.6; -1.2; 1.0; -4.7; 10.4	—
PRIMARY Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin Levels	1.8611; 1.8335; 0.0110; -0.0149; -0.0134; 0.0261	—
PRIMARY Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume Levels	91.36; 91.50; 0.68; -0.42; 0.65; -0.82	—
PRIMARY Change From Baseline in Hematology Parameter: Erythrocyte Levels	3.261; 3.406; -0.078; -0.022; -0.106; -0.184	—
PRIMARY Change From Baseline in Hematology Parameter: Hematocrit Levels	0.2955; 0.3110; -0.0042; -0.0028; -0.0058; -0.0192	—
PRIMARY Change From Baseline in Hematology Parameter: Hemoglobin Levels	97.3; 100.4; -2.1; -0.8; -3.8; -3.4	—
PRIMARY Change From Baseline in Hematology Parameter: Leukocyte Levels	11.383; 16.538; 1.438; -0.902; 0.186; -3.306	—
PRIMARY Change From Baseline in Hematology Parameter: Lymphocyte Levels	1.791; 2.323; 0.213; -0.470; 0.189; -1.147	—
PRIMARY Change From Baseline in Hematology Parameter: Lymphocytes to Leukocytes Ratio Reported in Percentage of Cells	10.67; 6.50; -1.00; 4.00; -2.50; 8.00	—
PRIMARY Change From Baseline in Hematology Parameter: Monocyte Levels	0.6182; 1.2567; 0.2720; 0.3470; 0.2830; -0.1200	—
PRIMARY Change From Baseline in Hematology Parameter: Monocytes to Leukocytes Ratio Reported in Percentage of Cells	7.67; 5.00; 2.00; 1.00; -5.50; 13.00	—
PRIMARY Change From Baseline in Hematology Parameter: Neutrophil Levels	7.957; 13.863; 0.152; -0.043; -0.552; -0.783	—
PRIMARY Change From Baseline in Hematology Parameter: Neutrophils to Leukocytes Ratio Reported in Percentage of Cells	75.67; 71.00; -3.50; 19.00; 5.00; 6.00	—
PRIMARY Change From Baseline in Hematology Parameter: Platelet Levels	260.76; 284.20; 2.93; 21.40; 17.38; 34.40	—
PRIMARY Change From Baseline in Electrocardiogram (ECG) Parameter: Heart Rate	84.3; 84.3; -1.4; -6.8; -0.9; -1.2	—
PRIMARY Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval	151.0; 151.0; 2.0; -2.0; 3.0; 3.0	—
PRIMARY Number of Participants With Prior Anti-epileptic Drugs (AEDs) and Pressors Usage	16; 4	—
SECONDARY Number of Participants With Relapse - Re-Initiation of Third-Line Agent	5; 1	—
SECONDARY Number of Participants With Treatment Response (Treatment Responders)	13; 4	—
SECONDARY Duration of Response	NA; NA	—
SECONDARY Maximum Plasma Concentration (Cmax) of SAGE-547	144.24; 200.82	—
SECONDARY Time to Attain Maximum Observed Plasma Concentration (Tmax) of SAGE-547	1.010; 60.150	—
SECONDARY Areas Under the Plasma SAGE-547 Concentration Time Curves From the Start of the Infusion Until the Time to the Last Sample (AUClast)	7677.6; 14260.0	—
SECONDARY Area Under the Plasma SAGE-547 Concentration-Time Curve in a 24 Hour Period (AUC24)	1590.3; 2728.3	—
SECONDARY Area Under the Plasma SAGE-547 Concentration-Time Curve (AUC1-96)	6290.6; 10801.7	—
SECONDARY Average Plasma Concentration (Cav) of SAGE-547	66.22; 113.62	—
SECONDARY Plasma Clearance (CL) of SAGE-547	1.3999; 1.2487	—
SECONDARY Change From Baseline in Modified Rankin Scale (mRS-9Q) Scores	5.0; 5.0; 0.0; 0.0; 0.0; 0.0	—
SECONDARY Change From Baseline in Clinical Global Impression: Severity Scale (CGI-S)	6.9; 6.8; -1.1; -1.2; -2.3; -1.8	—
SECONDARY Clinical Global Impression: Improvement Scale (CGI-I) Scores	4.0; 4.0; 4.0; 4.5; 3.6; 3.6	—
SECONDARY Change From Baseline in Glasgow Coma Scale (GCS) Scores	3.9; 3.5; -0.4; -0.2; -0.6; -0.5	—
SECONDARY Change From Baseline in Richmond Agitation Sedation Scale (RASS) Score	-4.8; -4.8; -0.1; 0.0; -0.1; 0.0	—
SECONDARY Number of Participants Who Survived	13; 5	—

Summary

The purpose of this study is to evaluate the safety and tolerability of SAGE-547 in participants in super-refractory status epilepticus (SRSE).

Eligibility Criteria

Inclusion Criteria

Participants 2 years of age and older.
Participants with an EEG-confirmed SRSE diagnosis under concomitant therapy with a continuous IV AED (third-line agent) for ≥ 24 hours. For this study, SRSE is defined by the following criteria and in accordance with those used at major epilepsy treatment centers:
Failure to respond to the administration of at least one first-line agent (e.g., benzodiazepine or other emergent initial AED treatment), according to institution standard of care, and
Failure to respond to at least one second-line agent (e.g., phenytoin, fosphenytoin, valproate, phenobarbital, levetiracetam or other urgent control AED) according to institution standard of care, and
Presence of one or more breakthrough seizures > 6 hours after initiation of the continuous IV AED/third-line agent (e.g., pentobarbital, midazolam, propofol).

Exclusion Criteria

Participants with SRSE due to anoxic/hypoxic encephalopathy, children (participants aged less than 18 years) with an encephalopathy due to an underlying progressive neurological disorder.
Participants with clinically significant electrocardiogram abnormalities.
Participants with a significant medical or surgical condition that may compromise vital organ systems, or other conditions that would place the participants at increased risk such as dialysis or acute respiratory distress syndrome, severe cardiogenic or vasodilatory shock requiring 2 or more pressors, fulminant hepatic failure, etc.
Participants who are receiving a continuous IV AED (third-line agent) for seizure suppression or burst-suppression that would require greater than 24 hours to wean.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02052739). 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.