SAGE-217 in Major Depressive Disorder: A Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial (705)

Objective: The objective of this Phase 3, double-blind, randomized, placebo-controlled study was to evaluate the efficacy and safety of SAGE- 217 in the treatment of adult subjects with major depressive disorder (MDD). Background: An estimated 300 million people worldwide are affected with MDD. Dysregulation of γ-aminobutyric acid (GABA) signaling has been associated with MDD. SAGE-217 is an investigational, oral, neuroactive steroid and GABAA receptor positive allosteric modulator that has demonstrated reductions in depressive symptoms in a Phase 2 double-blind, randomized, placebo-controlled study in MDD. Design/Methods: Subjects with MDD were randomized 1:1:1 to SAGE-217 30 mg, 20 mg, or placebo capsules. Subjects were treated for 14 days, then followed weekly for 4-weeks, and then again after four more weeks, and then again every 8 weeks through 182-days. The primary endpoint was change from baseline in Hamilton Depression Rating Scale (HAM-D) total score at Day 15 compared with placebo, assessed by a statistical analysis using an MMRM. Safety and tolerability were assessed by standard clinical assessments. Results: The double-blind treatment and the initial 4-week follow-up periods of this Phase 3 study will be completed by the end of 2019. Change in HAM-D scores against placebo will be reported at all assessment points. Data will be reported on HAM-D time points at Days 3–42 (including Day 15), HAM-D response (≥50% reduction) and remission (≤7) rates, Montgomery–Asberg Depression Rating Scale (MADRS), and Hamilton Anxiety Rating Scale (HAM-A) scores will be reported as secondary endpoints. Safety and tolerability data will also be presented. Conclusions: This Phase 3 study aims to confirm and extend the previous results in a larger study population utilizing two dose groups versus placebo. These results have the potential to be an important milestone in the development of SAGE-217 in the treatment of individuals with MDD. Disclosure: Dr. Mittal has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sage Therapeutics Inc and Sanofi. Dr. Mittal holds stock and/or stock options in Sanofi, JnJ, Gilead, Amgen, Walgreens, Pfizer, and PG Alkermes; Allergan; AMAG Pharmaceuticals, Inc.; Dare Bioscience; Fabre-Kramer; Lundbeck; Palatin Technologies; S1 Biopharma; Sage Therapeutics; Sprout Pharmaceuticals; Takeda. Dr. Clayton has received royalty, license fees, or contractual rights payments from Changes in Sexual Functioning Questionnaire. Dr. Clayton has received research support from Acadia; Alkermes; Allergan; AMAG Pharmaceuticals, Inc.; Dare Bioscience; Fabre-Kramer; Lundbeck; Palatin Technologies; S1 Biopharma; Sage Therapeutics; Sprout Pharmaceuticals; Takeda. Dr. Lasser has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sage Therapeutics, Inc.. Dr. Lasser holds stock and/or stock options in Sage Therapeutics, Inc. which sponsored research in which Dr. Lasser was involved as an investigator. Dr. Lasser holds stock and/or stock options in Sage Therapeutics, Inc.. Dr. Nandy has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sage Therapeutics, Inc.. Dr. Sankoh has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sage Therapeutics, Inc.. Dr. Campbell has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sage Therapeutics, Inc.Dr. Werneburg has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sage Therapeutics, Inc.. Dr. Silber has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sage Therapeutics, Inc.. Dr. Jonas has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sage Therapeutics Inc. Dr. Kanes has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sage Therapeutics, Inc.. Dr. Gunduz-Bruce has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sage Therapeutics, Inc.