Phase 2 Study of NV-5138 in Adults With Treatment Resistant Depression

A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of NV-5138 in Adults With Treatment Resistant Depression

This study will evaluate the efficacy and safety of NV-5138 in adults with TRD

The is a multicenter, randomized, double-blind, flexible- dose, placebo-controlled, parallel design of adjunctive NV-5138 in adults with TRD.

Inclusion Criteria:

• Male or female, aged 18 to 70 years at Screening.
• Diagnosis of Major Depressive Disorder (MDD) according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) for either recurrent or single episode MDD without psychotic features that is confirmed by the Mini International Neuropsychiatric Interview (MINI).
• Montgomery-Asberg Depression Rating Scale (MADRS) Total Score of ≥24 for the current MDE at all Screening visits and Baseline (Day 1).
• CGI-S score of ≥4 (moderately ill or worse) at the Screening visits and Baseline.
• History of inadequate response to ≥1 but ≤4 prior ADT therapies (including the current ADT for the current MDE) ≥ 2 weeks at Screening and ≥ 8 weeks at Baseline.
• Stable therapeutic dose of one of the following ADTs for the current MDE for ≥2 weeks prior to Screening and maintain the therapeutic dose throughout the study: citalopram, escitalopram, paroxetine, fluoxetine, sertraline, duloxetine, venlafaxine (IR or XR), desvenlafaxine, vilazodone, levomilnacipran, vortioxetine, bupropion or dextromethorphan//bupropion.
• Detectable blood level of the approved ADT at Visits 1 and 2 of the Screening Period.

Exclusion Criteria:

• MADRS Total Score improvement of ≥25% from the highest to the lowest score during the Screening Period and Baseline.
• Clinically significant abnormal laboratory profiles, vital signs, or electrocardiograms (ECGs), per Investigator judgment.
• Judged by the Investigator to be at significant risk for suicide or answers 'Yes' to items 4 or 5 on the Suicidal Ideation section of the C-SSRS in the 1 year before Screening; a history of suicide attempt in the last 2 years; or more than 2 lifetime suicide attempts.
• History of psychotic disorder, including but not limited to schizophrenia, MDD with psychotic features, or bipolar I/II disorder with and without psychotic features.
• Diagnosis within 12 months before Screening or current diagnosis of PTSD, OCD, panic disorder, intellectual disability, autism, acute stress disorder, or Cluster A or B personality disorder (per DSM-5 criteria).
• History of substance use disorder within 6 months prior to Screening or currently using or had positive results (UDS) at Screening or Baseline for drugs of abuse.
• History of alcohol and cannabis use disorder within 6 months prior to Screening and had a positive alcohol test at Baseline or a positive UDS for cannabis at Screening.