Study to assess the efficacy and safety of adjunctive NBI-1065845 in adults with Major Depressive Disorder (MDD)

Prior treatment

• 1.A current or prior psychiatric disorder diagnosis in the last 1 year that was the primary focus of treatment other than MDD (assessed by the MINI); a comorbid personality disorder that has been evident outside of depressive episodes or that may interfere with participation in the study; or a diagnosis of neurodegenerative disorder (including but not limited to dementia), eating disorder (except binge eating disorder), schizophrenia, schizoaffective disorder, bipolar disorder, MDD with psychotic features or mixed features, intellectual disability, or mental disorder due to a general medical condition as defined in DSM-5.
• 6.The subject’s depressive symptoms have previously demonstrated nonresponse to an adequate course of treatment with electroconvulsive therapy (ECT) in the current major depressive episode, defined as at least 7 treatments with unilateral/bilateral ECT.
• 10.An unstable medical condition or unstable chronic disease (including history of neurological [including cognitive impairment, myasthenia gravis], hepatic, renal, cardiovascular, gastrointestinal, pulmonary, autoimmune, or endocrine disease that may affect study participation or results) within 3 months before Day 1, or malignancy within 6 months before Day 1.

Other illness

• 12.History of epilepsy, seizures, or convulsions
• 13.History of neurological abnormalities including brain injury (including traumatic injury), perinatal cerebropathy, and postnatal brain damage, blood- brain barrier abnormality, and cavernous angioma.

Lab values

• 11.Any laboratory abnormality suggestive of clinically significant, poorly or unmanaged, undiagnosed disease.

Other

• 2.Are considered by the investigator to be at imminent risk of suicide or injury to self or others.
• 9.Pregnant (ie, positive pregnancy test at screening or baseline) or lactating or plans to become pregnant during the study.
• Any reason that makes the subject unsuitable for participation in this study (eg, subject is homeless, known to have difficulty complying with treatment or medical procedures, known to provide inaccurate medical information, or known to attempt participation in clinical trials inappropriately) per the investigator, Medical Monitor, and/or Sponsor.

• Completed informed consent.
  • 2.≥18 years of age at the time of signing the informed consent.
  • 4.The subject has a primary diagnosis of recurrent MDD (moderate or severe) or persistent depressive disorder. The MDD diagnosis must be confirmed using the Mini-International Neuropsychiatric Interview (MINI) in a face-to-face evaluation.
  • 5.The subject must be receiving oral antidepressant treatment(s) as defined in the protocol.
  • 6.Subject must have an Inadequate Response (IR) to oral antidepressant treatments that were administered as adequate courses (dose, duration, adherence) in the current episode of depression, as assessed using the Massachusetts General Hospital - Antidepressant Treatment Response Questionnaire (MGH-ATRQ).
  • 7.Total Hamilton Depression Rating Scale-17 Item (HAM-D17) score ≥22 at screening and at study baseline (Day 1).
• Willing and able to comply with all study procedures and restrictions in the opinion of the investigator.