AV-101 as Adjunct Antidepressant Therapy in Patients With Major Depression

Inclusion Criteria:

- Diagnosed with MDD, single or recurrent, and currently experiencing a MDE of at least
8 weeks in duration.

- Has a history of inadequate response to at least 1 approved antidepressant including
at least 1 and no more than 3 during the current depressive episode.

- Meet the threshold on the total HAMD-17 score of > 20

- If female, a status of nonchildbearing potential or use of an acceptable form of birth
control.

- Body mass index between 18 to 40 kg/m2.

- Other criteria may apply

Exclusion Criteria:

- History of bipolar disorder, schizophrenia or schizoaffective disorders, or any
history of psychotic symptoms in the current or previous depressive episodes.

- Any Axis I or Axis II Disorder, which at screening is clinically predominant to their
MDD or has been predominant to their MDD at any time within 6 months prior to
screening.

- Women who are pregnant or breastfeeding or a positive pregnancy test at screening or
baseline.

- Currently taking a prohibited adjunct therapy. Such drugs must be washed out for at
least 4 weeks prior to baseline.

- Current diagnosis of moderate or severe substance use (including alcohol) disorder
(abuse or dependence, as defined by DSM-5), with the exception of nicotine dependence,
at screening or within 6 months prior to screening.

- In the opinion of the investigator, the subject has a significant risk for suicidal
behavior

- Has received electroconvulsive therapy, or had repetitive transcranial magnetic
stimulation in the current episode.

- Has received vagus nerve stimulation at any time prior to screening.

- Any current or past history of any physical condition, which in the investigator's
opinion might put the subject at risk or interfere with study results interpretation.