Inclusion Criteria:
* Meet Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for MDD
* Current major depressive episode of at least 8 weeks and not exceeding 18 months in duration at Visit 1
* Have inadequate response to 1-3 antidepressant therapies given at adequate dose and duration in the current episode
* If female of childbearing potential, have a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test
Exclusion Criteria:
* DSM-5-based diagnosis of any disorder other than MDD that was the primary focus of treatment within 6 months before Visit 1
* Lifetime history of meeting DSM-5 criteria for:
1. Schizophrenia spectrum or other psychotic disorder
2. Bipolar or related disorder
3. Major neurocognitive disorder
4. Neurodevelopmental disorder of greater than mild severity or of a severity that impacts the participant's ability to consent, follow study directions, or otherwise safely participate in the study
5. Dissociative disorder
6. Posttraumatic stress disorder
7. MDD with psychotic features
* Significant suicide risk, as judged by the Investigator