Genecept Assay™ vs. Treatment-as-Usual to Evaluate Efficacy of Assay-Guided Treatment in Adults With MDD

In this randomized clinical trial, subjects will be assigned to either an assay-guided treatment condition (AGT) or a treatment-as-usual condition (TAU). All subjects will provide a DNA sample at the Screening Visit for the Genecept Assay ™. In the AGT condition, assay results will be provided to the treating investigator, who will use the results to guide antidepressant pharmacotherapy. In the TAU condition, the investigator will treat the subjects without the knowledge of the pharmacogenetic testing results. Assay results for all subjects will be provided to the investigator once all Week 8 visit procedures have been completed. Raters of the primary endpoint assessment and subjects will remain blinded to treatment assignment.

This study compares efficacy and safety outcomes in Major Depressive Disorder (MDD) adult patients randomized to assay-guided treatment (AGT) or treatment-as-usual (TAU). The treatment duration will be 8-weeks. Subjects will be assessed at visits at Week 2, 4, 6 and 8. Approximately 300 subjects will be randomized 1:1 to the two treatment group (AGT and TAU). This is a multi-center trial, with approximately 25 sites in the US. Randomization will be by IWRS. The treating investigator will be unblinded to treatment assignment (necessarily). Other site staff, sponsor staff (including site monitors) and all others will be blinded to treatment assignment for the duration of the subject's participation in the study. The (blinded) rater for the primary endpoint, the SIGH-D-17 Hamilton Depression Scale, will have no other contact with the subject such as collection of screening data, follow-up assessments, documentation of adverse events, etc. Blinded raters will not discuss subjects with other study staff.

After recruitment for main study is completed, an additional 70 subjects , age 65 years and older will be randomized to the Exploratory Elderly MDD Study. This follow-on sub-study will apply all procedures of the main study to this elderly population subset.

Eligibility Criteria:
Inclusion Criteria:

1. Age 18-75 years; Sub-Group Age =/\> 65 years
2. Ability to understand and provide informed consent
3. Ability to understand, read and speak English
4. Primary diagnosis of Major Depressive Disorder (without psychosis) based on DSM-5 criteria and MINI 7.0
5. SIGH-D-17 score \>18 (i.e., moderate depression) at Screening and Baseline
6. Failure of at least 1 prior adequate trial of standard antidepressant in the current major depressive episode (using ATRQ criteria - i.e., 6 weeks at adequate dose) due to inefficacy, side effects or intolerability
7. Subject is willing to follow study instructions, complete study assessments and likely to complete all required visits

Exclusion Criteria:

1. Severe personality traits (based on DSM-5 criteria) that in the opinion of the investigator may interfere with the participation in the study or the evaluation of efficacy and safety and all diagnosed Personality Disorders
2. Current DSM-5 diagnosis of Neurocognitive Disorders, Schizophrenia Spectrum (lifetime diagnosis) and other Psychotic Disorders, Bipolar and Related disorders (lifetime diagnosis\*), Trauma and Stress related Disorders, Obsessive Compulsive Disorder and Related Disorders. Other DSM-5 disorders that in the opinion of the investigator may interfere with the participation in the study or the evaluation of efficacy and safety.
3. DSM-5 diagnosis of Substance Related and Addictive Disorders diagnosed in the last 12 months (other than tobacco and caffeine)
4. History of Suicidal Behavior within 12 months of screening or presence of Active Suicidal Ideation with Intent in the past 12 months (Items 4 or 5) at Screening or Baseline, as determined by the Columbia Suicide Severity Rating Scale (C-SSRS), or subject is considered to be an acute suicide risk in the clinical judgment of the investigator
5. Previous homicidal behavior or acute homicidal risk at Screening or Baseline, in the clinical judgment of the investigator
6. Four (4) or more failed pharmacologic interventions for depression in the current major depressive episode (One of the four failed interventions must meet ATRQ criteria - i.e., 6 weeks at adequate dose).
7. Subjects who are not willing to take psychotropic medications for treatment of MDD.
8. Electroconvulsive therapy (ECT) or transcranial magnetic stimulation therapy (TMS) started within 90 days of screening or planned during the study.
9. Subjects with a vagus nerve or deep brain stimulator are prohibited from the trial.
10. Psychotherapy including cognitive behavioral therapy (CBT), or dialectical behavioral therapy (DBT) started within 90 days of screening or planned during the study.
11. Unstable or active medical condition(s) which in the opinion of the investigator would jeopardize the subject's safety or interfere with participation of the study or confound evaluation of efficacy or safety.
12. Current diagnosis of unstable hypothyroidism.
13. Females who are pregnant, nursing, or planning a pregnancy during the study or believe they may be pregnant at Screening or Baseline.
14. Participation in another investigative trial within 30 days of screening
15. Subject previously treated with the use of a similar psychotropic genetic testing assay.
16. Subject tests positive for illicit drug use on the urine drug screen (UDS) at the screen visit (including Marijuana where legal).