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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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An 8-Week Prospective Randomized, Controlled, Double-Blind Trial of the Genecept Assay ™ vs. Treatment-as-Usual to Evaluate Efficacy of Assay-Guided Treatment in Adults With Major Depressive Disorder (MDD)

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Genetic: Assay-guided treatment (AGT)
* Other: Treatment-as-usual (TAU)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-75 years; Sub-Group Age =/> 65 years Ability to understand and provide informed consent Ability to understand, read and speak English Primary diagnosis of Major Depressive Disorder (without psychosis) based on DSM-5 criteria and MINI 7.0 SIGH-D-17 score >18 (i.e., moderate depression) at Screening and Baseline 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 Subject is willing to follow study instructions, complete study assessments and likely to complete all required visits Exclusion Criteria: 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 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. DSM-5 diagnosis of Substance Related and Addictive Disorders diagnosed in the last 12 months (other than tobacco and caffeine) 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 Previous homicidal behavior or acute homicidal risk at Screening or Baseline, in the clinical judgment of the investigator 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). Subjects who are not willing to take psychotropic medications for treatment of MDD. Electroconvulsive therapy (ECT) or transcranial magnetic stimulation therapy (TMS) started within 90 days of screening or planned during the study. Subjects with a vagus nerve or deep brain stimulator are prohibited from the trial. Psychotherapy including cognitive behavioral therapy (CBT), or dialectical behavioral therapy (DBT) started within 90 days of screening or planned during the study. 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. Current diagnosis of unstable hypothyroidism. Females who are pregnant, nursing, or planning a pregnancy during the study or believe they may be pregnant at Screening or Baseline. Participation in another investigative trial within 30 days of screening Subject previously treated with the use of a similar psychotropic genetic testing assay. Subject tests positive for illicit drug use on the urine drug screen (UDS) at the screen visit (including Marijuana where legal).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Assay-guided treatment (AGT)<br>Assay results will be provided to the treating investigator, who will use the results to guide pharmacotherapy of the subject's MDD treatment. | Genetic: Assay-guided treatment (AGT)<br>* The assay provides information to guide pharmacotherapeutic decisions personalized to a patient's genetic profile, to maximize improvement in symptomatology and minimize treatment failure and treatment intolerability.<br>* Other names: Genecept Assay™;|
| Placebo Comparator: Treatment-as-usual (TAU)<br>The treating investigator will treat subjects of the TAU group without the knowledge of the pharmacogenetic testing results. | Other: Treatment-as-usual (TAU)<br>* Subjects are treated-as-usual without the aid of the assay.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in SIGH-D-17 Score at 8 Weeks. | SIGH-D-17: 17-item rater-administered Structured Interview Guide of the Hamilton Depression Rating Scale Scoring is based on the 17-item scale and scores range from 0 minimum to 52 maximum. Scores of 0-7 are considered as being normal, 8-16 suggest mild depression, 17-23 moderate depression and scores over 24 are indicative of severe depression; the maximum score being 52 on the 17-point scale. | Baseline to 8 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in QIDS-SR16 Score at 8 Weeks. | QIDS-SR16: 16-item Quick Inventory of Depressive Symptomatology Self-Report QIDS-SR16 ranges from a score of 0 minimum to 27 maximum. In terms of severity of depression, Scores of 0 to 5 reflect none, scores of 6 to 15 reflect mild, scores of 7-20 reflect moderate and scores of 21 to 27 reflect severe depression. | Baseline to 8 Weeks | 
| Percentage of Treatment Responders at Week 8 Based on ≥ 50% Reduction of SIGH-D-17 Score From Baseline. | SIGH-D-17: 17-item rater-administered Structured Interview Guide of the Hamilton Depression Rating Scale | Baseline to 8 Weeks | 
| Percentage of Treatment Responders at Week 8 Based on ≥ 50% Reduction of QIDS-SR16 Score From Baseline. | QIDS-SR16: 16-item Quick Inventory of Depressive Symptomatology Self-Report QIDS-SR16 ranges from a score of 0 minimum to 27 maximum. In terms of severity of depression, Scores of 0 to 5 reflect none, scores of 6 to 15 reflect mild, scores of 7-20 reflect moderate and scores of 21 to 27 reflect severe depression. | Baseline to 8 Weeks | 
| Percentage of Treatment Responders at Week 8 Based on ≤ 3 Score on the CGI-I. | CGI-I: Clinical Global Impression Improvement scale; a clinician-rated scale that measures the improvement or worsening of a patient's symptoms The CGI-I is rated on a 7-point scale, with the improvement in severity of illness scale using a range of responses from 1 (Very much improved) through to 7 (Very much worse). A score of 0 indicates Patient was not able to be assessed | Baseline to 8 Weeks | 
| Percentage of Remitters at Week 8 Based on ≤ 7 Score on the SIGH-D-17. | SIGH-D-17: 17-item rater-administered Structured Interview Guide of the Hamilton Depression Rating Scale Scoring is based on the 17-item scale and scores range from 0 minimum to 52 maximum. Scores of 0-7 are considered as being normal, 8-16 suggest mild depression, 17-23 moderate depression and scores over 24 are indicative of severe depression; the maximum score being 52 on the 17-point scale. | Baseline to 8 Weeks | 
| Percentage of Remitters at Week 8 Based on ≤ 5 Score on the QIDS-SR16. | QIDS-SR16: 16-item Quick Inventory of Depressive Symptomatology Self-Report QIDS-SR16 ranges from a score of 0 minimum to 27 maximum. In terms of severity of depression, Scores of 0 to 5 reflect none, scores of 6 to 15 reflect mild, scores of 7-20 reflect moderate and scores of 21 to 27 reflect severe depression. | Baseline to 8 Weeks | 
| Safety Outcomes Based on Frequency, Intensity and Burden of Side Effects Rating (FIBSER). | A 3-question patient-rated scale for assessing frequency, intensity, and burden of medication side effects for patients receiving treatment for depression. The Frequency, Intensity, and Burden of Side Effects-Rating (FIBSER) questionnaire uses 3 questions with a 6-point Likert measurement scale. A score of 0-2 on question 3 (burden of side effects) represents an acceptable low side-effect burden usually requiring no treatment adjustment. A score of 3 or 4 indicates moderate side-effect burden that should be evaluated further (eg, timing related to dose change, patient concerns, etc), and an adjustment such as a dose decrease considered. A score of 5 or 6 indicates a high burden warranting a change such as dose decrease, switching, or direct treatment of the side effect(s). | Baseline to 8 Weeks | 
| Safety Outcomes Based on Frequency and Severity of Reported Adverse Events. | Untoward medical occurrence in a subject administered a pharmaceutical product which does not necessarily have to have a causal relationship with treatment. As based on FIBSER The Frequency, Intensity, and Burden of Side Effects-Rating (FIBSER) questionnaire uses 3 questions with a 6-point Likert measurement scale. A score of 0-2 on question 3 (burden of side effects) represents an acceptable low side-effect burden usually requiring no treatment adjustment. A score of 3 or 4 indicates moderate side-effect burden that should be evaluated further (eg, timing related to dose change, patient concerns, etc), and an adjustment such as a dose decrease considered. A score of 5 or 6 indicates a high burden warranting a change such as dose decrease, switching, or direct treatment of the side effect(s). Scores refer to intensity, frequency and interference. | Screening to 8 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Genotyping, Genecept Assay™