A Clinical Trial of PRAX-114 in Participants With Major Depressive Disorder

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled clinical trial to assess the efficacy and safety of PRAX-114 in participants with moderate to severe major depressive disorder (MDD). Participants will be randomized to receive 28 days of either 40 mg PRAX-114 or placebo in a 1:1 ratio.

Official Title
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A Phase 2/3 Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Efficacy and Safety of PRAX-114 in Participants With Major Depressive Disorder

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: PRAX-114
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recurrent MDD diagnosis with a current episode duration of at least 8 weeks and no more than 24 months. HAM-D17 total score of ≥23 at Screening and Baseline. Body mass index (BMI) between 18 and 38 kg/m2 (inclusive). Exclusion Criteria: Lifetime history of seizures, including febrile seizures. Neurodegenerative disorder (eg, Alzheimer's disease, Parkinson's disease, multiple sclerosis, or Huntington's disease). Lifetime history of bipolar disorder, a psychotic disorder (eg, schizophrenia or schizoaffective disorder), or obsessive compulsive disorder or a history of a psychotic mood episode in last 2 years. Any current psychiatric disorder (other than MDD). Lifetime history of treatment resistant depression. Received electroconvulsive therapy (ECT) or vagus nerve stimulation (VNS) within the last year or transcranial magnetic stimulation (TMS) within the last 6 months prior to Screening. Daily consumption of more than 2 standard alcohol-containing beverages for males or more than 1 standard alcohol-containing beverages for females.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PRAX-114<br>40 mg PRAX-114 once daily | Drug: PRAX-114<br>* 40 mg once daily<br>|
| Placebo Comparator: Placebo<br>Placebo once daily | Drug: Placebo<br>* Placebo once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in 17-Item Hamilton Depression Rating Scale (HAM-D17) total score at Day 15 | The HAM-D17 is a depression rating scale consisting of 17 items; 9 items are scored on a 5-point scale (ranging from 0 to 4), and 8 items are scored on a 3-point scale (ranging from 0 to 2). The total score of the 17 items ranges from 0 to 52 with higher scores indicating greater depression. Therefore, a decrease in the total score or on individual item scores indicates improvement. | 15 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in HAM-D17 total score at Day 29 | The HAM-D17 is a depression rating scale consisting of 17 items; 9 items are scored on a 5-point scale (ranging from 0 to 4), and 8 items are scored on a 3-point scale (ranging from 0 to 2). The total score of the 17 items ranges from 0 to 52 with higher scores indicating greater depression. Therefore, a decrease in the total score or on individual item scores indicates improvement. | 29 days | 
| Change from baseline in HAM-D17 total score at all other time points | The HAM-D17 is a depression rating scale consisting of 17 items; 9 items are scored on a 5-point scale (ranging from 0 to 4), and 8 items are scored on a 3-point scale (ranging from 0 to 2). The total score of the 17 items ranges from 0 to 52 with higher scores indicating greater depression. Therefore, a decrease in the total score or on individual item scores indicates improvement. | 8 days, 22 days, 36 days, and 43 days | 
| Change from baseline in Clinical Global Impression-Severity (CGI-S) score at Day 15 and all other time points | The CGI-S assesses the clinician's impression of the participant's current depression symptoms. The clinician should use his/her total clinical experience with this patient population and rate the current severity of the participant's mental illness on a 7-point scale from 1 (Normal, not at all ill) to 7 (Among the most extremely ill patients). | 8 days, 15 days, 22 days, 29 days, 36 days, and 43 days | 
| Clinical Global Impression-Improvement (CGI-I) score at Day 15 and all other time points | The CGI-I assesses the participant's improvement (or worsening). The clinician is required to assess the participant's condition relative to Baseline (Day 1) on a 7-point scale from 1 (Very much improved) to 7 (Very much worse). | 8 days, 15 days, 22 days, 29 days, 36 days, and 43 days | 
| HAM-D17 response (reduction from baseline score of ≥50%) at Day 15, Day 29, and all other time points | The HAM-D17 is a depression rating scale consisting of 17 items; 9 items are scored on a 5-point scale (ranging from 0 to 4), and 8 items are scored on a 3-point scale (ranging from 0 to 2). The total score of the 17 items ranges from 0 to 52 with higher scores indicating greater depression. Therefore, a decrease in the total score or on individual item scores indicates improvement. | 8 days, 15 days, 22 days, 29 days, 36 days, and 43 days | 
| HAM-D17 remission (total score of ≤7) at Day 15, Day 29, and all other time points | The HAM-D17 is a depression rating scale consisting of 17 items; 9 items are scored on a 5-point scale (ranging from 0 to 4), and 8 items are scored on a 3-point scale (ranging from 0 to 2). The total score of the 17 items ranges from 0 to 52 with higher scores indicating greater depression. Therefore, a decrease in the total score or on individual item scores indicates improvement. | 8 days, 15 days, 22 days, 29 days, 36 days, and 43 days | 
| Change from baseline in the Symptoms of Depression Questionnaire (SDQ) total and sub-scale scores at Day 15 and all other time points | The SDQ is a 44-item, self-report scale assessing the severity of symptoms across several subtypes of depression. Items are scored on a 7-point scale (ranging from 1 to 6). The SDQ total score is the sum of all 44 item scores and ranges from 44 to 264 with higher scores indicating worse symptoms. | 8 days, 15 days, 22 days, 29 days, 36 days, and 43 days | 
| Patient Global Impression-Improvement (PGI-I) score at Day 15 and all other time points | The PGI-I scale is a global self-assessment used to rate the response of a participant's condition to therapy or intervention. It consists of 1 question that asks the participant to rate their current condition compared to how it was prior to beginning treatment on a scale of 1 (very much better) to 7 (very much worse). | 8 days, 15 days, 22 days, 29 days, 36 days, and 43 days | 
| Change from baseline in the Work and Social Adjustment Scale (WSAS) at Day 15 and all other time points | The WSAS assesses the degree to which mental health problems interfere with day-to-day functioning in 5 domains: work, social leisure activities, private leisure activities, home- management, and personal relationships. The WSAS total score is the sum of the 5 item scores and ranges from 0 to 40, with higher scores indicating poorer adjustment. | 8 days, 15 days, 22 days, 29 days, 36 days, and 43 days | 
| Change from baseline in the 12-Item Short Form Survey (SF-12) at Day 15 and all other time points | The SF-12 is composed of 12 questions covering 8 dimensions of health: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health. Total scores range from 0 (worse health) to 100 (better health). | 8 days, 15 days, 22 days, 29 days, 36 days, and 43 days | 
| Incidence and severity of Adverse Events (AE) | An AE is any untoward medical occurrence in a clinical trial participant, temporally associated with the use of study drug, whether or not considered related to the study drug. | 43 days | 
| Incidence of AEs by preferred term | The incidence of AEs will be reported by preferred term, including any terms related to clinically significant changes in body temperature, pulse rate, respiratory rate, blood pressure (systolic and diastolic), clinical laboratory measures (chemistry, hematology, urinalysis, and coagulation), and electrocardiogram parameters (heart rate, PR, QRS, QT, and corrected QT intervals). | Up to 43 days | 
| Incidence of Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicidal ideation or behavior | The C-SSRS is composed of 5 yes/no questions addressing suicidal behavior and 5 yes/no questions addressing suicidal ideation, with sub-questions assessing the severity. Incidence is measured as the number of yes answers indicating the presence of suicidal ideation or behavior. | Up to 43 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mood Disorders, Depressive Disorder, Depression, Depressive Disorder, Unipolar, Depressive Symptoms, Agents, GABA, Receptors, GABA-A, Allosteric Regulation