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

Study Overview
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Brief Summary
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The study will evaluate the safety and efficacy of AV-101.

Official Title
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Double-Blind, Placebo-Controlled, Phase 2 Trial to Test Efficacy and Safety of AV-101 (L-4-chlorokynurenine) as Adjunct to Current Antidepressant Therapy in Patients With Major Depressive Disorder (the ELEVATE Study)

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: AV-101
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

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: AV-101<br>L-4-chlorokynurenine 1440 mg daily for 14 days | Drug: AV-101<br>* Oral capsules taken once daily (in addition to open-label treatment with a commercially available antidepressant)<br>* Other names: L-4-chlorokynurenine;|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Oral capsules taken once daily (in addition to open-label treatment with a commercially available antidepressant)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Montgomery Åsberg Depression Rating Scale 10-item version (MADRS-10) | Depression questionnaire | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time course of improvement including response rates | 50% improvement on MADRS-10 | 2 weeks | 
| Safety and tolerability will be assessed by incidence of adverse events (AEs) | Also include EKG, labs etc. | 2 weeks |