Phase 2 Study of NV-5138 in Adults With Treatment Resistant Depression

Study Overview
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Brief Summary
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This study will evaluate the efficacy and safety of NV-5138 in adults with TRD

Detailed Description
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The is a multicenter, randomized, double-blind, flexible- dose, placebo-controlled, parallel design of adjunctive NV-5138 in adults with TRD.

Official Title
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A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of NV-5138 in Adults With Treatment Resistant Depression

Conditions
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Treatment Resistant Depression

Intervention / Treatment
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* Drug: NV-5138
* Drug: matched placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, aged 18 to 70 years at Screening. Diagnosis of Major Depressive Disorder (MDD) according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) for either recurrent or single episode MDD without psychotic features that is confirmed by the Mini International Neuropsychiatric Interview (MINI). Montgomery-Asberg Depression Rating Scale (MADRS) Total Score of ≥26 for the current MDE at all Screening visits and Baseline (Day 1). CGI-S score of ≥4 (moderately ill or worse) at all Screening visits and Baseline. History of inadequate response to ≥2 but ≤4 prior ADT therapies (including the current ADT for the current MDE) ≥ 2 weeks at Screening and ≥ 8 weeks at Baseline. Stable therapeutic dose of one of the following ADTs for the current MDE for ≥2 weeks prior to Screening and maintain the therapeutic dose throughout the study: citalopram, escitalopram, paroxetine, fluoxetine, sertraline, duloxetine, venlafaxine (IR or XR), desvenlafaxine, or vortioxetine. Detectable blood level of the approved ADT at Visits 1 and 2 of the Screening Period. Exclusion Criteria: MADRS Total Score improvement of ≥25% from the highest to the lowest score at any visit during the Screening Period. Clinically significant abnormal laboratory profiles, vital signs, or electrocardiograms (ECGs), per Investigator judgment. Judged by the Investigator to be at significant risk for suicide, violence, or homicide; or answers 'Yes' to items 4 or 5 on the Suicidal Ideation section of the C-SSRS at Screening or at Baseline; or has attempted suicide within the 6 months prior to Screening. History of psychotic disorder, including but not limited to schizophrenia, MDD with psychotic features, or bipolar I/II disorder with psychotic features. History of PTSD, OCD, panic disorder, intellectual disability, autism, acute stress disorder, or Cluster A or B personality disorder (per DSM-5 criteria). Any condition or procedure that may interfere with the absorption, metabolism, or elimination of the study medication (e.g., cholecystectomy or gastric bypass). In the Investigator's opinion, is unlikely to comply with the protocol or is unsuitable for any other reason. History of alcohol and/or substance use disorder within 6 months prior to Screening or is currently using or has positive results at Screening for drugs of abuse or has a positive alcohol result at any Screening or Baseline visit.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Interventional Model Description: randomized, double-blind, placebo-controlled
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NV-5138 400 mg oral capsules<br>Either 2 or 4 400 mg oral capsules administered once daily | Drug: NV-5138<br>* NV-5138 is a novel, orally bioavailable, selective, direct activator of mTORC1 cellular signaling<br>* Other names: SPN820;|
| Placebo Comparator: matched placebo<br>2 or 4 oral capsules administered once daily | Drug: matched placebo<br>* matched placebo oral capsules<br>* Other names: PBO;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the efficacy of NV-5138 as measured by the Montgomery-Asberg Depression Rating scale | Change from Baseline to end of treatment period on the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score. MADRS captures a clinician-rated score on a seven-point Likert scale for a score ranging from 0 to 60, with higher scores reflecting greater depression severity. | 5 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the efficacy as measured by Clinical Global Impression-Severity (CGI-s) score | Change from baseline to end of treatment period on the Clinical Global Impression-Severity score for NV-5138 treated patients as compared to placebo. The CGI-S is a clinican-rated seven point scale from 0-7 where a higher rating represents higher severity of illness. | 5 weeks |