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

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

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

Study Overview

• Status: Completed
• Conditions: Treatment Resistant Depression
• Intervention / Treatment: Drug: matched placebo; Drug: NV-5138

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 250
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Washington
    • Bellevue, Washington, United States, 98007
      • Northwest Clinical Research Center, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 ≥24 for the current MDE at all Screening visits and Baseline (Day 1).
• CGI-S score of ≥4 (moderately ill or worse) at the Screening visits and Baseline.
• History of inadequate response to ≥1 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, vilazodone, levomilnacipran, vortioxetine, bupropion or dextromethorphan//bupropion.
• 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 during the Screening Period and Baseline.
• Clinically significant abnormal laboratory profiles, vital signs, or electrocardiograms (ECGs), per Investigator judgment.
• Judged by the Investigator to be at significant risk for suicide or answers 'Yes' to items 4 or 5 on the Suicidal Ideation section of the C-SSRS in the 1 year before Screening; a history of suicide attempt in the last 2 years; or more than 2 lifetime suicide attempts.
• History of psychotic disorder, including but not limited to schizophrenia, MDD with psychotic features, or bipolar I/II disorder with and without psychotic features.
• Diagnosis within 12 months before Screening or current diagnosis of PTSD, OCD, panic disorder, intellectual disability, autism, acute stress disorder, or Cluster A or B personality disorder (per DSM-5 criteria).
• History of substance use disorder within 6 months prior to Screening or currently using or had positive results (UDS) at Screening or Baseline for drugs of abuse.
• History of alcohol and cannabis use disorder within 6 months prior to Screening and had a positive alcohol test at Baseline or a positive UDS for cannabis at Screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NV-5138 400 mg oral capsules; Participants received either 800 or 1600 mg NV-5138 (2 or 4, 400 mg capsules) once daily for 4 weeks. During the first week of the Treatment Period, all participants took 1600 mg once a day. Participants who experienced an intolerable adverse effect at 1600 mg at Week 2, could have their dose reduced to 800 mg. Participants who had an inadequate response to 800 mg might have their dose increased again to 1600 mg per Investigator judgment to maximize their treatment response; however, no dose adjustments were allowed after Week 3. The dose at Week 4 was the same as stable dose at Week 3. After completion of the 4-week treatment, all participants received placebo in a double-blinded fashion and continued the treatment for one week.	Drug: NV-5138; NV-5138 is a novel, orally bioavailable, selective, direct enhancer of mTORC1 cellular signaling; Other Names: SPN820
Placebo Comparator: matched placebo; Participants received either 2 or 4 capsules of placebo once daily for 5 weeks.	Drug: matched placebo; matched placebo oral capsules; Other Names: placebo; PBO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 4 in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score.	MADRS is a 10-item scale (Reported sadness, Apparent sadness, Inner tension, Reduced sleep, Reduced appetite, Concentration difficulties, Lassitude, Inability to feel, Pessimist thoughts, and Suicidal thoughts) where each item is scored from 0 to 6. The total score is the sum of the 10 items ranging from 0 to 60 where higher scores indicate more severe depression, and lower scores are better outcomes. A negative change from baseline indicates improvement in depressive symptoms.	Baseline to Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Each Scheduled Week in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score.	MADRS is a 10-item scale (Reported sadness, Apparent sadness, Inner tension, Reduced sleep, Reduced appetite, Concentration difficulties, Lassitude, Inability to feel, Pessimist thoughts, and Suicidal thoughts) where each item is scored from 0 to 6. The total score is the sum of the 10 items ranging from 0 to 60 where higher scores indicate more severe depression, and lower scores are better outcomes. A negative change from baseline indicates improvement in depressive symptoms.	Baseline to Weeks 1, 2 and 3
Change From Baseline to Each Scheduled Week in the Clinical Global Impression - Severity of Illness Score (CGI-S).	CGI-S is a single-item clinician rating of the clinician's assessment of the severity of symptoms in relation to the clinician's total experience with patients with that condition. The CGI-I is rated on a 7-point scale from 1 to 7, where 1 = "normal not at all ill" and 7 = "among the most extremely ill patients". Successful therapy is indicated by a lower overall score. A negative change from baseline indicates improvement in depressive symptoms.	Baseline to Weeks 1, 2, 3 and 4
Change From Baseline to Each Scheduled Week in the The Hamilton Depression Rating Scale - 6 Items (HAM-D6) Total Score.	The Hamilton Depression Rating Scale - 6 Items is a diagnostic questionnaire used to measure the severity of depressive episodes. It consists of 6 items (depressed mood, work and activities, somatic symptoms general, feeling of guilt, anxiety psychic, retardation) and each question is scored from 0 to 4 except for one item, somatic symptoms general, which is scored from 0 - 2 for a total score ranging 0 to 22. Higher scores indicate more severe conditions. A negative change from baseline indicates improvement in depressive symptoms.	Baseline to Weeks 1, 2, 3 and 4
Suicidal Ideation and Behavior as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS)	C-SSRS assessment included "yes" or "no" responses for 5 questions, each related to suicidal ideation (wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods, active suicidal ideation with some intent, active suicidal ideation with specific plan) and suicidal behavior (preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, suicide). Number of participants with a response of 'yes' to any suicidal ideation or suicidal behavior item as measured by C-SSRS is reported.	Baseline to Weeks 1, 2, 3 and 4

Collaborators and Investigators

• Sponsor: Navitor Pharmaceuticals, Inc.
• Collaborators: Supernus Pharmaceuticals, Inc.
• Investigators: Study Director: Thomas Laage, MD, Medical Monitor

Study record dates

Study Major Dates

• Study Start (Actual): January 18, 2022
• Primary Completion (Actual): January 21, 2025
• Study Completion (Actual): January 21, 2025

Study Registration Dates

• First Submitted: September 23, 2021
• First Submitted That Met QC Criteria: September 23, 2021
• First Posted (Actual): October 4, 2021

Study Record Updates

• Last Update Posted (Actual): April 17, 2026
• Last Update Submitted That Met QC Criteria: April 3, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Treatment-Resistant; NV-5138
• Other Study ID Numbers: NAV-17A-007; 820P201 (Other Identifier: Supernus Pharmaceuticals, Inc.)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No