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

NCT05066672 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: NAV-17A-007820P201
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Treatment Resistant Depression

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Change From Baseline to Each Scheduled Week in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score.

  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).

  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.

  Baseline to Weeks 1, 2, 3 and 4

• Suicidal Ideation and Behavior as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS)

  Baseline to Weeks 1, 2, 3 and 4

Study Arms (2)

NV-5138 400 mg oral capsules

EXPERIMENTAL

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

matched placebo

PLACEBO COMPARATOR

Participants received either 2 or 4 capsules of placebo once daily for 5 weeks.

Drug: matched placebo

Interventions

NV-5138 DRUG

NV-5138 is a novel, orally bioavailable, selective, direct enhancer of mTORC1 cellular signaling

Also known as: SPN820

NV-5138 400 mg oral capsules

matched placebo DRUG

matched placebo oral capsules

Also known as: placebo, PBO

matched placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Navitor Pharmaceuticals, Inc.: lead
• Supernus Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Northwest Clinical Research Center, Inc.

Bellevue, Washington, 98007, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Interventions

NV-5138

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Results Point of Contact

• Title: Gianpiera Ceresoli-Borroni
• Organization: Navitorpharma

gceresoliborroni@supernus.com

3018382521

Study Officials

• Thomas Laage, MD

  Medical Monitor

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: matched placebo
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: randomized, double-blind, placebo-controlled

Study Record Dates

• First Submitted: September 23, 2021
• First Posted: October 4, 2021
• Study Start: January 18, 2022
• Primary Completion: January 21, 2025
• Study Completion: January 21, 2025
• Last Updated: April 17, 2026
• Results First Posted: April 17, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)