Phase 2 Study of NV-5138 in Adults With Treatment Resista... | NCT05066672

NCT05066672

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
820P201	Other Identifier	Supernus Pharmaceuticals, Inc.

Status Module

Name	Class
Supernus Pharmaceuticals, Inc.	INDUSTRY

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
NV-5138	Drug	NV-5138 is a novel, orally bioavailable, selective, direct enhancer of mTORC1 cellular signaling	NV-5138 400 mg oral capsules

Outcomes Module

Primary Outcomes

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 Outcomes

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.

Eligibility Module

Eligibility Criteria

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.

Name	Affiliation	Role
Thomas Laage, MD	Medical Monitor	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Northwest Clinical Research Center, Inc.		Bellevue	Washington	98007	United States

Arm/Group Information

ID	Title	Description
FG000	NV-5138 (800 or 1600 mg)	Participants received either 800 or 1600 mg NV-5138 (2 or 4, 400 mg capsules) once daily for 4 weeks. After completion of the 4-week treatment, all participants received placebo in a double-blinded fashion and continued the treatment for one week. 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.
FG001	Placebo	Participants received either 2 or 4 capsules of placebo once daily for 5 weeks.

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED	The number of participants reported here is based on the Safety Population which includes all randomized participants who received at least one dose of study medication. Two enrolled participants were randomized in error and not dosed so they were not included in the Safety Population. Only 8 participants received 800 mg of NV-5138 throughout the study so they were not analyzed separately.	FG000126 subjects FG001122 subjects
COMPLETED		FG000104 subjects FG001104 subjects
NOT COMPLETED		FG00022 subjects FG00118 subjects

Type	Comment	Reasons
Withdrawal by Subject		FG0006 subjects FG0015 subjects
Noncompliance		FG0007 subjects FG001

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	NV-5138 (800 or 1600 mg)	Participants received either 800 or 1600 mg NV-5138 (2 or 4, 400 mg capsules) once daily for 4 weeks. After completion of the 4-week treatment, all participants received placebo in a double-blinded fashion and continued the treatment for one week. 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.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Secondary

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.

Full Analysis Set (FAS) is a subset of participants in the randomized population who take at least one dose of study medication and have a baseline assessment of Montgomery-Asberg Depression Rating Scale (MADRS) total score.

Posted

Mean

Standard Deviation

units on a scale

Baseline to Weeks 1, 2 and 3

ID	Title	Description
OG000	NV-5138 (800 or 1600 mg)

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	NV-5138 (800 or 1600 mg)	Participants received either 800 or 1600 mg NV-5138 (2 or 4, 400 mg capsules) once daily for 4 weeks. After completion of the 4-week treatment, all participants received placebo in a double-blinded fashion and continued the treatment for one week. 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. Only 8 participants received 800 mg of NV-5138 throughout the study so they were not analyzed separately.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jun 7, 2024	Sep 10, 2025	Prot_000.pdf
SAP	No	Yes	No	Statistical Analysis Plan	Jul 3, 2024	Sep 10, 2025	SAP_001.pdf

ID	Term
D003866	Depressive Disorder
D019964	Mood Disorders
D001523	Mental Disorders