Open-Label of SPN-820 in Adults With Major Depressive Disorder

An Open-Label, Single-Group Study to Evaluate the Efficacy and Safety of SPN-820 in Adults With Major Depressive Disorder

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT06235905

Enrollment

Registered

2024-02-01

Start date

2024-02-15

Completion date

2024-08-18

Last updated

2025-10-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Major Depressive Disorder

Brief summary

This study will evaluate of the efficacy and safety of SPN-820 in Adults With Major Depressive Disorder (MDD)

Detailed description

This is an open-label study of adjunctive SPN-820 (2400 mg) administered orally once every 3 days in adults with MDD

Interventions

DRUGNV-5138

NV-5138 is a novel, orally bioavailable, mechanistic target of rapamycin complex 1 (mTORC1) signaling enhancer

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Intervention model description

Open-label

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Inclusion criteria

* Male or female subject, aged 18 to 65 years (inclusive) at screening. * Diagnosis of 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) at screening. * MADRS total score of ≥22 for the current major depressive episode (MDE) at screening and baseline (day 1) before study medication (SM) administration. * CGI-S score of ≥4 (moderately ill or worse) at screening and baseline (day 1) before SM administration. * Stable, therapeutic dose of one of the following protocol-defined ADTs for the current MDE for ≥6 weeks prior to screening: citalopram, escitalopram, paroxetine, fluoxetine, sertraline, duloxetine, venlafaxine (immediate release or extended release), desvenlafaxine, vilazodone, levomilnacipran, vortioxetine, bupropion, or dextromethorphan/bupropion. * Stable therapeutic dose of the approved ADT throughout the study.

Exclusion criteria

* MADRS total score improvement of ≥25% from the highest to the lowest score from screening to baseline. * Clinically significant abnormal laboratory profiles, vital sign measurements, or ECGs prior to baseline. * Lifetime 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 the last 12 months before screening or current diagnosis of PTSD, OCD, panic disorder, acute stress disorder, or has a history of intellectual disability, autism, or cluster A or B personality disorder. * Suicidal behavior or suicidal ideation of type 4 or type 5 based on 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 substance use disorder within 6 months prior to screening or is currently using or has a positive result (urine drug screen) at screening or baseline for drugs of abuse. * History of alcohol use disorder within 6 months prior to screening. * In the investigator's opinion, is unlikely to comply with the protocol or is unsuitable for any other reason.

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline to Each Time Point in the Hamilton Depression Rating Scale-6 Items (HAM-D6) Total Score (HAM-D6).	10 days (end of study)	The HAM-D6 scale consists of 6 items: five of them (depressed mood, work and activities, feeling of guilt, anxiety, psychic, retardation) are scored on a scale of 0 to 4, and one item (somatic symptoms general) is scored on a scale 0 to 2. The total score is the sum of the 6 items ranging from 0 to 22, higher scores indicate severe depression, and lower scores are better outcomes.

Secondary

Measure	Time frame	Description
Change From Baseline to Each Time Point in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score.	10 days (end of study)	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.
Change From Baseline to Each Time Point in the Clinical Global Impression - Severity of Illness Score (CGI-S).	10 days (end of study)	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.
Suicidal Ideation and Behavior as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS)	10 days (end of study)	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.
Incidence of Treatment Emergent Adverse Events	10 days (end of study)	The incidence of treatment-emergent adverse events (TEAEs) was measured as the percent of participants who took at least one dose of SPN-820 and reported at least one adverse event during 10 days of adjunct treatment. The percent is calculated by dividing the number of participants who reported at least one Adverse Event by the number of participants in the Safety Population and then multiplying the product by 100. The higher the percent, the higher the incidence.

Countries

United States

Participant flow

Participants by arm

Arm	Count
SPN-820 (2400 mg) SPN-820 (2400 mg) oral capsules Participants received SPN-820 6 x 400 mg capsules administered orally every 3 days for a 7-day treatment period.	40
Total	40

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	1
Overall Study	Non-compliant with protocol procedures	1

Baseline characteristics

Characteristic	SPN-820 (2400 mg)
Age, Continuous	44.7 years STANDARD_DEVIATION 15.39
CGI-S	4.6 units on a scale STANDARD_DEVIATION 0.64
Ethnicity (NIH/OMB) Hispanic or Latino	16 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	24 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
HAM-D6 Total Score	13.6 units on a scale STANDARD_DEVIATION 1.69
MADRS Total Score	33.1 units on a scale STANDARD_DEVIATION 5.41
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	4 Participants
Race (NIH/OMB) Black or African American	3 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants
Race (NIH/OMB) White	32 Participants
Region of Enrollment United States	40 Participants
Sex: Female, Male Female	27 Participants
Sex: Female, Male Male	13 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 40
other Total, other adverse events	25 / 40
serious Total, serious adverse events	0 / 40

Outcome results

Primary

Change From Baseline to Each Time Point in the Hamilton Depression Rating Scale-6 Items (HAM-D6) Total Score (HAM-D6).

The HAM-D6 scale consists of 6 items: five of them (depressed mood, work and activities, feeling of guilt, anxiety, psychic, retardation) are scored on a scale of 0 to 4, and one item (somatic symptoms general) is scored on a scale 0 to 2. The total score is the sum of the 6 items ranging from 0 to 22, higher scores indicate severe depression, and lower scores are better outcomes.