Double-blind, Placebo-controlled Study in Adults With Major Depressive Disorder

NCT07226661 | Recruiting Phase 2 FDA Drug

• 1 other identifier: 821P203
• Study Type: interventional
• Target: 230
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the efficacy and safety of SPN-821 in adults with major depressive disorder

Conditions

Major Depressive Disorder (MDD)

Outcome Measures

Primary Outcomes (1)

• Change From Baseline to Day 29 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.

  4 weeks

Secondary Outcomes (1)

• Change From Baseline to Day 29 in the Clinical Global Impression - Severity of Illness Score (CGI-S).

  4 weeks

Study Arms (2)

SPN-821 2400 mg

EXPERIMENTAL

Three 800 mg oral tablets administered twice a week adjunctive to current antidepressant

Drug: SPN-821 2400 mg

Placebo

PLACEBO COMPARATOR

Three oral tablets administered twice a week adjunctive to current antidepressant

Drug: Placebo

Interventions

SPN-821 2400 mg DRUG

SPN-821 is a novel, orally bioavailable, selective, direct enhancer of mTORC1 cellular signaling

SPN-821 2400 mg

Placebo DRUG

Matched placebo oral tablets

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:

• Current diagnosis of MDD according to the DSM-5 for either single or recurrent MDE without psychotic features confirmed by the MINI
• Duration of current MDE of at least 8 weeks
• MADRS total score of ≥ 24 at the Screening Visit and Day 1 Visit
• CGI-S score of ≥ 4 (moderately ill or worse) at the Screening Visit and Day 1 Visit
• Stable, therapeutic dose of one of the following protocol-approved ADTs as a monotherapy for ≥ 8 weeks before the Screening Visit and ≥ 10 weeks at the Day 1 Visit. Additionally, inadequate response to the current ADT (less than 50% improvement in depressive symptoms) as confirmed by the ATRQ Investigator administered.

You may not qualify if:

• MADRS total score change of ≥ 25% from the Screening Visit to Day 1 Visit
• History of treatment resistant depression (TRD) defined as 3 or more failed ADTs of adequate dose (per ATRQ) and duration (at least 8 weeks) for the current MDE
• History of alcohol or substance use disorder according to DSM-5 criteria 6 months before the Screening Visit
• Evidence of significant risk for suicidal behavior during participation in the study in the Investigator's opinion
• Lifetime diagnosis of any psychotic disorder including MDD with psychosis, MDD with mixed features, bipolar I/II disorder, bipolar depression, schizophrenia, posttraumatic stress disorder, autism spectrum disorder, or any personality disorder or intellectual disability that would affect the ability of the participant to enroll in the study
• Diagnosis less then 12 months before screening of severe obsessive-compulsive disorder, acute stress disorder, panic disorder, eating disorders, or any other psychiatric condition that has been the primary focus of treatment, or diagnosis of generalized anxiety disorder less then 6 months before screening.
• History of cardiovascular, respiratory, gastrointestinal, renal, hepatic, and hematologic disorders, or other medical disorders that could impose undue risk or compromise the study in the Investigator's opinion
• Clinically significant abnormal result prior to Day 1 Visit per Investigator's judgment or abnormal renal function.
• Requires treatment with a medication or other substance that is prohibited by the protocol.

Sponsors & Collaborators

• Supernus Pharmaceuticals, Inc.: lead

Study Sites (1)

Collaborative Neuroscience Network

Garden Grove, California, 92845, United States

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Central Study Contacts

Gianpiera Ceresoli-Borroni, PhD

CONTACT

301-838-2521; gceresoliborroni@supernus.com

Study Design

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

Study Record Dates

• First Submitted: November 7, 2025
• First Posted: November 10, 2025
• Study Start: January 19, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): January 31, 2027
• Last Updated: March 24, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)