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

A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of SPN-821 as an Adjunctive Therapy in Adults With Major Depressive Disorder

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

Study Overview

• Status: Recruiting
• Conditions: Major Depressive Disorder (MDD)
• Intervention / Treatment: Drug: SPN-821 2400 mg; Drug: Placebo

Detailed Description

This is a multicenter, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of SPN-821 administered twice a week as adjunctive therapy to an approved antidepressant therapy in adult participants with MDD. The study includes a 2-week Screening Period, a 4-week Double blind Treatment Period, and a Safety Follow-up phone call one week after the completion of the Treatment Period.

• Study Type: Interventional
• Enrollment (Estimated): 230
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Gianpiera Ceresoli-Borroni, PhD; Phone Number: 301-838-2521; Email: gceresoliborroni@supernus.com

Study Locations

• United States
  • California
    • Garden Grove, California, United States, 92845
      • Recruiting
      • Collaborative Neuroscience Network

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

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: SPN-821 2400 mg; Three 800 mg oral tablets administered twice a week adjunctive to current antidepressant	Drug: SPN-821 2400 mg; SPN-821 is a novel, orally bioavailable, selective, direct enhancer of mTORC1 cellular signaling
Placebo Comparator: Placebo; Three oral tablets administered twice a week adjunctive to current antidepressant	Drug: Placebo; Matched placebo oral tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Day 29 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.	4 weeks

Collaborators and Investigators

• Sponsor: Supernus Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): January 31, 2027

Study Registration Dates

• First Submitted: November 7, 2025
• First Submitted That Met QC Criteria: November 7, 2025
• First Posted (Actual): November 10, 2025

Study Record Updates

• Last Update Posted (Actual): March 24, 2026
• Last Update Submitted That Met QC Criteria: March 19, 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, Major
• Other Study ID Numbers: 821P203

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