Double-blind, placebo-controlled test of SPN-821 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 trial will test whether adding SPN-821 twice weekly to an approved antidepressant helps adults with major depressive disorder who have not had enough improvement.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 230 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Supernus Pharmaceuticals, Inc. (industry)
• Locations: 1 site (Garden Grove, California)
• Trial ID: NCT07226661 on ClinicalTrials.gov

What this trial studies

This is a multicenter, randomized, double-blind, placebo-controlled Phase 2 trial of adjunctive SPN-821 (2400 mg) given twice weekly versus placebo in adults with major depressive disorder. Eligible participants remain on a stable, approved antidepressant monotherapy and must have a current depressive episode of at least eight weeks with moderate to severe symptoms. The protocol includes a 2-week screening period, a 4-week double-blind treatment period, and a safety follow-up phone call one week after treatment ends. Efficacy and safety will be tracked using standard clinical rating scales (such as MADRS and CGI-S) and routine clinical assessments.

Who should consider this trial

Good fit: Adults with MDD in a current episode of at least 8 weeks who are on a stable, approved antidepressant monotherapy for the required duration, have MADRS ≥24 and CGI-S ≥4, and show less than 50% improvement on their current antidepressant are ideal candidates.

Not a fit: Patients with treatment-resistant depression (three or more prior failed adequate antidepressant trials), a recent alcohol or substance use disorder, a large spontaneous improvement between screening and baseline, or those not on a stable monotherapy are unlikely to qualify or benefit.

Why it matters

Potential benefit: If successful, adding SPN-821 could reduce depressive symptoms for adults who have not responded adequately to a single antidepressant.

How similar studies have performed: Other adjunctive therapies for MDD have produced benefit in prior trials, but SPN-821 itself is investigational and does not yet have established clinical proof of benefit.

Eligibility criteria

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.

Where this trial is running

Garden Grove, California

• Collaborative Neuroscience Network — Garden Grove, California, United States (RECRUITING)

Study contacts

• Study coordinator: Gianpiera Ceresoli-Borroni, PhD

Conditions: Major Depressive Disorder