SPN-821 for Depression

Overseen By Gianpiera Ceresoli-Borroni, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Supernus Pharmaceuticals, Inc.

Must be taking: Antidepressants

Disqualifiers: Psychotic disorders, Bipolar, Substance use, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called SPN-821, used alongside current antidepressants to determine if it helps adults with major depressive disorder (MDD) improve. The study compares SPN-821 to a placebo (a dummy pill with no active ingredients) to assess its effectiveness and safety. Individuals experiencing a major depressive episode for at least 8 weeks without significant improvement from their current antidepressant may be suitable candidates. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires you to stay on a stable dose of a specific antidepressant for at least 10 weeks before starting. If you're on a different medication, you might need to switch to one of the approved ones.

Is there any evidence suggesting that SPN-821 is likely to be safe for humans?

Research shows that SPN-821 is being tested for safety in treating major depressive disorder. In earlier studies, a similar drug, SPN-820, was generally well-tolerated by patients. Participants took SPN-820 at a dose of 2400 mg every three days along with their usual antidepressants. Some side effects occurred, but most were mild and manageable.

Since SPN-821 is similar to SPN-820, it might have a similar safety profile. However, this trial is in an early stage, so safety is still being carefully monitored. This phase aims to assess the treatment's safety for people, identifying and studying any new side effects. Considering joining the trial contributes to understanding the safety of SPN-821 for treating depression. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

SPN-821 is unique because it targets depression with a different approach compared to typical antidepressants like SSRIs and SNRIs, which mainly focus on serotonin and norepinephrine pathways. SPN-821 is designed as an adjunctive treatment, meaning it's used in combination with existing antidepressants, potentially enhancing their effects. This treatment involves taking high-dose oral tablets just twice a week, offering a convenient dosing schedule that could improve patient adherence. Researchers are excited about SPN-821's potential to work through a novel mechanism, providing new hope for individuals who haven't found relief with standard treatments.

What evidence suggests that SPN-821 might be an effective treatment for depression?

Initial findings suggest that SPN-821, which participants in this trial may receive, can greatly reduce symptoms of depression in people with major depressive disorder. An earlier study showed that patients experienced a quick and noticeable drop in their depression levels when taking SPN-821. The treatment was well-tolerated, causing few side effects. However, similar drugs, such as SPN-820, did not help people with treatment-resistant depression, which is harder to treat. This suggests SPN-821 might be more effective for general depression rather than more difficult cases. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

Adults with Major Depressive Disorder (MDD) who score ≥24 on the MADRS and ≥4 on the CGI-S, indicating moderate illness. They must have been on a stable dose of an approved antidepressant for at least 8 weeks but with less than 50% improvement in symptoms. Excluded are those with significant risk of suicide, recent substance abuse, treatment-resistant depression, psychotic disorders, severe psychiatric conditions within specific timeframes or medical conditions that pose risks.

Inclusion Criteria

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

I have been diagnosed with major depression without psychosis.

Exclusion Criteria

MADRS total score change of ≥ 25% from the Screening Visit to Day 1 Visit

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

Treatment

Participants receive SPN-821 or placebo as adjunctive therapy to an approved antidepressant, administered twice a week

4 weeks

Follow-up

Participants receive a safety follow-up phone call to monitor safety and effectiveness after treatment

1 week

What Are the Treatments Tested in This Trial?

Interventions

• SPN-821

Trial Overview The trial is testing SPN-821 at a dose of 2400 mg against a placebo to assess its effectiveness and safety in treating MDD. Participants will be randomly assigned to receive either SPN-821 or placebo without knowing which one they're getting (double-blind).

How Is the Trial Designed?

Group I: SPN-821 2400 mg Experimental Treatment 1 Intervention

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

Group II: Placebo Placebo Group 1 Intervention

Three oral tablets administered twice a week adjunctive to current antidepressant

Who Is Running the Clinical Trial?

Supernus Pharmaceuticals, Inc.

Lead Sponsor

Trials

49

Recruited

14,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07226661

Double-blind, Placebo-controlled Study in Adults With ... Study Overview. Brief Summary. This study will evaluate the efficacy and safety of SPN-821 in adults with major depressive disorder.

2. ir.supernus.com ir.supernus.com/news-releases/news-release-details/supernus-announces-promising-data-open-label-phase-2a-study-spn

News Release Details Phase 2a study demonstrated rapid and substantial decrease in depressive symptoms. SPN-820 was well-tolerated with few adverse events.

3. hcplive.com hcplive.com/view/spn-820-fails-phase-2b-trial-treatment-resistant-depression

SPN-820 Fails Phase 2b Trial for Treatment-Resistant ... A phase 2b trial showed that, unlike patients with MDD, patients with treatment-resistant depression do not receive significant benefits from SPN-820.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9471356/

Efficacy and safety of mij821 in patients with treatment ... In this proof-of-concept study, MIJ821 was effective and tolerable in TRD. This study was funded by Novartis.

5. globenewswire.com globenewswire.com/news-release/2025/02/18/3028344/19871/en/Supernus-Announces-Topline-Results-from-Phase-2b-Study-in-Adults-with-Treatment-Resistant-Depression.html

Supernus Announces Topline Results from Phase 2b ... The Phase 2b study of SPN-820 in adults with treatment-resistant depression (TRD) did not demonstrate a statistically significant improvement on the primary ...

6. supernusmedical.com supernusmedical.com/pipeline/spn-820-821/publications

SPN-820 & SPN-821 – Publications by Supernus Medical Affairs Under investigation for the treatment of treatment-resistant depression. ... Publications may contain data outside the approved product labeling.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12455369/

Efficacy and Safety of Ammoxetine in Major Depressive Disorder This randomized clinical trial evaluates the efficacy and safety of ammoxetine 60 mg/d and 40 mg/d vs placebo in treating adult major depressive ...