Major Depressive Disorder (MDD)Phase 2NCT07226661
Double-blind, Placebo-controlled Study in Adults With Major Depressive Disorder
A Phase 2 study testing SPN-821 2400 mg in people with Major Depressive Disorder (MDD), run by Supernus Pharmaceuticals, Inc. at 40 sites in United States.
Trial summary
This study will evaluate the efficacy and safety of SPN-821 in adults with major depressive disorder Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Major Depressive Disorder (MDD)
- What is being tested?
- SPN-821 2400 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 230 participants
- Where
- 40 sitesUnited States
- Study dates
- 19 Jan 2026to 31 Jan 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 9Show fewer
- 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.
Trial locations and contacts
40 sites in 1 country. Contact the study team or a site near you to ask about taking part.
40 sites in 1 country
United States40 sites, 40 recruiting
- Recruiting
Cenexel Atlanta (ACMR)
Atlanta, Georgia, 30331
- Recruiting
Houston Clinical Trials
Bellaire, Texas, 77401
- Recruiting
University of Alabama
Birmingham, Alabama, 35233
- Recruiting
SPRI Clinical Trials
Brooklyn, New York, 11235
- Recruiting
New Hope Clinical Research
Charlotte, North Carolina, 28211
- Recruiting
Inland Psychiatric Medical Group
Chino, California, 91710
- Recruiting
Alpine Research Organization
Clinton, Utah, 84015
- Recruiting
CT Clinical Research
Cromwell, Connecticut, 06416
- Recruiting
Cenexel iResearch Atlanta
Decatur, Georgia, 30030
- Recruiting
Mountain View Clinical Research
Denver, Colorado, 80209
- Recruiting
Leading Edge Research (Eximia Network)
Encino, California, 91316
- Recruiting
Core Clinical Research
Everett, Washington, 98201
- Recruiting
Precise Clinical Research
Flowood, Mississippi, 39232
- Recruiting
Cenexel Collaborative Neuroscience Network
Garden Grove, California, 92845
- Recruiting
Baylor College of Medicine
Houston, Texas, 77030
- Recruiting
DM Clinical
Houston, Texas, 77081
- Recruiting
CNS Healthcare - Jacksonville
Jacksonville, Florida, 32256
- Recruiting
Vector Clinical Trials
Las Vegas, Nevada, 89128
- Recruiting
Synergy Research (ERG Network)
Lemon Grove, California, 91945
- Recruiting
Cenexel Marlton (HRI)
Marlton, New Jersey, 08053
- Recruiting
Avantis Clinical Research
Miami, Florida, 33155
- Recruiting
Catalina Research Institute (Elixia)
Montclair, California, 91763
- Recruiting
Manhattan Behavioral Medicine
New York, New York, 10036
- Recruiting
Psychiatric Care and Research Center
O'Fallon, Missouri, 63368
- Recruiting
Paradigm Research Professionals
Oklahoma City, Oklahoma, 73116
- Recruiting
ATP Clinical Research
Orange, California, 92866
- Recruiting
NRC Research Institute
Orange, California, 92868
- Recruiting
CNS Healthcare of Orlando
Orlando, Florida, 32801
- Recruiting
Space Coast Neuropsychiatric Research Institute
Palm Bay, Florida, 32905
- Recruiting
IMA Clinical Research Phoenix
Phoenix, Arizona, 85012
- Recruiting
Summit Headlands (Headlands Research)
Portland, Oregon, 97210
- Recruiting
Woodland Research Northwest (ERG)
Rogers, Arkansas, 72758
- Recruiting
Midwest Research Group
Saint Charles, Missouri, 63304
- Recruiting
Aura Wellness
Salt Lake City, Utah, 84105
- Recruiting
Lumos Clinical Research Center
San Jose, California, 95124
- Recruiting
Cenexel Tampa
Tampa, Florida, 33613
- Recruiting
Interventional Psychiatry of Tampa Bay
Tampa, Florida, 33629
- Recruiting
Inland Psychiatric Medical Group
Temecula, California, 92591
- Recruiting
AMR Conventions Research
Warrenville, Illinois, 60555
- Recruiting
Grayline Research Center
Wichita Falls, Texas, 76309
About this study
Official title: 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
Read the 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.
- Conditions
- Major Depressive Disorder (MDD)
- Being tested
- SPN-821 2400 mg, Placebo
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SPN-821 2400 mgDrug
SPN-821 is a novel, orally bioavailable, selective, direct enhancer of mTORC1 cellular signaling
PlaceboDrug
Matched placebo oral tablets
| Study group | Role | What they receive |
|---|---|---|
| SPN-821 2400 mg | Experimental | Three 800 mg oral tablets administered twice a week adjunctive to current antidepressant Receives: Drug: SPN-821 2400 mg |
| Placebo | Placebo comparator | Three oral tablets administered twice a week adjunctive to current antidepressant Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 4 weeks
Secondary outcomes (1)
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.
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2025
- Study start19 Jan 2026
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive Disorder (MDD)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 230 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Supernus Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07226661
- Sponsor's protocol ID
- 821P203
- Status last verified
- Oct 2026
- First submitted
- 7 Nov 2025
- Last updated
- 28 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07226661
- Acronym / sponsor ID
- 821P203
- Conditions
- Major Depressive Disorder (MDD)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 230 participants (estimated)
- Lead sponsor
- Supernus Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 19 Jan 2026 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Jan 2027 (estimated)
- First posted
- 10 Nov 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the efficacy and safety of SPN-821 in adults with major depressive disorder
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| SPN-821 2400 mg | Experimental | Drug: SPN-821 2400 mgThree 800 mg oral tablets administered twice a week adjunctive to current antidepressant |
| Placebo | Placebo comparator | Drug: PlaceboThree oral tablets administered twice a week adjunctive to current antidepressant |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SPN-821 2400 mgSPN-821 is a novel, orally bioavailable, selective, direct enhancer of mTORC1 cellular signaling | Drug | SPN-821 2400 mg |
| PlaceboMatched placebo oral tablets | Drug | Placebo |
Primary outcome
Change From Baseline to Day 29 in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score.
Time frame: 4 weeks
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.
1 secondary outcome
Change From Baseline to Day 29 in the Clinical Global Impression - Severity of Illness Score (CGI-S).
Time frame: 4 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
40 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing SPN-821 2400 mg in people with Major Depressive Disorder (MDD), run by Supernus Pharmaceuticals, Inc. at 40 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 28 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 40 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Gianpiera Ceresoli-Borroni, PhD (301-838-2521, gceresoliborroni@supernus.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline to Day 29 in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score. (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2026.