A Phase 2 Study of Zelquistinel or Placebo for the Reduction of Symptoms of Major Depressive Disorder

NCT07115329 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: GATE-251-C-203
• Study Type: interventional
• Target: 164
• Locations: 1 country
• Sites: 32

Brief Summary

The goal of this clinical trial is to learn if zelquistinel works to treat depression in adults. It will also learn about the safety of zelquistinel. The main questions it aims to answer are: Does zelquistinel reduce depression scores in participants compared to participants who take a placebo (a look-alike tablet that contains no zelquistinel1)? What medical problems are observed in participants who take zelquistinel? Participants will take one tablet of zelquistinel or placebo every week for 6 weeks. Participants will visit the clinic every week of the 6 week period to have the severity of their depression evaluated.

Conditions

Major Depressive Disorder

Keywords

zelquisitinel; GATE-251; N-Methyl-D-aspartate receptor positive allosteric modulator; NMDA receptor positive allosteric modulator

Outcome Measures

Primary Outcomes (1)

• Change in the Hamilton Depression Rating Scale-17 (HDRS-17) score compared to Placebo

  HDRS-17 is used to assess the severity of depression. The range of scores for the HDRS-17 is 0 - 52 with lower scores indicating a better outcome

  Change in score from baseline to 6 wweeks

Secondary Outcomes (1)

• Change in the Clinical Global Impressions - Severity (CGI-S) score compared to placebo

  Change in score from baseline to 6 weeks

Study Arms (2)

zelquisitinel (GATE-251 )

EXPERIMENTAL

zelquistinel (GATE-251) will be administered as a single 6 mg oral tablet one time each week for 6 weeks.

Drug: Zelquistinel

Placebo

PLACEBO COMPARATOR

Placebo tablet identical in appearance to the experimental treatment tablet, administered as as a single oral tablet one time each week for 6 weeks.

Drug: Zelquistinel

Interventions

Zelquistinel DRUG

Zelquistinel is a positive allosteric modulator of the N-Methyl-D-Aspartate (NMDA) receptor

Also known as: GATE-251

Placebo; zelquisitinel (GATE-251 )

Eligibility Criteria

• Age: 18 Years - 64 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female subject.
• Aged 18 to 64 years, inclusive.
• Subject has a first episode or recurrent episode diagnosis of MDD, defined by the Diagnosis and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), ≥3 weeks and ≤18 months. The diagnosis of MDD will be made by a central rater using the Structured Clinical Interview for DSM-5 Clinical Trials version (SCID-5-CT).
• Subject has a HDRS-17 total score of ≥18 at the Screening Visit (V1) and Baseline Visit (V2) as assessed by a central rater, with no more than a 25% change from the Screening Visit (V1) to the Baseline Visit (V2)
• Subject has HARS total score ≥15 at the Screening Visit (V1) and predose at the Baseline Visit (V2), AND
• Subject has ISI total score ≥10 at the Screening Visit (V1) and predose at the Baseline Visit (V2).
• Female subjects must meet 1 of the following:
• Surgically sterile or at least 2 years menopausal (ie, postmenopausal is defined as a woman with the absence of menses for at least 12 consecutive months). Menopausal status is to be confirmed by assessing the follicle stimulating hormone level at Screening Visit (V1), or,
• If a woman of childbearing potential, subject must use an acceptable method of birth control from date of Screening to the last evaluation at Day 71. Must have a documented negative point of care urine pregnancy test within 24 hours prior to first dosing.
• Male subjects, including those who are surgically sterile, must use a medically acceptable form of contraception from the time of randomization until the End of Week 6 Visit. Male subjects are strongly advised to inform female partners of the need for them to use highly effective birth control during this time period.
• Ability to understand the nature and requirements of the study and is willing to comply with the study restrictions and agree to return for the required assessments.
• Provides written informed consent to participate in the study.
• Is able to communicate with investigational site personnel, able to complete patient-reported outcome measures and in the opinion of the Investigator, can be reliably rated on assessment scales.
• Have an appropriate severity of illness of at least moderately ill corresponding to a CGI-S score of ≥4 at the Screening and Baseline Visits (V1 and V2, respectively), as assessed by a central rater.

You may not qualify if:

• A subject who meets any of the following criteria will be excluded from study participation:
• Evidence of treatment-resistant MDD, defined by having an inadequate response (≤25%) to 2 or more different medications approved for the treatment of MDD at an adequate dose (per locally approved label) for an adequate duration during the current episode using the Massachusetts General Hospital Antidepressant Treatment Rating Questionnaire (MGH ATRQ) assessed by a site rater.
• Current DSM-5 diagnosis of bipolar (or related disorders), antisocial personality disorder, obsessive compulsive disorder, borderline personality disorder,attention-deficit/ hyperactivity disorder, post-traumatic stress disorder, or panic attacks. Subjects not meeting full DSM-5 criteria for borderline personality disorder but exhibiting recurrent suicidal gestures, threats, or self-mutilating behaviors should also be excluded.
• Subject has a current or prior DSM-5 diagnosis of a psychotic disorder, or MDD with psychotic features.
• Subject has a score of \>4 on the CADSS at the Screening Visit (V1).
• Active seizure disorder.
• Traumatic brain injury with current signs or symptoms.
• Treatment with esketamine or ketamine, any psychedelic agent, or any experimental agent being evaluated to treat depression, whether as an antidepressant or for other use, within the past 12 months.
• o Treatment with any other experimental agents not used to treat depression within the past 3 months.
• Concomitant treatment with other Food and Drug Administration (FDA)-approved antidepressants or adjuvant agents or enhancers such as dextromethorphan, antipsychotics, mood stabilizers, sedatives, stimulants, or benzodiazepines. Subject must discontinue concomitant treatment at least 14 days prior to the Baseline Visit.
• o Subjects may continue anxiolytic agents, except for drugs that are also used to treat depression. Subjects may continue sleep aids, so long as they have been on a stable dose for at least 3 months and do not intend to change dose during the Double-Blind Treatment Period (Week 1 \[Day 1\] through End of Week 6). However, trazodone must be discontinued for at least 14 days prior to the Baseline Visit.
• Use of cannabis or cannabis-derived molecules, including tetrahydrocannabinol (THC), whether natural or chemically-synthesized, including hemp seed oil and cannabidiol (CBD) products (eg, gummies). Subject must discontinue the use of such products at least 14 days prior to the Baseline Visit, and THC must be below the limit of detection at the Baseline Visit.
• Positive test for any drug of abuse.
• Treated with any medical device or digital therapeutics for MDD, anxiety, insomnia, or other CNS indications within 90 days of screening in this study.
• History of electroconvulsive therapy, vagus nerve stimulation, deep brain stimulation, or repetitive transcranial magnetic stimulation within the past 5 years or has had a failure of response to electroconvulsive therapy at any time.

Sponsors & Collaborators

• Syndeio Biosciences, Inc: lead
• Worldwide Clinical Trials: collaborator

Study Sites (32)

NoesisPharma, LLC

Phoenix, Arizona, 85028, United States

RECRUITING

Del Sol Research Management

Tucson, Arizona, 85710, United States

RECRUITING

Catalina Research Institute, LLC

Montclair, California, 91763, United States

RECRUITING

Excell Research, Inc

Oceanside, California, 92056, United States

RECRUITING

Anderson Clinical Research

Redlands, California, 92374, United States

RECRUITING

Studyops Inc

San Francisco, California, 94102, United States

RECRUITING

Lumos Clinical Research Center

San Jose, California, 95124, United States

RECRUITING

Sunwise Clinical Research

Walnut Creek, California, 94596, United States

NOT YET RECRUITING

Clinical Neuroscience Solutions, Inc

Jacksonville, Florida, 32256, United States

NOT YET RECRUITING

Premier Clinical Research Institute Inc

Miami, Florida, 33122, United States

NOT YET RECRUITING

Aqualane Clinical Research

Naples, Florida, 34105, United States

RECRUITING

EquiPath Health and Research Tampa Bay, LLC

Riverview, Florida, 33578, United States

RECRUITING

Neuroscience Research Institute

West Palm Beach, Florida, 33407, United States

RECRUITING

Denali Health Atlanta, LLC

Stone Mountain, Georgia, 30038, United States

RECRUITING

EmVenio Research

Chicago, Illinois, 60622, United States

RECRUITING

Tandem Clinical Research

Metairie, Louisiana, 70006, United States

RECRUITING

Sunstone Therapies

Rockville, Maryland, 20850, United States

NOT YET RECRUITING

Continental Clinical Solutions

Towson, Maryland, 21204, United States

RECRUITING

Vitalix Clinical

Worcester, Massachusetts, 01608, United States

RECRUITING

Rochester Center for Behavioral Medicine

Rochester Hills, Michigan, 48307, United States

NOT YET RECRUITING

Neurobehavioral Research, Inc

Cedarhurst, New York, 11516, United States

NOT YET RECRUITING

IMA Clinical Research - NYC Midtown

New York, New York, 10036, United States

NOT YET RECRUITING

IMA Clinical Research - NYC Uptown

New York, New York, 10128, United States

RECRUITING

UNC Health Rex

Raleigh, North Carolina, 27607, United States

NOT YET RECRUITING

Insight Clinical Trials LLC

Independence, Ohio, 44131, United States

NOT YET RECRUITING

Lehigh Center for Clinical Research

Allentown, Pennsylvania, 18103, United States

NOT YET RECRUITING

Scranton Medical Institute, LLC

Moosic, Pennsylvania, 18507, United States

TERMINATED

Adams Clinical

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Psychiatric Consultants, PC

Franklin, Tennessee, 37067, United States

RECRUITING

Elevate Synapsis, LLC

Atascocita, Texas, 77346, United States

RECRUITING

Synapsis Bio

Atascocita, Texas, 77346, United States

NOT YET RECRUITING

Adams Clinical Dallas

DeSoto, Texas, 75115, United States

NOT YET RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants, investigators and site staff, and outcomes assessors will be blinded to treatment with zelquistinel or placebo.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 2 multicenter, randomized, double-blind, placebo-controlled, parallel-group, fixed dose clinical trial

Study Record Dates

• First Submitted: August 4, 2025
• First Posted: August 11, 2025
• Study Start: January 5, 2026
• Primary Completion (Estimated): March 30, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (32)