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Major Depressive DisorderPhase 2GATE-251NCT06547489

Zelquistinel or Placebo for the Reduction of Symptoms of Major Depressive Disorder

A Phase 2 study testing Zelquistinel in people with Major Depressive Disorder, run by Syndeio Biosciences, Inc at 34 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 to 64 years
Conditions the study is for
Major Depressive Disorder
What is being tested?
Zelquistinel
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
164 participants
Where
34 sitesUnited States
Study dates
3 Feb 2025to Dec 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 64 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Each subject must meet all of the following inclusion criteria to be eligible to participate in the study:
  • Male or female subjects.
  • Aged 18 to 64 years, inclusive.
  • Subject has a diagnosis of major depressive disorder (MDD), single or recurrent episode, defined by the Diagnosis and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5); if single episode, the duration must be ≥8 weeks and ≤24 months. The diagnosis of MDD will be made by a site rater and supported by the Structured Clinical Interview for DSM-5 - Clinical Trials version (SCID-5-CT) and confirmed by remote, independent raters from the Massachusetts General Hospital Clinical Trials Network and Institute with a State versus trait, Assessability, Face validity, Ecological validity, and Rule of three Ps (pervasive, persistent, and pathological) (SAFER) interview:
  • The current depressive episode is ≥8 weeks and ≤24 months in duration prior to the Screening Visit (V1);
  • 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); and
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  • Importantly, have a sufficient history and/or independent report verifying that the current depressive episode is causing clinically significant distress or impairment in functioning.
  • Subject has a Hamilton Depression Rating Scale-17 (HDRS-17) using the Structured Interview Guide for the Hamilton Rating Scale for Depression (SIGH-D) total score of ≥18 at the Screening Visit (V1) and Baseline Visit (V2) with no more than a 25% change from the Screening Visit (V1) to the Baseline Visit (V2).
  • (Inclusion 5 removed in protocol amendment 4)
  • (Inclusion 6 removed in protocol amendment 4)
  • 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 child bearing 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 last evaluation at Day 71. Male subjects are strongly advised to inform female partners of the need for them to use highly effective birth control during this time period.
  • Subject must be medically stable by physical examination, medical history, vital signs, laboratory evaluations, and 12-lead electrocardiogram performed at the Screening Visit (V1) and Baseline (V2). If abnormalities are found, the subject may be included if the Investigator, contract research organization (CRO) and sponsor medical monitors judge the abnormalities to be not clinically significant.
  • 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 trial.
  • 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

Who cannot join

  • Any 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 (ATRQ).
  • Current DSM-5 diagnosis of bipolar (or related disorders), antisocial personality disorder, obsessive compulsive disorder, borderline personality disorder, post-traumatic stress disorder, panic disorder, or attention-deficit/hyperactivity disorder. 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.
  • Current concomitant treatment with Food and Drug Administration (FDA)-approved antidepressants, antipsychotics, mood stabilizers, sedatives, or stimulants. Current or past treatment with esketamine, ketamine, or psychedelics is prohibited. Subject must have current concomitant treatment discontinued at least 14 days prior to the Baseline Visit (V2). Subjects may continue anxiolytic agents, except for drugs that are also used to treat depression, or benzodiazepines, or sleep aids [see Section 5.5.1 for a nonexhaustive list] (except trazodone) so long as they have been on a stable dose for at least 3 months and do not intend to change dose during double-blind treatment period (Day 1, Week 1 through end of Week 6 [Day 43]). Subjects who use cannabis or cannabis-derived molecules, including tetrahydrocannabinol (THC), whether natural or chemically-synthesized, hemp seed oil, or cannabidiol (CBD) products (eg, gummies), must be discontinued for at least 14 days prior to the Baseline Visit (V2).
  • Treatment with any experimental antidepressant agent or treatment with a psychedelic agent in an FDA-approved clinical study within the past 12 months.
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  • 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.
  • Subject has clinically significant renal dysfunction as assessed by the estimated glomerular filtration rate <70 mL/min using the Chronic Kidney Disease Epidemiology Collaboration - creatinine (CKD-EPI creatinine) methodology.
  • Subject has liver protein and enzyme (alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, total bilirubin, lactate dehydrogenase test result >1.5 times the upper limit of normal (subjects with a diagnosis of Gilbert's Syndrome may be eligible if no liver function or enzyme test results other than total bilirubin are >1.5 times upper limit of normal).
  • Subject has resting pulse rate (supine) <50 or >100 bpm at the Screening Visit (V1) or predose Baseline (V2).
  • Subject has resting diastolic blood pressure <50 mmHg at the Screening Visit (V1) or predose Baseline (V2).
  • Subject has cardiac PR interval >250 msec at the Screening Visit (V1) or predose Baseline (V2), or QTcF or QTcB interval >450 msec in males or >470 msec in females, or QRS interval >120 msec.
  • Evidence of alcohol abuse (>4 units of alcohol on most days; 1 unit=½ pint of beer, 1 glass of wine, or 1 ounce of hard liquor/spirits) or a positive saliva alcohol screen at Screening (V1) and predose at the Baseline Visit (V2). Alcohol consumption should be avoided for at least 24 hours prior to Baseline Visit (V2). Note: Subject may not be rescreened.
  • Abuse of illicit substances, including psychedelic mushrooms by DSM-5 definition of substance use disorder within the 12 months prior to the Screening Visit (V1). Positive urine test for any drug of abuse is exclusionary.
  • Positive urine test for any drug of abuse (except cannabis or cannabis-derived molecules such as THC whether natural or chemically-synthesized [see exclusion criterion 4]). Prescribed barbiturates may be continued so long as subjects have been on a stable dose for at least 3 months and may not change dose during the double-blind treatment period. Subjects may not be rescreened after failing a drug screen for a drug of abuse.
  • HIV infection, COVID-19 infection, or active hepatitis B or C, syphilis, or other ongoing infectious disease at the Screening Visit (V1).
  • Has laboratory evidence of hypothyroidism at Screening (V1) as measured by thyroid stimulating hormone (TSH) and reflex free thyroxine (T4). If TSH is abnormal and reflex T4 is normal, the subject may be included.
  • Has current unstable diabetes or glycosylated hemoglobin (HbA1c) >7% at Screening (V1).
  • Currently pregnant, planning to become pregnant during the course of the study, or nursing.
  • Currently working a night shift or may be required to work night shift during the course of this study, from Screening through completion of final polysomnography.
  • Malignancy in the last 5 years, with the exception of nonmetastatic basal cell or squamous cell carcinoma of the skin or localized carcinoma in situ of the cervix.
  • Subject has received new onset psychotherapy or had a change in the intensity of psychotherapy within 8-weeks prior to the Screening Visit (V1).
  • Currently taking prohibited prescription or over-the-counter medications including herbal therapies (eg, echinacea, ginseng, ginko, elderberry, turmeric, ginger, valerian, chamomile, or St John's wort) and THC or cannabis-containing products [see exclusion criterion 4], which may interfere with the required study psychiatric assessments.
  • History of allergy or sensitivity, or intolerance to zelquistinel, NMDAR ligands including ketamine, dextromethorphan, memantine, methadone, dextropropoxyphene, or ketobemidone.
  • Treatment with any other investigational study drugs not used to treat depression within 90 days of screening in this study.
  • Previously participated in this study or currently enrolled in any other clinical study.
  • Body mass index of >35 kg/m2 at the Screening Visit (V1).
  • Subject is an employee of Worldwide Clinical Trials (hereafter referred to as Worldwide), the Investigator or study site with direct involvement in the study or other studies under the direction of that Investigator or study site, as well as a family member of an employee or of the Investigator, or an employee of Gate Neurosciences, Inc., or a family member of an employee.
  • In the opinion of the Investigator,
  • The subject has a significant risk for suicidal behavior during the course of participation in the study, or
  • At the Screening Visit (V1) (the subject scores "Yes" on Items 4 or 5 in the Suicidal Ideation section of the Columbia Suicide Severity Rating Scale (C-SSRS) with reference to a 6-month period prior to Screening Visit (V1), or
  • At Screening (V1) the subject has had 1 or more suicidal attempts with reference to a 2-year period prior to Screening Visit (V1), or
  • The subject is considered to be an imminent danger to themself or others, or
  • At the Baseline Visit (V2) (the subject scores "Yes" on Items 4 or 5 in the Suicidal Ideation section of the C-SSRS
  • The subject is judged by the Investigator or CRO and Sponsor medical monitors to be inappropriate for the study for any reason.

Trial locations and contacts

34 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Karen Raudibaugh contact

781-786-1545

karen.raudibaugh@syndeio.bio

Kelly Kosko contact

215-510-6405

kelly.kosko@syndeio.bio

34 sites in 1 country

United States34 sites, 21 recruiting

  • Lehigh Center for Clinical Research

    Allentown, Pennsylvania, 18103

    Recruiting

  • Austin Clinical Trial Partners

    Austin, Texas, 78737

    Recruiting

  • Northwest Clinical Research Center

    Bellevue, Washington, 98007

    Withdrawn

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

    Recruiting

  • Boston Clinical Trials

    Boston, Massachusetts, 02131

    Withdrawn

  • Neurobehavioral Research, Inc.

    Cedarhurst, New York, 11516

    Recruiting

  • MCB Clinical Research Centers, Inc.

    Colorado Springs, Colorado, 80910

    Recruiting

  • Mountain View Clinical Research

    Denver, Colorado, 80209

    Recruiting

  • InSite Clinical Research, LLC

    DeSoto, Texas, 75115

    Recruiting

  • Revive Research Institute

    Elgin, Illinois, 60123

    Withdrawn

  • Wr-Pri, Llc

    Encino, California, 91316

    Withdrawn

  • University of Connecticut School of Medicine Psychiatry Department

    Farmington, Connecticut, 06030

    Recruiting

  • Baylor College of Medicine, Psychiatry and Behavioral Sciences

    Houston, Texas, 77030

    Withdrawn

  • University of Alabama at Birmingham-Huntsville

    Huntsville, Alabama, 35801

    Active, not recruiting

  • Insight Clinical Trials LLC

    Independence, Ohio, 44131

    Recruiting

  • Irvine Clinical Research

    Irvine, California, 92614

    Recruiting

  • Clinical Neuroscience Solutions, Inc.

    Jacksonville, Florida, 32256

    Recruiting

  • Vector Clinical Trials

    Las Vegas, Nevada, 89128

    Active, not recruiting

  • CalNeuro Research Group

    Los Angeles, California, 90025

    Recruiting

  • Quantum Research Associates Corp.

    Louisville, Kentucky, 40218

    Active, not recruiting

  • D&H Pompano Research Center, LLC

    Margate, Florida, 33063

    Recruiting

  • Clinical Neuroscience Solutions, Inc.

    Memphis, Tennessee, 38119

    Withdrawn

  • Premier Clinical Research Institute, Inc.

    Miami, Florida, 33122

    Recruiting

  • Miami Dade Medical Research Institute

    Miami, Florida, 33176

    Recruiting

  • Sooner Clinical Research, Inc.

    Oklahoma City, Oklahoma, 73116

    Withdrawn

  • Andes Clinical Research

    Orem, Utah, 84097

    Recruiting

  • Clinical Neuroscience Solutions, Inc.

    Orlando, Florida, 32801

    Recruiting

  • Mayflower Clinical

    Russells Mills, Massachusetts, 02747

    Recruiting

  • Clinical Trials of Texas LLC

    San Antonio, Texas, 78229

    Withdrawn

  • CenExel iRS (iResearch Savannah)

    Savannah, Georgia, 31405

    Recruiting

  • Pacific Clinical Research Management Group LLC

    Upland, California, 91786

    Terminated

  • Sunwise Clinical Research LLC

    Walnut Creek, California, 94549

    Recruiting

  • KUMC-Wichita

    Wichita, Kansas, 66160

    Withdrawn

  • Grayline Research Center

    Wichita Falls, Texas, 76309

    Recruiting

Other trials in United States

About this study

Official title: A Phase 2, Multicenter, Randomized, Double-blind Evaluation of the Efficacy and Safety of Oral GATE-251 or Placebo for the Reduction of Symptoms of Major Depressive Disorder in Adults

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 zelquistinel)?

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.

Read the detailed description

This is a Phase 2 multicenter, randomized, double-blind, placebo-controlled, parallel-group, fixed dose clinical trial designed to evaluate the safety and efficacy of zelquistinel versus placebo in subjects with symptoms of major depressive disorder. Each subject will participate in this study up to 98 days: up to 28 days for screening, 42 days for double-blind treatment, and a 4-week follow-up period. Subjects will return to the clinic one time each week to have the severity of their depression assessed using the Hamilton depression rating scale-17. Adverse events that occurred since the last study visit will be recorded.

Being tested
Zelquistinel
Keywords
zelquistinel, GATE-251
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.

  • ZelquistinelDrug

    Also called GATE-251

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

Study groups in NCT06547489
Study groupRoleWhat they receive
zelquistinel (GATE-251)Experimentalzelquistinel (GATE-251) will be administered as a single 10 mg oral tablet one time each week for 6 weeks.
Receives: Drug: Zelquistinel
PlaceboPlacebo comparatorPlacebo tablet identical in appearance to the experimental treatment tablet, administered as as a single oral tablet one time each week for 6 weeks.
Receives: Drug: Zelquistinel

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: Change in score from predose baseline to end of week 6

Secondary outcomes (1)

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

    The CGI-S is a 7-level rating scale used by a clinician to gauge depression severity. The range of scores is 0-7 with lower scores indicating a better outcome.

    Measured: Change in score from predose baseline to end of week 6

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Aug 2024
  2. Study start3 Feb 2025
  3. Primary completionSep 2027 (estimated)
  4. Study completionDec 2027 (estimated)

Resources

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
Model description
double-blind, placebo-controlled, fixed dose, parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
164 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06547489
Sponsor's protocol ID
GATE-251-C-202
Acronym
GATE-251
Status last verified
Jul 2026
First submitted
7 Aug 2024
Last updated
3 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Zelquistinel in people with Major Depressive Disorder, run by Syndeio Biosciences, Inc at 34 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 18 inclusion and 35 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 3 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 34 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 Karen Raudibaugh (781-786-1545, karen.raudibaugh@syndeio.bio), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in the Hamilton Depression Rating Scale-17 (HDRS-17) score compared to placebo (time frame: Change in score from predose baseline to end of week 6). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06547489.

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 3 Aug 2026.

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