Recruiting
Phase 2

GATE-251

Sponsor:

Syndeio Biosciences, Inc

Code:

NCT07115329

Conditions

Major Depressive Disorder

Eligibility Criteria

Sex: All

Age: 18 - 64

Healthy Volunteers: Not accepted

Interventions

Zelquistinel

Study Details

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

Study ID

NCT07115329

Start date

Jan 5, 2026

Status verified date

Jul, 2026

Completion date

Jun, 2028

Anticipated

Primary completion date

Mar 30, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 64

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • Subject has clinically significant renal dysfunction as assessed by the estimated glomerular filtration rate (eGFR) <70 mL/min/1.73 m2 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 × 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 × upper limit of normal).
  • Subject has resting radial pulse rate (supine) <60 or >100 bpm at the Screening Visit or predose Baseline, based on a single assessment.
  • Subject has resting diastolic blood pressure <50 mmHg at the Screening Visit or predose Baseline.
  • Subject has PR interval >250 msec at the Screening Visit or predose Baseline, or QT corrected for heart rate by Fridericia's formula (QTcF) or QT corrected for heart rate by Bazett's formula (QTcB) interval >450 msec in males or >470 msec in females, or QRS interval >120 msec, based on a single reading.
  • 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 and predose at the Baseline Visit. Alcohol consumption should be avoided for at least 24 hours prior to Baseline Visit.
  • Abuse of illicit substances by DSM-5 definition of substance use disorder within the 12 months prior to the Screening Visit.
  • Use of nicotine containing products (eg, cigarettes, cigars, vaping, and pipes). Nicotine containing products must be discontinued for at least 14 days prior to randomization, and nicotine or cotinine (metabolite) must be negative at Baseline.
  • Use of barbiturates. Prescribed barbiturates may be continued so long as the subject has been on a stable dose for at least 3 months and the dose may not change during the Double-Blind Treatment Period.
  • 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 Visit (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 Visit (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 the End of Week 6 Visit or completion of the final polysomnography for subjects who elect to participate in the polysomnography sessions.
  • 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 4-weeks prior to the Screening Visit (V1).
  • Currently taking prohibited prescription or over-the-counter medications including herbal therapies (eg, echinacea, ginseng, ginkgo, elderberry, turmeric, ginger, valerian, chamomile, or St John's wort) and THC- or cannabis-containing products (see Exclusion Criterion 9), which may interfere with the required study psychiatric assessments.
  • History of allergy, sensitivity, or intolerance to GATE-251 or NMDAR ligands including ketamine, dextromethorphan, memantine, methadone, dextropropoxyphene, or ketobemidone.
  • Previously participated in this study or Study GATE-251-C-202 or currently enrolled in any other clinical study.
  • Body mass index of >40 kg/m2 at the Screening Visit (V1).
  • Subject is an employee of Worldwide or the Investigator or study site with direct involvement in the study or other studies under the direction of that Investigator or study site; a family member of an employee 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 C-SSRS with reference to a 6-month period prior to Screening Visit (V1), or
  • At the Screening Visit (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 the Worldwide and Sponsor medical monitors to be appropriate for the study for any reason

Study Design

Enrollment

164 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: zelquisitinel (GATE-251 )

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

placebo comparator: Placebo

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

Interventions

Zelquistinel

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

Primary outcome measure

  • Change in the Hamilton Depression Rating Scale-17 (HDRS-17) score compared to Placebo [ Time Frame: Change in score from baseline to 6 wweeks ]

Central Contacts and Locations

Central contacts

Karen Raudibaugh

781-786-1545karen.raudibaugh@syndeio.bio

Sharon Ortiz

sharon.ortiz@syndeio.bio

Locations

NoesisPharma, LLC

Recruiting

Phoenix, Arizona, United States, 85028

Contacts

John P

602-795-1834jprater@noesispharma.com

Del Sol Research Management

Recruiting

Tucson, Arizona, United States, 85710

Contacts

S. Bupp

(520) 617-2203mailto:sbuppmd@delsolresearch.com

Catalina Research Institute, LLC

Recruiting

Montclair, California, United States, 91763

Contacts

Stephen V

909-590-8409stephen.volk@elixiahealth.com

Excell Research, Inc

Recruiting

Oceanside, California, United States, 92056

Contacts

Sherry S

760-758-2222soefjemd@excellresearch.com

Anderson Clinical Research

Recruiting

Redlands, California, United States, 92374

Contacts

Donald A

909-792-9007dla@andersonstudies.com

Studyops Inc

Recruiting

San Francisco, California, United States, 94102

Contacts

Erikson-Ridout

415-987-4722kridout@studyops.com

Lumos Clinical Research Center

Recruiting

San Jose, California, United States, 95124

Contacts

Sarbani M

408-402-5424md@lumosclinical.com

Aqualane Clinical Research

Recruiting

Naples, Florida, United States, 34105

Contacts

Matthew B

239-529-6780info@aqualaneresearch.com

EquiPath Health and Research Tampa Bay, LLC

Recruiting

Riverview, Florida, United States, 33578

Contacts

Conrado B

727-271-7738cbeckles@equipathhealth.com

Neuroscience Research Institute

Recruiting

West Palm Beach, Florida, United States, 33407

Contacts

Danesh A

561-578-8573dalam@neuroscienceresearchinstitute.com

Denali Health Atlanta, LLC

Recruiting

Stone Mountain, Georgia, United States, 30038

Contacts

Maria J

217-933-2108drmariajmd@denali-health.com

EmVenio Research

Recruiting

Chicago, Illinois, United States, 60622

Contacts

Mitchell G

(312)-238-9779mitchell.glaser@emvenio.com

Tandem Clinical Research

Recruiting

Metairie, Louisiana, United States, 70006

Contacts

Angela T

504-934-8092drtraylor@tandemclinicalresearch.com

Continental Clinical Solutions

Recruiting

Towson, Maryland, United States, 21204

Contacts

Marilyn M

410-616-9566mmartin@continentalclinical.com

Vitalix Clinical

Recruiting

Worcester, Massachusetts, United States, 01608

Contacts

James, MD

413-363-5206jcarroll@vitalixclinical.com

Rochester Center for Behavioral Medicine

Recruiting

Rochester Hills, Michigan, United States, 48307

Contacts

JYoung

248-608-8800jyoung@rcbm.net

IMA Clinical Research - NYC Midtown

Recruiting

New York, New York, United States, 10036

Contacts

E. Shalenberg

646-722-6214eli.shalenberg@imaresearch.com

IMA Clinical Research - NYC Uptown

Recruiting

New York, New York, United States, 10128

Contacts

Jason C

(212) 595-5012jason.careri@imaresearch.com

UNC Health Rex

Recruiting

Raleigh, North Carolina, United States, 27607

Contacts

SVaishnavi

sandeep.vaishnavi@unchealth.unc.edu

Adams Clinical

Recruiting

Philadelphia, Pennsylvania, United States, 19104

Contacts

Cassie B

267-207-2511cblanchard@adamsclinical.com

Psychiatric Consultants, PC

Recruiting

Franklin, Tennessee, United States, 37067

Contacts

James H

615-807-4023hartc@mac.com

Elevate Synapsis, LLC

Recruiting

Atascocita, Texas, United States, 77346

Contacts

Matthew B

(281) 339-8401mbrams@elevateclinical.com

Synapsis Bio

Recruiting

Atascocita, Texas, United States, 77346

Contacts

MBrams

mbrams@elevateclinical.com

More Information

Sponsor

Syndeio Biosciences, Inc

Last update posted

Jul 27, 2026

Last verified

Jul, 2026

Keywords

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-24. This information was provided to ClinicalTrials.gov by Syndeio Biosciences, Inc on 2026-07-27. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.