NCT06547489ClinicalTrials.gov

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

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

RecruitingTaking participants now, according to the registry record.

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In brief

Phase 2164 participants sought34 sites1 country

Registered in 1 registry

ClinicalTrials.govNCT06547489Open this record at ClinicalTrials.govSynced 2 months ago

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Trial information is shown as published by the registry, in its original language.

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How this study is set up

The points below are drawn from the public registry record for this study. Each one cites the field or sentence it came from. A dash (—) means the record does not state something — not that it is missing or wrong. Many well-run studies, especially small ones, leave some of these blank.

Present: Registered before enrolment beganFirst posted 2024-08-09; recorded start 2025-02-03
Present: Has a defined primary outcomeA primary outcome measure is listed in the record
Present: The primary outcome states a time frameThe primary outcome measure records a time frame
Present: Participants are randomly assignedAllocation is recorded as randomised
Present: Has a comparison groupThe record lists a placebo or comparator arm, or more than one study arm
Present: Uses blinding (masking)A masking level is recorded in the record
Not stated: An ethics committee is not stated in the registry recordThis registry's ingested record has no ethics-committee field
Not stated: Regulatory oversight (such as an IND or IDE) is not stated in the registry recordThis registry's ingested record has no regulatory-authorisation field
Not stated: A data monitoring committee is not stated in the registry recordThis registry's ingested record has no data-monitoring-committee fieldA data monitoring committee is not required for many smaller studies, and its absence here is not unusual.
Present: No cost to participants is mentioned in the recordChecked the summary, description and eligibility text; no cost-to-participant phrase found
Present: Sponsor has 2 other studies in this databaseCounted from the lead sponsor named in the record (Syndeio Biosciences, Inc)
Not stated: No posted results from this sponsor are in this database yetBased on the sponsor’s studies in this database

The record lists 1 condition.
Lead sponsor type recorded as: industry.
Intervention regulatory context: investigational, within a phased regulatory pathway.

These are facts from the public registry record, not a judgement about the study. Discuss any trial with your own doctor before taking part.

What these facts mean, and what to ask · ruleset v1

Trial stature

Three independent measures of this study, described from its registry record — not a recommendation about it. A rigorous study by investigators nobody has heard of is better evidence than a weak study led by a famous one. How these are scored.

Methodological rigourDEFINITIVE

A definitive-grade design for a phase 2 study, judged from its ClinicalTrials.gov record.

How this score is built

Randomised allocation20/20
Participants are randomly allocated between arms
Blinding20/20
Quadruple-blind
Control arm13/15
Placebo / sham control arm
Primary-outcome specificity10/10
Named primary outcome with a defined time frame
Endpoint type3/10
Surrogate or intermediate endpoint (conservative default)
Multi-centre8/8
Multi-centre: 34 sites
Data monitoring committee7/7
A data monitoring committee is in place
Prospective registration5/5
Registered before the study start date
Protocol / SAP posted0/5
No protocol or SAP posted to the registry

ScaleSMALL

A small study: 164 participants (target), run at 34 sites.

How this score is built

Enrolment21/40
164 participants (target)
Site count18/25
34 sites
Country count0/15
Single country
Planned duration8/10
Planned over about 34 months
Sponsor scale1/10
Syndeio Biosciences, Inc has led 3 trials in our corpus

Investigator standingUNKNOWN

We have no verifiable track record for the investigator named on this trial. That is common for early-career investigators and for records held outside ClinicalTrials.gov — it is not a negative signal.

How this score is built

Investigator standing0/100
No investigator recorded in the registry for this trial

These describe the registry record only, and today we hold ClinicalTrials.gov data. Absent fields lower a score, and absence often reflects registration practice rather than study quality. A high-stature trial is not necessarily safer or a better choice for you — enrolling in a large definitive trial can mean a higher chance of receiving placebo, while a small early-phase study may be the only route to a new therapy.

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 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.

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.

Conditions

Major Depressive Disorder

Eligibility

Eligibility
Sex	All
Ages	18 Years – 64 Years
Healthy volunteers	No

Eligibility as written in the registry

Inclusion Criteria: Each subject must meet all of the following inclusion criteria to be eligible to participate in the study: 1. Male or female subjects. 2. Aged 18 to 64 years, inclusive. 3. 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: 1. The current depressive episode is ≥8 weeks and ≤24 months in duration prior to the Screening Visit (V1); 2. 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 3. Importantly, have a sufficient history and/or independent report verifying that the current depressive episode is causing clinically significant distress or impairment in functioning. 4. 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). 5. (Inclusion 5 removed in protocol amendment 4) 6. (Inclusion 6 removed in protocol amendment 4) 7. Female subjects must meet 1 of the following: 1. 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, 2. 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. 8. 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. 9. 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. 10. 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. 11. Provides written informed consent to participate in the trial. 12. 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 Exclusion Criteria: Any subject who meets any of the following criteria will be excluded from study participation: 1. 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). 2. 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. 3. Subject has a current or prior DSM-5 diagnosis of a psychotic disorder, or MDD with psychotic features. 4. 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). 5. Treatment with any experimental antidepressant agent or treatment with a psychedelic agent in an FDA-approved clinical study within the past 12 months. 6. 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. 7. 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. 8. 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). 9. Subject has resting pulse rate (supine) \<50 or \>100 bpm at the Screening Visit (V1) or predose Baseline (V2). 10. Subject has resting diastolic blood pressure \<50 mmHg at the Screening Visit (V1) or predose Baseline (V2). 11. 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. 12. 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. 13. 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. 14. 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. 15. HIV infection, COVID-19 infection, or active hepatitis B or C, syphilis, or other ongoing infectious disease at the Screening Visit (V1). 16. 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. 17. Has current unstable diabetes or glycosylated hemoglobin (HbA1c) \>7% at Screening (V1). 18. Currently pregnant, planning to become pregnant during the course of the study, or nursing. 19. 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. 20. 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. 21. Subject has received new onset psychotherapy or had a change in the intensity of psychotherapy within 8-weeks prior to the Screening Visit (V1). 22. 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. 23. History of allergy or sensitivity, or intolerance to zelquistinel, NMDAR ligands including ketamine, dextromethorphan, memantine, methadone, dextropropoxyphene, or ketobemidone. 24. Treatment with any other investigational study drugs not used to treat depression within 90 days of screening in this study. 25. Previously participated in this study or currently enrolled in any other clinical study. 26. Body mass index of \>35 kg/m2 at the Screening Visit (V1). 27. 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. 28. In the opinion of the Investigator, 1. The subject has a significant risk for suicidal behavior during the course of participation in the study, or 2. 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 3. 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 4. The subject is considered to be an imminent danger to themself or others, or 5. At the Baseline Visit (V2) (the subject scores "Yes" on Items 4 or 5 in the Suicidal Ideation section of the C-SSRS 29. The subject is judged by the Investigator or CRO and Sponsor medical monitors to be inappropriate for the study for any reason.

Eligibility in plain statements

This record's criteria have not been broken into separate statements yet. The registry text above is complete and is the authoritative version.

Study design

Study design
Study type	Interventional
Phase	Phase 2
Allocation	Randomised
Intervention model	PARALLEL
Primary purpose	TREATMENT
Masking	QUADRUPLE (4)
Enrolment	164 participants sought

Sponsor and collaborators

Syndeio Biosciences, Inc Sponsor
Worldwide Clinical Trials Collaborators

Arms and interventions

zelquistinel (GATE-251)EXPERIMENTAL
zelquistinel (GATE-251) will be administered as a single 10 mg oral tablet one time each week for 6 weeks.
PlaceboPLACEBO_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.

Interventions

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

Outcome measures

Primary outcome
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
Time frame Change in score from predose baseline to end of week 6
Secondary outcome
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.
Time frame Change in score from predose baseline to end of week 6

Dates

Dates
Start date	February 3, 2025 (actual)
Primary completion	September 1, 2027 (estimated)
Completion	December 1, 2027 (estimated)
First posted	August 9, 2024 (actual)
Last updated	August 3, 2026
Results posted	Not stated in the registry record
Status last verified	July 2026

Actual means the event happened. Estimated means the sponsor expects it. The two mean different things.

Locations

21 sites are recruiting

United States

United States
Facility	City	State or region	Status
Lehigh Center for Clinical Research	Allentown	Pennsylvania	Recruiting
Austin Clinical Trial Partners	Austin	Texas	Recruiting
Northwest Clinical Research Center	Bellevue	Washington	Withdrawn
University of Alabama at Birmingham	Birmingham	Alabama	Recruiting
Boston Clinical Trials	Boston	Massachusetts	Withdrawn
Neurobehavioral Research, Inc.	Cedarhurst	New York	Recruiting
MCB Clinical Research Centers, Inc.	Colorado Springs	Colorado	Recruiting
InSite Clinical Research, LLC	DeSoto	Texas	Recruiting
Mountain View Clinical Research	Denver	Colorado	Recruiting
Revive Research Institute	Elgin	Illinois	Withdrawn
Wr-Pri, Llc	Encino	California	Withdrawn
University of Connecticut School of Medicine Psychiatry Department	Farmington	Connecticut	Recruiting
Baylor College of Medicine, Psychiatry and Behavioral Sciences	Houston	Texas	Withdrawn
University of Alabama at Birmingham-Huntsville	Huntsville	Alabama	Active, not recruiting
Insight Clinical Trials LLC	Independence	Ohio	Recruiting
Irvine Clinical Research	Irvine	California	Recruiting
Clinical Neuroscience Solutions, Inc.	Jacksonville	Florida	Recruiting
Vector Clinical Trials	Las Vegas	Nevada	Active, not recruiting
CalNeuro Research Group	Los Angeles	California	Recruiting
Quantum Research Associates Corp.	Louisville	Kentucky	Active, not recruiting
D&H Pompano Research Center, LLC	Margate	Florida	Recruiting
Clinical Neuroscience Solutions, Inc.	Memphis	Tennessee	Withdrawn
Miami Dade Medical Research Institute	Miami	Florida	Recruiting
Premier Clinical Research Institute, Inc.	Miami	Florida	Recruiting
Sooner Clinical Research, Inc.	Oklahoma City	Oklahoma	Withdrawn
Andes Clinical Research	Orem	Utah	Recruiting
Clinical Neuroscience Solutions, Inc.	Orlando	Florida	Recruiting
Mayflower Clinical	Russells Mills	Massachusetts	Recruiting
Clinical Trials of Texas LLC	San Antonio	Texas	Withdrawn
CenExel iRS (iResearch Savannah)	Savannah	Georgia	Recruiting
Pacific Clinical Research Management Group LLC	Upland	California	Terminated
Sunwise Clinical Research LLC	Walnut Creek	California	Recruiting
KUMC-Wichita	Wichita	Kansas	Withdrawn
Grayline Research Center	Wichita Falls	Texas	Recruiting

Study documents

No documents are linked in this registry record.

Changes over time

No changes have been recorded since we first ingested this record.

A change is recorded each time the sponsor updates the registry record. Status, dates, enrolment and sites appear here as they move.

Registry: ClinicalTrials.gov · NCT########

https://xmedica.io/trials/ctgov/NCT06547489

Categories

Registered in 1 registry

Interested in this study?

How this study is set up

Summary

Conditions

Eligibility

Eligibility as written in the registry

Eligibility in plain statements

Study design

Sponsor and collaborators

Arms and interventions

Interventions

Outcome measures

Dates

Locations

United States

Study documents

Changes over time