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

NCT06547489 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: GATE-251-C-202
• Study Type: interventional
• Target: 164
• Locations: 1 country
• Sites: 34

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 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.

Conditions

Major Depressive Disorder

Keywords

zelquistinel; GATE-251

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 6 weeks

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)

zelquistinel (GATE-251)

EXPERIMENTAL

zelquistinel (GATE-251) will be administered as a single 10 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; zelquistinel (GATE-251)

Eligibility Criteria

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

You may qualify if:

• 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 ≥3 weeks and ≤18 months. The diagnosis of MDD will be made by a site psychiatrist 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 ≥3 weeks and ≤18 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
• 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 ≥22 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).
• Subject has Hamilton Anxiety Rating Scale (HARS) total score ≥15 at the Screening Visit (V1) and predose at the Baseline Visit (V2).
• Subject has Insomnia Severity Index (ISI) total score ≥15 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 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.

You may not qualify if:

• 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, 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.
• 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 heart rate (supine) \<60 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.
• HIV infection, COVID-19 infection, or active hepatitis B or C, syphilis, or other ongoing infectious disease at the Screening Visit (V1).

Sponsors & Collaborators

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

Study Sites (34)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

RECRUITING

University of Alabama at Birmingham-Huntsville

Huntsville, Alabama, 35801, United States

RECRUITING

Wr-Pri, Llc

Encino, California, 91316, United States

WITHDRAWN

Irvine Clinical Research

Irvine, California, 92614, United States

RECRUITING

CalNeuro Research Group

Los Angeles, California, 90025, United States

RECRUITING

Pacific Clinical Research Management Group LLC

Upland, California, 91786, United States

TERMINATED

Sunwise Clinical Research LLC

Walnut Creek, California, 94549, United States

RECRUITING

MCB Clinical Research Centers, Inc.

Colorado Springs, Colorado, 80910, United States

RECRUITING

Mountain View Clinical Research

Denver, Colorado, 80209, United States

RECRUITING

University of Connecticut School of Medicine Psychiatry Department

Farmington, Connecticut, 06030, United States

RECRUITING

Clinical Neuroscience Solutions, Inc.

Jacksonville, Florida, 32256, United States

RECRUITING

D&H Pompano Research Center, LLC

Margate, Florida, 33063, United States

RECRUITING

Premier Clinical Research Institute, Inc.

Miami, Florida, 33122, United States

RECRUITING

Miami Dade Medical Research Institute

Miami, Florida, 33176, United States

RECRUITING

Clinical Neuroscience Solutions, Inc.

Orlando, Florida, 32801, United States

RECRUITING

CenExel iRS (iResearch Savannah)

Savannah, Georgia, 31405, United States

RECRUITING

Revive Research Institute

Elgin, Illinois, 60123, United States

WITHDRAWN

KUMC-Wichita

Wichita, Kansas, 66160, United States

RECRUITING

Quantum Research Associates Corp.

Louisville, Kentucky, 40218, United States

RECRUITING

Boston Clinical Trials

Boston, Massachusetts, 02131, United States

WITHDRAWN

Mayflower Clinical

Russells Mills, Massachusetts, 02747, United States

RECRUITING

Vector Clinical Trials

Las Vegas, Nevada, 89128, United States

RECRUITING

Neurobehavioral Research, Inc.

Cedarhurst, New York, 11516, United States

RECRUITING

Insight Clinical Trials LLC

Independence, Ohio, 44131, United States

RECRUITING

Sooner Clinical Research, Inc.

Oklahoma City, Oklahoma, 73116, United States

WITHDRAWN

Lehigh Center for Clinical Research

Allentown, Pennsylvania, 18103, United States

RECRUITING

Clinical Neuroscience Solutions, Inc.

Memphis, Tennessee, 38119, United States

ACTIVE NOT RECRUITING

Austin Clinical Trial Partners

Austin, Texas, 78737, United States

RECRUITING

InSite Clinical Research, LLC

DeSoto, Texas, 75115, United States

RECRUITING

Baylor College of Medicine, Psychiatry and Behavioral Sciences

Houston, Texas, 77030, United States

WITHDRAWN

Clinical Trials of Texas LLC

San Antonio, Texas, 78229, United States

WITHDRAWN

Grayline Research Center

Wichita Falls, Texas, 76309, United States

RECRUITING

Andes Clinical Research

Orem, Utah, 84097, United States

RECRUITING

Northwest Clinical Research Center

Bellevue, Washington, 98007, United States

WITHDRAWN

MeSH Terms

Conditions

Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Aaron Koenig, MD

  Gate Neurosciences

  STUDY CHAIR

Central Study Contacts

Karen Raudibaugh

CONTACT

781-786-1545; karen.raudibaugh@gateneuro.com

Kelly Kosko

CONTACT

215-510-6405; kelly.kosko@gateneuro.com

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 blind to treatment with zelquistinel or placebo.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: double-blind, placebo-controlled, fixed dose, parallel groups

Study Record Dates

• First Submitted: August 7, 2024
• First Posted: August 9, 2024
• Study Start: February 3, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (34)