Zelquistinel in the Treatment of Major Depressive Disorder

NCT03586427 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 3125-201-002
• Study Type: interventional
• Target: 251
• Locations: 1 country
• Sites: 25

Brief Summary

The purpose of this study is to evaluate the efficacy at 1 day post initial oral dose of zelquistinel (AGN-241751) compared with placebo in participants with Major Depressive Disorder (MDD).

Conditions

Depressive Disorder, Major

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score

  The MADRS is a clinician-rated scale to assess depressive symptomatology during the preceding week. Participants are rated on 10 items (feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and lack of interest) each on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score ranges from 0 to 60 with a higher score indicating more depression. A negative change score indicates improvement.

  Baseline to Day 1

Secondary Outcomes (1)

• Change From Baseline in MADRS Total Score at Week 3

  Baseline to Week 3

Study Arms (5)

AGN-241751 Dose 1

EXPERIMENTAL

AGN-241751 Dose 1 administered as 1 tablet taken orally every day

Drug: AGN-241751

AGN-241751 Dose 2

EXPERIMENTAL

AGN-241751 Dose 2 administered as 1 tablet taken orally every day

Drug: AGN-241751

AGN-241751 Dose 3

EXPERIMENTAL

AGN-241751 Dose 3 administered as 1 tablet taken orally every day

Drug: AGN-241751

AGN-241751 Dose 4

EXPERIMENTAL

AGN-241751 Dose 4 administered as 1 tablet taken orally every day

Drug: AGN-241751

Placebo

PLACEBO COMPARATOR

Placebo administered as 1 tablet taken orally every day

Drug: Placebo

Interventions

AGN-241751 DRUG

AGN-241751 administered orally as a single tablet

AGN-241751 Dose 1; AGN-241751 Dose 2; AGN-241751 Dose 3; AGN-241751 Dose 4

Placebo DRUG

Placebo administered orally as a single tablet

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent from the participant has been obtained prior to any study -related procedures (as described in Appendix 3).
• Male or female participants must be 18 to 65 years of age, inclusive, at the time of signing the informed consent.
• Meet Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for MDD (based on confirmation from the modified Structured Clinical Interview for DSM disorders \[SCID\]), with a current major depressive episode of at least 8 weeks and not exceeding 18 months in duration at Visit 1.
• Have a minimum score of 26 on the rater-administered Montgomery-Asberg depression rating scale (MADRS) and a minimum score of 24 on the computer-administered MADRS at both Visit 1 (Screening) and Visit 2 (Baseline).
• Have a difference of no greater than 7 points between the rater-administered MADRS and computer-administered MADRS at both Visit 1 (Screening) and Visit 2 (Baseline).
• Have a clinical global impression-severity (CGI-S) score ≥ 4 at both Visit 1 (Screening) and Visit 2 (Baseline).
• Have a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test if a woman of childbearing potential (WOCBP).
• Female participants willing to minimize the risk of becoming pregnancy for the duration of the clinical study and follow-up period. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• not a WOCBP OR
• A WOCBP who agrees to follow the contraceptive guidance in Appendix 5 of protocol during the treatment period and for at least 5 terminal half-lives after the last dose of study treatment.
• Male participants willing to minimize the risk of inducing pregnancy for the duration of the clinical study and follow-up period. A male participant must agree to use contraception as detailed in Appendix 5 of this protocol during the treatment period and for at least 5 terminal half-lives after the last dose of study treatment and refrain from donating sperm during this period.
• Able, as assessed by the investigator, and willing to follow study instructions and likely to complete all required study visits.
• Normal physical-examination findings, clinical-laboratory test results, and electrocardiogram (ECG) results from Visit 1 (Screening) or abnormal results that are determined to be not clinically significant by the investigator.
• Body mass index (BMI) within the range 18 and 40 kg/m\^2 (inclusive).
• Eligibility confirmed through a formal adjudication process (see Section 9 Diagnostic Assessments).

You may not qualify if:

• Psychiatric and Treatment-Related Criteria
• DSM-5-based diagnosis of any disorder other than MDD that was the primary focus of treatment within 6 months before Visit 1. Comorbid generalized anxiety disorder, social anxiety disorder, or specific phobias are acceptable provided they play a secondary role in the balance of symptoms and are not the primary driver of treatment decisions.
• Lifetime history of meeting DSM-5 criteria for:
• Schizophrenia spectrum or other psychotic disorder
• Bipolar or related disorder
• Major neurocognitive disorder
• Neurodevelopmental disorder of greater than mild severity or of a severity that impacts the participant's ability to consent, follow study directions, or otherwise safely participate in the study
• Dissociative disorder
• Posttraumatic stress disorder
• MDD with psychotic features
• History of meeting DSM-5 criteria for alcohol or substance use disorder (other than nicotine or caffeine) within the 6 months before Visit 1.
• DSM-5-based diagnosis of any personality disorder of sufficient severity to interfere with participation in this study in the opinion of the investigator.
• History (based on participant report and/or medical records, and investigator judgment) of:
• Inadequate response to electroconvulsive therapy (ECT), a monoamine oxidase inhibitor, ketamine, or adjunctive treatment with an antipsychotic
• Treatment with clozapine or any depot antipsychotic

Sponsors & Collaborators

• Syndeio Biosciences, Inc: lead

Study Sites (25)

Health Initiatives Research PLLC

Fayetteville, Arkansas, 72703, United States

Location

Synexus US - Cerritos

Cerritos, California, 90703, United States

Location

Wake Research - Pharmacology Research Institute

Encino, California, 91316, United States

Location

Wake Research - Pharmacology Research Institute

Newport Beach, California, 92660, United States

Location

Pacific Research Partners, LLC

Oakland, California, 94607, United States

Location

North County Clinical Research, Inc.

Oceanside, California, 92054, United States

Location

Collaborative Neuroscience Network

Torrance, California, 90502, United States

Location

Elite Clinical Trials, Inc.

Wildomar, California, 92595, United States

Location

Synexus US - Atlanta

Atlanta, Georgia, 30328, United States

Location

Atlanta Center for Medical Research

Atlanta, Georgia, 30331, United States

Location

Pillar Clinical Research

Lincolnwood, Illinois, 60712, United States

Location

Boston Clinical Trials

Boston, Massachusetts, 02131, United States

Location

Hassman Research Institute

Berlin, New Jersey, 08009, United States

Location

Center for Emotional Fitness

Cherry Hill, New Jersey, 08002, United States

Location

Neurobehavioral Research, Inc

Cedarhurst, New York, 11516, United States

Location

Synexus US - Queens

Jamaica, New York, 11432, United States

Location

Eastside Comprehensive Medical Center

New York, New York, 10128, United States

Location

Finger Lakes Clinical Research

Rochester, New York, 14618, United States

Location

Neuro-Behavioral Clinical Research, Inc

North Canton, Ohio, 44720, United States

Location

IPS Research

Oklahoma City, Oklahoma, 73106, United States

Location

Clinical Neuroscience Solutions, Inc - Memphis, TN

Memphis, Tennessee, 38119, United States

Location

Research Strategies of Memphis, LLC

Memphis, Tennessee, 38119, United States

Location

Donald J. Garcia, Jr., MD, PA

Austin, Texas, 78737, United States

Location

FutureSearch Trials of Dallas, LP

Dallas, Texas, 75231, United States

Location

Northwest Clinical Research Center

Bellevue, Washington, 98007, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Syndeio Bio, Inc

aaron.koenig@syndeio.bio

2407438967

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2018
• First Posted: July 13, 2018
• Study Start: June 13, 2018
• Primary Completion: July 22, 2019
• Study Completion: August 21, 2019
• Last Updated: April 27, 2026
• Results First Posted: August 2, 2022

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (25)