Study to Assess the Effects of Oral NMRA-335140 Versus Placebo in Participants With Major Depressive Disorder

July 2, 2026 updated by: Neumora Therapeutics, Inc.

A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Effects of Oral NMRA-335140 Versus Placebo in Participants With Major Depressive Disorder

This is a randomized, double-blind, placebo-controlled, multicenter study to evaluate the effects of NMRA-335140 (formerly BTRX-335140) on symptoms of depression in participants with Major Depressive Disorder (MDD). The study design consists of a Screening Period (up to 28 days), and a 6-week Treatment Period (during which participants will receive either NMRA-335140 or placebo). At the completion of the 6-week Treatment Period, participants who complete the study, provide informed consent, and meet the eligibility criteria may enter an open-label extension study (NMRA-335140-501).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
430

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Brazil
      • Rio de Janeiro, Brazil, 22270-060
        • Neumora Investigator Site
      • São Paulo, Brazil, 01236030
        • Neumora Investigator Site
    • Paraná
      • Curitiba, Paraná, Brazil, 80240280
        • Neumora Investigator Site
    • Rio Grande do Sul
      • Porto Alegre, Rio Grande do Sul, Brazil, 90610-001
        • Neumora Investigator Site
    • São Paulo
      • Santa Cecília, São Paulo, Brazil, 01228-000
        • Neumora Investigator Site
      • São Bernardo do Campo, São Paulo, Brazil, 09726150
        • Neumora Investigator Site
      • São José do Rio Preto, São Paulo, Brazil, 15090-000
        • Neumora Investigator Site
  • Canada
    • British Columbia
      • Kelowna, British Columbia, Canada, V1Y 1Z9
        • Neumora Investigator Site
    • Ontario
      • Hamilton, Ontario, Canada, L8S 1B7
        • Neumora Investigator Site
      • Markham, Ontario, Canada, L3R 1A3
        • Neumora Investigator Site
      • Toronto, Ontario, Canada, L5L 1W8
        • Neumora Investigator Site
      • Toronto, Ontario, Canada, M5S 1M2
        • Neumora Investigator Site
  • Chile
      • Antofagasta, Chile, 1270244
        • Neumora Investigator Site
      • Santiago, Chile, 7560356
        • Neumora Investigator Site
      • Santiago, Chile, 7561282
        • Neumora Investigator Site
    • Santiago Metropolitan
      • Santiago, Santiago Metropolitan, Chile, 7500710
        • Neumora Investigator Site
      • Santiago, Santiago Metropolitan, Chile, 8330034
        • Neumora Investigator Site
  • United States
    • California
      • Encino, California, United States, 91316
        • Neumora Investigator Site
      • Garden Grove, California, United States, 92845
        • Neumora Investigator Site
      • Los Alamitos, California, United States, 90720
        • Neumora Investigator Site
      • Newport Beach, California, United States, 92660
        • Neumora Investigator Site
      • Orange, California, United States, 92868
        • Neumora Investigator Site
      • Santa Ana, California, United States, 92704
        • Neumora Investigator Site
    • Connecticut
      • Norwalk, Connecticut, United States, 06851
        • Neumora Investigator Site
    • Florida
      • Bradenton, Florida, United States, 34205
        • Neumora Investigator Site
      • Hollywood, Florida, United States, 33024
        • Neumora Investigator Site
      • Homestead, Florida, United States, 33032
        • Neumora Investigator Site
      • Lauderhill, Florida, United States, 33161
        • Neumora Investigator Site
      • Maitland, Florida, United States, 32751
        • Neumora Investigator Site
      • Miami, Florida, United States, 33126
        • Neumora Investigator Site
      • Miami, Florida, United States, 33137
        • Neumora Investigator Site
      • Miami, Florida, United States, 33122
        • Neumora Investigator Sites
      • Miami, Florida, United States, 33133
        • Neumora Investigator Site
      • Miami, Florida, United States, 33186
        • Neumora Investigator Site
      • Miami Lakes, Florida, United States, 33016
        • Neumora Investigator Site
      • Miami Lakes, Florida, United States, 33014
        • Neumora Investigator Site
      • Orlando, Florida, United States, 32801
        • Neumora Investigator Site
      • Orlando, Florida, United States, 32807
        • Neumora Investigator Site
      • Orlando, Florida, United States, 32803
        • Neumora Investigator Site
      • Pinellas Park, Florida, United States, 33782
        • Neumora Investigator Site
      • Pompano Beach, Florida, United States, 33060
        • Neumora Investigator Site
      • Tampa, Florida, United States, 33607
        • Neumora Investigator Site
      • Tampa, Florida, United States, 33613
        • Neumora Investigator Site#1
      • Tampa, Florida, United States, 33613
        • Neumora Investigator Site
    • Georgia
      • Atlanta, Georgia, United States, 30328
        • Neumora Investigator Site
      • Atlanta, Georgia, United States, 30338
        • Neumora Investigator Site
      • Atlanta, Georgia, United States, 30318
        • Neumora Investigator Site
    • Louisiana
      • Marrero, Louisiana, United States, 70072
        • Neumora Investigator Site
      • New Orleans, Louisiana, United States, 70115
        • Neumora Investigator Site
    • Maryland
      • Baltimore, Maryland, United States, 21208
        • Neumora Investigator Site
      • Towson, Maryland, United States, 21204
        • Neumora Investigator Site
    • Massachusetts
      • Boston, Massachusetts, United States, 02116
        • Neumora Investigator Site
      • Boston, Massachusetts, United States, 02131
        • Neumora Investigator Site
      • Watertown, Massachusetts, United States, 02472
        • Neumora Investigator Site
    • Minnesota
      • Mankato, Minnesota, United States, 56001
        • Neumora Investigator Site
    • New Jersey
      • Princeton, New Jersey, United States, 08540
        • Neumora Investigator Site
      • Toms River, New Jersey, United States, 08755
        • Neumora Investigator Site
    • New Mexico
      • Albuquerque, New Mexico, United States, 87109
        • Neumora Investigator Site
    • New York
      • Buffalo, New York, United States, 14215
        • Neumora Investigator Site
      • Inwood, New York, United States, 11096
        • Neumora Investigator Site
      • New York, New York, United States, 10017
        • Neumora Investigator Site
      • The Bronx, New York, United States, 10461
        • Neumora Investigator Site
    • North Carolina
      • Monroe, North Carolina, United States, 28112
        • Neumora Investigator Site
    • Ohio
      • North Canton, Ohio, United States, 44720
        • Neumora Investigator Site
    • Oklahoma
      • Edmond, Oklahoma, United States, 73013
        • Neumora Investigator Site
      • Oklahoma City, Oklahoma, United States, 73118
        • Neumora Investigator Site
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Neumora Investigator Site
    • South Carolina
      • North Charleston, South Carolina, United States, 29405
        • Neumora Investigator Site
    • Tennessee
      • Memphis, Tennessee, United States, 38119
        • Neumora Investigator Site
    • Texas
      • Austin, Texas, United States, 78737
        • Neumora Investigator Site
      • Dallas, Texas, United States, 75243
        • Neumora Investigator Site
      • Houston, Texas, United States, 77030
        • Neumora Investigator Site
    • Washington
      • Bellevue, Washington, United States, 98007
        • Neumora Investigator Site
      • Everett, Washington, United States, 98201
        • Neumora Investigator Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Key Inclusion criteria:

  • Have a primary Diagnostic and Statistical Manual of Mental Disorders Fifth Edition Text Revised (DSM-5-TR) diagnosis of MDD without psychotic features confirmed by Structured Clinical Interview for DSM 5 Disorders, Clinical Trials Version (SCID 5 CT) at screening (this may be a first or recurrent episode).
  • Participant's current major depressive episode must be confirmed by independent assessment.
  • The symptoms of the current MDD episode have been present for more than 4 weeks prior to the Screening Visit, but no longer than 12 months prior to the Screening Visit.
  • Have a MADRS total score of 25 or higher at Screening and Baseline.
  • A change in MADRS total score between Screening and Baseline of ≤20%.

Key Exclusion criteria:

  • Have failed 2 or more courses of antidepressant treatment at sufficient doses for at least 6 to 8 weeks for the current MDD episode.
  • Currently or in the past year have been diagnosed with a personality disorder per DSM-5-TR or in the past 3 years have been diagnosed with any of the following DSM-5-TR disorders: anorexia nervosa, bulimia nervosa, or binge eating disorder. Participants with comorbid generalized anxiety disorder, social anxiety disorder, simple phobias, or panic disorder for whom MDD is considered the primary diagnosis are not excluded.
  • Have a lifetime diagnosis of bipolar 1 or 2, schizophrenia, schizoaffective, schizophreniform, obsessive compulsive disorder, or post traumatic stress disorder (PTSD).
  • Have moderate to severe substance or alcohol use disorder, per DSM-5-TR criteria, within the 12 months prior to screening (excluding nicotine).
  • Are actively suicidal (eg, any suicide attempts within the past 12 months) or are at serious suicidal risk as indicated by any current suicidal intent, including a plan, as assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) (score of "YES" on suicidal ideation Item 4 or 5 within 3 months prior to Visit 1 [screening]) and/or based on clinical evaluation by the Investigator; or are homicidal, in the opinion of the Investigator. Participants who are currently hospitalized for MDD symptoms or suicidality are not allowed into the study. If there is a recent history (within 3 months of screening) of hospitalization due to MDD symptoms, the participant should be discussed with the Medical Monitor for eligibility.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: NMRA-335140 80 milligrams (mg) once daily (QD)
Participants will receive a NMRA- 335140 tablet at a dose of 80 mg once daily (QD)
Drug: NMRA-335140
Participants will receive NMRA-335140 at a dose of 80 mg QD, orally
Other Names:
  • CYM-53093
  • Navacaprant
  • BTRX 335140
Placebo Comparator: Placebo
Placebo participants will receive matching placebo tablet once daily.
Drug: Placebo
Placebo will be administered orally

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change from Baseline to Week 6 in the Montgomery-Asberg Depression Rating Scale (MADRS) total score
Time Frame: Baseline and up to Week 6
The MADRS is a 10-item, clinician-rated scale that evaluates the participant's depressive symptomatology during the past week. Participants are rated on items assessing feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty in concentration, and lack of interest. Each item will be scored on a 7-point scale with a score of 0 reflecting no symptoms and a score of 6 reflecting symptoms of maximum severity. Thus, scores in the MADRS range from 0 to 60, with increasing scores indicating increasing severity.
Baseline and up to Week 6

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change from Baseline to Week 6 assessed in the Snaith-Hamilton Pleasure Scale (SHAPS) total score
Time Frame: Baseline and up to Week 6
The SHAPS is a 14-item participant-reported instrument which measures anhedonia. It has been shown to be valid and reliable in normal and clinical samples, with adequate construct validity, satisfactory test-retest reliability and high internal consistency. The scale will be completed by the participant and reviewed by site personnel qualified to oversee completeness. Each of the 14 items has a set of 4 responses, 2 of which endorse agreement (Definitely Agree, Agree) and 2 of which endorse disagreement (Disagree, Strongly Disagree). A total score can be derived by summing the response items, where those answered with "strongly agree" will be coded as a 1, while a "strongly disagree" response will be coded as 4. Therefore, scores on the SHAPS can range from 14 to 56, with higher scores corresponding to higher levels of anhedonia.
Baseline and up to Week 6

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Neumora Therapeutics, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 20, 2023

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 6, 2026

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 17, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 21, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 21, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 28, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 6, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 2, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NMRA-335140-302
  • KOASTAL-2 (Other Identifier: Neumora Therapeutics)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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