Major Depressive DisorderPhase 3NCT06029426

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

A Phase 3 study testing NMRA-335140 in people with Major Depressive Disorder, run by Neumora Therapeutics, Inc. at 64 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Major Depressive Disorder
What is being tested?: NMRA-335140
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 383 participants
Where: 64 sitesUnited States
Study dates: 20 Sep 2023to 15 Jan 2025
Phase: Phase 3
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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%.

Who cannot join

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 the 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 posttraumatic 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 (e.g., 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.

Trial locations and contacts

64 sites in 1 country.

City, postcode or hospital

64 sites in 1 country

United States64 sites

Neumora Investigator Site
Allentown, Pennsylvania, 18104
Neumora Investigator Site
Austin, Texas, 78737
Neumora Investigator Site
Bellevue, Washington, 98007
Neumora Investigator Site
Bellflower, California, 90706
Neumora Investigator Site
Bentonville, Arkansas, 72712
Neumora Investigator Site
Bloomfield Hills, Michigan, 48302
Neumora Investigator Site
Boston, Massachusetts, 02116
Neumora Investigator Site
Brooklyn, New York, 11224
Neumora Investigator Site
Cedarhurst, New York, 11516
Neumora Investigator Site
Charlottesville, Virginia, 22903
Neumora Investigator Site
Chicago, Illinois, 60634
Neumora Investigator Site
Cleveland, Ohio, 44106
Neumora Investigator Site
Colorado Springs, Colorado, 80910
Neumora Investigator Site
Columbus, Ohio, 43210
Neumora Investigator Site
Dallas, Texas, 75235
Neumora Investigator Site
Dayton, Ohio, 45417
Neumora Investigator Site
Evanston, Illinois, 60201
Neumora Investigator Site
Everett, Washington, 98201
Neumora Investigator Site
Flowood, Mississippi, 39232
Neumora Investigator Site
Gainesville, Florida, 32607
Neumora Investigator Site
Garden Grove, California, 92845
Neumora Investigator Site
Garfield Heights, Ohio, 44125
Neumora Investigator Site
Glendale, California, 91206
Neumora Investigator Site
Hallandale, Florida, 33009
Neumora Investigator Site
Houston, Texas, 77030
Neumora Investigator Site
Houston, Texas, 77090
Neumora Investigator Site
Huntsville, Alabama, 35801
Neumora Investigator Site
Imperial, California, 92251
Neumora Investigator Site
Jacksonville, Florida, 32256
Neumora Investigator Site
Lafayette, California, 94549
Neumora Investigator Site
Las Vegas, Nevada, 89102
Neumora Investigator Site
Lauderhill, Florida, 33319
Neumora Investigator Site-1
Little Rock, Arkansas, 72211
Neumora Investigator Site
Little Rock, Arkansas, 72211
Neumora Investigator Site
Long Beach, California, 90807
Neumora Investigator Site
Los Angeles, California, 90015
Neumora Investigator Site
Maitland, Florida, 32751
Neumora Investigator Site
Marietta, Georgia, 30060
Neumora Investigator Site
Media, Pennsylvania, 19063
Neumora Investigator Site
Memphis, Tennessee, 38119
Neumora Investigator Site
Methuen, Massachusetts, 01844
Neumora Investigator Site
Miami, Florida, 33122
Neumora Investigator Site
Miami, Florida, 33125
Neumora Investigator Site
Miami, Florida, 33183
Neumora Investigator Site
Miami Lakes, Florida, 33016
Neumora Investigator Site
New York, New York, 10036
Neumora Investigator Site
Oceanside, California, 92056
Neumora Investigator Site
Orange, California, 92868
Neumora Investigator Site
Orlando, Florida, 32801
Neumora Investigator Site
Phoenix, Arizona, 85012
Neumora Investigator Site
Plymouth Meeting, Pennsylvania, 19462
Neumora Investigator Site
Riverside, California, 92506
Neumora Investigator Site
Rogers, Arkansas, 72758
Neumora Investigator Site
Saint Charles, Missouri, 63304
Neumora Investigator Site
San Jose, California, 95124
Neumora Investigator Site #1
Sherman Oaks, California, 91403
Neumora Investigator Site
Sherman Oaks, California, 91403
Neumora Investigator Site
Staten Island, New York, 10314
Neumora Investigator Site
Tampa, Florida, 33607
Neumora Investigator Site
Temecula, California, 92591
Neumora Investigator Site
Torrance, California, 90504
Neumora Investigator Site
Warrenville, Illinois, 60555
Neumora Investigator Site
Watertown, Massachusetts, 02472
Neumora Investigator Site
Wichita Falls, Texas, 76309

Other trials in United States

About this study

Official title: 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, multi-center 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 extension study (NMRA-335140 501).

Conditions: Major Depressive Disorder
Being tested: NMRA-335140, Placebo
Keywords: Major Depressive Disorder, NMRA-335140, Placebo-controlled, Double-blind, Navacaprant, NMRA335140, NMRA 335140
Medical subject headings: Depressive Disorder, Major

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

NMRA-335140Drug
Also called BTRX 335140, CYM-53093, Navacaprant
Participants will receive NMRA-335140 at a dose of 80 mg QD, orally
PlaceboDrug
Placebo will be administered orally

Study groups in NCT06029426
Study group	Role	What they receive
NMRA-335140 80 milligrams (mg) once daily (QD)	Experimental	Participants will receive a NMRA-335140 tablet at a dose of 80 mg once daily (QD) Receives: Drug: NMRA-335140
Placebo	Placebo comparator	Placebo participants will receive matching placebo tablet orally, once daily. Participants who complete the study may be eligible to participate in a separate 52-week open-label long term study. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Change from Baseline to Week 6 in the Montgomery Asberg Depression Rating Scale (MADRS) total score
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.
Measured: Baseline and up to Week 6

Secondary outcomes (1)

Change from Baseline to Week 6 assessed in the Snaith-Hamilton Pleasure Scale (SHAPS) total score
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.
Measured: Baseline and up to Week 6

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

20 Sep 202315 Jan 2025

First posted8 Sep 2023
Study start20 Sep 2023
Primary completion3 Dec 2024
Study completion15 Jan 2025

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 383 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT06029426
Sponsor's protocol ID: NMRA-335140-301
Other IDs: KOASTAL-1
Status last verified: Nov 2025
First submitted: 1 Sep 2023
Last updated: 26 Nov 2025
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Major Depressive Disorder trials

Study at a glance

From the registry record, last updated by the sponsor on 26 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT06029426
Acronym / sponsor ID: NMRA-335140-301
Conditions: Major Depressive Disorder
Keywords: Major Depressive Disorder, NMRA-335140, Placebo-controlled, Double-blind, Navacaprant, NMRA335140, NMRA 335140
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 383 participants (actual)
Lead sponsor: Neumora Therapeutics, Inc.Industry (pharma, biotech, devices)
Study start: 20 Sep 2023 (actual)
Primary completion: 3 Dec 2024 (actual)
Study completion: 15 Jan 2025 (actual)
First posted: 8 Sep 2023 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
NMRA-335140 80 milligrams (mg) once daily (QD)	Experimental	Drug: NMRA-335140Participants will receive a NMRA-335140 tablet at a dose of 80 mg once daily (QD)
Placebo	Placebo comparator	Drug: PlaceboPlacebo participants will receive matching placebo tablet orally, once daily. Participants who complete the study may be eligible to participate in a separate 52-week open-label long term study.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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 (5 listed)

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 the 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 posttraumatic 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 (e.g., 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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
NMRA-335140Also: BTRX 335140, CYM-53093, NavacaprantParticipants will receive NMRA-335140 at a dose of 80 mg QD, orally	Drug	NMRA-335140 80 milligrams (mg) once daily (QD)
PlaceboPlacebo will be administered orally	Drug	Placebo

Primary outcome

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.

1 secondary outcome

Change from Baseline to Week 6 assessed in the Snaith-Hamilton Pleasure Scale (SHAPS) total score
Time frame: Baseline and up to Week 6

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Nov 2025.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

64 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing NMRA-335140 in people with Major Depressive Disorder, run by Neumora Therapeutics, Inc. at 64 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 64 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change from Baseline to Week 6 in the Montgomery Asberg Depression Rating Scale (MADRS) total score (time frame: Baseline and up to Week 6). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06029426.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Nov 2025.