Major Depressive DisorderPhase 3NCT06058039
Study to Assess the Effects of Oral NMRA-335140 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 71 sites in 8 countries.
Trial summary
This randomized, double-blind, placebo-controlled, multicenter study will evaluate the effects of NMRA-335140 (formerly BTRX-335140) on symptoms of depression in participants with Major Depressive Disorder (MDD). Read more about this study
- 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
- 422 participants
- Where
- 71 sitesin 8 countries
- Study dates
- 21 Dec 2023to 11 Jun 2026
- 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 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 ideations 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
71 sites in 8 countries.
71 sites in 8 countries
United States34 sites
Neumora Investigator Site
Atlanta, Georgia, 30328
Neumora Investigator Site
Austin, Texas, 78759
Neumora Investigator Site
Berlin, New Jersey, 08009
Neumora Investigator Site
Brandon, Florida, 33511
Neumora Investigator Site
Cerritos, California, 90703
Neumora Investigator Site
Charlotte, North Carolina, 28211
Neumora Investigator Site
Decatur, Georgia, 30030
Neumora Investigator Site
DeSoto, Texas, 75115
Neumora Investigator Site
Fort Worth, Texas, 76104
Neumora Investigator Site
Hialeah, Florida, 33012
Neumora Investigator Site
Hialeah, Florida, 33016
Neumora Investigator Site
Irvine, California, 92614
Neumora Investigator Site
Jacksonville, Florida, 32256
Neumora Investigator Site
Long Beach, California, 90807
Neumora Investigator Site
Miami, Florida, 33143
Neumora Investigator Site
Miami, Florida, 33165
Neumora Investigator site
Miami, Florida, 33174
Neumora Investigator Site
Miami Beach, Florida, 33140
Neumora Investigator site
Miami Springs, Florida, 33166
Neumora Investigator Site
New Haven, Connecticut, 06520
Neumora Investigator Site
New York, New York, 10029
Neumora Investigator Site
New York, New York, 10036
Neumora Investigator Site
Omaha, Nebraska, 68112
Neumora Investigator Site
Palm Bay, Florida, 32905
Neumora Investigator Site
Pembroke Pines, Florida, 33024
Neumora Investigator Site
Plano, Texas, 75093
Neumora Investigator Site
Pompano Beach, Florida, 33060
Neumora Investigator Site
Saint Augustine, Florida, 32086
Neumora Investigator Site
San Diego, California, 92103
Neumora Investigator Site
San Francisco, California, 94107
Neumora Investigator Site
Savannah, Georgia, 31405
Neumora Investigator Site
Springfield, Massachusetts, 01103
Neumora Investigator Site
St Louis, Missouri, 63141
Neumora Investigator Site
Staten Island, New York, 10310
Bulgaria9 sites
Neumora Investigator Site
Cherven Bryag, Pleven, 5980
Neumora Investigator Site
Kardzhali, 6600
Neumora Investigator Site
Pleven, 5800
Neumora Investigator Site
Sofia, Sofia-Grad, 1408
Neumora Investigator Site
Sofia, Sofia-Grad, 1463
Neumora Investigator Site
Sofia, Sofia-Grad, 1680
Neumora Investigator Site
Targovishte, 7700
Neumora Investigator Site #1
Varna, 9020
Neumora Investigator Site
Varna, 9020
Poland7 sites
Neumora Investigator Site
Bialystok, Podlaskie Voivodeship, 15-879
Neumora Investigator Site
Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-133
Neumora Investigator Site
Gdansk, Pomeranian Voivodeship, 80-438
Neumora Investigator Site
Lublin, Lublin Voivodeship, 20-109
Neumora Investigator Site
Lublin, Lublin Voivodeship, 20-582
Neumora Investigator Site
Suchy Las, Greater Poland Voivodeship, 62-002
Neumora Investigator Site
Wroclaw, Lower Silesian Voivodeship, 50-414
France6 sites
Neumora Investigator Site
Angers, Maine-et-Loire, 49100
Neumora Investigator Site
Clermont-Ferrand, Auvergne-Rhône-Alpes, 63000
Neumora Investigator Site
Douai, Hauts-de-France, 59500
Neumora Investigator Site
La Roche-sur-Yon, Vendée, 85000
Neumora Investigator Site
Montpellier, Hérault, 34295
Neumora Investigator Site
Poitiers, Vienne, 86000
Czechia5 sites
Neumora Investigator Site #1
Kladno, South Bohemian, 272 01
Neumora Investigator Site
Kladno, 272 01
Neumora Investigator Site
Pilsen, Plzen, 301 00
Neumora Investigator Site
Prague, Prague, 186 00
Neumora Investigator Site
Prague, 109 00
Germany5 sites
Neumora Investigator Site #1
Berlin, 10117
Neumora Investigator Site
Berlin, 10117
Neumora Investigator Site
Berlin, 10629
Neumora Investigator Site
Berlin, 13187
Neumora Investigator Site
Hamburg, 20253
Finland3 sites
Neumora Investigator Site
Helsinki, Etelä-Suomen Lääni, 00100
Neumora Investigator Site
Oulu, Oulun Lääni, 90100
Neumora Investigator Site
Turku, Etelä-Suomen Lääni, 20520
Sweden2 sites
Neumora Investigator Site
Lund, Skåne County, 222 22
Neumora Investigator Site
Stockholm, Stockholm County, 113 29
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 randomized, double-blind, placebo-controlled, multicenter study will 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 35 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).
- 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 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 QD Receives: Drug: NMRA-335140 |
| Placebo | Placebo comparator | Placebo participants will receive matching placebo tablet once daily 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.
- First posted28 Sep 2023
- Study start21 Dec 2023
- Primary completion4 May 2026
- Study completion11 Jun 2026
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
- 422 participants (actual)
Sponsor and investigators
- Lead sponsor
- Neumora Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06058039
- Sponsor's protocol ID
- NMRA-335140-303
- Other IDs
- KOASTAL-3
- Status last verified
- Jul 2026
- First submitted
- 21 Sep 2023
- Last updated
- 6 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Jul 2026. 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
- NCT06058039
- Acronym / sponsor ID
- NMRA-335140-303
- 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
- 422 participants (actual)
- Lead sponsor
- Neumora Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 21 Dec 2023 (actual)
- Primary completion
- 4 May 2026 (actual)
- Study completion
- 11 Jun 2026 (actual)
- First posted
- 28 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.
This randomized, double-blind, placebo-controlled, multicenter study will 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 35 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 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 QD |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo participants will receive matching placebo tablet once daily |
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 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 ideations 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 6 Jul 2026.
- 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.
71 sites in 8 countries: 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 71 sites in 8 countries.
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 6 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 71 sites in United States, Bulgaria, Poland, France, Czechia and 3 more countries. 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?
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 6 Jul 2026.