Major Depressive DisorderPhase 3NCT06058013
Study to Assess 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 74 sites in 4 countries.
Trial summary
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). 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
- 430 participants
- Where
- 74 sitesin 4 countries
- Study dates
- 20 Dec 2023to 17 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 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.
Trial locations and contacts
74 sites in 4 countries.
74 sites in 4 countries
United States57 sites
Neumora Investigator Site
Albuquerque, New Mexico, 87109
Neumora Investigator Site
Atlanta, Georgia, 30318
Neumora Investigator Site
Atlanta, Georgia, 30328
Neumora Investigator Site
Atlanta, Georgia, 30338
Neumora Investigator Site
Austin, Texas, 78737
Neumora Investigator Site
Baltimore, Maryland, 21208
Neumora Investigator Site
Bellevue, Washington, 98007
Neumora Investigator Site
Boston, Massachusetts, 02116
Neumora Investigator Site
Boston, Massachusetts, 02131
Neumora Investigator Site
Bradenton, Florida, 34205
Neumora Investigator Site
Buffalo, New York, 14215
Neumora Investigator Site
Dallas, Texas, 75243
Neumora Investigator site
Edmond, Oklahoma, 73013
Neumora Investigator Site
Encino, California, 91316
Neumora Investigator Site
Everett, Washington, 98201
Neumora Investigator Site
Garden Grove, California, 92845
Neumora Investigator Site
Hollywood, Florida, 33024
Neumora Investigator Site
Homestead, Florida, 33032
Neumora Investigator Site
Houston, Texas, 77030
Neumora Investigator Site
Inwood, New York, 11096
Neumora Investigator Site
Lauderhill, Florida, 33161
Neumora Investigator Site
Los Alamitos, California, 90720
Neumora Investigator Site
Maitland, Florida, 32751
Neumora Investigator Site
Mankato, Minnesota, 56001
Neumora Investigator Site
Marrero, Louisiana, 70072
Neumora Investigator Site
Memphis, Tennessee, 38119
Neumora Investigator Sites
Miami, Florida, 33122
Neumora Investigator Site
Miami, Florida, 33126
Neumora Investigator Site
Miami, Florida, 33133
Neumora Investigator Site
Miami, Florida, 33137
Neumora Investigator Site
Miami, Florida, 33186
Neumora Investigator Site
Miami Lakes, Florida, 33014
Neumora Investigator Site
Miami Lakes, Florida, 33016
Neumora Investigator Site
Monroe, North Carolina, 28112
Neumora Investigator Site
New Orleans, Louisiana, 70115
Neumora Investigator Site
New York, New York, 10017
Neumora Investigator Site
Newport Beach, California, 92660
Neumora Investigator Site
North Canton, Ohio, 44720
Neumora Investigator Site
North Charleston, South Carolina, 29405
Neumora Investigator Site
Norwalk, Connecticut, 06851
Neumora Investigator Site
Oklahoma City, Oklahoma, 73118
Neumora Investigator Site
Orange, California, 92868
Neumora Investigator Site
Orlando, Florida, 32801
Neumora Investigator Site
Orlando, Florida, 32803
Neumora Investigator Site
Orlando, Florida, 32807
Neumora Investigator Site
Philadelphia, Pennsylvania, 19104
Neumora Investigator Site
Pinellas Park, Florida, 33782
Neumora Investigator Site
Pompano Beach, Florida, 33060
Neumora Investigator Site
Princeton, New Jersey, 08540
Neumora Investigator Site
Santa Ana, California, 92704
Neumora Investigator Site
Tampa, Florida, 33607
Neumora Investigator Site#1
Tampa, Florida, 33613
Neumora Investigator Site
Tampa, Florida, 33613
Neumora Investigator Site
The Bronx, New York, 10461
Neumora Investigator Site
Toms River, New Jersey, 08755
Neumora Investigator Site
Towson, Maryland, 21204
Neumora Investigator Site
Watertown, Massachusetts, 02472
Brazil7 sites
Neumora Investigator Site
Curitiba, Paraná, 80240280
Neumora Investigator Site
Porto Alegre, Rio Grande do Sul, 90610-001
Neumora Investigator Site
Rio de Janeiro, 22270-060
Neumora Investigator Site
Santa Cecília, São Paulo, 01228-000
Neumora Investigator Site
São Bernardo do Campo, São Paulo, 09726150
Neumora Investigator Site
São José do Rio Preto, São Paulo, 15090-000
Neumora Investigator Site
São Paulo, 01236030
Canada5 sites
Neumora Investigator Site
Hamilton, Ontario, L8S 1B7
Neumora Investigator Site
Kelowna, British Columbia, V1Y 1Z9
Neumora Investigator site
Markham, Ontario, L3R 1A3
Neumora Investigator Site
Toronto, Ontario, L5L 1W8
Neumora Investigator Site
Toronto, Ontario, M5S 1M2
Chile5 sites
Neumora Investigator Site
Antofagasta, 1270244
Neumora Investigator Site
Santiago, Santiago Metropolitan, 7500710
Neumora Investigator Site
Santiago, Santiago Metropolitan, 8330034
Neumora Investigator Site
Santiago, 7560356
Neumora Investigator Site
Santiago, 7561282
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, 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).
- 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 once daily (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 start20 Dec 2023
- Primary completion6 May 2026
- Study completion17 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
- 430 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
- NCT06058013
- Sponsor's protocol ID
- NMRA-335140-302
- Other IDs
- KOASTAL-2
- 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
- NCT06058013
- Acronym / sponsor ID
- NMRA-335140-302
- 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
- 430 participants (actual)
- Lead sponsor
- Neumora Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 20 Dec 2023 (actual)
- Primary completion
- 6 May 2026 (actual)
- Study completion
- 17 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 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 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 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 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.
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.
74 sites in 4 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 74 sites in 4 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 74 sites in United States, Brazil, Canada, Chile. 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.