Major Depressive Episode Associated With Bipolar II DisorderPhase 2NCT06429722
To Evaluate the Effects of NMRA-335140 on Symptoms of Major Depression in Participants With Bipolar II Disorder.
A Phase 2 study testing NMRA-335140 80 mg in people with Major Depressive Episode Associated With Bipolar II Disorder, run by Neumora Therapeutics, Inc. at 21 sites in United States.
Trial summary
This is a randomized, double-blind, placebo-controlled pilot study aiming to evaluate the effects of NMRA-335140 on symptoms of major depression in adults with Bipolar (BP) II disorder. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Major Depressive Episode Associated With Bipolar II Disorder
- What is being tested?
- NMRA-335140 80 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 21 sitesUnited States
- Study dates
- 13 May 2024to 30 May 2025
- Phase
- Phase 2
- 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 BP II disorder with a current major depressive episode (MDE), 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 MDE and lifetime history of hypomanic episodes must be confirmed by independent assessment.
- The symptoms of the current MDE 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 (adequate dose and duration, i.e., minimum 6 weeks) or mood stabilizer/antipsychotic treatment (each or in combination) for treatment of depressive symptoms in the current MDE.
- Have currently or in the past year any of the following DSM-5-TR disorders: bipolar episodes with mixed features (including the current MDE), bipolar II with rapid cycling pattern (4 or more distinct mood episodes during a 12-month period). Participants with comorbid generalized anxiety disorder, social anxiety disorder, simple phobias, panic disorder, for whom bipolar II MDE is considered the primary diagnosis are not excluded.
- Have a lifetime diagnosis of bipolar I disorder (manic episode schizophrenia, schizoaffective disorder, schizophreniform disorder, anorexia nervosa, bulimia nervosa, cluster B personality disorder, post-traumatic stress disorder (PTSD), or obsessive- compulsive disorder.
- 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.
- Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Trial locations and contacts
21 sites in 1 country.
21 sites in 1 country
United States21 sites
Neumora Investigator Site
Bellevue, Washington, 98007
Neumora Investigator Site
Brooklyn, New York, 11229
Neumora Investigator Site
Flowood, Mississippi, 39232
Neumora Investigator Site
Gainesville, Florida, 32607
Neumora Investigator Site
Garden Grove, California, 92845
Neumora Investigator Site
Houston, Texas, 77030
Neumora Investigator Site
Lauderhill, Florida, 33161
Neumora Investigator Site
Little Rock, Arkansas, 72211
Neumora Investigator Site
Long Beach, California, 90807
Neumora Investigator Site
Maitland, Florida, 32751
Neumora Investigator Site
Marietta, Georgia, 30060
Neumora Investigator Site
Marlton, New Jersey, 08053
Neumora Investigator Site
Miami, Florida, 33122
Neumora Investigator Site
Miami Lakes, Florida, 33016
Neumora Investigator Site
Phoenix, Arizona, 85012
Neumora Investigator Site
Princeton, New Jersey, 08540
Neumora Investigator Site
San Jose, California, 95124
Neumora Investigator Site
Savannah, Georgia, 31405
Neumora Investigator Site
Toms River, New Jersey, 08755
Neumora Investigator Site
Torrance, California, 90504
Neumora Investigator Site
Watertown, Massachusetts, 02472
About this study
Official title: A Phase 2a, Randomized, Double-blind, Placebo-controlled Pilot Study to Evaluate the Effects of Oral NMRA-335140 Versus Placebo in Participants With a Major Depressive Episode Associated With Bipolar II Disorder
This is a randomized, double-blind, placebo-controlled pilot study aiming to evaluate the effects of NMRA-335140 on symptoms of major depression in adults with Bipolar (BP) II disorder. The study design consists of a Screening Period (up to 28 days), a 6-week Treatment Period (during which participants will receive either NMRA-335140 or placebo), and a 6-week Safety Follow-up Period.
- Being tested
- NMRA-335140 80 mg, Placebo
- Keywords
- NMRA-335140, Navacaprant, BTRX-335140, CYM-53093, Bipolar II Disorder, Major Depressive Episode, Placebo-controlled, Double-blind, NMRA335140, NMRA 335140
- Medical subject headings
- Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NMRA-335140 80 mgDrug
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 80 mg |
| 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 May 2024
- Study start13 May 2024
- Primary completion9 Apr 2025
- Study completion30 May 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive Episode Associated With Bipolar II 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 18 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
- NCT06429722
- Sponsor's protocol ID
- NMRA-335140-202
- Status last verified
- Mar 2026
- First submitted
- 21 May 2024
- Last updated
- 30 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2a, Randomized, Double-blind, Placebo-controlled Pilot Study to Evaluate the Effects of Oral NMRA-335140 Versus Placebo in Participants With a Major Depressive Episode Associated With Bipolar II Disorder
- ClinicalTrials.gov ID
- NCT06429722
- Acronym / sponsor ID
- NMRA-335140-202
- Keywords
- NMRA-335140, Navacaprant, BTRX-335140, CYM-53093, Bipolar II Disorder, Major Depressive Episode, Placebo-controlled, Double-blind
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Neumora Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 13 May 2024 (actual)
- Primary completion
- 9 Apr 2025 (actual)
- Study completion
- 30 May 2025 (actual)
- First posted
- 28 May 2024 (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 pilot study aiming to evaluate the effects of NMRA-335140 on symptoms of major depression in adults with Bipolar (BP) II disorder. The study design consists of a Screening Period (up to 28 days), a 6-week Treatment Period (during which participants will receive either NMRA-335140 or placebo), and a 6-week Safety Follow-up Period.
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-335140 80 mgParticipants 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 BP II disorder with a current major depressive episode (MDE), 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 MDE and lifetime history of hypomanic episodes must be confirmed by independent assessment.
- The symptoms of the current MDE 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 (6 listed)
- Have failed 2 or more courses of antidepressant (adequate dose and duration, i.e., minimum 6 weeks) or mood stabilizer/antipsychotic treatment (each or in combination) for treatment of depressive symptoms in the current MDE.
- Have currently or in the past year any of the following DSM-5-TR disorders: bipolar episodes with mixed features (including the current MDE), bipolar II with rapid cycling pattern (4 or more distinct mood episodes during a 12-month period). Participants with comorbid generalized anxiety disorder, social anxiety disorder, simple phobias, panic disorder, for whom bipolar II MDE is considered the primary diagnosis are not excluded.
- Have a lifetime diagnosis of bipolar I disorder (manic episode schizophrenia, schizoaffective disorder, schizophreniform disorder, anorexia nervosa, bulimia nervosa, cluster B personality disorder, post-traumatic stress disorder (PTSD), or obsessive- compulsive disorder.
- 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.
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-335140 80 mgAlso: 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 30 Mar 2026.
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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.
21 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing NMRA-335140 80 mg in people with Major Depressive Episode Associated With Bipolar II Disorder, run by Neumora Therapeutics, Inc. at 21 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 6 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 30 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 30 Mar 2026.