Study to Assess the Safety and Effectiveness of NMRA-335140-501

Long-term Study to Assess the Safety and Effectiveness of NMRA-335140 in Participants With Major Depressive Disorder

This is a 52-week open-label extension (OLE) study that will evaluate the safety, tolerability, and effectiveness of NMRA-335140 in participants with major depressive disorder (MDD). Participants who completed a parent study investigating the efficacy and safety of NMRA-335140 as a treatment for MDD (ie, NMRA-335140-301, NMRA-335140-302, or NMRA-335140-303), and complete the 6 weeks double-blind treatment, provide informed consent, and meet eligibility criteria, may enter this extension study.

Study Overview

• Status: Recruiting
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: NMRA-335140

• Study Type: Interventional
• Enrollment (Estimated): 1000
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Study Contact; Email: explore@koastalstudy.com

Study Locations

• Brazil
  • São Paulo, Brazil, 01236030
    • Recruiting
    • Neumora Investigator Site
  • Paraná
    • Curitiba, Paraná, Brazil, 80240280
      • Recruiting
      • Neumora Investigator Site
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90610-001
      • Active, not recruiting
      • Neumora Investigator Site
  • Rio de Janeiro
    • Botafogo - Rio de Janeiro, Rio de Janeiro, Brazil, 22270-060
      • Recruiting
      • Neumora Investigator Site
  • São Paulo
    • Santa Cecília, São Paulo, Brazil, 01228-000
      • Recruiting
      • Neumora Investigator Site
    • São Bernardo do Campo, São Paulo, Brazil, 09726150
      • Recruiting
      • Neumora Investigator Site
    • São José do Rio Preto, São Paulo, Brazil, 15090-000
      • Active, not recruiting
      • Neumora Investigator Site
• Bulgaria
  • Kardzhali, Bulgaria, 6600
    • Active, not recruiting
    • Neumora Investigator Site
  • Pleven, Bulgaria, 5800
    • Completed
    • Neumora Investigator Site
  • Varna, Bulgaria, 9020
    • Active, not recruiting
    • Neumora Investigator Site
  • Pleven
    • Cherven Bryag, Pleven, Bulgaria, 5980
      • Completed
      • Neumora Investigator Site
  • Sofia-Grad
    • Sofia, Sofia-Grad, Bulgaria, 1408
      • Recruiting
      • Neumora Investigator Site
    • Sofia, Sofia-Grad, Bulgaria, 1680
      • Active, not recruiting
      • Neumora Investigator Site
    • Sofia, Sofia-Grad, Bulgaria, 1463
      • Active, not recruiting
      • Neumora Investigator Site
  • Targovishte
    • Varosha, Targovishte, Bulgaria, 7700
      • Active, not recruiting
      • Neumora Investigator Site
• Canada
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 1Z9
      • Active, not recruiting
      • Neumora Investigator Site
  • Ontario
    • Hamilton, Ontario, Canada, L8S 1B7
      • Active, not recruiting
      • Neumora Investigator Site
    • Markham, Ontario, Canada, L3R 1A3
      • Completed
      • Neumora Investigator Site
    • Mississauga, Ontario, Canada, L5L 1W8
      • Active, not recruiting
      • Neumora Investigator Site
    • Toronto, Ontario, Canada, M5S 1M2
      • Active, not recruiting
      • Neumora Investigator Site
• Chile
  • Antofagasta, Chile, 1270244
    • Recruiting
    • Neumora Investigator Site
  • Santiago Metropolitan
    • Santiago, Santiago Metropolitan, Chile, 7500710
      • Recruiting
      • Neumora Investigator Site
    • Santiago, Santiago Metropolitan, Chile, 7560356
      • Recruiting
      • Neumora Investigator Site
    • Santiago, Santiago Metropolitan, Chile, 7561282
      • Active, not recruiting
      • Neumora Investigator Site
    • Santiago, Santiago Metropolitan, Chile, 8330034
      • Active, not recruiting
      • Neumora Investigator Site
• Czechia
  • Kladno, Czechia, 272 01
    • Recruiting
    • Neumora Investigator Site
  • Prague, Czechia, 109 00
    • Completed
    • Neumora Investigator Site
  • Plzeň
    • Pilsen, Plzeň, Czechia, 301 00
      • Recruiting
      • Neumora Investigator Site
  • Prague
    • Prague, Prague, Czechia, 186 00
      • Active, not recruiting
      • Neumora Investigator Site
  • South Bohemian
    • Kladno, South Bohemian, Czechia, 272 01
      • Completed
      • Neumora Investigator Site
• Finland
  • Etelä-Suomen Lääni
    • Helsinki, Etelä-Suomen Lääni, Finland, 00100
      • Recruiting
      • Neumora Investigator Site
    • Turku, Etelä-Suomen Lääni, Finland, 20520
      • Completed
      • Neumora Investigator Site
  • Oulun Lääni
    • Oulu, Oulun Lääni, Finland, 90100
      • Active, not recruiting
      • Neumora Investigator Site
• France
  • Auvergne-Rhône-Alpes
    • Clermont-Ferrand, Auvergne-Rhône-Alpes, France, 63000
      • Active, not recruiting
      • Neumora Investigator Site
  • Hauts-de-France
    • Douai, Hauts-de-France, France, 59500
      • Recruiting
      • Neumora Investigator Site
  • Hérault
    • Montpellier, Hérault, France, 34295
      • Active, not recruiting
      • Neumora Investigator Site
  • Vendée
    • La Roche-sur-Yon, Vendée, France, 85000
      • Recruiting
      • Neumora Investigator Site
  • Vienne
    • Poitiers, Vienne, France, 86000
      • Completed
      • Neumora Investigator Site
• Germany
  • Berlin, Germany, 10629
    • Recruiting
    • Neumora Investigator Site
  • Berlin, Germany, 13187
    • Recruiting
    • Neumora Investigator Site
  • Berlin, Germany, 10117
    • Completed
    • Neumora Investigator Site #1
  • Berlin, Germany, 10117
    • Active, not recruiting
    • Neumora Investigator Site
  • Hamburg, Germany, 20253
    • Completed
    • Neumora Investigator Site
• Poland
  • Greater Poland Voivodeship
    • Suchy Las, Greater Poland Voivodeship, Poland, 62-002
      • Active, not recruiting
      • Neumora Investigator Site
  • Kuyavian-Pomeranian Voivodeship
    • Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland, 85-133
      • Active, not recruiting
      • Neumora Investigator Site
  • Lower Silesian Voivodeship
    • Wroclaw, Lower Silesian Voivodeship, Poland, 50-414
      • Recruiting
      • Neumora Investigator Site
  • Lublin Voivodeship
    • Lublin, Lublin Voivodeship, Poland, 20-582
      • Completed
      • Neumora Investigator Site
    • Lublin, Lublin Voivodeship, Poland, 20-109
      • Completed
      • Neumora Investigator Site
  • Podkarpackie Voivodeship
    • Białystok, Podkarpackie Voivodeship, Poland, 15-879
      • Recruiting
      • Neumora Investigator Site
  • Pomeranian Voivodeship
    • Gdansk, Pomeranian Voivodeship, Poland, 80-438
      • Completed
      • Neumora Investigator Site
• Sweden
  • Skåne County
    • Lund, Skåne County, Sweden, 222 22
      • Recruiting
      • Neumora Investigator Site
  • Stolkholm Ian
    • Stockholm, Stolkholm Ian, Sweden, 113 29
      • Active, not recruiting
      • Neumora Investigator Site
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
      • Recruiting
      • Neumora Investigator Site
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • Active, not recruiting
      • Neumora Investigator Site
  • Arkansas
    • Bentonville, Arkansas, United States, 72712
      • Active, not recruiting
      • Neumora Investigator Site
    • Little Rock, Arkansas, United States, 72211
      • Completed
      • Neumora Investigator Site #1
    • Little Rock, Arkansas, United States, 72211
      • Active, not recruiting
      • Neumora Investigator Site
    • Rogers, Arkansas, United States, 72758
      • Completed
      • Neumora Investigator Site
  • California
    • Bellflower, California, United States, 90706
      • Active, not recruiting
      • Neumora Investigator Site
    • Cerritos, California, United States, 90703
      • Active, not recruiting
      • Neumora Investigator Site
    • Encino, California, United States, 91316
      • Active, not recruiting
      • Neumora Investigator Site
    • Garden Grove, California, United States, 92845
      • Active, not recruiting
      • Neumora Investigator Site
    • Glendale, California, United States, 91206
      • Active, not recruiting
      • Neumora Investigator Site
    • Imperial, California, United States, 92251
      • Active, not recruiting
      • Neumora Investigator Site
    • Irvine, California, United States, 92614
      • Recruiting
      • Neumora Investigator Site
    • Lafayette, California, United States, 94549
      • Active, not recruiting
      • Neumora Investigator Site
    • Long Beach, California, United States, 90807
      • Recruiting
      • Neumora Investigator Site #1
    • Long Beach, California, United States, 90807
      • Active, not recruiting
      • Neumora Investigator Site
    • Los Angeles, California, United States, 90015
      • Recruiting
      • Neumora Investigator Site
    • Newport Beach, California, United States, 92660
      • Recruiting
      • Neumora Investigator Site
    • Oceanside, California, United States, 92056
      • Active, not recruiting
      • Neumora Investigator Site
    • Orange, California, United States, 92868
      • Completed
      • Neumora Investigator Site
    • Orange, California, United States, 92868
      • Active, not recruiting
      • Neumora Investigator Site #1
    • Riverside, California, United States, 92506
      • Completed
      • Neumora Investigator Site
    • San Diego, California, United States, 92103
      • Active, not recruiting
      • Neumora Investigator Site
    • San Francisco, California, United States, 94107
      • Active, not recruiting
      • Neumora Investigator Site
    • San Jose, California, United States, 95124
      • Active, not recruiting
      • Neumora Investigator Site
    • Santa Ana, California, United States, 92704
      • Completed
      • Neumora Investigator Site
    • Sherman Oaks, California, United States, 91403
      • Active, not recruiting
      • Neumora Investigator Site
    • Temecula, California, United States, 92591
      • Active, not recruiting
      • Neumora Investigator Site
    • Torrance, California, United States, 90504
      • Active, not recruiting
      • Neumora Investigator Site
  • Colorado
    • Colorado Springs, Colorado, United States, 80910
      • Completed
      • Neumora Investigator Site
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Recruiting
      • Neumora Investigator Site
    • Norwalk, Connecticut, United States, 06851
      • Completed
      • Neumora Investigator Site
  • Florida
    • Bradenton, Florida, United States, 34205
      • Recruiting
      • Neumora Investigator Site
    • Brandon, Florida, United States, 33511
      • Recruiting
      • Neumora Investigator Site
    • Gainesville, Florida, United States, 32607
      • Active, not recruiting
      • Neumora Investigator Site
    • Hallandale, Florida, United States, 33009
      • Active, not recruiting
      • Neumora Investigator Site
    • Hialeah, Florida, United States, 33012
      • Recruiting
      • Neumora Investigator Site
    • Hialeah, Florida, United States, 33016
      • Active, not recruiting
      • Neumora Investigator Site
    • Hollywood, Florida, United States, 33024
      • Recruiting
      • Neumora Investigator Site
    • Jacksonville, Florida, United States, 32256
      • Active, not recruiting
      • Neumora Investigator Site
    • Lauderhill, Florida, United States, 33319
      • Active, not recruiting
      • Neumora Investigator Site
    • Maitland, Florida, United States, 32751
      • Active, not recruiting
      • Neumora Investigator Site
    • Miami, Florida, United States, 33174
      • Recruiting
      • Neumora Investigator Site
    • Miami, Florida, United States, 33143
      • Recruiting
      • Neumora Investigator Site
    • Miami, Florida, United States, 33165
      • Recruiting
      • Neumora Investigator Site
    • Miami, Florida, United States, 33183
      • Active, not recruiting
      • Neumora Investigator Site
    • Miami, Florida, United States, 33133
      • Active, not recruiting
      • Neumora Investigator Site
    • Miami, Florida, United States, 33122
      • Active, not recruiting
      • Neumora Investigator Site
    • Miami, Florida, United States, 33126
      • Active, not recruiting
      • Neumora Investigator Site
    • Miami, Florida, United States, 33137
      • Active, not recruiting
      • Neumora Investigator Site
    • Miami Beach, Florida, United States, 33140
      • Recruiting
      • Neumora Investigator Site
    • Miami Lakes, Florida, United States, 33014
      • Active, not recruiting
      • Neumora Investigator Site
    • Miami Lakes, Florida, United States, 33016
      • Completed
      • Neumora Investigator Site #1
    • Miami Lakes, Florida, United States, 33016
      • Recruiting
      • Neumora Investigator Site #2
    • Miami Springs, Florida, United States, 33166
      • Active, not recruiting
      • Neumora Investigator Site
    • Orlando, Florida, United States, 32807
      • Recruiting
      • Neumora Investigator Site
    • Orlando, Florida, United States, 32803
      • Recruiting
      • Neumora Investigator Site
    • Orlando, Florida, United States, 32801
      • Recruiting
      • Neumora Investigator Site #1
    • Orlando, Florida, United States, 32801
      • Active, not recruiting
      • Neumora Investigator Site
    • Pembroke Pines, Florida, United States, 33024
      • Recruiting
      • Neumora Investigator Site
    • Pompano Beach, Florida, United States, 33060
      • Recruiting
      • Neumora Investigator Site #1
    • Pompano Beach, Florida, United States, 33060
      • Active, not recruiting
      • Neumora Investigator Site
    • Saint Augustine, Florida, United States, 32086
      • Completed
      • Neumora Investigator Site
    • Tampa, Florida, United States, 33613
      • Active, not recruiting
      • Neumora Investigator Site
    • Tampa, Florida, United States, 33607
      • Active, not recruiting
      • Neumora Investigator Site
    • Tampa, Florida, United States, 33613
      • Active, not recruiting
      • Neumora Investigator Site #1
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Recruiting
      • Neumora Investigator Site
    • Atlanta, Georgia, United States, 30318
      • Recruiting
      • Neumora Investigator Site
    • Atlanta, Georgia, United States, 30338
      • Completed
      • Neumora Investigator Site
    • Atlanta, Georgia, United States, 30328
      • Active, not recruiting
      • Neumora Investigator Site #1
    • Decatur, Georgia, United States, 30030
      • Active, not recruiting
      • Neumora Investigator Site
    • Marietta, Georgia, United States, 30060
      • Active, not recruiting
      • Neumora Investigator Site
    • Savannah, Georgia, United States, 31405
      • Active, not recruiting
      • Neumora Investigator Site
  • Illinois
    • Chicago, Illinois, United States, 60634
      • Active, not recruiting
      • Neumora Investigator Site
    • Warrenville, Illinois, United States, 60555
      • Active, not recruiting
      • Neumora Investigator Site
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • Completed
      • Neumora Investigator Site
    • New Orleans, Louisiana, United States, 70115
      • Recruiting
      • Neumora Investigator Site
  • Maryland
    • Baltimore, Maryland, United States, 21208
      • Recruiting
      • Neumora Investigator Site
    • Towson, Maryland, United States, 21204
      • Recruiting
      • Neumora Investigator Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02131
      • Recruiting
      • Neumora Investigator Site
    • Boston, Massachusetts, United States, 02116
      • Active, not recruiting
      • Neumora Investigator Site
    • Methuen, Massachusetts, United States, 01844
      • Completed
      • Neumora Investigator Site
    • Springfield, Massachusetts, United States, 01103
      • Recruiting
      • Neumora Investigator Site
    • Watertown, Massachusetts, United States, 02472
      • Active, not recruiting
      • Neumora Investigator Site
  • Michigan
    • Bloomfield Township, Michigan, United States, 48302
      • Completed
      • Neumora Investigator Site
  • Minnesota
    • Mankato, Minnesota, United States, 56001
      • Active, not recruiting
      • Neumora Investigator Site
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • Active, not recruiting
      • Neumora Investigator Site
  • Missouri
    • Saint Charles, Missouri, United States, 63304
      • Completed
      • Neumora Investigator Site
    • St Louis, Missouri, United States, 63141
      • Recruiting
      • Neumora Investigator Site
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • Completed
      • Neumora Investigator Site
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Recruiting
      • Neumora Investigator Site
    • Princeton, New Jersey, United States, 08540
      • Recruiting
      • Neumora Investigator Site
    • Toms River, New Jersey, United States, 08755
      • Recruiting
      • Neumora Investigator Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Active, not recruiting
      • Neumora Investigator Site
  • New York
    • Brooklyn, New York, United States, 11224
      • Active, not recruiting
      • Neumora Investigator Site
    • Buffalo, New York, United States, 14215
      • Active, not recruiting
      • Neumora Investigator Site
    • Cedarhurst, New York, United States, 11516
      • Active, not recruiting
      • Neumora Investigator Site
    • Inwood, New York, United States, 11096
      • Recruiting
      • Neumora Investigator Site
    • New York, New York, United States, 10029
      • Active, not recruiting
      • Neumora Investigator Site
    • New York, New York, United States, 10017
      • Active, not recruiting
      • Neumora Investigator Site
    • New York, New York, United States, 10036
      • Active, not recruiting
      • Neumora Investigator Site
    • Staten Island, New York, United States, 10314
      • Completed
      • Neumora Investigator Site
    • Staten Island, New York, United States, 10310
      • Active, not recruiting
      • Neumora Investigator Site
    • The Bronx, New York, United States, 10461
      • Recruiting
      • Neumora Investigator Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28211
      • Recruiting
      • Neumora Investigator Site
    • Monroe, North Carolina, United States, 28112
      • Active, not recruiting
      • Neumora Investigator Site
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Active, not recruiting
      • Neumora Investigator Site
    • Dayton, Ohio, United States, 45417
      • Active, not recruiting
      • Neumora Investigator Site
    • North Canton, Ohio, United States, 44720
      • Active, not recruiting
      • Neumora Investigator Site
  • Oklahoma
    • Edmond, Oklahoma, United States, 73013
      • Recruiting
      • Neumora Investigator Site
    • Oklahoma City, Oklahoma, United States, 73118
      • Recruiting
      • Neumora Investigator Site
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18104
      • Recruiting
      • Neumora Investigator Site
    • Media, Pennsylvania, United States, 19063
      • Completed
      • Neumora Investigator Site
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Neumora Investigator Site
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Active, not recruiting
      • Neumora Investigator Site
  • Texas
    • Austin, Texas, United States, 78759
      • Recruiting
      • Neumora Investigator Site
    • Austin, Texas, United States, 78737
      • Active, not recruiting
      • Neumora Investigator Site
    • Dallas, Texas, United States, 75243
      • Recruiting
      • Neumora Investigator Site
    • DeSoto, Texas, United States, 75115
      • Recruiting
      • Neumora Investigator Site
    • Fort Worth, Texas, United States, 76104
      • Recruiting
      • Neumora Investigator Site
    • Houston, Texas, United States, 77030
      • Recruiting
      • Neumora Investigator Site #1
    • Houston, Texas, United States, 77090
      • Active, not recruiting
      • Neumora Investigator Site
    • Houston, Texas, United States, 77030
      • Completed
      • Neumora Investigator Site
    • Wichita Falls, Texas, United States, 76309
      • Completed
      • Neumora Investigator Site
  • Washington
    • Bellevue, Washington, United States, 98007
      • Active, not recruiting
      • Neumora Investigator Site
    • Everett, Washington, United States, 98201
      • Active, not recruiting
      • Neumora Investigator Site #1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

Rollover participants are eligible for the study if the following inclusion criteria are met:

• Completed a previous NMRA-335140 Phase 3 MDD study (example: NMRA-335140-301, NMRA-335140-302, or NMRA-335140-303) according to the completion definition in the parent study protocol.
• Signed an informed consent form (ICF) for this study.
• Willing to comply with the contraception requirements described in the inclusion criteria of the parent study protocol.
• Willing to comply with the concomitant medication/therapy restrictions described in the exclusion criteria of the parent study protocol.

Key Exclusion Criteria:

Rollover participants are excluded from the study if any of the following exclusion criteria are met:

• Diagnosed with another Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) disorder that would have been exclusionary in the parent study (eg, personality disorder, bipolar 1 or 2, schizophrenia, any other psychotic disorder, or moderate or severe substance or alcohol use disorder [excluding nicotine]).
• Considered to be at significant risk of suicide in the judgment of the Investigator. This includes participants who are actively suicidal (eg, any suicide attempts during the parent study) or are at serious suicidal risk as indicated by any current suicidal intent, including a plan, as assessed by the C-SSRS ("Since Last Visit" version, score of "YES" on suicidal ideation Item 4 or 5) and/or based on clinical evaluation by the Investigator; or are homicidal, in the opinion of the Investigator.
• Non-adherent with study medication (took ≤70% of study drug over any 2-week visit interval) or procedures during the parent study.
• Experienced treatment emergent adverse events (TEAEs) considered related to the study medication from the parent study and judged by the Investigator to be clinically significant to render the participant ineligible for enrollment.
• Have an abnormality on ocular examination that would prohibit continued study participation as determined by the Investigator.
• Use of disallowed concomitant medication or therapy that would have been exclusionary in the parent study, may compromise the safety of the participant, and/or confound the interpretation of protocol assessments.
• Considered by the Investigator to be inappropriate for any other reason.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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) during a 52-week treatment period.	Drug: NMRA-335140; Participants will receive NMRA-335140 at a dose of 80 mg once daily (QD), orally during a 52-week treatment period.; Other Names: BTRX-335140; CYM-53093; Navacaprant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability assessments based on Treatment Emergent Adverse Events (TEAEs) and validated clinical scales	An AE is any untoward medical occurrence in a participant or clinical trial participant, temporally associated with the use of trial intervention, whether or not considered related to the trial intervention. Any AE occurring following the start of treatment or occurring before treatment but increasing in severity afterward were counted as treatment-emergent AE (TEAE). Clinically significant abnormalities in Clinical Laboratory Evaluations, ECGs, Vital Signs, Physical and Ophthalmological examinations, Corneal Specular Microscopy, Columbia Suicide Severity Rating Scale (C-SSRS), and Sexual Functioning Questionnaire-14 (CSFQ-14) will be reported as TEAEs.	Up to 54 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) total score over time.	Change from baseline in MADRS total score over time will be reported. The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total score of 60. Higher scores represent a more severe condition.	Baseline and up to Week 54
Change from Baseline in the Snaith-Hamilton Pleasure Scale (SHAPS) total score over time	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 responses; items answered with strongly agree are coded as 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 54
Change from Baseline in the Patient Health Questionnaire-9 (PHQ-9) total score over time.	Change from baseline in PHQ-9 total score over time will be reported. The 9-item PHQ-9 scale scores each of the 9 symptom domains of the Diagnostic and Statistical Manual of Mental Disorders-5th Edition (DSM-5) diagnostic criteria for recurrent or single episode major depressive disorder (MDD) criteria and used both as a screening tool and a measure of response to treatment for depression. Each item is rated on a 4-point scale (0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day). The participant's item responses are summed to provide a total score (range of 0 to 27), with higher scores indicating greater severity of depressive symptoms.	Baseline and up to Week 54
Change from Baseline in PHQ-9 Anhedonia Item #1 over time.	The PHQ-9 is a participant-rated assessment scale for the evaluation of depression symptoms over the past 2 weeks. The PHQ-9 is a reliable and valid measure of depression and depression severity. The questionnaire consists of 9 items and each item is scored from 0 to 3. Participants will be asked how often they have been bothered by symptoms over the past 2 weeks (Not at all [0], Several days [1], More than half the time [2], or Nearly every day [3]). Higher scores indicate higher levels of depression.	Baseline and up to Week 54
Change from Baseline in the Hamilton Anxiety Rating Scale (HAM-A) total score over time.	The HAM-A is a clinician-rated instrument administered to assess severity of anxiety, its improvement during the course of treatment, and the timing of such improvement. This instrument will be completed by qualified and trained Investigator site raters based on a semi-structured interview for his/her assessment of the participant. The scale consists of 14 items. Each item is rated on a scale of 0 (feeling not present) to 4 (very severe prevalence of the feeling). The HAM-A total score is the sum of the 14 items and the score ranges from 0 to 56.	Baseline and up to Week 54
Change from Baseline in the Clinical Global Impression Scale of Severity (CGI-S)	Change from baseline in the CGI-S total score over time will be reported. The CGI-S evaluates the severity of psychopathology on a scale of 0 to 7. Considering total clinical experience, a participant is assessed on severity of mental illness at the time of rating according to: 0=not assessed; 1=normal (not at all ill); 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill participants. The CGI-S permits a global evaluation of the participant's condition at a given time.	Baseline and up to Week 54
Clinical Global Impression Scale of Improvement (CGI-I) score at each timepoint	The CGI-I scale is a clinician-rated instrument that measures the improvement of the participant's symptoms of depression. It is a 7-point scale where a score of 1 indicates that the participant is "very much improved," a score of 4 indicates that the participant has experienced "no change," and a score of 7 indicates that the participant is "very much worse."	Baseline and up to Week 54
Percentage of participants whose MADRS total score decreased by greater than or equal to 50% from Baseline over time		Up to Week 54
Percentage of participants whose MADRS total score decreased to 10 or less over time		Up to Week 54
Change from baseline in the Sheehan Disability Scale (SDS) over time	The SDS is a participant-rated instrument which was developed to assess functional impairment in 3 related domains of work/school, social, and family life. It is a brief self rated tool where the participant rates the 3 items on an anchored 10 point visual analog scale. Following the participant's self assessment, the rater should review the Work/School and Days Lost items to confirm appropriateness of the selected rating by evaluating the impact of MDD symptoms across those sectors. The SDS may be administered via telephone assessment; however, the participant must be provided with a portable document format (PDF) copy of the assessment for reference of the visual analog scale when selecting their ratings.	Baseline and up to Week 54

Collaborators and Investigators

• Sponsor: Neumora Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2023
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: September 1, 2023
• First Submitted That Met QC Criteria: September 1, 2023
• First Posted (Actual): September 8, 2023

Study Record Updates

• Last Update Posted (Actual): May 12, 2026
• Last Update Submitted That Met QC Criteria: May 10, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Safety; Efficacy; Major Depressive Disorder; Long-term; NMRA-335140; Navacaprant; NMRA335140; NMRA 335140
• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major; BTRX-335140
• Other Study ID Numbers: NMRA-335140-501; KOASTAL-LT (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