Study to Assess the Effects of Oral NMRA-335140 in Participants With Major Depressive Disorder

NCT06058039 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: NMRA-335140-303KOASTAL-3
• Study Type: interventional
• Target: 332
• Locations: 8 countries
• Sites: 71

Brief 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). 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

Keywords

Major Depressive Disorder; NMRA-335140; Placebo-controlled; Double-blind; Navacaprant; NMRA335140; NMRA 335140

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  Baseline and up to Week 6

Study Arms (2)

NMRA-335140 80 milligrams (mg) once daily (QD)

EXPERIMENTAL

Participants will receive a NMRA-335140 tablet at a dose of 80 mg QD

Drug: NMRA-335140

Placebo

PLACEBO COMPARATOR

Placebo participants will receive matching placebo tablet once daily

Drug: Placebo

Interventions

NMRA-335140 DRUG

Participants will receive NMRA-335140 at a dose of 80 mg QD, orally

Also known as: BTRX-335140, CYM-53093, Navacaprant

NMRA-335140 80 milligrams (mg) once daily (QD)

Placebo DRUG

Placebo will be administered orally

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Neumora Therapeutics, Inc.: lead

Study Sites (71)

Neumora Investigator Site

Cerritos, California, 90703, United States

Location

Neumora Investigator Site

Irvine, California, 92614, United States

Location

Neumora Investigator Site

Long Beach, California, 90807, United States

Location

Neumora Investigator Site

San Diego, California, 92103, United States

Location

Neumora Investigator Site

San Francisco, California, 94107, United States

Location

Neumora Investigator Site

New Haven, Connecticut, 06520, United States

Location

Neumora Investigator Site

Brandon, Florida, 33511, United States

Location

Neumora Investigator Site

Hialeah, Florida, 33012, United States

Location

Neumora Investigator Site

Hialeah, Florida, 33016, United States

Location

Neumora Investigator Site

Jacksonville, Florida, 32256, United States

Location

Neumora Investigator Site

Miami, Florida, 33143, United States

Location

Neumora Investigator Site

Miami, Florida, 33165, United States

Location

Neumora Investigator site

Miami, Florida, 33174, United States

Location

Neumora Investigator Site

Miami Beach, Florida, 33140, United States

Location

Neumora Investigator site

Miami Springs, Florida, 33166, United States

Location

Neumora Investigator Site

Palm Bay, Florida, 32905, United States

Location

Neumora Investigator Site

Pembroke Pines, Florida, 33024, United States

Location

Neumora Investigator Site

Pompano Beach, Florida, 33060, United States

Location

Neumora Investigator Site

Saint Augustine, Florida, 32086, United States

Location

Neumora Investigator Site

Atlanta, Georgia, 30328, United States

Location

Neumora Investigator Site

Decatur, Georgia, 30030, United States

Location

Neumora Investigator Site

Savannah, Georgia, 31405, United States

Location

Neumora Investigator Site

Springfield, Massachusetts, 01103, United States

Location

Neumora Investigator Site

St Louis, Missouri, 63141, United States

Location

Neumora Investigator Site

Omaha, Nebraska, 68112, United States

Location

Neumora Investigator Site

Berlin, New Jersey, 08009, United States

Location

Neumora Investigator Site

New York, New York, 10029, United States

Location

Neumora Investigator Site

New York, New York, 10036, United States

Location

Neumora Investigator Site

Staten Island, New York, 10310, United States

Location

Neumora Investigator Site

Charlotte, North Carolina, 28211, United States

Location

Neumora Investigator Site

Austin, Texas, 78759, United States

Location

Neumora Investigator Site

DeSoto, Texas, 75115, United States

Location

Neumora Investigator Site

Fort Worth, Texas, 76104, United States

Location

Neumora Investigator Site

Plano, Texas, 75093, United States

Location

Neumora Investigator Site

Cherven Bryag, Pleven, 5980, Bulgaria

Location

Neumora Investigator Site

Sofia, Sofia-Grad, 1408, Bulgaria

Location

Neumora Investigator Site

Sofia, Sofia-Grad, 1463, Bulgaria

Location

Neumora Investigator Site

Sofia, Sofia-Grad, 1680, Bulgaria

Location

Neumora Investigator Site

Kardzhali, 6600, Bulgaria

Location

Neumora Investigator Site

Pleven, 5800, Bulgaria

Location

Neumora Investigator Site

Targovishte, 7700, Bulgaria

Location

Neumora Investigator Site #1

Varna, 9020, Bulgaria

Location

Neumora Investigator Site

Varna, 9020, Bulgaria

Location

Neumora Investigator Site

Pilsen, Plzen, 301 00, Czechia

Location

Neumora Investigator Site

Prague, Prague, 186 00, Czechia

Location

Neumora Investigator Site #1

Kladno, South Bohemian, 272 01, Czechia

Location

Neumora Investigator Site

Kladno, 272 01, Czechia

Location

Neumora Investigator Site

Prague, 109 00, Czechia

Location

Neumora Investigator Site

Helsinki, Etelä-Suomen Lääni, 00100, Finland

Location

Neumora Investigator Site

Turku, Etelä-Suomen Lääni, 20520, Finland

Location

Neumora Investigator Site

Oulu, Oulun Lääni, 90100, Finland

Location

Neumora Investigator Site

Clermont-Ferrand, Auvergne-Rhône-Alpes, 63000, France

Location

Neumora Investigator Site

Douai, Hauts-de-France, 59500, France

Location

Neumora Investigator Site

Montpellier, Hérault, 34295, France

Location

Neumora Investigator Site

Angers, Maine-et-Loire, 49100, France

Location

Neumora Investigator Site

La Roche-sur-Yon, Vendée, 85000, France

Location

Neumora Investigator Site

Poitiers, Vienne, 86000, France

Location

Neumora Investigator Site #1

Berlin, 10117, Germany

Location

Neumora Investigator Site

Berlin, 10117, Germany

Location

Neumora Investigator Site

Berlin, 10629, Germany

Location

Neumora Investigator Site

Berlin, 13187, Germany

Location

Neumora Investigator Site

Hamburg, 20253, Germany

Location

Neumora Investigator Site

Suchy Las, Greater Poland Voivodeship, 62-002, Poland

Location

Neumora Investigator Site

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-133, Poland

Location

Neumora Investigator Site

Wroclaw, Lower Silesian Voivodeship, 50-414, Poland

Location

Neumora Investigator Site

Lublin, Lublin Voivodeship, 20-109, Poland

Location

Neumora Investigator Site

Lublin, Lublin Voivodeship, 20-582, Poland

Location

Neumora Investigator Site

Bialystok, Podlaskie Voivodeship, 15-879, Poland

Location

Neumora Investigator Site

Gdansk, Pomeranian Voivodeship, 80-438, Poland

Location

Neumora Investigator Site

Lund, Skåne County, 222 22, Sweden

Location

Neumora Investigator Site

Stockholm, Stockholm County, 113 29, Sweden

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

BTRX-335140

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Sponsor will also be blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2023
• First Posted: September 28, 2023
• Study Start: December 21, 2023
• Primary Completion: May 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

SE (2); US (34); CZ (5); PL (7); DE (5); FR (6); FI (3); BU (9)