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

NCT06058013 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: NMRA-335140-302KOASTAL-2
• Study Type: interventional
• Target: 332
• Locations: 4 countries
• Sites: 74

Brief 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). 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

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 once daily (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 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.

Sponsors & Collaborators

• Neumora Therapeutics, Inc.: lead

Study Sites (74)

Neumora Investigator Site

Encino, California, 91316, United States

Location

Neumora Investigator Site

Garden Grove, California, 92845, United States

Location

Neumora Investigator Site

Los Alamitos, California, 90720, United States

Location

Neumora Investigator Site

Newport Beach, California, 92660, United States

Location

Neumora Investigator Site

Orange, California, 92868, United States

Location

Neumora Investigator Site

Santa Ana, California, 92704, United States

Location

Neumora Investigator Site

Norwalk, Connecticut, 06851, United States

Location

Neumora Investigator Site

Bradenton, Florida, 34205, United States

Location

Neumora Investigator Site

Hollywood, Florida, 33024, United States

Location

Neumora Investigator Site

Homestead, Florida, 33032, United States

Location

Neumora Investigator Site

Lauderhill, Florida, 33161, United States

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Neumora Investigator Site

Maitland, Florida, 32751, United States

Location

Neumora Investigator Sites

Miami, Florida, 33122, United States

Location

Neumora Investigator Site

Miami, Florida, 33126, United States

Location

Neumora Investigator Site

Miami, Florida, 33133, United States

Location

Neumora Investigator Site

Miami, Florida, 33137, United States

Location

Neumora Investigator Site

Miami, Florida, 33186, United States

Location

Neumora Investigator Site

Miami Lakes, Florida, 33014, United States

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Neumora Investigator Site

Miami Lakes, Florida, 33016, United States

Location

Neumora Investigator Site

Orlando, Florida, 32801, United States

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Neumora Investigator Site

Orlando, Florida, 32803, United States

Location

Neumora Investigator Site

Orlando, Florida, 32807, United States

Location

Neumora Investigator Site

Pinellas Park, Florida, 33782, United States

Location

Neumora Investigator Site

Pompano Beach, Florida, 33060, United States

Location

Neumora Investigator Site

Tampa, Florida, 33607, United States

Location

Neumora Investigator Site#1

Tampa, Florida, 33613, United States

Location

Neumora Investigator Site

Tampa, Florida, 33613, United States

Location

Neumora Investigator Site

Atlanta, Georgia, 30318, United States

Location

Neumora Investigator Site

Atlanta, Georgia, 30328, United States

Location

Neumora Investigator Site

Atlanta, Georgia, 30338, United States

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Neumora Investigator Site

Marrero, Louisiana, 70072, United States

Location

Neumora Investigator Site

New Orleans, Louisiana, 70115, United States

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Neumora Investigator Site

Baltimore, Maryland, 21208, United States

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Neumora Investigator Site

Towson, Maryland, 21204, United States

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Neumora Investigator Site

Boston, Massachusetts, 02116, United States

Location

Neumora Investigator Site

Boston, Massachusetts, 02131, United States

Location

Neumora Investigator Site

Watertown, Massachusetts, 02472, United States

Location

Neumora Investigator Site

Mankato, Minnesota, 56001, United States

Location

Neumora Investigator Site

Princeton, New Jersey, 08540, United States

Location

Neumora Investigator Site

Toms River, New Jersey, 08755, United States

Location

Neumora Investigator Site

Albuquerque, New Mexico, 87109, United States

Location

Neumora Investigator Site

Buffalo, New York, 14215, United States

Location

Neumora Investigator Site

Inwood, New York, 11096, United States

Location

Neumora Investigator Site

New York, New York, 10017, United States

Location

Neumora Investigator Site

The Bronx, New York, 10461, United States

Location

Neumora Investigator Site

Monroe, North Carolina, 28112, United States

Location

Neumora Investigator Site

North Canton, Ohio, 44720, United States

Location

Neumora Investigator site

Edmond, Oklahoma, 73013, United States

Location

Neumora Investigator Site

Oklahoma City, Oklahoma, 73118, United States

Location

Neumora Investigator Site

Philadelphia, Pennsylvania, 19104, United States

Location

Neumora Investigator Site

North Charleston, South Carolina, 29405, United States

Location

Neumora Investigator Site

Memphis, Tennessee, 38119, United States

Location

Neumora Investigator Site

Austin, Texas, 78737, United States

Location

Neumora Investigator Site

Dallas, Texas, 75243, United States

Location

Neumora Investigator Site

Houston, Texas, 77030, United States

Location

Neumora Investigator Site

Bellevue, Washington, 98007, United States

Location

Neumora Investigator Site

Everett, Washington, 98201, United States

Location

Neumora Investigator Site

Curitiba, Paraná, 80240280, Brazil

Location

Neumora Investigator Site

Porto Alegre, Rio Grande do Sul, 90610-001, Brazil

Location

Neumora Investigator Site

Santa Cecília, São Paulo, 01228-000, Brazil

Location

Neumora Investigator Site

São Bernardo do Campo, São Paulo, 09726150, Brazil

Location

Neumora Investigator Site

São José do Rio Preto, São Paulo, 15090-000, Brazil

Location

Neumora Investigator Site

Rio de Janeiro, 22270-060, Brazil

Location

Neumora Investigator Site

São Paulo, 01236030, Brazil

Location

Neumora Investigator Site

Kelowna, British Columbia, V1Y 1Z9, Canada

Location

Neumora Investigator Site

Hamilton, Ontario, L8S 1B7, Canada

Location

Neumora Investigator site

Markham, Ontario, L3R 1A3, Canada

Location

Neumora Investigator Site

Toronto, Ontario, L5L 1W8, Canada

Location

Neumora Investigator Site

Toronto, Ontario, M5S 1M2, Canada

Location

Neumora Investigator Site

Santiago, Santiago Metropolitan, 7500710, Chile

Location

Neumora Investigator Site

Santiago, Santiago Metropolitan, 8330034, Chile

Location

Neumora Investigator Site

Antofagasta, 1270244, Chile

Location

Neumora Investigator Site

Santiago, 7560356, Chile

Location

Neumora Investigator Site

Santiago, 7561282, Chile

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 20, 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

BR (7); US (57); CL (5); CA (5)