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

Phase 3

Recruiting

• Conditions: Major Depressive Disorder
• Interventions: Drug: NMRA-335140; Drug: Placebo

• Registration Number: NCT06058039
• Lead Sponsor: Neumora Therapeutics, Inc.

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-09-21
• Study First Submitted QC: 2023-09-21
• Study First Posted: 2023-09-28
• Study Start: 2023-12-21
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-06
• Last Update Posted: 2024-12-09
• Primary Completion: 2025-03
• Study Completion: 2025-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 332

Inclusion Criteria

• 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

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Exclusion Criteria

• 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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
NMRA-335140 80 milligrams (mg) once daily (QD)	NMRA-335140	Participants will receive a NMRA-335140 tablet at a dose of 80 mg QD
Placebo	Placebo	Placebo participants will receive matching placebo tablet once daily

Primary Outcome Measures

Name	Time	Method
Change from Baseline to Week 6 in the Montgomery-Asberg Depression Rating Scale (MADRS) total score	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.

Secondary Outcome Measures

Name	Time	Method
Change from Baseline to Week 6 assessed in the Snaith-Hamilton Pleasure Scale (SHAPS) total score	Baseline and up to Week 6	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.

Trial Locations

Locations (2)

Neumora Investigator Site; 🇸🇪 Stockholm, Stockholms Län, Sweden

Neumora Investigator site; 🇺🇸 Miami, Florida, United States