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

Sponsor

Neumora Therapeutics, Inc. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT06029426

Collaborator

(none)

332

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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 extension study (NMRA 335140 501).

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: NMRA 335140 Drug: Placebo	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

332 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

A Phase 3, Randomized, Double Blind, Placebo Controlled Study to Evaluate the Effects of Oral NMRA 335140 Versus Placebo in Participants With Major Depressive Disorder

Anticipated Study Start Date :

Sep 1, 2023

Anticipated Primary Completion Date :

Dec 1, 2024

Anticipated Study Completion Date :

Jul 1, 2025

Arms and Interventions

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)	Drug: NMRA 335140 Participants will receive NMRA-335140 at a dose of 80 mg QD, orally Other Names: BTRX 335140 CYM-53093 Navacaprant
Placebo Comparator: Placebo Placebo participants will receive matching placebo tablet orally, once daily. Participants who complete the study may be eligible to participate in a separate 52-week open-label long term study.	Drug: Placebo Placebo will be administered orally

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)

Drug: NMRA 335140

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

Other Names:

BTRX 335140

CYM-53093

Navacaprant

Placebo Comparator: Placebo

Placebo participants will receive matching placebo tablet orally, once daily. Participants who complete the study may be eligible to participate in a separate 52-week open-label long term study.

Drug: Placebo

Placebo will be administered orally

Outcome Measures

Primary Outcome Measures

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

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key 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 exclusion criteria:

Have failed 2 or more courses of antidepressant treatment for the current MDD episode.
Have currently or in the past year any of the following DSM-5-TR disorders: personality disorder, 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, 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 (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.