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

Major Depressive Disorder Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06029426
• Other study ID #: NMRA-335140-301
• Secondary ID: KOASTAL-1
• Status: Recruiting
• Phase: Phase 3
• Start date: September 20, 2023
• Est. completion date: July 2025

Study information

• Verified date: June 2024
• Source: Neumora Therapeutics, Inc.
• Contact: Study Contact
• Email: explore[@]koastalstudy.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a randomized, double blind, placebo controlled, multi-center 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 332
• Est. completion date: July 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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 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 posttraumatic 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. 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.

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

Drug:
• NMRA 335140
Participants will receive NMRA-335140 at a dose of 80 mg QD, orally
• Placebo
Placebo will be administered orally

Locations

Country	Name	City	State
United States	Neumora Investigator Site	Allentown	Pennsylvania
United States	Neumora Investigator Site	Austin	Texas
United States	Neumora Investigator Site	Bellevue	Washington
United States	Neumora Investigator Site	Bellflower	California
United States	Neumora Investigator Site	Bentonville	Arkansas
United States	Neumora Investigator Site	Bloomfield Hills	Michigan
United States	Neumora Investigator Site	Boston	Massachusetts
United States	Neumora Investigator Site	Brooklyn	New York
United States	Neumora Investigator Site	Cedarhurst	New York
United States	Neumora Investigator Site	Charlottesville	Virginia
United States	Neumora Investigator Site	Chicago	Illinois
United States	Neumora Investigator Site	Cleveland	Ohio
United States	Neumora Investigator Site	Colorado Springs	Colorado
United States	Neumora Investigator Site	Columbus	Ohio
United States	Neumora Investigator Site	Dallas	Texas
United States	Neumora Investigator Site	Dayton	Ohio
United States	Neumora Investigator Site	Evanston	Illinois
United States	Neumora Investigator Site	Everett	Washington
United States	Neumora Investigator Site	Flowood	Mississippi
United States	Neumora Investigator Site	Gainesville	Florida
United States	Neumora Investigator Site	Garden Grove	California
United States	Neumora Investigator Site	Garfield Heights	Ohio
United States	Neumora Investigator Site	Glendale	California
United States	Neumora Investigator Site	Hallandale Beach	Florida
United States	Neumora Investigator Site	Houston	Texas
United States	Neumora Investigator Site	Houston	Texas
United States	Neumora Investigator Site	Huntsville	Alabama
United States	Neumora Investigator Site	Imperial	California
United States	Neumora Investigator Site	Jacksonville	Florida
United States	Neumora Investigator Site	Lafayette	California
United States	Neumora Investigator Site	Las Vegas	Nevada
United States	Neumora Investigator Site	Lauderhill	Florida
United States	Neumora Investigator Site	Little Rock	Arkansas
United States	Neumora Investigator Site	Long Beach	California
United States	Neumora Investigator Site	Los Angeles	California
United States	Neumora Investigator Site	Maitland	Florida
United States	Neumora Investigator Site	Marietta	Georgia
United States	Neumora Investigator Site	Media	Pennsylvania
United States	Neumora Investigator Site	Memphis	Tennessee
United States	Neumora Investigator Site	Methuen	Massachusetts
United States	Neumora Investigator Site	Miami	Florida
United States	Neumora Investigator Site	Miami	Florida
United States	Neumora Investigator Site	Miami	Florida
United States	Neumora Investigator Site	Miami Lakes	Florida
United States	Neumora Investigator Site	New York	New York
United States	Neumora Investigator Site	Oceanside	California
United States	Neumora Investigator Site	Orange	California
United States	Neumora Investigator Site	Orlando	Florida
United States	Neumora Investigator Site	Phoenix	Arizona
United States	Neumora Investigator Site	Plymouth Meeting	Pennsylvania
United States	Neumora Investigator Site	Riverside	California
United States	Neumora Investigator Site	Rogers	Arkansas
United States	Neumora Investigator Site	Saint Charles	Missouri
United States	Neumora Investigator Site	San Jose	California
United States	Neumora Investigator Site	Sherman Oaks	California
United States	Neumora Investigator Site #1	Sherman Oaks	California
United States	Neumora Investigator Site	Staten Island	New York
United States	Neumora Investigator Site	Tampa	Florida
United States	Neumora Investigator Site	Temecula	California
United States	Neumora Investigator Site	Torrance	California
United States	Neumora Investigator Site	Warrenville	Illinois
United States	Neumora Investigator Site	Watertown	Massachusetts
United States	Neumora Investigator Site	Wichita Falls	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Neumora Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change from Baseline to Week 6 assessed in the Snaith-Hamilton Pleasure Scale (SHAPS) total score	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.	Baseline and up to Week 6