Study to Assess 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: NCT06058013
• Other study ID #: NMRA-335140-302
• Secondary ID: KOASTAL-2
• Status: Recruiting
• Phase: Phase 3
• Start date: December 20, 2023
• Est. completion date: May 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, 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 332
• Est. completion date: May 2025
• Est. primary completion date: January 2025
• 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 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.

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
Canada	Neumora Investigator Site	Kelowna	British Columbia
Canada	Neumora Investigator site	Markham	Ontario
United States	Neumora Investigator Site	Atlanta	Georgia
United States	Neumora Investigator Site	Baltimore	Maryland
United States	Neumora Investigator Site	Boston	Massachusetts
United States	Neumora Investigator site	Edmond	Oklahoma
United States	Neumora Investigator Site	Homestead	Florida
United States	Neumora Investigator Site	Lauderhill	Florida
United States	Neumora Investigator site	Marrero	Louisiana
United States	Neumora Investigator Site	Memphis	Tennessee
United States	Neumora Investigator Site	Miami	Florida
United States	Neumora Investigator Site	Miami Lakes	Florida
United States	Neumora Investigator Site	Monroe	North Carolina
United States	Neumora Investigator Site #1	New York	New York
United States	Neumora Investigator Site	Norwalk	Connecticut
United States	Neumora Investigator Site	Oklahoma City	Oklahoma
United States	Neumora Investigator Site	Orange	California
United States	Neumora Investigator Site	Orlando	Florida
United States	Neumora Investigator Site	Orlando	Florida
United States	Neumora Investigator Site	Princeton	New Jersey
United States	Neumora Investigator Site	Toms River	New Jersey
United States	Neumora Investigator Site	Towson	Maryland
United States	Neumora Investigator Site	Watertown	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Neumora Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Canada, 

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